Actinomycosis: etiology, clinical features, diagnosis, treatment, and ...
Review Article Infections Caused by Actinomyces neuii : A Case … · 2019. 7. 30. · Members of...
Transcript of Review Article Infections Caused by Actinomyces neuii : A Case … · 2019. 7. 30. · Members of...
Review ArticleInfections Caused by Actinomyces neuii A Case Series andReview of an Unusual Bacterium
Nathan Zelyas1 Susan Gee1 Barb Nilsson2 Tracy Bennett3 and Robert Rennie1
1Provincial Laboratory for Public Health Walter Mackenzie Health Sciences Centre University of Alberta Hospital 8440-112 StreetEdmonton AB Canada T6G 2J22Queen Elizabeth II Hospital 10409-98 Street Grande Prairie AB Canada T8V 2E83Red Deer Regional Hospital 3942-50a Avenue Red Deer AB Canada T4N 4E7
Correspondence should be addressed to Nathan Zelyas nzelyasualbertaca
Received 24 July 2015 Accepted 28 December 2015
Copyright copy 2016 Nathan Zelyas et al This is an open access article distributed under the Creative Commons Attribution Licensewhich permits unrestricted use distribution and reproduction in any medium provided the original work is properly cited
Background Actinomyces neuii is a Gram-positive bacillus rarely implicated in human infections However its occurrence is beingincreasingly recognized with the use of improved identification systems Objective To analyse A neuii infections in AlbertaCanada and review the literature regarding this unusual pathogen Methods Cases of A neuii were identified in 2013-2014 inAlberta Samples were cultured aerobically and anaerobically A predominant catalase positive Gram-positive coryneform bacilluswith no branching was isolated in each case Testing was initially done with API-CORYNE (bioMerieux) and isolates were sentto the Provincial Laboratory for Public Health for further testing Isolatesrsquo identities were confirmed by matrix-assisted laserdesorption ionization time-of-flightmass spectrometrymicrobial identification system (MALDI-TOFMSMIS bioMerieux) andorDNA sequencing Results Six cases of A neuii infection were identified All patients had soft tissue infections typically incisionand drainage were done followed by a course of antibiotics Agents used included cephalexin ertapenem ciprofloxacin andclindamycin All had favourable outcomes Conclusions While A neuii is infrequently recognized it can cause a diverse arrayof infections Increased use of MALDI-TOF MS MIS is leading to increased detection thus understanding the pathogenicity ofthis bacterium and its typical susceptibility profile will aid clinical decision-making
1 Introduction
Members of the genus Actinomyces are the commonest causeof the oft-described disease actinomycosis This clinicalsyndrome is characterized by its chronic course the invasionof multiple tissue planes the formation of sinus tracts andmasses resembling malignancy the production of ldquosulfurgranulesrdquo and its relapsing nature when short courses ofantimicrobials are used [1ndash3] Although actinomycosis typi-cally involves cervicofacial thoracic and abdominal regionsActinomyces species can cause a variety of infections includ-ing abscesses and skin infections in various locations [4ndash6]ocular infections [5] urinary tract infections [4 6] genitalinfections [4 6] intrauterine contraceptive device infections[5 7] appendicitis [4] cholecystitis [4] osteomyelitis [5 6]bacteremia [4ndash6] endocarditis [8 9] CNS infections [10ndash13]and many others [14]
Organisms belonging to the Actinomyces genus are typi-cally aerotolerant Gram-positive rods that grow in branchingfilaments Isolates are usually catalase and urease negative
CAMP negative and nonpigmented and produce succinicand lactic acid as major end products of metabolism [15]However not all Actinomyces species share all of thesecharacteristics and one of these is the clinically relevantActinomyces neuii
Prior to 1994 A neuii isolates were classified as mem-bers of CDC (Centers for Disease Control) fermentativecoryneform group 1 or group 1-like [16 17] These isolateswere common in that they were Gram-positive coryneformrods nonmotile catalase positive urease negative esculinhydrolysis negative CAMP positive and fermented glucosemaltose sucrose mannose and xylose [16 17] Sequencingof the 16S rRNA genes of CDC coryneform group 1 andgroup 1-like isolates revealed that they are closely relatedsubspecies belonging to the Actinomyces genus A neuiisubsp neuii and A neuii subsp anitratus [18] The termldquoneuiirdquo was chosen to honour Dr Harold Neu a well-knownphysician of infectious diseases ldquoanitratusrdquo was chosen toreflect the lack of nitrate reduction by A neuii susp anitratus[18]
Hindawi Publishing CorporationCanadian Journal of Infectious Diseases and Medical MicrobiologyVolume 2016 Article ID 6017605 7 pageshttpdxdoiorg10115520166017605
2 Canadian Journal of Infectious Diseases and Medical Microbiology
Since its classification A neuii has been implicated ina number of human infections [19] However due to itsunusual laboratory characteristics isolates have likely beendismissed as members of the Corynebacterium genus and itsoccurrence in clinical specimens is probably underreportedIndeed the use of advanced bacterial identification systemssuch as matrix-assisted laser desorption ionization time-of-flight mass spectrometry microbial identification systems(MALDI-TOF MS MIS) in clinical laboratories will likelyresult in an increased frequency of correctly identifying bac-teria that were previously difficult to identify using traditionalphenotypic methods [20 21] Because of the increasinglywidespread use of MALDI-TOF MS MIS understandingthe significance of isolating previously underrecognizedpathogens is important in guiding laboratory reporting andclinical practices
The present study examines cases of A neuii infectionsdetected in several community and tertiary care laboratoriesand confirmed by a reference microbiology laboratory Theliterature regarding A neuii infections is reviewed and com-pared to the findings in this series of cases
2 Methods
Clinical specimens were submitted to local microbiologylaboratories during 2013-2014 in Alberta Canada Sampleswere initially examined microscopically after Gram stain-ing and cultured aerobically and if deemed appropriateanaerobically on typical culture media including sheep bloodagar brain heart infusion agar and phenylethyl alcoholagar (Dalynn Biologicals Inc Calgary Alberta) Isolateswere initially identified by producing characteristic convexcircular smooth and white colonies with entire edges withconsistent Gram stain appearance catalase reaction andmajor acid end-product profiles as determined by gas-liquidchromatography If the specimen was submitted and initiallyworked up by a local microbiology laboratory isolates sus-pected of being A neuii were further identified using theAPI-CORYNE (bioMerieux France) test strip Further con-firmation of isolatesrsquo identities was performed at the AlbertaProvincial Laboratory for Public Health Edmonton Albertausing the VITEK MS MALDI-TOF MS MIS (bioMerieuxFrance) andor 16S rRNA gene sequencing The VITEK MSMALDI-TOF MS MIS assay was carried out according tothe manufacturer The in vitro diagnostic database used forcomparing spectra was VITEK MS v20 Knowledge Base(bioMerieux France) matches with a ge999 confidencewere accepted as A neuii
In order to carry out the sequencing of a portion ofthe 16S rRNA gene genomic DNA was extracted usinga pure culture of organism growing on sheep blood agarincubated anaerobically at 35∘C A sweep of organism wassuspended in 12mM Tris buffer pH 74 and centrifugedat 13000timesg for 3 minutes The pellet was resuspended inrapid lysis buffer (100mM NaCl 10mM Tris-HCl pH 831mM EDTA pH 90 1 Triton X-100) and subjected tothree freezethaw cycles of minus80∘C for 15 minutes followedby complete thawing This preparation was then boiled for15 minutes cooled to room temperature and centrifuged
at 13000timesg for 15 minutes Nucleic acid in the supernatantwas used for conventional polymerase chain reaction (PCR)with the following previously described 16S rRNA geneprimers 16S-F 51015840AGA GTT TGA TCA TGG CTC AG 31015840and 16S-R 51015840GGA CTA CCA GGG TAT CTA AT 31015840 [46]Amplification reactions were carried out using PlatinumPfx DNA Polymerase (Thermo Fisher Scientific WalthamMA USA) according to the manufacturer with the followingcycling conditions 94∘C for 2 minutes then 25 cycles of94∘C for 15 seconds 50∘C for 30 seconds and 68∘C for 20seconds After product cleanup and quantification with theChargeSwitchKit and theNanoDrop 2000 (ThermoFisherScientific) respectively DNA sequencing was performedusing the BigDye Cycle Sequencing and BigDye XTermi-nator Purification Kits (Thermo Fisher Scientific) on theApplied Biosystems 3500xL Genetic Analyzer (ThermoFisher Scientific) Sequence data was viewed and editedusing the BioEdit program and uploaded to the RibosomeDatabase Project to obtain sequence matches [47] All butone of the sequences obtained were over 350 nucleotidesdespite multiple attempts one amplicon yielded only 257nucleotides of high quality sequence (see SupplementaryData in the Supplementary Material available online athttpdxdoiorg10115520166017605) In each case a seq-match (S ab) score of 1000 (signifying 100 identity) wasfound with at least one other submitted A neuii rRNA genenucleotide sequence Identification to the subspecies level wasnot performed
Susceptibility testing was carried out using gradientdiffusion Etest strips (bioMerieux France) under the con-ditions described for anaerobic organisms by the Clinicaland Laboratory Standards Institute (CLSI [48]) Brieflya 05 McFarland suspension of organism was inoculatedonto Anaerobic Laked Blood Agar (Dalynn Biologicals Inc)and incubated at 36∘C anaerobically for 48 hours Minimalinhibitory concentrations (MICs) were determined as per themanufacturerrsquos instructions Breakpoints were interpretedas per CLSI guidelines for anaerobic bacteria [48] Patientinformation was obtained from specimen requisitions andthe treating physiciansThework described in this paper doesnot require ethics review as defined in Section 24 of theTri-Council Policy Statement Ethical Conduct for ResearchInvolving Humans [49]
3 Results
Actinomyces neuii was isolated from eight patients fromFebruary 2013 to July 2014 patient information was avail-able for six of these cases (Table 1) From each patient apredominant Gram-positive catalase positive coryneformbacillus was isolated Gas chromatography revealed a majorsuccinic acid peak for the isolates In all three cases wherethe isolate was initially worked up by a local laboratory theAPI-CORYNE test strip correctly identified the organismas A neuii The first five isolates were confirmed as Aneuii using 16S rRNA gene sequencing this allowed thelaboratoryrsquos VITEK MS MALDI-TOF MS MIS instrumentto be validated for identifying A neuii and therefore beused without further extensive confirmatory testing Patient
Canadian Journal of Infectious Diseases and Medical Microbiology 3
Table1Ch
aracteris
ticso
fpatientsfrom
which
Aneuiiw
asdetected
andsusceptib
ilityprofi
leso
fisolates
Agesex
Com
orbiditie
saInfection
Gram
smearb
Coisolates
MICso
fAneuii
isolates(mgL)
cTreatm
ent
30M
Previous
head
injury
right
ACLrepair
Leftthigh
abscess
4+WBC
4+GPC
4+GPB
Prevotellabivia
Anaerob
icGPC
PenicillinGle0016
Amoxclav
0016
Imipenem
0023
Vancom
ycin
05
Clindamycinge256
Incisio
nand
drainage
Cephalexin7days
45M
TIID
Mdyslip
idem
iaLeftingu
inal
abscess
3+WBC
2+GPC
2+GNB
1+GPB
Staphylococcus
lugdun
ensis
Anaerob
icGPC
PenicillinGle0016
Amoxclav
0016
Imipenem
0023
Vancom
ycin
05
Clindamycin
le0016
Incisio
nand
drainage
Cephalexin7days
46M
Paraplegiarenal
calculiatria
lfib
rillation
previous
endo
carditissacral
ulcer
Rightaxillary
abscess
3+WBC
3+GPB
2+GPC
Non
e
PenicillinGle003
Amoxclavle0016
Imipenem
0023
Vancom
ycinle05
Clindamycin
le0016
Incisio
nand
drainage
Cephalexin
(unk
nown
duratio
n)
48M
Hypertension
TIID
Mobesity
previous
Fournierrsquos
gang
renediabetic
foot
infections
Rightg
roin
abscess
3+WBC
3+GPB
3+GNB
2+GPC
Proteusm
irabilis
Staphylococcus
lugdun
ensis
Actin
omycessp
Mixed
anaerobes
PenicillinG000
6Amoxclavle0016
Imipenem
0023
Vancom
ycin
05
Clindamycin
0023
Incisio
nand
drainage
Ceft
riaxone
3days
Ertapenem
5days
Amoxclav10
days
68M
Bilateral
spermatocele
swith
spermatocelectomies
Posto
perativ
erig
htscrotum
abscess
2+WBC
3+GPC
2+GPB
2+GNB
Coagu
lase-negative
Staphylococcus
Coryn
eform
bacillu
sPropionibacterium
sp
PenicillinGle0016
Amoxclavle0016
Imipenem
0032
Vancom
ycin
05
Clindamycin
0032
Ciprofl
oxacin
28days
85F
Hypertension
hypo
thyroidism
celiacd
isease
Postb
iopsyleft
ankleu
lcer
3+GNB
2+GPC
Acinetobacter
baum
anniicalcoaceticu
scomplex
Streptococcusa
galactiae
PenicillinGle006
Amoxclavle0016
Imipenem
0023
Vancom
ycin
038
Clindamycin
0023
Wou
ndcare
Clindamycin
10days
Cephalexin7days
a TIIDMtypeIId
iabetesm
ellitusA
CLanteriorc
ruciateligam
ent
b WBC
whitebloo
dcellsG
PCG
ram-positive
cocciGPB
Gram-positive
bacilliG
NB
Gram-negativeb
acilliforW
BC1+representslt1cellp
erhigh
power
field(times100oilimmersio
nlens)2+
represents1ndash5c
ells
3+represents6ndash
10cellsand
4+representsgt10
cellsfor
bacteria1+representsle1cellp
erhigh
power
field2+represents2ndash10
cells3+represents11ndash
50cellsand
4+representsgt50
cells
c MICm
inim
alinhibitory
concentration
amoxclavam
oxicillin-clav
ulanate
4 Canadian Journal of Infectious Diseases and Medical Microbiology
ages ranged from 30 to 85 years all but one of the patientswere male There was no obvious trend in patient comor-bidities While one of the specimens was collected from alower extremity skin ulcer the remaining five were collectedfrom abscesses in different locations Gram smears usuallyrevealed the presence of multiple types of bacteria in theclinical specimens and the resulting cultures grew at leasttwo different bacterial species as coisolates in all but onecase (Table 1) The most common coisolates were anaerobicbacteria but themore common skin and soft tissue infectiousagent Staphylococcus lugdunensis was isolated in two casesSusceptibility testing showed that all of the A neuii isolateshad low minimal inhibitory concentrations to penicillinbroader spectrum 120573-lactams and vancomycin one isolatehad an MIC ge 256mgL to clindamycin while the othershadMICs of le0032mgL Treatment of the abscesses usuallyinvolved incision and drainage followed by seven- to 18-daycourses of a120573-lactam though one of the abscesses was treatedwith a four-week course of ciprofloxacin without drainageNone of the patients were noted to have relapses followingtherapy
4 Discussion
Actinomyces neuii has been isolated in a wide range of clinicalscenarios but has rarely been reported in the literatureThereare less than 100 cases reported in the literature of A neuiiinfections we and others have hypothesized that dismissal asa commensal coryneform bacillus may be the reason Whilethere have only been scattered reports of A neuii causinginfection since interest in the organism was originally raisedin the mid-1990s the frequency of reports recognizing itas a pathogen has recently increased likely due to the useof advanced identification systems Abscesses are the mostcommon manifestation of A neuii infection with more thanhalf of the reported cases describing abscesses or infectedatheromas (Table 2) [6 17 19 22ndash45] A number of otherinfectious entities implicating A neuii have been describedincluding ulcer infections cellulitis urinary tract infectionsand prostatitis (Table 2)
There have been two reported cases ofA neuii chorioam-nionitis one of which resulted in neonatal sepsis afterpremature delivery [19 27] In the latter case the organismwas isolated from multiple sites from the neonate includingthe external ear canal a gastric aspirate and blood [27]
As demonstrated by the above caseA neuii can also causemore invasive infections There are multiple other cases ofA neuii bacteremia various prostheses infections two casesof chronic osteomyelitis two cases of peritoneal dialysis-associated peritonitis and single cases of native aorticvalve endocarditis chronic pericarditis and lymphadenitisinterestingly there have been multiple reports of A neuiicausing endophthalmitis the majority of which occurredpostoperatively (Table 2)
Intriguingly there has been only one case reported of Aneuii causing a classical clinical picture of actinomycosis withrecurrent breast abscesses fistula formation filamentousgrowth and sulfur granules [23]This is in agreementwith thefindings of our study as none of the patients exhibited such
findings nor did they require extended durations of antibiotictherapy
The infections caused byA neuii described in the presentstudy were all associated with abscess formation in soft tissueexcept for one which was isolated from an ankle ulcer Thelatter case may not actually represent an infection as therewere no white cells in the clinical specimen The age range ofpatients infected with A neuii in the literature is 0ndash94 yearswith a mean of 50 years this is comparable with the ages ofpatients in this study While reports in the literature show analmost even number of males and females acquiring A neuiiinfections themajority of the patients in our studyweremalethis is likely due to the small number of cases examined
Previous studies found that abscesses typically includedmixed anaerobic organisms and skin flora as coisolates(Table 2) This is similar to the present study in which fourof six specimens grew anaerobic bacteria and one grewcoagulase-negative staphylococci as well the patient fromwhom A neuii was isolated in pure culture had Gram-positive cocci seen in the direct smear making it possible thatthis was also a mixed anaerobic infection from which at leastone anaerobe failed to grow in culture However this studyalso had a larger variety of aerobic coisolates in specimensthan was reported in previous studies It is difficult to assessthe specific role of A neuii in these mixed infections butits presence in polymicrobial abscesses makes up the vastmajority of cases Improved identification of A neuii in thelaboratory will undoubtedly help to clarify its role in disease
There are few studies describing the use of MALDI-TOFMSMIS in identifying A neuii One other study showed thatthe VITEK MS system was able to correctly identify A neuiito the species level in eight of 12 instances [21] Three groupsused Bruker MALDI-TOF MS MIS (Bruker Billerica MAUSA) two isolates were designated as A neuii with a ldquosecuregenus probable species identificationrdquo level of confidence[20 30] while the degree of certainty in identification ofthe other isolate was not described [45] Due to the limitedamount of experience with either type of MALDI-TOF MSMIS there is no current evidence that one system is superiorto the other in identifying A neuii
The majority of tested isolates show susceptibility to 120573-lactams including penicillin G ampicillin cefazolin cefurox-ime ceftriaxone and imipenem [17 19 27 28 34ndash36 4042 43] Other agents with in vitro activity against A neuiiinclude clindamycin erythromycin tetracycline and van-comycin [17 19 27 28 35 36 40 42] Fluoroquinolones(including ciprofloxacin and levofloxacin) aminoglycosides(including gentamicin and amikacin) and trimethoprim-sulfamethoxazole frequently demonstrate less in vitro activityagainst isolates [19 35 36 40]
Similar to previous studies the isolates in the currentseries were generally quite susceptible to the tested antibi-otics All isolates had low MICs to penicillin amoxicillin-clavulanate and vancomycin only one isolate showed resis-tance to clindamycin
As shown in Table 2 treatment regimens in the literatureare varied and have been dictated by the type and severityof infection In general successful treatment regimens ofteninvolved the use of 120573-lactam antibiotics as well as appropriate
Canadian Journal of Infectious Diseases and Medical Microbiology 5
Table2Ch
aracteris
ticso
fpreviou
slyrepo
rted
caseso
fAneuiiinfections
intheliterature
Infection
Num
bero
fcases
Coisolates
Treatm
ent
Outcomes
References
Abscessinfected
atheromaa
56
Coagu
lase-negatives
taph
ylococci
Enterococcus
spp
Corynebacterium
spp
Anaerob
es
Incisio
nanddrainagew
ithor
with
out
antib
iotic
therapy(usually120573-la
ctam
soccasio
nally
tetracyclin
eciprofl
oxacin)
Generallyfavourable
ifsource
controlis
achieved
[6171922ndash
26]
Cutaneou
sinfectio
nb9
Coagu
lase-negatives
taph
ylococci(eight
cases)
Not
repo
rted
Favourable
[1719]
Genito
urinaryinfectionc
6Non
eAntibiotic
therapywith120573-la
ctam
sFavourable
[1927]
Bacterem
iad
8Non
e
Twocasesreportedtherapy
Ampicillinwith
gentam
icin
(twoweeks)
follo
wed
byPO
penicillin(fo
urweeks)
Initialciprofl
oxacin
follo
wed
byim
ipenem
e
Generallyfavourable
(one
mortality)
[1927]
Endo
carditis
1Non
e
Aorticvalvee
xcision
with
homograft
implantatio
nfollo
wed
byam
picillin
(threew
eeks)ceftriaxone
(ninew
eeks)
andthen
POdo
xycycline
(ninem
onths)
Favourable
[28]
Chronicp
ericarditis
1Non
ePeric
ardialflu
iddrainage
andantib
iotic
therapy(specific
antib
iotic
snot
repo
rted)
Not
repo
rted
[29]
Lymph
adenitis
1Virid
ansg
roup
streptococci
Prevotellatim
onensis
Anaerob
icGram-positive
cocci
Lymph
node
andfistulaexcisio
nfollo
wed
byIV
andthen
POam
oxicillin-clavulanate(sixmon
ths)
Favourable
[30]
Oste
omyelitis
2Dermabacterh
ominis(one
case)
Surgicalcuretta
gefollo
wed
by120573-la
ctam
therapyform
ultip
lemon
ths
Favourable
[2531]
Periton
itis(second
aryto
periton
eald
ialysis
)2
Non
e
Catheter
retentionwith
either
intraperito
nealcefazolin
andcefta
zidime
(twoweeks)followed
bypenicillinG
(four
weeks)or
intraperito
neal
ampicillin
teicop
lanin
andtobram
ycin
(twoweeks)
Favourable
[3233]
Endo
phthalmitis
6Non
eVa
rious
syste
mic(POor
IV)a
nddirect
(intravitrealorsub
conjun
ctival
injectionsdrops)a
ntibiotic
sFavourable
[34ndash
38]
Prostheticmaterial
infectionf
8Ty
pically
none
Coagu
lase-negatives
taph
ylococciand
mixed
anaerobes(breastim
plantcase)
Removalreplacemento
fprosthetic
materialfollowed
byprolon
gedantib
iotic
therapy(w
eeks
toon
eyeardepend
ingon
theinfectio
n)
Favourable
[2539ndash4
5]
a Including
breast
axillaryinguinaliliacc
rest
ischiorectalandpilonidalabscessesone
case
ofhidradenitissup
purativ
amostsitesw
eren
otspecified
b Including
ulcerinfectio
nsdiabetic
foot
ulcerinfectio
nsand
cellu
litis
c Including
urinarytractinfectio
nsprosta
titis
andchorioam
nion
itis
d Including
onec
aseo
fneonatalsepsis
second
aryto
chorioam
nion
itisther
emaining
casesh
adun
clear
orun
repo
rted
sources
e Thep
atient
treated
with
thisregimen
isthes
inglem
ortalityrepo
rted
intheliterature
associated
with
Aneuiiinfectio
nf Including
infections
ofan
intravenou
scatheteram
echanicalh
eartvalveah
ipprosthesis
apenile
prosthesis
breastim
plants
andventric
ulop
erito
nealshun
ts
6 Canadian Journal of Infectious Diseases and Medical Microbiology
surgical interventions This was also the case in the presentstudy as almost all of the treatments involved incision anddrainage of abscesses with subsequent 120573-lactam courses
While A neuii is not a commonly identified organismthere are numerous reports of it causing both invasive andnoninvasive disease Fortunately it is a very susceptibleorganism that can often be treated with 120573-lactams followingdrainage of abscesses or other surgical management Under-standing its clinical significance and typical susceptibilitypatterns will ease decision-making when the organism isencountered as it surely will be with the current widespreaduse of MALDI-TOF MS MIS
Conflict of Interests
The authors have no conflict of interests to declare
References
[1] K P Schaal and H-J Lee ldquoActinomycete infections inhumansmdasha reviewrdquo Gene vol 115 no 1-2 pp 201ndash211 1992
[2] R A Smego Jr and G Foglia ldquoActinomycosisrdquo Clinical Infec-tious Diseases vol 26 no 6 pp 1255ndash1263 1998
[3] V KWong T D Turmezei and V CWeston ldquoActinomycosisrdquoBritish Medical Journal vol 343 Article ID d6099 2011
[4] L J M Sabbe D Van De Merwe L Schouls A BergmansM Vaneechoutte and P Vandamme ldquoClinical spectrum ofinfections due to the newly described Actinomyces species Aturicensis A radingae and A europaeusrdquo Journal of ClinicalMicrobiology vol 37 no 1 pp 8ndash13 1999
[5] V Hall P R Talbot S L Stubbs and B I Duerden ldquoIdenti-fication of clinical isolates of Actinomyces species by amplified16S ribosomal DNA restriction analysisrdquo Journal of ClinicalMicrobiology vol 39 no 10 pp 3555ndash3562 2001
[6] J E Clarridge III and Q Zhang ldquoGenotypic diversity of clinicalActinomyces species phenotype source and disease correlationamong genospeciesrdquo Journal of Clinical Microbiology vol 40no 9 pp 3442ndash3448 2002
[7] A S Fiorino ldquoIntrauterine contraceptive device-associatedactinomycotic abscess and Actinomyces detection on cervicalsmearrdquo Obstetrics and Gynecology vol 87 no 1 pp 142ndash1491996
[8] KWestling C Lidman and AThalme ldquoTricuspid valve endo-carditis caused by a new species of Actinomyces Actinomycesfunkeirdquo Scandinavian Journal of Infectious Diseases vol 34 no3 pp 206ndash207 2001
[9] A Jitmuang ldquoPrimary actinomycotic endocarditis a casereport and literature reviewrdquo Journal of the Medical Associationof Thailand vol 91 no 6 pp 931ndash936 2008
[10] S Ushikoshi I Koyanagi K Hida Y Iwasaki and H AbeldquoSpinal intrathecal actinomycosis a case reportrdquo Surgical Neu-rology vol 50 no 3 pp 221ndash225 1998
[11] S Wang R L Wolf J H Woo et al ldquoActinomycotic braininfection registered diffusion perfusion MR imaging and MRspectroscopyrdquoNeuroradiology vol 48 no 5 pp 346ndash350 2006
[12] L Ghafghaichi S Troy I Budvytiene N Banaei and E JBaron ldquoMixed infection involving Actinomyces Aggregatibac-ter and Fusobacterium species presenting as perispinal tumorrdquoAnaerobe vol 16 no 2 pp 174ndash178 2010
[13] K Imamura H Kamitani H Nakayasu Y Asai and KNakashima ldquoPurulent meningitis caused by Actinomyces suc-cessfully treated with rifampicin a case reportrdquo InternalMedicine vol 50 no 10 pp 1121ndash1125 2011
[14] E Kononen and W G Wade ldquoActinomyces and related organ-isms in human infectionsrdquo Clinical Microbiology Reviews vol28 no 2 pp 419ndash442 2015
[15] J Versalovic K C Carroll G Funke J H Jorgensen M LLandry and D W Warnock Manual of Clinical MicrobiologyASM Press Washington DC USA 2011
[16] T E NarsquoWas D G Hollis CWMoss and R EWeaver ldquoCom-parison of biochemical morphologic and chemical character-istics of centers for disease control fermentative coryneformgroups 1 2 and A-4rdquo Journal of Clinical Microbiology vol 25no 8 pp 1354ndash1358 1987
[17] G Funke G M Lucchini G E Pfyffer M Marchiani and Avon Graevenitz ldquoCharacteristics of CDC group 1 and group1-like coryneform bacteria isolated from clinical specimensrdquoJournal of Clinical Microbiology vol 31 no 11 pp 2907ndash29121993
[18] G Funke S Stubbs A von Graevenitz and M D CollinsldquoAssignment of human-derived CDC group 1 coryneformbacteria and CDC group 1-like coryneform bacteria to thegenus Actinomyces as Actinomyces neuii subsp neuii sp novsubsp nov and Actinomyces neuii subsp anitratus subsp novrdquoInternational Journal of Systematic Bacteriology vol 44 no 1pp 167ndash171 1994
[19] G Funke andA vonGraevenitz ldquoInfections due toActinomycesneuii (former lsquoCDC coryneform group 1rsquo bacteria)rdquo Infectionvol 23 no 2 pp 73ndash75 1995
[20] L S Y Ng J H C Sim L C Eng S Menon and T Y TanldquoComparison of phenotypic methods and matrix-assisted laserdesorption ionisation time-of-flight mass spectrometry for theidentification of aero-tolerant Actinomyces spp isolated fromsoft-tissue infectionsrdquoEuropean Journal of ClinicalMicrobiologyand Infectious Diseases vol 31 no 8 pp 1749ndash1752 2012
[21] O Garner AMochon J Branda et al ldquoMulti-centre evaluationof mass spectrometric identification of anaerobic bacteria usingthe VITEK MS systemrdquo Clinical Microbiology and Infectionvol 20 no 4 pp 335ndash339 2014
[22] C Lacoste M-C Escande J Klijanienko P Jammet and CNos ldquoBreast Actinomyces neuii abscess simulating primarymalignancy a case diagnosed by fine-needle aspirationrdquo Diag-nostic Cytopathology vol 37 no 4 pp 311ndash312 2009
[23] A Roustan M Al Nakib and L Boubli ldquoPrimary actino-mycosis of the breast due to Actinomyces neuiirdquo Journal deGynecologie Obstetrique et Biologie de la Reproduction vol 39no 1 pp 64ndash67 2010
[24] J L Gomez-Garces A Burillo Y Gil and J A Saez-Nieto ldquoSofttissue infections caused by Actinomyces neuii a rare pathogenrdquoJournal of Clinical Microbiology vol 48 no 4 pp 1508ndash15092010
[25] K De Vreese and J Verhaegen ldquoIdentification of coryneformActinomyces neuii by MALDI-TOF MS 5 case reports andreview of literaturerdquo Acta Clinica Belgica vol 68 no 3 pp 210ndash214 2013
[26] J M Olson and J C Vary Jr ldquoPrimary cutaneous Actinomycesneuii infection of the breast successfully treated with doxycy-clinerdquo Cutis vol 92 no 6 pp E3ndashE4 2013
[27] C Mann S Dertinger G Hartmann R Schurz and B SimmaldquoActinomyces neuii and neonatal sepsisrdquo Infection vol 30 no3 pp 178ndash180 2002
Canadian Journal of Infectious Diseases and Medical Microbiology 7
[28] E Cohen J Bishara B Medalion A Sagie and M GartyldquoInfective endocarditis due to Actinomyces neuiirdquo ScandinavianJournal of Infectious Diseases vol 39 no 2 pp 180ndash183 2007
[29] P-Y Levy P-E Fournier R Charrel D Metras G Habiband D Raoult ldquoMolecular analysis of pericardial fluid a 7-yearexperiencerdquo European Heart Journal vol 27 no 16 pp 1942ndash1946 2006
[30] K Walther E Bruder D Goldenberger J Mayr U B Schaadand N Ritz ldquoActinomyces neuii isolated from a 20-month-old girl with cervical lymphadenitisrdquo Journal of the PediatricInfectious Diseases Society vol 4 no 3 pp e32ndashe37 2015
[31] B Van Bosterhaut P Boucquey M Janssens G Wauters andM Delmee ldquoChronic osteomyelitis due to Actinomyces neuiisubspecies neuii and Dermabacter hominisrdquo European Journalof Clinical Microbiology and Infectious Diseases vol 21 no 6pp 486ndash487 2002
[32] S Varughese and J Bargman ldquoActinomyces neuii PDperitonitismdashresolution of infection without catheter removalrdquoPeritoneal Dialysis International vol 34 no 7 pp 815ndash8162014
[33] R Dıaz M A Bajo G Del Peso A Garcıa-Perea R Sanchez-Villanueva and R Selgas ldquoActinomyces peritonitis removal ofthe peritoneal catheter unnecessary for resolutionrdquo NDT Plusvol 3 no 3 pp 296ndash297 2010
[34] P E Coudron R C Harris M G Vaughan and H P DaltonldquoTwo similar but atypical strains of coryneform group A-4isolated from patients with endophthalmitisrdquo Journal of ClinicalMicrobiology vol 22 no 4 pp 475ndash477 1985
[35] J M Garelick A J Khodabakhsh and R G Josephberg ldquoAcutepostoperative endophthalmitis caused by Actinomyces neuiirdquoAmerican Journal of Ophthalmology vol 133 no 1 pp 145ndash1472002
[36] V S Raman N Evans B Shreshta and R CunninghamldquoChronic postoperative endophthalmitis caused byActinomycesneuiirdquo Journal of Cataract and Refractive Surgery vol 30 no 12pp 2641ndash2643 2004
[37] J J Perez-Santonja E Campos-Mollo E Fuentes-Campos JSamper-Gimenez and J L Alio ldquoActinomyces neuii subspeciesanitratus chronic endophthalmitis after cataract surgeryrdquo Euro-pean Journal of Ophthalmology vol 17 no 3 pp 445ndash447 2007
[38] SGraffiA Peretz andMNaftali ldquoEndogenous endophthalmi-tis with an unusual infective agentActinomyces neuiirdquoEuropeanJournal of Ophthalmology vol 22 no 5 pp 834ndash835 2012
[39] S Brunner S Graf P Riegel and M Altwegg ldquoCatalase-negative Actinomyces neuii subsp neuii isolated from aninfected mammary prosthesisrdquo International Journal of MedicalMicrobiology vol 290 no 3 pp 285ndash287 2000
[40] R R Watkins K Anthony S Schroder and G S HallldquoVentriculoperitoneal shunt infection caused by Actinomycesneuii subsp neuiirdquo Journal of Clinical Microbiology vol 46 no5 pp 1888ndash1889 2008
[41] H Rieber R Schwarz O KramerW Cordier and L FrommeltldquoActinomyces neuii subsp neuii associated with periprostheticinfection in total hip arthroplasty as causative agentrdquo Journal ofClinical Microbiology vol 47 no 12 pp 4183ndash4184 2009
[42] S Grundmann J Huebner J Stuplich et al ldquoProsthetic valveendocarditis due to Actinomyces neuii successfully treated withantibiotic therapyrdquo Journal of Clinical Microbiology vol 48 no3 pp 1008ndash1011 2010
[43] R S Hsi J M Hotaling E S Spencer P L Bollyky andT J Walsh ldquoIsolated infection of a decommissioned penile
prosthesis reservoir with Actinomyces neuiirdquo Journal of SexualMedicine vol 8 no 3 pp 923ndash926 2011
[44] I A Anderson F Jarral K Sethi and P D Chumas ldquoPaediatricventriculoperitoneal shunt infection caused by Actinomycesneuiirdquo BMJ Case Reports 2014
[45] P Seng S Bayle A Alliez F RomainD Casanova andA SteinldquoThe microbial epidemiology of breast implant infections in aregional referral centre for plastic and reconstructive surgery inthe south of Francerdquo International Journal of Infectious Diseasesvol 35 pp 62ndash66 2015
[46] D J Lane ldquo16S23S rRNA sequencingrdquo in Nucleic Acid Tech-niques in Bacterial Systematics E Stackebrandt and M Good-fellow Eds pp 115ndash175 John Wiley amp Sons Chichester UK1991
[47] J R Cole Q Wang J A Fish et al ldquoRibosomal DatabaseProject data and tools for high throughput rRNA analysisrdquoNucleic Acids Research vol 42 no 1 pp D633ndashD642 2014
[48] Clinical and Laboratory Standards Institute ldquoPerformancestandards for Antimicrobial Susceptibility Testing 25th infor-mational supplementrdquo Tech Rep M100-S25 Clinical and Lab-oratory Standards Institute 2015
[49] Canadian Institutes of Health Research Natural Sciences andEngineering Research Council of Canada and Social Sciencesand Humanities Research Council of Canada ldquoTri-CouncilPolicy Statement Ethical Conduct for Research InvolvingHumansrdquo December 2014
Submit your manuscripts athttpwwwhindawicom
Stem CellsInternational
Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014
Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014
MEDIATORSINFLAMMATION
of
Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014
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Disease Markers
Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014
BioMed Research International
OncologyJournal of
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Oxidative Medicine and Cellular Longevity
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PPAR Research
The Scientific World JournalHindawi Publishing Corporation httpwwwhindawicom Volume 2014
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Research and TreatmentAIDS
Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014
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Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014
Parkinsonrsquos Disease
Evidence-Based Complementary and Alternative Medicine
Volume 2014Hindawi Publishing Corporationhttpwwwhindawicom
2 Canadian Journal of Infectious Diseases and Medical Microbiology
Since its classification A neuii has been implicated ina number of human infections [19] However due to itsunusual laboratory characteristics isolates have likely beendismissed as members of the Corynebacterium genus and itsoccurrence in clinical specimens is probably underreportedIndeed the use of advanced bacterial identification systemssuch as matrix-assisted laser desorption ionization time-of-flight mass spectrometry microbial identification systems(MALDI-TOF MS MIS) in clinical laboratories will likelyresult in an increased frequency of correctly identifying bac-teria that were previously difficult to identify using traditionalphenotypic methods [20 21] Because of the increasinglywidespread use of MALDI-TOF MS MIS understandingthe significance of isolating previously underrecognizedpathogens is important in guiding laboratory reporting andclinical practices
The present study examines cases of A neuii infectionsdetected in several community and tertiary care laboratoriesand confirmed by a reference microbiology laboratory Theliterature regarding A neuii infections is reviewed and com-pared to the findings in this series of cases
2 Methods
Clinical specimens were submitted to local microbiologylaboratories during 2013-2014 in Alberta Canada Sampleswere initially examined microscopically after Gram stain-ing and cultured aerobically and if deemed appropriateanaerobically on typical culture media including sheep bloodagar brain heart infusion agar and phenylethyl alcoholagar (Dalynn Biologicals Inc Calgary Alberta) Isolateswere initially identified by producing characteristic convexcircular smooth and white colonies with entire edges withconsistent Gram stain appearance catalase reaction andmajor acid end-product profiles as determined by gas-liquidchromatography If the specimen was submitted and initiallyworked up by a local microbiology laboratory isolates sus-pected of being A neuii were further identified using theAPI-CORYNE (bioMerieux France) test strip Further con-firmation of isolatesrsquo identities was performed at the AlbertaProvincial Laboratory for Public Health Edmonton Albertausing the VITEK MS MALDI-TOF MS MIS (bioMerieuxFrance) andor 16S rRNA gene sequencing The VITEK MSMALDI-TOF MS MIS assay was carried out according tothe manufacturer The in vitro diagnostic database used forcomparing spectra was VITEK MS v20 Knowledge Base(bioMerieux France) matches with a ge999 confidencewere accepted as A neuii
In order to carry out the sequencing of a portion ofthe 16S rRNA gene genomic DNA was extracted usinga pure culture of organism growing on sheep blood agarincubated anaerobically at 35∘C A sweep of organism wassuspended in 12mM Tris buffer pH 74 and centrifugedat 13000timesg for 3 minutes The pellet was resuspended inrapid lysis buffer (100mM NaCl 10mM Tris-HCl pH 831mM EDTA pH 90 1 Triton X-100) and subjected tothree freezethaw cycles of minus80∘C for 15 minutes followedby complete thawing This preparation was then boiled for15 minutes cooled to room temperature and centrifuged
at 13000timesg for 15 minutes Nucleic acid in the supernatantwas used for conventional polymerase chain reaction (PCR)with the following previously described 16S rRNA geneprimers 16S-F 51015840AGA GTT TGA TCA TGG CTC AG 31015840and 16S-R 51015840GGA CTA CCA GGG TAT CTA AT 31015840 [46]Amplification reactions were carried out using PlatinumPfx DNA Polymerase (Thermo Fisher Scientific WalthamMA USA) according to the manufacturer with the followingcycling conditions 94∘C for 2 minutes then 25 cycles of94∘C for 15 seconds 50∘C for 30 seconds and 68∘C for 20seconds After product cleanup and quantification with theChargeSwitchKit and theNanoDrop 2000 (ThermoFisherScientific) respectively DNA sequencing was performedusing the BigDye Cycle Sequencing and BigDye XTermi-nator Purification Kits (Thermo Fisher Scientific) on theApplied Biosystems 3500xL Genetic Analyzer (ThermoFisher Scientific) Sequence data was viewed and editedusing the BioEdit program and uploaded to the RibosomeDatabase Project to obtain sequence matches [47] All butone of the sequences obtained were over 350 nucleotidesdespite multiple attempts one amplicon yielded only 257nucleotides of high quality sequence (see SupplementaryData in the Supplementary Material available online athttpdxdoiorg10115520166017605) In each case a seq-match (S ab) score of 1000 (signifying 100 identity) wasfound with at least one other submitted A neuii rRNA genenucleotide sequence Identification to the subspecies level wasnot performed
Susceptibility testing was carried out using gradientdiffusion Etest strips (bioMerieux France) under the con-ditions described for anaerobic organisms by the Clinicaland Laboratory Standards Institute (CLSI [48]) Brieflya 05 McFarland suspension of organism was inoculatedonto Anaerobic Laked Blood Agar (Dalynn Biologicals Inc)and incubated at 36∘C anaerobically for 48 hours Minimalinhibitory concentrations (MICs) were determined as per themanufacturerrsquos instructions Breakpoints were interpretedas per CLSI guidelines for anaerobic bacteria [48] Patientinformation was obtained from specimen requisitions andthe treating physiciansThework described in this paper doesnot require ethics review as defined in Section 24 of theTri-Council Policy Statement Ethical Conduct for ResearchInvolving Humans [49]
3 Results
Actinomyces neuii was isolated from eight patients fromFebruary 2013 to July 2014 patient information was avail-able for six of these cases (Table 1) From each patient apredominant Gram-positive catalase positive coryneformbacillus was isolated Gas chromatography revealed a majorsuccinic acid peak for the isolates In all three cases wherethe isolate was initially worked up by a local laboratory theAPI-CORYNE test strip correctly identified the organismas A neuii The first five isolates were confirmed as Aneuii using 16S rRNA gene sequencing this allowed thelaboratoryrsquos VITEK MS MALDI-TOF MS MIS instrumentto be validated for identifying A neuii and therefore beused without further extensive confirmatory testing Patient
Canadian Journal of Infectious Diseases and Medical Microbiology 3
Table1Ch
aracteris
ticso
fpatientsfrom
which
Aneuiiw
asdetected
andsusceptib
ilityprofi
leso
fisolates
Agesex
Com
orbiditie
saInfection
Gram
smearb
Coisolates
MICso
fAneuii
isolates(mgL)
cTreatm
ent
30M
Previous
head
injury
right
ACLrepair
Leftthigh
abscess
4+WBC
4+GPC
4+GPB
Prevotellabivia
Anaerob
icGPC
PenicillinGle0016
Amoxclav
0016
Imipenem
0023
Vancom
ycin
05
Clindamycinge256
Incisio
nand
drainage
Cephalexin7days
45M
TIID
Mdyslip
idem
iaLeftingu
inal
abscess
3+WBC
2+GPC
2+GNB
1+GPB
Staphylococcus
lugdun
ensis
Anaerob
icGPC
PenicillinGle0016
Amoxclav
0016
Imipenem
0023
Vancom
ycin
05
Clindamycin
le0016
Incisio
nand
drainage
Cephalexin7days
46M
Paraplegiarenal
calculiatria
lfib
rillation
previous
endo
carditissacral
ulcer
Rightaxillary
abscess
3+WBC
3+GPB
2+GPC
Non
e
PenicillinGle003
Amoxclavle0016
Imipenem
0023
Vancom
ycinle05
Clindamycin
le0016
Incisio
nand
drainage
Cephalexin
(unk
nown
duratio
n)
48M
Hypertension
TIID
Mobesity
previous
Fournierrsquos
gang
renediabetic
foot
infections
Rightg
roin
abscess
3+WBC
3+GPB
3+GNB
2+GPC
Proteusm
irabilis
Staphylococcus
lugdun
ensis
Actin
omycessp
Mixed
anaerobes
PenicillinG000
6Amoxclavle0016
Imipenem
0023
Vancom
ycin
05
Clindamycin
0023
Incisio
nand
drainage
Ceft
riaxone
3days
Ertapenem
5days
Amoxclav10
days
68M
Bilateral
spermatocele
swith
spermatocelectomies
Posto
perativ
erig
htscrotum
abscess
2+WBC
3+GPC
2+GPB
2+GNB
Coagu
lase-negative
Staphylococcus
Coryn
eform
bacillu
sPropionibacterium
sp
PenicillinGle0016
Amoxclavle0016
Imipenem
0032
Vancom
ycin
05
Clindamycin
0032
Ciprofl
oxacin
28days
85F
Hypertension
hypo
thyroidism
celiacd
isease
Postb
iopsyleft
ankleu
lcer
3+GNB
2+GPC
Acinetobacter
baum
anniicalcoaceticu
scomplex
Streptococcusa
galactiae
PenicillinGle006
Amoxclavle0016
Imipenem
0023
Vancom
ycin
038
Clindamycin
0023
Wou
ndcare
Clindamycin
10days
Cephalexin7days
a TIIDMtypeIId
iabetesm
ellitusA
CLanteriorc
ruciateligam
ent
b WBC
whitebloo
dcellsG
PCG
ram-positive
cocciGPB
Gram-positive
bacilliG
NB
Gram-negativeb
acilliforW
BC1+representslt1cellp
erhigh
power
field(times100oilimmersio
nlens)2+
represents1ndash5c
ells
3+represents6ndash
10cellsand
4+representsgt10
cellsfor
bacteria1+representsle1cellp
erhigh
power
field2+represents2ndash10
cells3+represents11ndash
50cellsand
4+representsgt50
cells
c MICm
inim
alinhibitory
concentration
amoxclavam
oxicillin-clav
ulanate
4 Canadian Journal of Infectious Diseases and Medical Microbiology
ages ranged from 30 to 85 years all but one of the patientswere male There was no obvious trend in patient comor-bidities While one of the specimens was collected from alower extremity skin ulcer the remaining five were collectedfrom abscesses in different locations Gram smears usuallyrevealed the presence of multiple types of bacteria in theclinical specimens and the resulting cultures grew at leasttwo different bacterial species as coisolates in all but onecase (Table 1) The most common coisolates were anaerobicbacteria but themore common skin and soft tissue infectiousagent Staphylococcus lugdunensis was isolated in two casesSusceptibility testing showed that all of the A neuii isolateshad low minimal inhibitory concentrations to penicillinbroader spectrum 120573-lactams and vancomycin one isolatehad an MIC ge 256mgL to clindamycin while the othershadMICs of le0032mgL Treatment of the abscesses usuallyinvolved incision and drainage followed by seven- to 18-daycourses of a120573-lactam though one of the abscesses was treatedwith a four-week course of ciprofloxacin without drainageNone of the patients were noted to have relapses followingtherapy
4 Discussion
Actinomyces neuii has been isolated in a wide range of clinicalscenarios but has rarely been reported in the literatureThereare less than 100 cases reported in the literature of A neuiiinfections we and others have hypothesized that dismissal asa commensal coryneform bacillus may be the reason Whilethere have only been scattered reports of A neuii causinginfection since interest in the organism was originally raisedin the mid-1990s the frequency of reports recognizing itas a pathogen has recently increased likely due to the useof advanced identification systems Abscesses are the mostcommon manifestation of A neuii infection with more thanhalf of the reported cases describing abscesses or infectedatheromas (Table 2) [6 17 19 22ndash45] A number of otherinfectious entities implicating A neuii have been describedincluding ulcer infections cellulitis urinary tract infectionsand prostatitis (Table 2)
There have been two reported cases ofA neuii chorioam-nionitis one of which resulted in neonatal sepsis afterpremature delivery [19 27] In the latter case the organismwas isolated from multiple sites from the neonate includingthe external ear canal a gastric aspirate and blood [27]
As demonstrated by the above caseA neuii can also causemore invasive infections There are multiple other cases ofA neuii bacteremia various prostheses infections two casesof chronic osteomyelitis two cases of peritoneal dialysis-associated peritonitis and single cases of native aorticvalve endocarditis chronic pericarditis and lymphadenitisinterestingly there have been multiple reports of A neuiicausing endophthalmitis the majority of which occurredpostoperatively (Table 2)
Intriguingly there has been only one case reported of Aneuii causing a classical clinical picture of actinomycosis withrecurrent breast abscesses fistula formation filamentousgrowth and sulfur granules [23]This is in agreementwith thefindings of our study as none of the patients exhibited such
findings nor did they require extended durations of antibiotictherapy
The infections caused byA neuii described in the presentstudy were all associated with abscess formation in soft tissueexcept for one which was isolated from an ankle ulcer Thelatter case may not actually represent an infection as therewere no white cells in the clinical specimen The age range ofpatients infected with A neuii in the literature is 0ndash94 yearswith a mean of 50 years this is comparable with the ages ofpatients in this study While reports in the literature show analmost even number of males and females acquiring A neuiiinfections themajority of the patients in our studyweremalethis is likely due to the small number of cases examined
Previous studies found that abscesses typically includedmixed anaerobic organisms and skin flora as coisolates(Table 2) This is similar to the present study in which fourof six specimens grew anaerobic bacteria and one grewcoagulase-negative staphylococci as well the patient fromwhom A neuii was isolated in pure culture had Gram-positive cocci seen in the direct smear making it possible thatthis was also a mixed anaerobic infection from which at leastone anaerobe failed to grow in culture However this studyalso had a larger variety of aerobic coisolates in specimensthan was reported in previous studies It is difficult to assessthe specific role of A neuii in these mixed infections butits presence in polymicrobial abscesses makes up the vastmajority of cases Improved identification of A neuii in thelaboratory will undoubtedly help to clarify its role in disease
There are few studies describing the use of MALDI-TOFMSMIS in identifying A neuii One other study showed thatthe VITEK MS system was able to correctly identify A neuiito the species level in eight of 12 instances [21] Three groupsused Bruker MALDI-TOF MS MIS (Bruker Billerica MAUSA) two isolates were designated as A neuii with a ldquosecuregenus probable species identificationrdquo level of confidence[20 30] while the degree of certainty in identification ofthe other isolate was not described [45] Due to the limitedamount of experience with either type of MALDI-TOF MSMIS there is no current evidence that one system is superiorto the other in identifying A neuii
The majority of tested isolates show susceptibility to 120573-lactams including penicillin G ampicillin cefazolin cefurox-ime ceftriaxone and imipenem [17 19 27 28 34ndash36 4042 43] Other agents with in vitro activity against A neuiiinclude clindamycin erythromycin tetracycline and van-comycin [17 19 27 28 35 36 40 42] Fluoroquinolones(including ciprofloxacin and levofloxacin) aminoglycosides(including gentamicin and amikacin) and trimethoprim-sulfamethoxazole frequently demonstrate less in vitro activityagainst isolates [19 35 36 40]
Similar to previous studies the isolates in the currentseries were generally quite susceptible to the tested antibi-otics All isolates had low MICs to penicillin amoxicillin-clavulanate and vancomycin only one isolate showed resis-tance to clindamycin
As shown in Table 2 treatment regimens in the literatureare varied and have been dictated by the type and severityof infection In general successful treatment regimens ofteninvolved the use of 120573-lactam antibiotics as well as appropriate
Canadian Journal of Infectious Diseases and Medical Microbiology 5
Table2Ch
aracteris
ticso
fpreviou
slyrepo
rted
caseso
fAneuiiinfections
intheliterature
Infection
Num
bero
fcases
Coisolates
Treatm
ent
Outcomes
References
Abscessinfected
atheromaa
56
Coagu
lase-negatives
taph
ylococci
Enterococcus
spp
Corynebacterium
spp
Anaerob
es
Incisio
nanddrainagew
ithor
with
out
antib
iotic
therapy(usually120573-la
ctam
soccasio
nally
tetracyclin
eciprofl
oxacin)
Generallyfavourable
ifsource
controlis
achieved
[6171922ndash
26]
Cutaneou
sinfectio
nb9
Coagu
lase-negatives
taph
ylococci(eight
cases)
Not
repo
rted
Favourable
[1719]
Genito
urinaryinfectionc
6Non
eAntibiotic
therapywith120573-la
ctam
sFavourable
[1927]
Bacterem
iad
8Non
e
Twocasesreportedtherapy
Ampicillinwith
gentam
icin
(twoweeks)
follo
wed
byPO
penicillin(fo
urweeks)
Initialciprofl
oxacin
follo
wed
byim
ipenem
e
Generallyfavourable
(one
mortality)
[1927]
Endo
carditis
1Non
e
Aorticvalvee
xcision
with
homograft
implantatio
nfollo
wed
byam
picillin
(threew
eeks)ceftriaxone
(ninew
eeks)
andthen
POdo
xycycline
(ninem
onths)
Favourable
[28]
Chronicp
ericarditis
1Non
ePeric
ardialflu
iddrainage
andantib
iotic
therapy(specific
antib
iotic
snot
repo
rted)
Not
repo
rted
[29]
Lymph
adenitis
1Virid
ansg
roup
streptococci
Prevotellatim
onensis
Anaerob
icGram-positive
cocci
Lymph
node
andfistulaexcisio
nfollo
wed
byIV
andthen
POam
oxicillin-clavulanate(sixmon
ths)
Favourable
[30]
Oste
omyelitis
2Dermabacterh
ominis(one
case)
Surgicalcuretta
gefollo
wed
by120573-la
ctam
therapyform
ultip
lemon
ths
Favourable
[2531]
Periton
itis(second
aryto
periton
eald
ialysis
)2
Non
e
Catheter
retentionwith
either
intraperito
nealcefazolin
andcefta
zidime
(twoweeks)followed
bypenicillinG
(four
weeks)or
intraperito
neal
ampicillin
teicop
lanin
andtobram
ycin
(twoweeks)
Favourable
[3233]
Endo
phthalmitis
6Non
eVa
rious
syste
mic(POor
IV)a
nddirect
(intravitrealorsub
conjun
ctival
injectionsdrops)a
ntibiotic
sFavourable
[34ndash
38]
Prostheticmaterial
infectionf
8Ty
pically
none
Coagu
lase-negatives
taph
ylococciand
mixed
anaerobes(breastim
plantcase)
Removalreplacemento
fprosthetic
materialfollowed
byprolon
gedantib
iotic
therapy(w
eeks
toon
eyeardepend
ingon
theinfectio
n)
Favourable
[2539ndash4
5]
a Including
breast
axillaryinguinaliliacc
rest
ischiorectalandpilonidalabscessesone
case
ofhidradenitissup
purativ
amostsitesw
eren
otspecified
b Including
ulcerinfectio
nsdiabetic
foot
ulcerinfectio
nsand
cellu
litis
c Including
urinarytractinfectio
nsprosta
titis
andchorioam
nion
itis
d Including
onec
aseo
fneonatalsepsis
second
aryto
chorioam
nion
itisther
emaining
casesh
adun
clear
orun
repo
rted
sources
e Thep
atient
treated
with
thisregimen
isthes
inglem
ortalityrepo
rted
intheliterature
associated
with
Aneuiiinfectio
nf Including
infections
ofan
intravenou
scatheteram
echanicalh
eartvalveah
ipprosthesis
apenile
prosthesis
breastim
plants
andventric
ulop
erito
nealshun
ts
6 Canadian Journal of Infectious Diseases and Medical Microbiology
surgical interventions This was also the case in the presentstudy as almost all of the treatments involved incision anddrainage of abscesses with subsequent 120573-lactam courses
While A neuii is not a commonly identified organismthere are numerous reports of it causing both invasive andnoninvasive disease Fortunately it is a very susceptibleorganism that can often be treated with 120573-lactams followingdrainage of abscesses or other surgical management Under-standing its clinical significance and typical susceptibilitypatterns will ease decision-making when the organism isencountered as it surely will be with the current widespreaduse of MALDI-TOF MS MIS
Conflict of Interests
The authors have no conflict of interests to declare
References
[1] K P Schaal and H-J Lee ldquoActinomycete infections inhumansmdasha reviewrdquo Gene vol 115 no 1-2 pp 201ndash211 1992
[2] R A Smego Jr and G Foglia ldquoActinomycosisrdquo Clinical Infec-tious Diseases vol 26 no 6 pp 1255ndash1263 1998
[3] V KWong T D Turmezei and V CWeston ldquoActinomycosisrdquoBritish Medical Journal vol 343 Article ID d6099 2011
[4] L J M Sabbe D Van De Merwe L Schouls A BergmansM Vaneechoutte and P Vandamme ldquoClinical spectrum ofinfections due to the newly described Actinomyces species Aturicensis A radingae and A europaeusrdquo Journal of ClinicalMicrobiology vol 37 no 1 pp 8ndash13 1999
[5] V Hall P R Talbot S L Stubbs and B I Duerden ldquoIdenti-fication of clinical isolates of Actinomyces species by amplified16S ribosomal DNA restriction analysisrdquo Journal of ClinicalMicrobiology vol 39 no 10 pp 3555ndash3562 2001
[6] J E Clarridge III and Q Zhang ldquoGenotypic diversity of clinicalActinomyces species phenotype source and disease correlationamong genospeciesrdquo Journal of Clinical Microbiology vol 40no 9 pp 3442ndash3448 2002
[7] A S Fiorino ldquoIntrauterine contraceptive device-associatedactinomycotic abscess and Actinomyces detection on cervicalsmearrdquo Obstetrics and Gynecology vol 87 no 1 pp 142ndash1491996
[8] KWestling C Lidman and AThalme ldquoTricuspid valve endo-carditis caused by a new species of Actinomyces Actinomycesfunkeirdquo Scandinavian Journal of Infectious Diseases vol 34 no3 pp 206ndash207 2001
[9] A Jitmuang ldquoPrimary actinomycotic endocarditis a casereport and literature reviewrdquo Journal of the Medical Associationof Thailand vol 91 no 6 pp 931ndash936 2008
[10] S Ushikoshi I Koyanagi K Hida Y Iwasaki and H AbeldquoSpinal intrathecal actinomycosis a case reportrdquo Surgical Neu-rology vol 50 no 3 pp 221ndash225 1998
[11] S Wang R L Wolf J H Woo et al ldquoActinomycotic braininfection registered diffusion perfusion MR imaging and MRspectroscopyrdquoNeuroradiology vol 48 no 5 pp 346ndash350 2006
[12] L Ghafghaichi S Troy I Budvytiene N Banaei and E JBaron ldquoMixed infection involving Actinomyces Aggregatibac-ter and Fusobacterium species presenting as perispinal tumorrdquoAnaerobe vol 16 no 2 pp 174ndash178 2010
[13] K Imamura H Kamitani H Nakayasu Y Asai and KNakashima ldquoPurulent meningitis caused by Actinomyces suc-cessfully treated with rifampicin a case reportrdquo InternalMedicine vol 50 no 10 pp 1121ndash1125 2011
[14] E Kononen and W G Wade ldquoActinomyces and related organ-isms in human infectionsrdquo Clinical Microbiology Reviews vol28 no 2 pp 419ndash442 2015
[15] J Versalovic K C Carroll G Funke J H Jorgensen M LLandry and D W Warnock Manual of Clinical MicrobiologyASM Press Washington DC USA 2011
[16] T E NarsquoWas D G Hollis CWMoss and R EWeaver ldquoCom-parison of biochemical morphologic and chemical character-istics of centers for disease control fermentative coryneformgroups 1 2 and A-4rdquo Journal of Clinical Microbiology vol 25no 8 pp 1354ndash1358 1987
[17] G Funke G M Lucchini G E Pfyffer M Marchiani and Avon Graevenitz ldquoCharacteristics of CDC group 1 and group1-like coryneform bacteria isolated from clinical specimensrdquoJournal of Clinical Microbiology vol 31 no 11 pp 2907ndash29121993
[18] G Funke S Stubbs A von Graevenitz and M D CollinsldquoAssignment of human-derived CDC group 1 coryneformbacteria and CDC group 1-like coryneform bacteria to thegenus Actinomyces as Actinomyces neuii subsp neuii sp novsubsp nov and Actinomyces neuii subsp anitratus subsp novrdquoInternational Journal of Systematic Bacteriology vol 44 no 1pp 167ndash171 1994
[19] G Funke andA vonGraevenitz ldquoInfections due toActinomycesneuii (former lsquoCDC coryneform group 1rsquo bacteria)rdquo Infectionvol 23 no 2 pp 73ndash75 1995
[20] L S Y Ng J H C Sim L C Eng S Menon and T Y TanldquoComparison of phenotypic methods and matrix-assisted laserdesorption ionisation time-of-flight mass spectrometry for theidentification of aero-tolerant Actinomyces spp isolated fromsoft-tissue infectionsrdquoEuropean Journal of ClinicalMicrobiologyand Infectious Diseases vol 31 no 8 pp 1749ndash1752 2012
[21] O Garner AMochon J Branda et al ldquoMulti-centre evaluationof mass spectrometric identification of anaerobic bacteria usingthe VITEK MS systemrdquo Clinical Microbiology and Infectionvol 20 no 4 pp 335ndash339 2014
[22] C Lacoste M-C Escande J Klijanienko P Jammet and CNos ldquoBreast Actinomyces neuii abscess simulating primarymalignancy a case diagnosed by fine-needle aspirationrdquo Diag-nostic Cytopathology vol 37 no 4 pp 311ndash312 2009
[23] A Roustan M Al Nakib and L Boubli ldquoPrimary actino-mycosis of the breast due to Actinomyces neuiirdquo Journal deGynecologie Obstetrique et Biologie de la Reproduction vol 39no 1 pp 64ndash67 2010
[24] J L Gomez-Garces A Burillo Y Gil and J A Saez-Nieto ldquoSofttissue infections caused by Actinomyces neuii a rare pathogenrdquoJournal of Clinical Microbiology vol 48 no 4 pp 1508ndash15092010
[25] K De Vreese and J Verhaegen ldquoIdentification of coryneformActinomyces neuii by MALDI-TOF MS 5 case reports andreview of literaturerdquo Acta Clinica Belgica vol 68 no 3 pp 210ndash214 2013
[26] J M Olson and J C Vary Jr ldquoPrimary cutaneous Actinomycesneuii infection of the breast successfully treated with doxycy-clinerdquo Cutis vol 92 no 6 pp E3ndashE4 2013
[27] C Mann S Dertinger G Hartmann R Schurz and B SimmaldquoActinomyces neuii and neonatal sepsisrdquo Infection vol 30 no3 pp 178ndash180 2002
Canadian Journal of Infectious Diseases and Medical Microbiology 7
[28] E Cohen J Bishara B Medalion A Sagie and M GartyldquoInfective endocarditis due to Actinomyces neuiirdquo ScandinavianJournal of Infectious Diseases vol 39 no 2 pp 180ndash183 2007
[29] P-Y Levy P-E Fournier R Charrel D Metras G Habiband D Raoult ldquoMolecular analysis of pericardial fluid a 7-yearexperiencerdquo European Heart Journal vol 27 no 16 pp 1942ndash1946 2006
[30] K Walther E Bruder D Goldenberger J Mayr U B Schaadand N Ritz ldquoActinomyces neuii isolated from a 20-month-old girl with cervical lymphadenitisrdquo Journal of the PediatricInfectious Diseases Society vol 4 no 3 pp e32ndashe37 2015
[31] B Van Bosterhaut P Boucquey M Janssens G Wauters andM Delmee ldquoChronic osteomyelitis due to Actinomyces neuiisubspecies neuii and Dermabacter hominisrdquo European Journalof Clinical Microbiology and Infectious Diseases vol 21 no 6pp 486ndash487 2002
[32] S Varughese and J Bargman ldquoActinomyces neuii PDperitonitismdashresolution of infection without catheter removalrdquoPeritoneal Dialysis International vol 34 no 7 pp 815ndash8162014
[33] R Dıaz M A Bajo G Del Peso A Garcıa-Perea R Sanchez-Villanueva and R Selgas ldquoActinomyces peritonitis removal ofthe peritoneal catheter unnecessary for resolutionrdquo NDT Plusvol 3 no 3 pp 296ndash297 2010
[34] P E Coudron R C Harris M G Vaughan and H P DaltonldquoTwo similar but atypical strains of coryneform group A-4isolated from patients with endophthalmitisrdquo Journal of ClinicalMicrobiology vol 22 no 4 pp 475ndash477 1985
[35] J M Garelick A J Khodabakhsh and R G Josephberg ldquoAcutepostoperative endophthalmitis caused by Actinomyces neuiirdquoAmerican Journal of Ophthalmology vol 133 no 1 pp 145ndash1472002
[36] V S Raman N Evans B Shreshta and R CunninghamldquoChronic postoperative endophthalmitis caused byActinomycesneuiirdquo Journal of Cataract and Refractive Surgery vol 30 no 12pp 2641ndash2643 2004
[37] J J Perez-Santonja E Campos-Mollo E Fuentes-Campos JSamper-Gimenez and J L Alio ldquoActinomyces neuii subspeciesanitratus chronic endophthalmitis after cataract surgeryrdquo Euro-pean Journal of Ophthalmology vol 17 no 3 pp 445ndash447 2007
[38] SGraffiA Peretz andMNaftali ldquoEndogenous endophthalmi-tis with an unusual infective agentActinomyces neuiirdquoEuropeanJournal of Ophthalmology vol 22 no 5 pp 834ndash835 2012
[39] S Brunner S Graf P Riegel and M Altwegg ldquoCatalase-negative Actinomyces neuii subsp neuii isolated from aninfected mammary prosthesisrdquo International Journal of MedicalMicrobiology vol 290 no 3 pp 285ndash287 2000
[40] R R Watkins K Anthony S Schroder and G S HallldquoVentriculoperitoneal shunt infection caused by Actinomycesneuii subsp neuiirdquo Journal of Clinical Microbiology vol 46 no5 pp 1888ndash1889 2008
[41] H Rieber R Schwarz O KramerW Cordier and L FrommeltldquoActinomyces neuii subsp neuii associated with periprostheticinfection in total hip arthroplasty as causative agentrdquo Journal ofClinical Microbiology vol 47 no 12 pp 4183ndash4184 2009
[42] S Grundmann J Huebner J Stuplich et al ldquoProsthetic valveendocarditis due to Actinomyces neuii successfully treated withantibiotic therapyrdquo Journal of Clinical Microbiology vol 48 no3 pp 1008ndash1011 2010
[43] R S Hsi J M Hotaling E S Spencer P L Bollyky andT J Walsh ldquoIsolated infection of a decommissioned penile
prosthesis reservoir with Actinomyces neuiirdquo Journal of SexualMedicine vol 8 no 3 pp 923ndash926 2011
[44] I A Anderson F Jarral K Sethi and P D Chumas ldquoPaediatricventriculoperitoneal shunt infection caused by Actinomycesneuiirdquo BMJ Case Reports 2014
[45] P Seng S Bayle A Alliez F RomainD Casanova andA SteinldquoThe microbial epidemiology of breast implant infections in aregional referral centre for plastic and reconstructive surgery inthe south of Francerdquo International Journal of Infectious Diseasesvol 35 pp 62ndash66 2015
[46] D J Lane ldquo16S23S rRNA sequencingrdquo in Nucleic Acid Tech-niques in Bacterial Systematics E Stackebrandt and M Good-fellow Eds pp 115ndash175 John Wiley amp Sons Chichester UK1991
[47] J R Cole Q Wang J A Fish et al ldquoRibosomal DatabaseProject data and tools for high throughput rRNA analysisrdquoNucleic Acids Research vol 42 no 1 pp D633ndashD642 2014
[48] Clinical and Laboratory Standards Institute ldquoPerformancestandards for Antimicrobial Susceptibility Testing 25th infor-mational supplementrdquo Tech Rep M100-S25 Clinical and Lab-oratory Standards Institute 2015
[49] Canadian Institutes of Health Research Natural Sciences andEngineering Research Council of Canada and Social Sciencesand Humanities Research Council of Canada ldquoTri-CouncilPolicy Statement Ethical Conduct for Research InvolvingHumansrdquo December 2014
Submit your manuscripts athttpwwwhindawicom
Stem CellsInternational
Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014
Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014
MEDIATORSINFLAMMATION
of
Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014
Behavioural Neurology
EndocrinologyInternational Journal of
Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014
Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014
Disease Markers
Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014
BioMed Research International
OncologyJournal of
Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014
Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014
Oxidative Medicine and Cellular Longevity
Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014
PPAR Research
The Scientific World JournalHindawi Publishing Corporation httpwwwhindawicom Volume 2014
Immunology ResearchHindawi Publishing Corporationhttpwwwhindawicom Volume 2014
Journal of
ObesityJournal of
Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014
Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014
Computational and Mathematical Methods in Medicine
OphthalmologyJournal of
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Diabetes ResearchJournal of
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Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014
Research and TreatmentAIDS
Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014
Gastroenterology Research and Practice
Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014
Parkinsonrsquos Disease
Evidence-Based Complementary and Alternative Medicine
Volume 2014Hindawi Publishing Corporationhttpwwwhindawicom
Canadian Journal of Infectious Diseases and Medical Microbiology 3
Table1Ch
aracteris
ticso
fpatientsfrom
which
Aneuiiw
asdetected
andsusceptib
ilityprofi
leso
fisolates
Agesex
Com
orbiditie
saInfection
Gram
smearb
Coisolates
MICso
fAneuii
isolates(mgL)
cTreatm
ent
30M
Previous
head
injury
right
ACLrepair
Leftthigh
abscess
4+WBC
4+GPC
4+GPB
Prevotellabivia
Anaerob
icGPC
PenicillinGle0016
Amoxclav
0016
Imipenem
0023
Vancom
ycin
05
Clindamycinge256
Incisio
nand
drainage
Cephalexin7days
45M
TIID
Mdyslip
idem
iaLeftingu
inal
abscess
3+WBC
2+GPC
2+GNB
1+GPB
Staphylococcus
lugdun
ensis
Anaerob
icGPC
PenicillinGle0016
Amoxclav
0016
Imipenem
0023
Vancom
ycin
05
Clindamycin
le0016
Incisio
nand
drainage
Cephalexin7days
46M
Paraplegiarenal
calculiatria
lfib
rillation
previous
endo
carditissacral
ulcer
Rightaxillary
abscess
3+WBC
3+GPB
2+GPC
Non
e
PenicillinGle003
Amoxclavle0016
Imipenem
0023
Vancom
ycinle05
Clindamycin
le0016
Incisio
nand
drainage
Cephalexin
(unk
nown
duratio
n)
48M
Hypertension
TIID
Mobesity
previous
Fournierrsquos
gang
renediabetic
foot
infections
Rightg
roin
abscess
3+WBC
3+GPB
3+GNB
2+GPC
Proteusm
irabilis
Staphylococcus
lugdun
ensis
Actin
omycessp
Mixed
anaerobes
PenicillinG000
6Amoxclavle0016
Imipenem
0023
Vancom
ycin
05
Clindamycin
0023
Incisio
nand
drainage
Ceft
riaxone
3days
Ertapenem
5days
Amoxclav10
days
68M
Bilateral
spermatocele
swith
spermatocelectomies
Posto
perativ
erig
htscrotum
abscess
2+WBC
3+GPC
2+GPB
2+GNB
Coagu
lase-negative
Staphylococcus
Coryn
eform
bacillu
sPropionibacterium
sp
PenicillinGle0016
Amoxclavle0016
Imipenem
0032
Vancom
ycin
05
Clindamycin
0032
Ciprofl
oxacin
28days
85F
Hypertension
hypo
thyroidism
celiacd
isease
Postb
iopsyleft
ankleu
lcer
3+GNB
2+GPC
Acinetobacter
baum
anniicalcoaceticu
scomplex
Streptococcusa
galactiae
PenicillinGle006
Amoxclavle0016
Imipenem
0023
Vancom
ycin
038
Clindamycin
0023
Wou
ndcare
Clindamycin
10days
Cephalexin7days
a TIIDMtypeIId
iabetesm
ellitusA
CLanteriorc
ruciateligam
ent
b WBC
whitebloo
dcellsG
PCG
ram-positive
cocciGPB
Gram-positive
bacilliG
NB
Gram-negativeb
acilliforW
BC1+representslt1cellp
erhigh
power
field(times100oilimmersio
nlens)2+
represents1ndash5c
ells
3+represents6ndash
10cellsand
4+representsgt10
cellsfor
bacteria1+representsle1cellp
erhigh
power
field2+represents2ndash10
cells3+represents11ndash
50cellsand
4+representsgt50
cells
c MICm
inim
alinhibitory
concentration
amoxclavam
oxicillin-clav
ulanate
4 Canadian Journal of Infectious Diseases and Medical Microbiology
ages ranged from 30 to 85 years all but one of the patientswere male There was no obvious trend in patient comor-bidities While one of the specimens was collected from alower extremity skin ulcer the remaining five were collectedfrom abscesses in different locations Gram smears usuallyrevealed the presence of multiple types of bacteria in theclinical specimens and the resulting cultures grew at leasttwo different bacterial species as coisolates in all but onecase (Table 1) The most common coisolates were anaerobicbacteria but themore common skin and soft tissue infectiousagent Staphylococcus lugdunensis was isolated in two casesSusceptibility testing showed that all of the A neuii isolateshad low minimal inhibitory concentrations to penicillinbroader spectrum 120573-lactams and vancomycin one isolatehad an MIC ge 256mgL to clindamycin while the othershadMICs of le0032mgL Treatment of the abscesses usuallyinvolved incision and drainage followed by seven- to 18-daycourses of a120573-lactam though one of the abscesses was treatedwith a four-week course of ciprofloxacin without drainageNone of the patients were noted to have relapses followingtherapy
4 Discussion
Actinomyces neuii has been isolated in a wide range of clinicalscenarios but has rarely been reported in the literatureThereare less than 100 cases reported in the literature of A neuiiinfections we and others have hypothesized that dismissal asa commensal coryneform bacillus may be the reason Whilethere have only been scattered reports of A neuii causinginfection since interest in the organism was originally raisedin the mid-1990s the frequency of reports recognizing itas a pathogen has recently increased likely due to the useof advanced identification systems Abscesses are the mostcommon manifestation of A neuii infection with more thanhalf of the reported cases describing abscesses or infectedatheromas (Table 2) [6 17 19 22ndash45] A number of otherinfectious entities implicating A neuii have been describedincluding ulcer infections cellulitis urinary tract infectionsand prostatitis (Table 2)
There have been two reported cases ofA neuii chorioam-nionitis one of which resulted in neonatal sepsis afterpremature delivery [19 27] In the latter case the organismwas isolated from multiple sites from the neonate includingthe external ear canal a gastric aspirate and blood [27]
As demonstrated by the above caseA neuii can also causemore invasive infections There are multiple other cases ofA neuii bacteremia various prostheses infections two casesof chronic osteomyelitis two cases of peritoneal dialysis-associated peritonitis and single cases of native aorticvalve endocarditis chronic pericarditis and lymphadenitisinterestingly there have been multiple reports of A neuiicausing endophthalmitis the majority of which occurredpostoperatively (Table 2)
Intriguingly there has been only one case reported of Aneuii causing a classical clinical picture of actinomycosis withrecurrent breast abscesses fistula formation filamentousgrowth and sulfur granules [23]This is in agreementwith thefindings of our study as none of the patients exhibited such
findings nor did they require extended durations of antibiotictherapy
The infections caused byA neuii described in the presentstudy were all associated with abscess formation in soft tissueexcept for one which was isolated from an ankle ulcer Thelatter case may not actually represent an infection as therewere no white cells in the clinical specimen The age range ofpatients infected with A neuii in the literature is 0ndash94 yearswith a mean of 50 years this is comparable with the ages ofpatients in this study While reports in the literature show analmost even number of males and females acquiring A neuiiinfections themajority of the patients in our studyweremalethis is likely due to the small number of cases examined
Previous studies found that abscesses typically includedmixed anaerobic organisms and skin flora as coisolates(Table 2) This is similar to the present study in which fourof six specimens grew anaerobic bacteria and one grewcoagulase-negative staphylococci as well the patient fromwhom A neuii was isolated in pure culture had Gram-positive cocci seen in the direct smear making it possible thatthis was also a mixed anaerobic infection from which at leastone anaerobe failed to grow in culture However this studyalso had a larger variety of aerobic coisolates in specimensthan was reported in previous studies It is difficult to assessthe specific role of A neuii in these mixed infections butits presence in polymicrobial abscesses makes up the vastmajority of cases Improved identification of A neuii in thelaboratory will undoubtedly help to clarify its role in disease
There are few studies describing the use of MALDI-TOFMSMIS in identifying A neuii One other study showed thatthe VITEK MS system was able to correctly identify A neuiito the species level in eight of 12 instances [21] Three groupsused Bruker MALDI-TOF MS MIS (Bruker Billerica MAUSA) two isolates were designated as A neuii with a ldquosecuregenus probable species identificationrdquo level of confidence[20 30] while the degree of certainty in identification ofthe other isolate was not described [45] Due to the limitedamount of experience with either type of MALDI-TOF MSMIS there is no current evidence that one system is superiorto the other in identifying A neuii
The majority of tested isolates show susceptibility to 120573-lactams including penicillin G ampicillin cefazolin cefurox-ime ceftriaxone and imipenem [17 19 27 28 34ndash36 4042 43] Other agents with in vitro activity against A neuiiinclude clindamycin erythromycin tetracycline and van-comycin [17 19 27 28 35 36 40 42] Fluoroquinolones(including ciprofloxacin and levofloxacin) aminoglycosides(including gentamicin and amikacin) and trimethoprim-sulfamethoxazole frequently demonstrate less in vitro activityagainst isolates [19 35 36 40]
Similar to previous studies the isolates in the currentseries were generally quite susceptible to the tested antibi-otics All isolates had low MICs to penicillin amoxicillin-clavulanate and vancomycin only one isolate showed resis-tance to clindamycin
As shown in Table 2 treatment regimens in the literatureare varied and have been dictated by the type and severityof infection In general successful treatment regimens ofteninvolved the use of 120573-lactam antibiotics as well as appropriate
Canadian Journal of Infectious Diseases and Medical Microbiology 5
Table2Ch
aracteris
ticso
fpreviou
slyrepo
rted
caseso
fAneuiiinfections
intheliterature
Infection
Num
bero
fcases
Coisolates
Treatm
ent
Outcomes
References
Abscessinfected
atheromaa
56
Coagu
lase-negatives
taph
ylococci
Enterococcus
spp
Corynebacterium
spp
Anaerob
es
Incisio
nanddrainagew
ithor
with
out
antib
iotic
therapy(usually120573-la
ctam
soccasio
nally
tetracyclin
eciprofl
oxacin)
Generallyfavourable
ifsource
controlis
achieved
[6171922ndash
26]
Cutaneou
sinfectio
nb9
Coagu
lase-negatives
taph
ylococci(eight
cases)
Not
repo
rted
Favourable
[1719]
Genito
urinaryinfectionc
6Non
eAntibiotic
therapywith120573-la
ctam
sFavourable
[1927]
Bacterem
iad
8Non
e
Twocasesreportedtherapy
Ampicillinwith
gentam
icin
(twoweeks)
follo
wed
byPO
penicillin(fo
urweeks)
Initialciprofl
oxacin
follo
wed
byim
ipenem
e
Generallyfavourable
(one
mortality)
[1927]
Endo
carditis
1Non
e
Aorticvalvee
xcision
with
homograft
implantatio
nfollo
wed
byam
picillin
(threew
eeks)ceftriaxone
(ninew
eeks)
andthen
POdo
xycycline
(ninem
onths)
Favourable
[28]
Chronicp
ericarditis
1Non
ePeric
ardialflu
iddrainage
andantib
iotic
therapy(specific
antib
iotic
snot
repo
rted)
Not
repo
rted
[29]
Lymph
adenitis
1Virid
ansg
roup
streptococci
Prevotellatim
onensis
Anaerob
icGram-positive
cocci
Lymph
node
andfistulaexcisio
nfollo
wed
byIV
andthen
POam
oxicillin-clavulanate(sixmon
ths)
Favourable
[30]
Oste
omyelitis
2Dermabacterh
ominis(one
case)
Surgicalcuretta
gefollo
wed
by120573-la
ctam
therapyform
ultip
lemon
ths
Favourable
[2531]
Periton
itis(second
aryto
periton
eald
ialysis
)2
Non
e
Catheter
retentionwith
either
intraperito
nealcefazolin
andcefta
zidime
(twoweeks)followed
bypenicillinG
(four
weeks)or
intraperito
neal
ampicillin
teicop
lanin
andtobram
ycin
(twoweeks)
Favourable
[3233]
Endo
phthalmitis
6Non
eVa
rious
syste
mic(POor
IV)a
nddirect
(intravitrealorsub
conjun
ctival
injectionsdrops)a
ntibiotic
sFavourable
[34ndash
38]
Prostheticmaterial
infectionf
8Ty
pically
none
Coagu
lase-negatives
taph
ylococciand
mixed
anaerobes(breastim
plantcase)
Removalreplacemento
fprosthetic
materialfollowed
byprolon
gedantib
iotic
therapy(w
eeks
toon
eyeardepend
ingon
theinfectio
n)
Favourable
[2539ndash4
5]
a Including
breast
axillaryinguinaliliacc
rest
ischiorectalandpilonidalabscessesone
case
ofhidradenitissup
purativ
amostsitesw
eren
otspecified
b Including
ulcerinfectio
nsdiabetic
foot
ulcerinfectio
nsand
cellu
litis
c Including
urinarytractinfectio
nsprosta
titis
andchorioam
nion
itis
d Including
onec
aseo
fneonatalsepsis
second
aryto
chorioam
nion
itisther
emaining
casesh
adun
clear
orun
repo
rted
sources
e Thep
atient
treated
with
thisregimen
isthes
inglem
ortalityrepo
rted
intheliterature
associated
with
Aneuiiinfectio
nf Including
infections
ofan
intravenou
scatheteram
echanicalh
eartvalveah
ipprosthesis
apenile
prosthesis
breastim
plants
andventric
ulop
erito
nealshun
ts
6 Canadian Journal of Infectious Diseases and Medical Microbiology
surgical interventions This was also the case in the presentstudy as almost all of the treatments involved incision anddrainage of abscesses with subsequent 120573-lactam courses
While A neuii is not a commonly identified organismthere are numerous reports of it causing both invasive andnoninvasive disease Fortunately it is a very susceptibleorganism that can often be treated with 120573-lactams followingdrainage of abscesses or other surgical management Under-standing its clinical significance and typical susceptibilitypatterns will ease decision-making when the organism isencountered as it surely will be with the current widespreaduse of MALDI-TOF MS MIS
Conflict of Interests
The authors have no conflict of interests to declare
References
[1] K P Schaal and H-J Lee ldquoActinomycete infections inhumansmdasha reviewrdquo Gene vol 115 no 1-2 pp 201ndash211 1992
[2] R A Smego Jr and G Foglia ldquoActinomycosisrdquo Clinical Infec-tious Diseases vol 26 no 6 pp 1255ndash1263 1998
[3] V KWong T D Turmezei and V CWeston ldquoActinomycosisrdquoBritish Medical Journal vol 343 Article ID d6099 2011
[4] L J M Sabbe D Van De Merwe L Schouls A BergmansM Vaneechoutte and P Vandamme ldquoClinical spectrum ofinfections due to the newly described Actinomyces species Aturicensis A radingae and A europaeusrdquo Journal of ClinicalMicrobiology vol 37 no 1 pp 8ndash13 1999
[5] V Hall P R Talbot S L Stubbs and B I Duerden ldquoIdenti-fication of clinical isolates of Actinomyces species by amplified16S ribosomal DNA restriction analysisrdquo Journal of ClinicalMicrobiology vol 39 no 10 pp 3555ndash3562 2001
[6] J E Clarridge III and Q Zhang ldquoGenotypic diversity of clinicalActinomyces species phenotype source and disease correlationamong genospeciesrdquo Journal of Clinical Microbiology vol 40no 9 pp 3442ndash3448 2002
[7] A S Fiorino ldquoIntrauterine contraceptive device-associatedactinomycotic abscess and Actinomyces detection on cervicalsmearrdquo Obstetrics and Gynecology vol 87 no 1 pp 142ndash1491996
[8] KWestling C Lidman and AThalme ldquoTricuspid valve endo-carditis caused by a new species of Actinomyces Actinomycesfunkeirdquo Scandinavian Journal of Infectious Diseases vol 34 no3 pp 206ndash207 2001
[9] A Jitmuang ldquoPrimary actinomycotic endocarditis a casereport and literature reviewrdquo Journal of the Medical Associationof Thailand vol 91 no 6 pp 931ndash936 2008
[10] S Ushikoshi I Koyanagi K Hida Y Iwasaki and H AbeldquoSpinal intrathecal actinomycosis a case reportrdquo Surgical Neu-rology vol 50 no 3 pp 221ndash225 1998
[11] S Wang R L Wolf J H Woo et al ldquoActinomycotic braininfection registered diffusion perfusion MR imaging and MRspectroscopyrdquoNeuroradiology vol 48 no 5 pp 346ndash350 2006
[12] L Ghafghaichi S Troy I Budvytiene N Banaei and E JBaron ldquoMixed infection involving Actinomyces Aggregatibac-ter and Fusobacterium species presenting as perispinal tumorrdquoAnaerobe vol 16 no 2 pp 174ndash178 2010
[13] K Imamura H Kamitani H Nakayasu Y Asai and KNakashima ldquoPurulent meningitis caused by Actinomyces suc-cessfully treated with rifampicin a case reportrdquo InternalMedicine vol 50 no 10 pp 1121ndash1125 2011
[14] E Kononen and W G Wade ldquoActinomyces and related organ-isms in human infectionsrdquo Clinical Microbiology Reviews vol28 no 2 pp 419ndash442 2015
[15] J Versalovic K C Carroll G Funke J H Jorgensen M LLandry and D W Warnock Manual of Clinical MicrobiologyASM Press Washington DC USA 2011
[16] T E NarsquoWas D G Hollis CWMoss and R EWeaver ldquoCom-parison of biochemical morphologic and chemical character-istics of centers for disease control fermentative coryneformgroups 1 2 and A-4rdquo Journal of Clinical Microbiology vol 25no 8 pp 1354ndash1358 1987
[17] G Funke G M Lucchini G E Pfyffer M Marchiani and Avon Graevenitz ldquoCharacteristics of CDC group 1 and group1-like coryneform bacteria isolated from clinical specimensrdquoJournal of Clinical Microbiology vol 31 no 11 pp 2907ndash29121993
[18] G Funke S Stubbs A von Graevenitz and M D CollinsldquoAssignment of human-derived CDC group 1 coryneformbacteria and CDC group 1-like coryneform bacteria to thegenus Actinomyces as Actinomyces neuii subsp neuii sp novsubsp nov and Actinomyces neuii subsp anitratus subsp novrdquoInternational Journal of Systematic Bacteriology vol 44 no 1pp 167ndash171 1994
[19] G Funke andA vonGraevenitz ldquoInfections due toActinomycesneuii (former lsquoCDC coryneform group 1rsquo bacteria)rdquo Infectionvol 23 no 2 pp 73ndash75 1995
[20] L S Y Ng J H C Sim L C Eng S Menon and T Y TanldquoComparison of phenotypic methods and matrix-assisted laserdesorption ionisation time-of-flight mass spectrometry for theidentification of aero-tolerant Actinomyces spp isolated fromsoft-tissue infectionsrdquoEuropean Journal of ClinicalMicrobiologyand Infectious Diseases vol 31 no 8 pp 1749ndash1752 2012
[21] O Garner AMochon J Branda et al ldquoMulti-centre evaluationof mass spectrometric identification of anaerobic bacteria usingthe VITEK MS systemrdquo Clinical Microbiology and Infectionvol 20 no 4 pp 335ndash339 2014
[22] C Lacoste M-C Escande J Klijanienko P Jammet and CNos ldquoBreast Actinomyces neuii abscess simulating primarymalignancy a case diagnosed by fine-needle aspirationrdquo Diag-nostic Cytopathology vol 37 no 4 pp 311ndash312 2009
[23] A Roustan M Al Nakib and L Boubli ldquoPrimary actino-mycosis of the breast due to Actinomyces neuiirdquo Journal deGynecologie Obstetrique et Biologie de la Reproduction vol 39no 1 pp 64ndash67 2010
[24] J L Gomez-Garces A Burillo Y Gil and J A Saez-Nieto ldquoSofttissue infections caused by Actinomyces neuii a rare pathogenrdquoJournal of Clinical Microbiology vol 48 no 4 pp 1508ndash15092010
[25] K De Vreese and J Verhaegen ldquoIdentification of coryneformActinomyces neuii by MALDI-TOF MS 5 case reports andreview of literaturerdquo Acta Clinica Belgica vol 68 no 3 pp 210ndash214 2013
[26] J M Olson and J C Vary Jr ldquoPrimary cutaneous Actinomycesneuii infection of the breast successfully treated with doxycy-clinerdquo Cutis vol 92 no 6 pp E3ndashE4 2013
[27] C Mann S Dertinger G Hartmann R Schurz and B SimmaldquoActinomyces neuii and neonatal sepsisrdquo Infection vol 30 no3 pp 178ndash180 2002
Canadian Journal of Infectious Diseases and Medical Microbiology 7
[28] E Cohen J Bishara B Medalion A Sagie and M GartyldquoInfective endocarditis due to Actinomyces neuiirdquo ScandinavianJournal of Infectious Diseases vol 39 no 2 pp 180ndash183 2007
[29] P-Y Levy P-E Fournier R Charrel D Metras G Habiband D Raoult ldquoMolecular analysis of pericardial fluid a 7-yearexperiencerdquo European Heart Journal vol 27 no 16 pp 1942ndash1946 2006
[30] K Walther E Bruder D Goldenberger J Mayr U B Schaadand N Ritz ldquoActinomyces neuii isolated from a 20-month-old girl with cervical lymphadenitisrdquo Journal of the PediatricInfectious Diseases Society vol 4 no 3 pp e32ndashe37 2015
[31] B Van Bosterhaut P Boucquey M Janssens G Wauters andM Delmee ldquoChronic osteomyelitis due to Actinomyces neuiisubspecies neuii and Dermabacter hominisrdquo European Journalof Clinical Microbiology and Infectious Diseases vol 21 no 6pp 486ndash487 2002
[32] S Varughese and J Bargman ldquoActinomyces neuii PDperitonitismdashresolution of infection without catheter removalrdquoPeritoneal Dialysis International vol 34 no 7 pp 815ndash8162014
[33] R Dıaz M A Bajo G Del Peso A Garcıa-Perea R Sanchez-Villanueva and R Selgas ldquoActinomyces peritonitis removal ofthe peritoneal catheter unnecessary for resolutionrdquo NDT Plusvol 3 no 3 pp 296ndash297 2010
[34] P E Coudron R C Harris M G Vaughan and H P DaltonldquoTwo similar but atypical strains of coryneform group A-4isolated from patients with endophthalmitisrdquo Journal of ClinicalMicrobiology vol 22 no 4 pp 475ndash477 1985
[35] J M Garelick A J Khodabakhsh and R G Josephberg ldquoAcutepostoperative endophthalmitis caused by Actinomyces neuiirdquoAmerican Journal of Ophthalmology vol 133 no 1 pp 145ndash1472002
[36] V S Raman N Evans B Shreshta and R CunninghamldquoChronic postoperative endophthalmitis caused byActinomycesneuiirdquo Journal of Cataract and Refractive Surgery vol 30 no 12pp 2641ndash2643 2004
[37] J J Perez-Santonja E Campos-Mollo E Fuentes-Campos JSamper-Gimenez and J L Alio ldquoActinomyces neuii subspeciesanitratus chronic endophthalmitis after cataract surgeryrdquo Euro-pean Journal of Ophthalmology vol 17 no 3 pp 445ndash447 2007
[38] SGraffiA Peretz andMNaftali ldquoEndogenous endophthalmi-tis with an unusual infective agentActinomyces neuiirdquoEuropeanJournal of Ophthalmology vol 22 no 5 pp 834ndash835 2012
[39] S Brunner S Graf P Riegel and M Altwegg ldquoCatalase-negative Actinomyces neuii subsp neuii isolated from aninfected mammary prosthesisrdquo International Journal of MedicalMicrobiology vol 290 no 3 pp 285ndash287 2000
[40] R R Watkins K Anthony S Schroder and G S HallldquoVentriculoperitoneal shunt infection caused by Actinomycesneuii subsp neuiirdquo Journal of Clinical Microbiology vol 46 no5 pp 1888ndash1889 2008
[41] H Rieber R Schwarz O KramerW Cordier and L FrommeltldquoActinomyces neuii subsp neuii associated with periprostheticinfection in total hip arthroplasty as causative agentrdquo Journal ofClinical Microbiology vol 47 no 12 pp 4183ndash4184 2009
[42] S Grundmann J Huebner J Stuplich et al ldquoProsthetic valveendocarditis due to Actinomyces neuii successfully treated withantibiotic therapyrdquo Journal of Clinical Microbiology vol 48 no3 pp 1008ndash1011 2010
[43] R S Hsi J M Hotaling E S Spencer P L Bollyky andT J Walsh ldquoIsolated infection of a decommissioned penile
prosthesis reservoir with Actinomyces neuiirdquo Journal of SexualMedicine vol 8 no 3 pp 923ndash926 2011
[44] I A Anderson F Jarral K Sethi and P D Chumas ldquoPaediatricventriculoperitoneal shunt infection caused by Actinomycesneuiirdquo BMJ Case Reports 2014
[45] P Seng S Bayle A Alliez F RomainD Casanova andA SteinldquoThe microbial epidemiology of breast implant infections in aregional referral centre for plastic and reconstructive surgery inthe south of Francerdquo International Journal of Infectious Diseasesvol 35 pp 62ndash66 2015
[46] D J Lane ldquo16S23S rRNA sequencingrdquo in Nucleic Acid Tech-niques in Bacterial Systematics E Stackebrandt and M Good-fellow Eds pp 115ndash175 John Wiley amp Sons Chichester UK1991
[47] J R Cole Q Wang J A Fish et al ldquoRibosomal DatabaseProject data and tools for high throughput rRNA analysisrdquoNucleic Acids Research vol 42 no 1 pp D633ndashD642 2014
[48] Clinical and Laboratory Standards Institute ldquoPerformancestandards for Antimicrobial Susceptibility Testing 25th infor-mational supplementrdquo Tech Rep M100-S25 Clinical and Lab-oratory Standards Institute 2015
[49] Canadian Institutes of Health Research Natural Sciences andEngineering Research Council of Canada and Social Sciencesand Humanities Research Council of Canada ldquoTri-CouncilPolicy Statement Ethical Conduct for Research InvolvingHumansrdquo December 2014
Submit your manuscripts athttpwwwhindawicom
Stem CellsInternational
Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014
Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014
MEDIATORSINFLAMMATION
of
Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014
Behavioural Neurology
EndocrinologyInternational Journal of
Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014
Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014
Disease Markers
Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014
BioMed Research International
OncologyJournal of
Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014
Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014
Oxidative Medicine and Cellular Longevity
Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014
PPAR Research
The Scientific World JournalHindawi Publishing Corporation httpwwwhindawicom Volume 2014
Immunology ResearchHindawi Publishing Corporationhttpwwwhindawicom Volume 2014
Journal of
ObesityJournal of
Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014
Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014
Computational and Mathematical Methods in Medicine
OphthalmologyJournal of
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Diabetes ResearchJournal of
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Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014
Research and TreatmentAIDS
Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014
Gastroenterology Research and Practice
Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014
Parkinsonrsquos Disease
Evidence-Based Complementary and Alternative Medicine
Volume 2014Hindawi Publishing Corporationhttpwwwhindawicom
4 Canadian Journal of Infectious Diseases and Medical Microbiology
ages ranged from 30 to 85 years all but one of the patientswere male There was no obvious trend in patient comor-bidities While one of the specimens was collected from alower extremity skin ulcer the remaining five were collectedfrom abscesses in different locations Gram smears usuallyrevealed the presence of multiple types of bacteria in theclinical specimens and the resulting cultures grew at leasttwo different bacterial species as coisolates in all but onecase (Table 1) The most common coisolates were anaerobicbacteria but themore common skin and soft tissue infectiousagent Staphylococcus lugdunensis was isolated in two casesSusceptibility testing showed that all of the A neuii isolateshad low minimal inhibitory concentrations to penicillinbroader spectrum 120573-lactams and vancomycin one isolatehad an MIC ge 256mgL to clindamycin while the othershadMICs of le0032mgL Treatment of the abscesses usuallyinvolved incision and drainage followed by seven- to 18-daycourses of a120573-lactam though one of the abscesses was treatedwith a four-week course of ciprofloxacin without drainageNone of the patients were noted to have relapses followingtherapy
4 Discussion
Actinomyces neuii has been isolated in a wide range of clinicalscenarios but has rarely been reported in the literatureThereare less than 100 cases reported in the literature of A neuiiinfections we and others have hypothesized that dismissal asa commensal coryneform bacillus may be the reason Whilethere have only been scattered reports of A neuii causinginfection since interest in the organism was originally raisedin the mid-1990s the frequency of reports recognizing itas a pathogen has recently increased likely due to the useof advanced identification systems Abscesses are the mostcommon manifestation of A neuii infection with more thanhalf of the reported cases describing abscesses or infectedatheromas (Table 2) [6 17 19 22ndash45] A number of otherinfectious entities implicating A neuii have been describedincluding ulcer infections cellulitis urinary tract infectionsand prostatitis (Table 2)
There have been two reported cases ofA neuii chorioam-nionitis one of which resulted in neonatal sepsis afterpremature delivery [19 27] In the latter case the organismwas isolated from multiple sites from the neonate includingthe external ear canal a gastric aspirate and blood [27]
As demonstrated by the above caseA neuii can also causemore invasive infections There are multiple other cases ofA neuii bacteremia various prostheses infections two casesof chronic osteomyelitis two cases of peritoneal dialysis-associated peritonitis and single cases of native aorticvalve endocarditis chronic pericarditis and lymphadenitisinterestingly there have been multiple reports of A neuiicausing endophthalmitis the majority of which occurredpostoperatively (Table 2)
Intriguingly there has been only one case reported of Aneuii causing a classical clinical picture of actinomycosis withrecurrent breast abscesses fistula formation filamentousgrowth and sulfur granules [23]This is in agreementwith thefindings of our study as none of the patients exhibited such
findings nor did they require extended durations of antibiotictherapy
The infections caused byA neuii described in the presentstudy were all associated with abscess formation in soft tissueexcept for one which was isolated from an ankle ulcer Thelatter case may not actually represent an infection as therewere no white cells in the clinical specimen The age range ofpatients infected with A neuii in the literature is 0ndash94 yearswith a mean of 50 years this is comparable with the ages ofpatients in this study While reports in the literature show analmost even number of males and females acquiring A neuiiinfections themajority of the patients in our studyweremalethis is likely due to the small number of cases examined
Previous studies found that abscesses typically includedmixed anaerobic organisms and skin flora as coisolates(Table 2) This is similar to the present study in which fourof six specimens grew anaerobic bacteria and one grewcoagulase-negative staphylococci as well the patient fromwhom A neuii was isolated in pure culture had Gram-positive cocci seen in the direct smear making it possible thatthis was also a mixed anaerobic infection from which at leastone anaerobe failed to grow in culture However this studyalso had a larger variety of aerobic coisolates in specimensthan was reported in previous studies It is difficult to assessthe specific role of A neuii in these mixed infections butits presence in polymicrobial abscesses makes up the vastmajority of cases Improved identification of A neuii in thelaboratory will undoubtedly help to clarify its role in disease
There are few studies describing the use of MALDI-TOFMSMIS in identifying A neuii One other study showed thatthe VITEK MS system was able to correctly identify A neuiito the species level in eight of 12 instances [21] Three groupsused Bruker MALDI-TOF MS MIS (Bruker Billerica MAUSA) two isolates were designated as A neuii with a ldquosecuregenus probable species identificationrdquo level of confidence[20 30] while the degree of certainty in identification ofthe other isolate was not described [45] Due to the limitedamount of experience with either type of MALDI-TOF MSMIS there is no current evidence that one system is superiorto the other in identifying A neuii
The majority of tested isolates show susceptibility to 120573-lactams including penicillin G ampicillin cefazolin cefurox-ime ceftriaxone and imipenem [17 19 27 28 34ndash36 4042 43] Other agents with in vitro activity against A neuiiinclude clindamycin erythromycin tetracycline and van-comycin [17 19 27 28 35 36 40 42] Fluoroquinolones(including ciprofloxacin and levofloxacin) aminoglycosides(including gentamicin and amikacin) and trimethoprim-sulfamethoxazole frequently demonstrate less in vitro activityagainst isolates [19 35 36 40]
Similar to previous studies the isolates in the currentseries were generally quite susceptible to the tested antibi-otics All isolates had low MICs to penicillin amoxicillin-clavulanate and vancomycin only one isolate showed resis-tance to clindamycin
As shown in Table 2 treatment regimens in the literatureare varied and have been dictated by the type and severityof infection In general successful treatment regimens ofteninvolved the use of 120573-lactam antibiotics as well as appropriate
Canadian Journal of Infectious Diseases and Medical Microbiology 5
Table2Ch
aracteris
ticso
fpreviou
slyrepo
rted
caseso
fAneuiiinfections
intheliterature
Infection
Num
bero
fcases
Coisolates
Treatm
ent
Outcomes
References
Abscessinfected
atheromaa
56
Coagu
lase-negatives
taph
ylococci
Enterococcus
spp
Corynebacterium
spp
Anaerob
es
Incisio
nanddrainagew
ithor
with
out
antib
iotic
therapy(usually120573-la
ctam
soccasio
nally
tetracyclin
eciprofl
oxacin)
Generallyfavourable
ifsource
controlis
achieved
[6171922ndash
26]
Cutaneou
sinfectio
nb9
Coagu
lase-negatives
taph
ylococci(eight
cases)
Not
repo
rted
Favourable
[1719]
Genito
urinaryinfectionc
6Non
eAntibiotic
therapywith120573-la
ctam
sFavourable
[1927]
Bacterem
iad
8Non
e
Twocasesreportedtherapy
Ampicillinwith
gentam
icin
(twoweeks)
follo
wed
byPO
penicillin(fo
urweeks)
Initialciprofl
oxacin
follo
wed
byim
ipenem
e
Generallyfavourable
(one
mortality)
[1927]
Endo
carditis
1Non
e
Aorticvalvee
xcision
with
homograft
implantatio
nfollo
wed
byam
picillin
(threew
eeks)ceftriaxone
(ninew
eeks)
andthen
POdo
xycycline
(ninem
onths)
Favourable
[28]
Chronicp
ericarditis
1Non
ePeric
ardialflu
iddrainage
andantib
iotic
therapy(specific
antib
iotic
snot
repo
rted)
Not
repo
rted
[29]
Lymph
adenitis
1Virid
ansg
roup
streptococci
Prevotellatim
onensis
Anaerob
icGram-positive
cocci
Lymph
node
andfistulaexcisio
nfollo
wed
byIV
andthen
POam
oxicillin-clavulanate(sixmon
ths)
Favourable
[30]
Oste
omyelitis
2Dermabacterh
ominis(one
case)
Surgicalcuretta
gefollo
wed
by120573-la
ctam
therapyform
ultip
lemon
ths
Favourable
[2531]
Periton
itis(second
aryto
periton
eald
ialysis
)2
Non
e
Catheter
retentionwith
either
intraperito
nealcefazolin
andcefta
zidime
(twoweeks)followed
bypenicillinG
(four
weeks)or
intraperito
neal
ampicillin
teicop
lanin
andtobram
ycin
(twoweeks)
Favourable
[3233]
Endo
phthalmitis
6Non
eVa
rious
syste
mic(POor
IV)a
nddirect
(intravitrealorsub
conjun
ctival
injectionsdrops)a
ntibiotic
sFavourable
[34ndash
38]
Prostheticmaterial
infectionf
8Ty
pically
none
Coagu
lase-negatives
taph
ylococciand
mixed
anaerobes(breastim
plantcase)
Removalreplacemento
fprosthetic
materialfollowed
byprolon
gedantib
iotic
therapy(w
eeks
toon
eyeardepend
ingon
theinfectio
n)
Favourable
[2539ndash4
5]
a Including
breast
axillaryinguinaliliacc
rest
ischiorectalandpilonidalabscessesone
case
ofhidradenitissup
purativ
amostsitesw
eren
otspecified
b Including
ulcerinfectio
nsdiabetic
foot
ulcerinfectio
nsand
cellu
litis
c Including
urinarytractinfectio
nsprosta
titis
andchorioam
nion
itis
d Including
onec
aseo
fneonatalsepsis
second
aryto
chorioam
nion
itisther
emaining
casesh
adun
clear
orun
repo
rted
sources
e Thep
atient
treated
with
thisregimen
isthes
inglem
ortalityrepo
rted
intheliterature
associated
with
Aneuiiinfectio
nf Including
infections
ofan
intravenou
scatheteram
echanicalh
eartvalveah
ipprosthesis
apenile
prosthesis
breastim
plants
andventric
ulop
erito
nealshun
ts
6 Canadian Journal of Infectious Diseases and Medical Microbiology
surgical interventions This was also the case in the presentstudy as almost all of the treatments involved incision anddrainage of abscesses with subsequent 120573-lactam courses
While A neuii is not a commonly identified organismthere are numerous reports of it causing both invasive andnoninvasive disease Fortunately it is a very susceptibleorganism that can often be treated with 120573-lactams followingdrainage of abscesses or other surgical management Under-standing its clinical significance and typical susceptibilitypatterns will ease decision-making when the organism isencountered as it surely will be with the current widespreaduse of MALDI-TOF MS MIS
Conflict of Interests
The authors have no conflict of interests to declare
References
[1] K P Schaal and H-J Lee ldquoActinomycete infections inhumansmdasha reviewrdquo Gene vol 115 no 1-2 pp 201ndash211 1992
[2] R A Smego Jr and G Foglia ldquoActinomycosisrdquo Clinical Infec-tious Diseases vol 26 no 6 pp 1255ndash1263 1998
[3] V KWong T D Turmezei and V CWeston ldquoActinomycosisrdquoBritish Medical Journal vol 343 Article ID d6099 2011
[4] L J M Sabbe D Van De Merwe L Schouls A BergmansM Vaneechoutte and P Vandamme ldquoClinical spectrum ofinfections due to the newly described Actinomyces species Aturicensis A radingae and A europaeusrdquo Journal of ClinicalMicrobiology vol 37 no 1 pp 8ndash13 1999
[5] V Hall P R Talbot S L Stubbs and B I Duerden ldquoIdenti-fication of clinical isolates of Actinomyces species by amplified16S ribosomal DNA restriction analysisrdquo Journal of ClinicalMicrobiology vol 39 no 10 pp 3555ndash3562 2001
[6] J E Clarridge III and Q Zhang ldquoGenotypic diversity of clinicalActinomyces species phenotype source and disease correlationamong genospeciesrdquo Journal of Clinical Microbiology vol 40no 9 pp 3442ndash3448 2002
[7] A S Fiorino ldquoIntrauterine contraceptive device-associatedactinomycotic abscess and Actinomyces detection on cervicalsmearrdquo Obstetrics and Gynecology vol 87 no 1 pp 142ndash1491996
[8] KWestling C Lidman and AThalme ldquoTricuspid valve endo-carditis caused by a new species of Actinomyces Actinomycesfunkeirdquo Scandinavian Journal of Infectious Diseases vol 34 no3 pp 206ndash207 2001
[9] A Jitmuang ldquoPrimary actinomycotic endocarditis a casereport and literature reviewrdquo Journal of the Medical Associationof Thailand vol 91 no 6 pp 931ndash936 2008
[10] S Ushikoshi I Koyanagi K Hida Y Iwasaki and H AbeldquoSpinal intrathecal actinomycosis a case reportrdquo Surgical Neu-rology vol 50 no 3 pp 221ndash225 1998
[11] S Wang R L Wolf J H Woo et al ldquoActinomycotic braininfection registered diffusion perfusion MR imaging and MRspectroscopyrdquoNeuroradiology vol 48 no 5 pp 346ndash350 2006
[12] L Ghafghaichi S Troy I Budvytiene N Banaei and E JBaron ldquoMixed infection involving Actinomyces Aggregatibac-ter and Fusobacterium species presenting as perispinal tumorrdquoAnaerobe vol 16 no 2 pp 174ndash178 2010
[13] K Imamura H Kamitani H Nakayasu Y Asai and KNakashima ldquoPurulent meningitis caused by Actinomyces suc-cessfully treated with rifampicin a case reportrdquo InternalMedicine vol 50 no 10 pp 1121ndash1125 2011
[14] E Kononen and W G Wade ldquoActinomyces and related organ-isms in human infectionsrdquo Clinical Microbiology Reviews vol28 no 2 pp 419ndash442 2015
[15] J Versalovic K C Carroll G Funke J H Jorgensen M LLandry and D W Warnock Manual of Clinical MicrobiologyASM Press Washington DC USA 2011
[16] T E NarsquoWas D G Hollis CWMoss and R EWeaver ldquoCom-parison of biochemical morphologic and chemical character-istics of centers for disease control fermentative coryneformgroups 1 2 and A-4rdquo Journal of Clinical Microbiology vol 25no 8 pp 1354ndash1358 1987
[17] G Funke G M Lucchini G E Pfyffer M Marchiani and Avon Graevenitz ldquoCharacteristics of CDC group 1 and group1-like coryneform bacteria isolated from clinical specimensrdquoJournal of Clinical Microbiology vol 31 no 11 pp 2907ndash29121993
[18] G Funke S Stubbs A von Graevenitz and M D CollinsldquoAssignment of human-derived CDC group 1 coryneformbacteria and CDC group 1-like coryneform bacteria to thegenus Actinomyces as Actinomyces neuii subsp neuii sp novsubsp nov and Actinomyces neuii subsp anitratus subsp novrdquoInternational Journal of Systematic Bacteriology vol 44 no 1pp 167ndash171 1994
[19] G Funke andA vonGraevenitz ldquoInfections due toActinomycesneuii (former lsquoCDC coryneform group 1rsquo bacteria)rdquo Infectionvol 23 no 2 pp 73ndash75 1995
[20] L S Y Ng J H C Sim L C Eng S Menon and T Y TanldquoComparison of phenotypic methods and matrix-assisted laserdesorption ionisation time-of-flight mass spectrometry for theidentification of aero-tolerant Actinomyces spp isolated fromsoft-tissue infectionsrdquoEuropean Journal of ClinicalMicrobiologyand Infectious Diseases vol 31 no 8 pp 1749ndash1752 2012
[21] O Garner AMochon J Branda et al ldquoMulti-centre evaluationof mass spectrometric identification of anaerobic bacteria usingthe VITEK MS systemrdquo Clinical Microbiology and Infectionvol 20 no 4 pp 335ndash339 2014
[22] C Lacoste M-C Escande J Klijanienko P Jammet and CNos ldquoBreast Actinomyces neuii abscess simulating primarymalignancy a case diagnosed by fine-needle aspirationrdquo Diag-nostic Cytopathology vol 37 no 4 pp 311ndash312 2009
[23] A Roustan M Al Nakib and L Boubli ldquoPrimary actino-mycosis of the breast due to Actinomyces neuiirdquo Journal deGynecologie Obstetrique et Biologie de la Reproduction vol 39no 1 pp 64ndash67 2010
[24] J L Gomez-Garces A Burillo Y Gil and J A Saez-Nieto ldquoSofttissue infections caused by Actinomyces neuii a rare pathogenrdquoJournal of Clinical Microbiology vol 48 no 4 pp 1508ndash15092010
[25] K De Vreese and J Verhaegen ldquoIdentification of coryneformActinomyces neuii by MALDI-TOF MS 5 case reports andreview of literaturerdquo Acta Clinica Belgica vol 68 no 3 pp 210ndash214 2013
[26] J M Olson and J C Vary Jr ldquoPrimary cutaneous Actinomycesneuii infection of the breast successfully treated with doxycy-clinerdquo Cutis vol 92 no 6 pp E3ndashE4 2013
[27] C Mann S Dertinger G Hartmann R Schurz and B SimmaldquoActinomyces neuii and neonatal sepsisrdquo Infection vol 30 no3 pp 178ndash180 2002
Canadian Journal of Infectious Diseases and Medical Microbiology 7
[28] E Cohen J Bishara B Medalion A Sagie and M GartyldquoInfective endocarditis due to Actinomyces neuiirdquo ScandinavianJournal of Infectious Diseases vol 39 no 2 pp 180ndash183 2007
[29] P-Y Levy P-E Fournier R Charrel D Metras G Habiband D Raoult ldquoMolecular analysis of pericardial fluid a 7-yearexperiencerdquo European Heart Journal vol 27 no 16 pp 1942ndash1946 2006
[30] K Walther E Bruder D Goldenberger J Mayr U B Schaadand N Ritz ldquoActinomyces neuii isolated from a 20-month-old girl with cervical lymphadenitisrdquo Journal of the PediatricInfectious Diseases Society vol 4 no 3 pp e32ndashe37 2015
[31] B Van Bosterhaut P Boucquey M Janssens G Wauters andM Delmee ldquoChronic osteomyelitis due to Actinomyces neuiisubspecies neuii and Dermabacter hominisrdquo European Journalof Clinical Microbiology and Infectious Diseases vol 21 no 6pp 486ndash487 2002
[32] S Varughese and J Bargman ldquoActinomyces neuii PDperitonitismdashresolution of infection without catheter removalrdquoPeritoneal Dialysis International vol 34 no 7 pp 815ndash8162014
[33] R Dıaz M A Bajo G Del Peso A Garcıa-Perea R Sanchez-Villanueva and R Selgas ldquoActinomyces peritonitis removal ofthe peritoneal catheter unnecessary for resolutionrdquo NDT Plusvol 3 no 3 pp 296ndash297 2010
[34] P E Coudron R C Harris M G Vaughan and H P DaltonldquoTwo similar but atypical strains of coryneform group A-4isolated from patients with endophthalmitisrdquo Journal of ClinicalMicrobiology vol 22 no 4 pp 475ndash477 1985
[35] J M Garelick A J Khodabakhsh and R G Josephberg ldquoAcutepostoperative endophthalmitis caused by Actinomyces neuiirdquoAmerican Journal of Ophthalmology vol 133 no 1 pp 145ndash1472002
[36] V S Raman N Evans B Shreshta and R CunninghamldquoChronic postoperative endophthalmitis caused byActinomycesneuiirdquo Journal of Cataract and Refractive Surgery vol 30 no 12pp 2641ndash2643 2004
[37] J J Perez-Santonja E Campos-Mollo E Fuentes-Campos JSamper-Gimenez and J L Alio ldquoActinomyces neuii subspeciesanitratus chronic endophthalmitis after cataract surgeryrdquo Euro-pean Journal of Ophthalmology vol 17 no 3 pp 445ndash447 2007
[38] SGraffiA Peretz andMNaftali ldquoEndogenous endophthalmi-tis with an unusual infective agentActinomyces neuiirdquoEuropeanJournal of Ophthalmology vol 22 no 5 pp 834ndash835 2012
[39] S Brunner S Graf P Riegel and M Altwegg ldquoCatalase-negative Actinomyces neuii subsp neuii isolated from aninfected mammary prosthesisrdquo International Journal of MedicalMicrobiology vol 290 no 3 pp 285ndash287 2000
[40] R R Watkins K Anthony S Schroder and G S HallldquoVentriculoperitoneal shunt infection caused by Actinomycesneuii subsp neuiirdquo Journal of Clinical Microbiology vol 46 no5 pp 1888ndash1889 2008
[41] H Rieber R Schwarz O KramerW Cordier and L FrommeltldquoActinomyces neuii subsp neuii associated with periprostheticinfection in total hip arthroplasty as causative agentrdquo Journal ofClinical Microbiology vol 47 no 12 pp 4183ndash4184 2009
[42] S Grundmann J Huebner J Stuplich et al ldquoProsthetic valveendocarditis due to Actinomyces neuii successfully treated withantibiotic therapyrdquo Journal of Clinical Microbiology vol 48 no3 pp 1008ndash1011 2010
[43] R S Hsi J M Hotaling E S Spencer P L Bollyky andT J Walsh ldquoIsolated infection of a decommissioned penile
prosthesis reservoir with Actinomyces neuiirdquo Journal of SexualMedicine vol 8 no 3 pp 923ndash926 2011
[44] I A Anderson F Jarral K Sethi and P D Chumas ldquoPaediatricventriculoperitoneal shunt infection caused by Actinomycesneuiirdquo BMJ Case Reports 2014
[45] P Seng S Bayle A Alliez F RomainD Casanova andA SteinldquoThe microbial epidemiology of breast implant infections in aregional referral centre for plastic and reconstructive surgery inthe south of Francerdquo International Journal of Infectious Diseasesvol 35 pp 62ndash66 2015
[46] D J Lane ldquo16S23S rRNA sequencingrdquo in Nucleic Acid Tech-niques in Bacterial Systematics E Stackebrandt and M Good-fellow Eds pp 115ndash175 John Wiley amp Sons Chichester UK1991
[47] J R Cole Q Wang J A Fish et al ldquoRibosomal DatabaseProject data and tools for high throughput rRNA analysisrdquoNucleic Acids Research vol 42 no 1 pp D633ndashD642 2014
[48] Clinical and Laboratory Standards Institute ldquoPerformancestandards for Antimicrobial Susceptibility Testing 25th infor-mational supplementrdquo Tech Rep M100-S25 Clinical and Lab-oratory Standards Institute 2015
[49] Canadian Institutes of Health Research Natural Sciences andEngineering Research Council of Canada and Social Sciencesand Humanities Research Council of Canada ldquoTri-CouncilPolicy Statement Ethical Conduct for Research InvolvingHumansrdquo December 2014
Submit your manuscripts athttpwwwhindawicom
Stem CellsInternational
Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014
Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014
MEDIATORSINFLAMMATION
of
Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014
Behavioural Neurology
EndocrinologyInternational Journal of
Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014
Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014
Disease Markers
Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014
BioMed Research International
OncologyJournal of
Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014
Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014
Oxidative Medicine and Cellular Longevity
Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014
PPAR Research
The Scientific World JournalHindawi Publishing Corporation httpwwwhindawicom Volume 2014
Immunology ResearchHindawi Publishing Corporationhttpwwwhindawicom Volume 2014
Journal of
ObesityJournal of
Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014
Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014
Computational and Mathematical Methods in Medicine
OphthalmologyJournal of
Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014
Diabetes ResearchJournal of
Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014
Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014
Research and TreatmentAIDS
Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014
Gastroenterology Research and Practice
Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014
Parkinsonrsquos Disease
Evidence-Based Complementary and Alternative Medicine
Volume 2014Hindawi Publishing Corporationhttpwwwhindawicom
Canadian Journal of Infectious Diseases and Medical Microbiology 5
Table2Ch
aracteris
ticso
fpreviou
slyrepo
rted
caseso
fAneuiiinfections
intheliterature
Infection
Num
bero
fcases
Coisolates
Treatm
ent
Outcomes
References
Abscessinfected
atheromaa
56
Coagu
lase-negatives
taph
ylococci
Enterococcus
spp
Corynebacterium
spp
Anaerob
es
Incisio
nanddrainagew
ithor
with
out
antib
iotic
therapy(usually120573-la
ctam
soccasio
nally
tetracyclin
eciprofl
oxacin)
Generallyfavourable
ifsource
controlis
achieved
[6171922ndash
26]
Cutaneou
sinfectio
nb9
Coagu
lase-negatives
taph
ylococci(eight
cases)
Not
repo
rted
Favourable
[1719]
Genito
urinaryinfectionc
6Non
eAntibiotic
therapywith120573-la
ctam
sFavourable
[1927]
Bacterem
iad
8Non
e
Twocasesreportedtherapy
Ampicillinwith
gentam
icin
(twoweeks)
follo
wed
byPO
penicillin(fo
urweeks)
Initialciprofl
oxacin
follo
wed
byim
ipenem
e
Generallyfavourable
(one
mortality)
[1927]
Endo
carditis
1Non
e
Aorticvalvee
xcision
with
homograft
implantatio
nfollo
wed
byam
picillin
(threew
eeks)ceftriaxone
(ninew
eeks)
andthen
POdo
xycycline
(ninem
onths)
Favourable
[28]
Chronicp
ericarditis
1Non
ePeric
ardialflu
iddrainage
andantib
iotic
therapy(specific
antib
iotic
snot
repo
rted)
Not
repo
rted
[29]
Lymph
adenitis
1Virid
ansg
roup
streptococci
Prevotellatim
onensis
Anaerob
icGram-positive
cocci
Lymph
node
andfistulaexcisio
nfollo
wed
byIV
andthen
POam
oxicillin-clavulanate(sixmon
ths)
Favourable
[30]
Oste
omyelitis
2Dermabacterh
ominis(one
case)
Surgicalcuretta
gefollo
wed
by120573-la
ctam
therapyform
ultip
lemon
ths
Favourable
[2531]
Periton
itis(second
aryto
periton
eald
ialysis
)2
Non
e
Catheter
retentionwith
either
intraperito
nealcefazolin
andcefta
zidime
(twoweeks)followed
bypenicillinG
(four
weeks)or
intraperito
neal
ampicillin
teicop
lanin
andtobram
ycin
(twoweeks)
Favourable
[3233]
Endo
phthalmitis
6Non
eVa
rious
syste
mic(POor
IV)a
nddirect
(intravitrealorsub
conjun
ctival
injectionsdrops)a
ntibiotic
sFavourable
[34ndash
38]
Prostheticmaterial
infectionf
8Ty
pically
none
Coagu
lase-negatives
taph
ylococciand
mixed
anaerobes(breastim
plantcase)
Removalreplacemento
fprosthetic
materialfollowed
byprolon
gedantib
iotic
therapy(w
eeks
toon
eyeardepend
ingon
theinfectio
n)
Favourable
[2539ndash4
5]
a Including
breast
axillaryinguinaliliacc
rest
ischiorectalandpilonidalabscessesone
case
ofhidradenitissup
purativ
amostsitesw
eren
otspecified
b Including
ulcerinfectio
nsdiabetic
foot
ulcerinfectio
nsand
cellu
litis
c Including
urinarytractinfectio
nsprosta
titis
andchorioam
nion
itis
d Including
onec
aseo
fneonatalsepsis
second
aryto
chorioam
nion
itisther
emaining
casesh
adun
clear
orun
repo
rted
sources
e Thep
atient
treated
with
thisregimen
isthes
inglem
ortalityrepo
rted
intheliterature
associated
with
Aneuiiinfectio
nf Including
infections
ofan
intravenou
scatheteram
echanicalh
eartvalveah
ipprosthesis
apenile
prosthesis
breastim
plants
andventric
ulop
erito
nealshun
ts
6 Canadian Journal of Infectious Diseases and Medical Microbiology
surgical interventions This was also the case in the presentstudy as almost all of the treatments involved incision anddrainage of abscesses with subsequent 120573-lactam courses
While A neuii is not a commonly identified organismthere are numerous reports of it causing both invasive andnoninvasive disease Fortunately it is a very susceptibleorganism that can often be treated with 120573-lactams followingdrainage of abscesses or other surgical management Under-standing its clinical significance and typical susceptibilitypatterns will ease decision-making when the organism isencountered as it surely will be with the current widespreaduse of MALDI-TOF MS MIS
Conflict of Interests
The authors have no conflict of interests to declare
References
[1] K P Schaal and H-J Lee ldquoActinomycete infections inhumansmdasha reviewrdquo Gene vol 115 no 1-2 pp 201ndash211 1992
[2] R A Smego Jr and G Foglia ldquoActinomycosisrdquo Clinical Infec-tious Diseases vol 26 no 6 pp 1255ndash1263 1998
[3] V KWong T D Turmezei and V CWeston ldquoActinomycosisrdquoBritish Medical Journal vol 343 Article ID d6099 2011
[4] L J M Sabbe D Van De Merwe L Schouls A BergmansM Vaneechoutte and P Vandamme ldquoClinical spectrum ofinfections due to the newly described Actinomyces species Aturicensis A radingae and A europaeusrdquo Journal of ClinicalMicrobiology vol 37 no 1 pp 8ndash13 1999
[5] V Hall P R Talbot S L Stubbs and B I Duerden ldquoIdenti-fication of clinical isolates of Actinomyces species by amplified16S ribosomal DNA restriction analysisrdquo Journal of ClinicalMicrobiology vol 39 no 10 pp 3555ndash3562 2001
[6] J E Clarridge III and Q Zhang ldquoGenotypic diversity of clinicalActinomyces species phenotype source and disease correlationamong genospeciesrdquo Journal of Clinical Microbiology vol 40no 9 pp 3442ndash3448 2002
[7] A S Fiorino ldquoIntrauterine contraceptive device-associatedactinomycotic abscess and Actinomyces detection on cervicalsmearrdquo Obstetrics and Gynecology vol 87 no 1 pp 142ndash1491996
[8] KWestling C Lidman and AThalme ldquoTricuspid valve endo-carditis caused by a new species of Actinomyces Actinomycesfunkeirdquo Scandinavian Journal of Infectious Diseases vol 34 no3 pp 206ndash207 2001
[9] A Jitmuang ldquoPrimary actinomycotic endocarditis a casereport and literature reviewrdquo Journal of the Medical Associationof Thailand vol 91 no 6 pp 931ndash936 2008
[10] S Ushikoshi I Koyanagi K Hida Y Iwasaki and H AbeldquoSpinal intrathecal actinomycosis a case reportrdquo Surgical Neu-rology vol 50 no 3 pp 221ndash225 1998
[11] S Wang R L Wolf J H Woo et al ldquoActinomycotic braininfection registered diffusion perfusion MR imaging and MRspectroscopyrdquoNeuroradiology vol 48 no 5 pp 346ndash350 2006
[12] L Ghafghaichi S Troy I Budvytiene N Banaei and E JBaron ldquoMixed infection involving Actinomyces Aggregatibac-ter and Fusobacterium species presenting as perispinal tumorrdquoAnaerobe vol 16 no 2 pp 174ndash178 2010
[13] K Imamura H Kamitani H Nakayasu Y Asai and KNakashima ldquoPurulent meningitis caused by Actinomyces suc-cessfully treated with rifampicin a case reportrdquo InternalMedicine vol 50 no 10 pp 1121ndash1125 2011
[14] E Kononen and W G Wade ldquoActinomyces and related organ-isms in human infectionsrdquo Clinical Microbiology Reviews vol28 no 2 pp 419ndash442 2015
[15] J Versalovic K C Carroll G Funke J H Jorgensen M LLandry and D W Warnock Manual of Clinical MicrobiologyASM Press Washington DC USA 2011
[16] T E NarsquoWas D G Hollis CWMoss and R EWeaver ldquoCom-parison of biochemical morphologic and chemical character-istics of centers for disease control fermentative coryneformgroups 1 2 and A-4rdquo Journal of Clinical Microbiology vol 25no 8 pp 1354ndash1358 1987
[17] G Funke G M Lucchini G E Pfyffer M Marchiani and Avon Graevenitz ldquoCharacteristics of CDC group 1 and group1-like coryneform bacteria isolated from clinical specimensrdquoJournal of Clinical Microbiology vol 31 no 11 pp 2907ndash29121993
[18] G Funke S Stubbs A von Graevenitz and M D CollinsldquoAssignment of human-derived CDC group 1 coryneformbacteria and CDC group 1-like coryneform bacteria to thegenus Actinomyces as Actinomyces neuii subsp neuii sp novsubsp nov and Actinomyces neuii subsp anitratus subsp novrdquoInternational Journal of Systematic Bacteriology vol 44 no 1pp 167ndash171 1994
[19] G Funke andA vonGraevenitz ldquoInfections due toActinomycesneuii (former lsquoCDC coryneform group 1rsquo bacteria)rdquo Infectionvol 23 no 2 pp 73ndash75 1995
[20] L S Y Ng J H C Sim L C Eng S Menon and T Y TanldquoComparison of phenotypic methods and matrix-assisted laserdesorption ionisation time-of-flight mass spectrometry for theidentification of aero-tolerant Actinomyces spp isolated fromsoft-tissue infectionsrdquoEuropean Journal of ClinicalMicrobiologyand Infectious Diseases vol 31 no 8 pp 1749ndash1752 2012
[21] O Garner AMochon J Branda et al ldquoMulti-centre evaluationof mass spectrometric identification of anaerobic bacteria usingthe VITEK MS systemrdquo Clinical Microbiology and Infectionvol 20 no 4 pp 335ndash339 2014
[22] C Lacoste M-C Escande J Klijanienko P Jammet and CNos ldquoBreast Actinomyces neuii abscess simulating primarymalignancy a case diagnosed by fine-needle aspirationrdquo Diag-nostic Cytopathology vol 37 no 4 pp 311ndash312 2009
[23] A Roustan M Al Nakib and L Boubli ldquoPrimary actino-mycosis of the breast due to Actinomyces neuiirdquo Journal deGynecologie Obstetrique et Biologie de la Reproduction vol 39no 1 pp 64ndash67 2010
[24] J L Gomez-Garces A Burillo Y Gil and J A Saez-Nieto ldquoSofttissue infections caused by Actinomyces neuii a rare pathogenrdquoJournal of Clinical Microbiology vol 48 no 4 pp 1508ndash15092010
[25] K De Vreese and J Verhaegen ldquoIdentification of coryneformActinomyces neuii by MALDI-TOF MS 5 case reports andreview of literaturerdquo Acta Clinica Belgica vol 68 no 3 pp 210ndash214 2013
[26] J M Olson and J C Vary Jr ldquoPrimary cutaneous Actinomycesneuii infection of the breast successfully treated with doxycy-clinerdquo Cutis vol 92 no 6 pp E3ndashE4 2013
[27] C Mann S Dertinger G Hartmann R Schurz and B SimmaldquoActinomyces neuii and neonatal sepsisrdquo Infection vol 30 no3 pp 178ndash180 2002
Canadian Journal of Infectious Diseases and Medical Microbiology 7
[28] E Cohen J Bishara B Medalion A Sagie and M GartyldquoInfective endocarditis due to Actinomyces neuiirdquo ScandinavianJournal of Infectious Diseases vol 39 no 2 pp 180ndash183 2007
[29] P-Y Levy P-E Fournier R Charrel D Metras G Habiband D Raoult ldquoMolecular analysis of pericardial fluid a 7-yearexperiencerdquo European Heart Journal vol 27 no 16 pp 1942ndash1946 2006
[30] K Walther E Bruder D Goldenberger J Mayr U B Schaadand N Ritz ldquoActinomyces neuii isolated from a 20-month-old girl with cervical lymphadenitisrdquo Journal of the PediatricInfectious Diseases Society vol 4 no 3 pp e32ndashe37 2015
[31] B Van Bosterhaut P Boucquey M Janssens G Wauters andM Delmee ldquoChronic osteomyelitis due to Actinomyces neuiisubspecies neuii and Dermabacter hominisrdquo European Journalof Clinical Microbiology and Infectious Diseases vol 21 no 6pp 486ndash487 2002
[32] S Varughese and J Bargman ldquoActinomyces neuii PDperitonitismdashresolution of infection without catheter removalrdquoPeritoneal Dialysis International vol 34 no 7 pp 815ndash8162014
[33] R Dıaz M A Bajo G Del Peso A Garcıa-Perea R Sanchez-Villanueva and R Selgas ldquoActinomyces peritonitis removal ofthe peritoneal catheter unnecessary for resolutionrdquo NDT Plusvol 3 no 3 pp 296ndash297 2010
[34] P E Coudron R C Harris M G Vaughan and H P DaltonldquoTwo similar but atypical strains of coryneform group A-4isolated from patients with endophthalmitisrdquo Journal of ClinicalMicrobiology vol 22 no 4 pp 475ndash477 1985
[35] J M Garelick A J Khodabakhsh and R G Josephberg ldquoAcutepostoperative endophthalmitis caused by Actinomyces neuiirdquoAmerican Journal of Ophthalmology vol 133 no 1 pp 145ndash1472002
[36] V S Raman N Evans B Shreshta and R CunninghamldquoChronic postoperative endophthalmitis caused byActinomycesneuiirdquo Journal of Cataract and Refractive Surgery vol 30 no 12pp 2641ndash2643 2004
[37] J J Perez-Santonja E Campos-Mollo E Fuentes-Campos JSamper-Gimenez and J L Alio ldquoActinomyces neuii subspeciesanitratus chronic endophthalmitis after cataract surgeryrdquo Euro-pean Journal of Ophthalmology vol 17 no 3 pp 445ndash447 2007
[38] SGraffiA Peretz andMNaftali ldquoEndogenous endophthalmi-tis with an unusual infective agentActinomyces neuiirdquoEuropeanJournal of Ophthalmology vol 22 no 5 pp 834ndash835 2012
[39] S Brunner S Graf P Riegel and M Altwegg ldquoCatalase-negative Actinomyces neuii subsp neuii isolated from aninfected mammary prosthesisrdquo International Journal of MedicalMicrobiology vol 290 no 3 pp 285ndash287 2000
[40] R R Watkins K Anthony S Schroder and G S HallldquoVentriculoperitoneal shunt infection caused by Actinomycesneuii subsp neuiirdquo Journal of Clinical Microbiology vol 46 no5 pp 1888ndash1889 2008
[41] H Rieber R Schwarz O KramerW Cordier and L FrommeltldquoActinomyces neuii subsp neuii associated with periprostheticinfection in total hip arthroplasty as causative agentrdquo Journal ofClinical Microbiology vol 47 no 12 pp 4183ndash4184 2009
[42] S Grundmann J Huebner J Stuplich et al ldquoProsthetic valveendocarditis due to Actinomyces neuii successfully treated withantibiotic therapyrdquo Journal of Clinical Microbiology vol 48 no3 pp 1008ndash1011 2010
[43] R S Hsi J M Hotaling E S Spencer P L Bollyky andT J Walsh ldquoIsolated infection of a decommissioned penile
prosthesis reservoir with Actinomyces neuiirdquo Journal of SexualMedicine vol 8 no 3 pp 923ndash926 2011
[44] I A Anderson F Jarral K Sethi and P D Chumas ldquoPaediatricventriculoperitoneal shunt infection caused by Actinomycesneuiirdquo BMJ Case Reports 2014
[45] P Seng S Bayle A Alliez F RomainD Casanova andA SteinldquoThe microbial epidemiology of breast implant infections in aregional referral centre for plastic and reconstructive surgery inthe south of Francerdquo International Journal of Infectious Diseasesvol 35 pp 62ndash66 2015
[46] D J Lane ldquo16S23S rRNA sequencingrdquo in Nucleic Acid Tech-niques in Bacterial Systematics E Stackebrandt and M Good-fellow Eds pp 115ndash175 John Wiley amp Sons Chichester UK1991
[47] J R Cole Q Wang J A Fish et al ldquoRibosomal DatabaseProject data and tools for high throughput rRNA analysisrdquoNucleic Acids Research vol 42 no 1 pp D633ndashD642 2014
[48] Clinical and Laboratory Standards Institute ldquoPerformancestandards for Antimicrobial Susceptibility Testing 25th infor-mational supplementrdquo Tech Rep M100-S25 Clinical and Lab-oratory Standards Institute 2015
[49] Canadian Institutes of Health Research Natural Sciences andEngineering Research Council of Canada and Social Sciencesand Humanities Research Council of Canada ldquoTri-CouncilPolicy Statement Ethical Conduct for Research InvolvingHumansrdquo December 2014
Submit your manuscripts athttpwwwhindawicom
Stem CellsInternational
Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014
Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014
MEDIATORSINFLAMMATION
of
Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014
Behavioural Neurology
EndocrinologyInternational Journal of
Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014
Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014
Disease Markers
Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014
BioMed Research International
OncologyJournal of
Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014
Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014
Oxidative Medicine and Cellular Longevity
Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014
PPAR Research
The Scientific World JournalHindawi Publishing Corporation httpwwwhindawicom Volume 2014
Immunology ResearchHindawi Publishing Corporationhttpwwwhindawicom Volume 2014
Journal of
ObesityJournal of
Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014
Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014
Computational and Mathematical Methods in Medicine
OphthalmologyJournal of
Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014
Diabetes ResearchJournal of
Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014
Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014
Research and TreatmentAIDS
Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014
Gastroenterology Research and Practice
Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014
Parkinsonrsquos Disease
Evidence-Based Complementary and Alternative Medicine
Volume 2014Hindawi Publishing Corporationhttpwwwhindawicom
6 Canadian Journal of Infectious Diseases and Medical Microbiology
surgical interventions This was also the case in the presentstudy as almost all of the treatments involved incision anddrainage of abscesses with subsequent 120573-lactam courses
While A neuii is not a commonly identified organismthere are numerous reports of it causing both invasive andnoninvasive disease Fortunately it is a very susceptibleorganism that can often be treated with 120573-lactams followingdrainage of abscesses or other surgical management Under-standing its clinical significance and typical susceptibilitypatterns will ease decision-making when the organism isencountered as it surely will be with the current widespreaduse of MALDI-TOF MS MIS
Conflict of Interests
The authors have no conflict of interests to declare
References
[1] K P Schaal and H-J Lee ldquoActinomycete infections inhumansmdasha reviewrdquo Gene vol 115 no 1-2 pp 201ndash211 1992
[2] R A Smego Jr and G Foglia ldquoActinomycosisrdquo Clinical Infec-tious Diseases vol 26 no 6 pp 1255ndash1263 1998
[3] V KWong T D Turmezei and V CWeston ldquoActinomycosisrdquoBritish Medical Journal vol 343 Article ID d6099 2011
[4] L J M Sabbe D Van De Merwe L Schouls A BergmansM Vaneechoutte and P Vandamme ldquoClinical spectrum ofinfections due to the newly described Actinomyces species Aturicensis A radingae and A europaeusrdquo Journal of ClinicalMicrobiology vol 37 no 1 pp 8ndash13 1999
[5] V Hall P R Talbot S L Stubbs and B I Duerden ldquoIdenti-fication of clinical isolates of Actinomyces species by amplified16S ribosomal DNA restriction analysisrdquo Journal of ClinicalMicrobiology vol 39 no 10 pp 3555ndash3562 2001
[6] J E Clarridge III and Q Zhang ldquoGenotypic diversity of clinicalActinomyces species phenotype source and disease correlationamong genospeciesrdquo Journal of Clinical Microbiology vol 40no 9 pp 3442ndash3448 2002
[7] A S Fiorino ldquoIntrauterine contraceptive device-associatedactinomycotic abscess and Actinomyces detection on cervicalsmearrdquo Obstetrics and Gynecology vol 87 no 1 pp 142ndash1491996
[8] KWestling C Lidman and AThalme ldquoTricuspid valve endo-carditis caused by a new species of Actinomyces Actinomycesfunkeirdquo Scandinavian Journal of Infectious Diseases vol 34 no3 pp 206ndash207 2001
[9] A Jitmuang ldquoPrimary actinomycotic endocarditis a casereport and literature reviewrdquo Journal of the Medical Associationof Thailand vol 91 no 6 pp 931ndash936 2008
[10] S Ushikoshi I Koyanagi K Hida Y Iwasaki and H AbeldquoSpinal intrathecal actinomycosis a case reportrdquo Surgical Neu-rology vol 50 no 3 pp 221ndash225 1998
[11] S Wang R L Wolf J H Woo et al ldquoActinomycotic braininfection registered diffusion perfusion MR imaging and MRspectroscopyrdquoNeuroradiology vol 48 no 5 pp 346ndash350 2006
[12] L Ghafghaichi S Troy I Budvytiene N Banaei and E JBaron ldquoMixed infection involving Actinomyces Aggregatibac-ter and Fusobacterium species presenting as perispinal tumorrdquoAnaerobe vol 16 no 2 pp 174ndash178 2010
[13] K Imamura H Kamitani H Nakayasu Y Asai and KNakashima ldquoPurulent meningitis caused by Actinomyces suc-cessfully treated with rifampicin a case reportrdquo InternalMedicine vol 50 no 10 pp 1121ndash1125 2011
[14] E Kononen and W G Wade ldquoActinomyces and related organ-isms in human infectionsrdquo Clinical Microbiology Reviews vol28 no 2 pp 419ndash442 2015
[15] J Versalovic K C Carroll G Funke J H Jorgensen M LLandry and D W Warnock Manual of Clinical MicrobiologyASM Press Washington DC USA 2011
[16] T E NarsquoWas D G Hollis CWMoss and R EWeaver ldquoCom-parison of biochemical morphologic and chemical character-istics of centers for disease control fermentative coryneformgroups 1 2 and A-4rdquo Journal of Clinical Microbiology vol 25no 8 pp 1354ndash1358 1987
[17] G Funke G M Lucchini G E Pfyffer M Marchiani and Avon Graevenitz ldquoCharacteristics of CDC group 1 and group1-like coryneform bacteria isolated from clinical specimensrdquoJournal of Clinical Microbiology vol 31 no 11 pp 2907ndash29121993
[18] G Funke S Stubbs A von Graevenitz and M D CollinsldquoAssignment of human-derived CDC group 1 coryneformbacteria and CDC group 1-like coryneform bacteria to thegenus Actinomyces as Actinomyces neuii subsp neuii sp novsubsp nov and Actinomyces neuii subsp anitratus subsp novrdquoInternational Journal of Systematic Bacteriology vol 44 no 1pp 167ndash171 1994
[19] G Funke andA vonGraevenitz ldquoInfections due toActinomycesneuii (former lsquoCDC coryneform group 1rsquo bacteria)rdquo Infectionvol 23 no 2 pp 73ndash75 1995
[20] L S Y Ng J H C Sim L C Eng S Menon and T Y TanldquoComparison of phenotypic methods and matrix-assisted laserdesorption ionisation time-of-flight mass spectrometry for theidentification of aero-tolerant Actinomyces spp isolated fromsoft-tissue infectionsrdquoEuropean Journal of ClinicalMicrobiologyand Infectious Diseases vol 31 no 8 pp 1749ndash1752 2012
[21] O Garner AMochon J Branda et al ldquoMulti-centre evaluationof mass spectrometric identification of anaerobic bacteria usingthe VITEK MS systemrdquo Clinical Microbiology and Infectionvol 20 no 4 pp 335ndash339 2014
[22] C Lacoste M-C Escande J Klijanienko P Jammet and CNos ldquoBreast Actinomyces neuii abscess simulating primarymalignancy a case diagnosed by fine-needle aspirationrdquo Diag-nostic Cytopathology vol 37 no 4 pp 311ndash312 2009
[23] A Roustan M Al Nakib and L Boubli ldquoPrimary actino-mycosis of the breast due to Actinomyces neuiirdquo Journal deGynecologie Obstetrique et Biologie de la Reproduction vol 39no 1 pp 64ndash67 2010
[24] J L Gomez-Garces A Burillo Y Gil and J A Saez-Nieto ldquoSofttissue infections caused by Actinomyces neuii a rare pathogenrdquoJournal of Clinical Microbiology vol 48 no 4 pp 1508ndash15092010
[25] K De Vreese and J Verhaegen ldquoIdentification of coryneformActinomyces neuii by MALDI-TOF MS 5 case reports andreview of literaturerdquo Acta Clinica Belgica vol 68 no 3 pp 210ndash214 2013
[26] J M Olson and J C Vary Jr ldquoPrimary cutaneous Actinomycesneuii infection of the breast successfully treated with doxycy-clinerdquo Cutis vol 92 no 6 pp E3ndashE4 2013
[27] C Mann S Dertinger G Hartmann R Schurz and B SimmaldquoActinomyces neuii and neonatal sepsisrdquo Infection vol 30 no3 pp 178ndash180 2002
Canadian Journal of Infectious Diseases and Medical Microbiology 7
[28] E Cohen J Bishara B Medalion A Sagie and M GartyldquoInfective endocarditis due to Actinomyces neuiirdquo ScandinavianJournal of Infectious Diseases vol 39 no 2 pp 180ndash183 2007
[29] P-Y Levy P-E Fournier R Charrel D Metras G Habiband D Raoult ldquoMolecular analysis of pericardial fluid a 7-yearexperiencerdquo European Heart Journal vol 27 no 16 pp 1942ndash1946 2006
[30] K Walther E Bruder D Goldenberger J Mayr U B Schaadand N Ritz ldquoActinomyces neuii isolated from a 20-month-old girl with cervical lymphadenitisrdquo Journal of the PediatricInfectious Diseases Society vol 4 no 3 pp e32ndashe37 2015
[31] B Van Bosterhaut P Boucquey M Janssens G Wauters andM Delmee ldquoChronic osteomyelitis due to Actinomyces neuiisubspecies neuii and Dermabacter hominisrdquo European Journalof Clinical Microbiology and Infectious Diseases vol 21 no 6pp 486ndash487 2002
[32] S Varughese and J Bargman ldquoActinomyces neuii PDperitonitismdashresolution of infection without catheter removalrdquoPeritoneal Dialysis International vol 34 no 7 pp 815ndash8162014
[33] R Dıaz M A Bajo G Del Peso A Garcıa-Perea R Sanchez-Villanueva and R Selgas ldquoActinomyces peritonitis removal ofthe peritoneal catheter unnecessary for resolutionrdquo NDT Plusvol 3 no 3 pp 296ndash297 2010
[34] P E Coudron R C Harris M G Vaughan and H P DaltonldquoTwo similar but atypical strains of coryneform group A-4isolated from patients with endophthalmitisrdquo Journal of ClinicalMicrobiology vol 22 no 4 pp 475ndash477 1985
[35] J M Garelick A J Khodabakhsh and R G Josephberg ldquoAcutepostoperative endophthalmitis caused by Actinomyces neuiirdquoAmerican Journal of Ophthalmology vol 133 no 1 pp 145ndash1472002
[36] V S Raman N Evans B Shreshta and R CunninghamldquoChronic postoperative endophthalmitis caused byActinomycesneuiirdquo Journal of Cataract and Refractive Surgery vol 30 no 12pp 2641ndash2643 2004
[37] J J Perez-Santonja E Campos-Mollo E Fuentes-Campos JSamper-Gimenez and J L Alio ldquoActinomyces neuii subspeciesanitratus chronic endophthalmitis after cataract surgeryrdquo Euro-pean Journal of Ophthalmology vol 17 no 3 pp 445ndash447 2007
[38] SGraffiA Peretz andMNaftali ldquoEndogenous endophthalmi-tis with an unusual infective agentActinomyces neuiirdquoEuropeanJournal of Ophthalmology vol 22 no 5 pp 834ndash835 2012
[39] S Brunner S Graf P Riegel and M Altwegg ldquoCatalase-negative Actinomyces neuii subsp neuii isolated from aninfected mammary prosthesisrdquo International Journal of MedicalMicrobiology vol 290 no 3 pp 285ndash287 2000
[40] R R Watkins K Anthony S Schroder and G S HallldquoVentriculoperitoneal shunt infection caused by Actinomycesneuii subsp neuiirdquo Journal of Clinical Microbiology vol 46 no5 pp 1888ndash1889 2008
[41] H Rieber R Schwarz O KramerW Cordier and L FrommeltldquoActinomyces neuii subsp neuii associated with periprostheticinfection in total hip arthroplasty as causative agentrdquo Journal ofClinical Microbiology vol 47 no 12 pp 4183ndash4184 2009
[42] S Grundmann J Huebner J Stuplich et al ldquoProsthetic valveendocarditis due to Actinomyces neuii successfully treated withantibiotic therapyrdquo Journal of Clinical Microbiology vol 48 no3 pp 1008ndash1011 2010
[43] R S Hsi J M Hotaling E S Spencer P L Bollyky andT J Walsh ldquoIsolated infection of a decommissioned penile
prosthesis reservoir with Actinomyces neuiirdquo Journal of SexualMedicine vol 8 no 3 pp 923ndash926 2011
[44] I A Anderson F Jarral K Sethi and P D Chumas ldquoPaediatricventriculoperitoneal shunt infection caused by Actinomycesneuiirdquo BMJ Case Reports 2014
[45] P Seng S Bayle A Alliez F RomainD Casanova andA SteinldquoThe microbial epidemiology of breast implant infections in aregional referral centre for plastic and reconstructive surgery inthe south of Francerdquo International Journal of Infectious Diseasesvol 35 pp 62ndash66 2015
[46] D J Lane ldquo16S23S rRNA sequencingrdquo in Nucleic Acid Tech-niques in Bacterial Systematics E Stackebrandt and M Good-fellow Eds pp 115ndash175 John Wiley amp Sons Chichester UK1991
[47] J R Cole Q Wang J A Fish et al ldquoRibosomal DatabaseProject data and tools for high throughput rRNA analysisrdquoNucleic Acids Research vol 42 no 1 pp D633ndashD642 2014
[48] Clinical and Laboratory Standards Institute ldquoPerformancestandards for Antimicrobial Susceptibility Testing 25th infor-mational supplementrdquo Tech Rep M100-S25 Clinical and Lab-oratory Standards Institute 2015
[49] Canadian Institutes of Health Research Natural Sciences andEngineering Research Council of Canada and Social Sciencesand Humanities Research Council of Canada ldquoTri-CouncilPolicy Statement Ethical Conduct for Research InvolvingHumansrdquo December 2014
Submit your manuscripts athttpwwwhindawicom
Stem CellsInternational
Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014
Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014
MEDIATORSINFLAMMATION
of
Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014
Behavioural Neurology
EndocrinologyInternational Journal of
Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014
Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014
Disease Markers
Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014
BioMed Research International
OncologyJournal of
Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014
Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014
Oxidative Medicine and Cellular Longevity
Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014
PPAR Research
The Scientific World JournalHindawi Publishing Corporation httpwwwhindawicom Volume 2014
Immunology ResearchHindawi Publishing Corporationhttpwwwhindawicom Volume 2014
Journal of
ObesityJournal of
Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014
Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014
Computational and Mathematical Methods in Medicine
OphthalmologyJournal of
Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014
Diabetes ResearchJournal of
Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014
Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014
Research and TreatmentAIDS
Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014
Gastroenterology Research and Practice
Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014
Parkinsonrsquos Disease
Evidence-Based Complementary and Alternative Medicine
Volume 2014Hindawi Publishing Corporationhttpwwwhindawicom
Canadian Journal of Infectious Diseases and Medical Microbiology 7
[28] E Cohen J Bishara B Medalion A Sagie and M GartyldquoInfective endocarditis due to Actinomyces neuiirdquo ScandinavianJournal of Infectious Diseases vol 39 no 2 pp 180ndash183 2007
[29] P-Y Levy P-E Fournier R Charrel D Metras G Habiband D Raoult ldquoMolecular analysis of pericardial fluid a 7-yearexperiencerdquo European Heart Journal vol 27 no 16 pp 1942ndash1946 2006
[30] K Walther E Bruder D Goldenberger J Mayr U B Schaadand N Ritz ldquoActinomyces neuii isolated from a 20-month-old girl with cervical lymphadenitisrdquo Journal of the PediatricInfectious Diseases Society vol 4 no 3 pp e32ndashe37 2015
[31] B Van Bosterhaut P Boucquey M Janssens G Wauters andM Delmee ldquoChronic osteomyelitis due to Actinomyces neuiisubspecies neuii and Dermabacter hominisrdquo European Journalof Clinical Microbiology and Infectious Diseases vol 21 no 6pp 486ndash487 2002
[32] S Varughese and J Bargman ldquoActinomyces neuii PDperitonitismdashresolution of infection without catheter removalrdquoPeritoneal Dialysis International vol 34 no 7 pp 815ndash8162014
[33] R Dıaz M A Bajo G Del Peso A Garcıa-Perea R Sanchez-Villanueva and R Selgas ldquoActinomyces peritonitis removal ofthe peritoneal catheter unnecessary for resolutionrdquo NDT Plusvol 3 no 3 pp 296ndash297 2010
[34] P E Coudron R C Harris M G Vaughan and H P DaltonldquoTwo similar but atypical strains of coryneform group A-4isolated from patients with endophthalmitisrdquo Journal of ClinicalMicrobiology vol 22 no 4 pp 475ndash477 1985
[35] J M Garelick A J Khodabakhsh and R G Josephberg ldquoAcutepostoperative endophthalmitis caused by Actinomyces neuiirdquoAmerican Journal of Ophthalmology vol 133 no 1 pp 145ndash1472002
[36] V S Raman N Evans B Shreshta and R CunninghamldquoChronic postoperative endophthalmitis caused byActinomycesneuiirdquo Journal of Cataract and Refractive Surgery vol 30 no 12pp 2641ndash2643 2004
[37] J J Perez-Santonja E Campos-Mollo E Fuentes-Campos JSamper-Gimenez and J L Alio ldquoActinomyces neuii subspeciesanitratus chronic endophthalmitis after cataract surgeryrdquo Euro-pean Journal of Ophthalmology vol 17 no 3 pp 445ndash447 2007
[38] SGraffiA Peretz andMNaftali ldquoEndogenous endophthalmi-tis with an unusual infective agentActinomyces neuiirdquoEuropeanJournal of Ophthalmology vol 22 no 5 pp 834ndash835 2012
[39] S Brunner S Graf P Riegel and M Altwegg ldquoCatalase-negative Actinomyces neuii subsp neuii isolated from aninfected mammary prosthesisrdquo International Journal of MedicalMicrobiology vol 290 no 3 pp 285ndash287 2000
[40] R R Watkins K Anthony S Schroder and G S HallldquoVentriculoperitoneal shunt infection caused by Actinomycesneuii subsp neuiirdquo Journal of Clinical Microbiology vol 46 no5 pp 1888ndash1889 2008
[41] H Rieber R Schwarz O KramerW Cordier and L FrommeltldquoActinomyces neuii subsp neuii associated with periprostheticinfection in total hip arthroplasty as causative agentrdquo Journal ofClinical Microbiology vol 47 no 12 pp 4183ndash4184 2009
[42] S Grundmann J Huebner J Stuplich et al ldquoProsthetic valveendocarditis due to Actinomyces neuii successfully treated withantibiotic therapyrdquo Journal of Clinical Microbiology vol 48 no3 pp 1008ndash1011 2010
[43] R S Hsi J M Hotaling E S Spencer P L Bollyky andT J Walsh ldquoIsolated infection of a decommissioned penile
prosthesis reservoir with Actinomyces neuiirdquo Journal of SexualMedicine vol 8 no 3 pp 923ndash926 2011
[44] I A Anderson F Jarral K Sethi and P D Chumas ldquoPaediatricventriculoperitoneal shunt infection caused by Actinomycesneuiirdquo BMJ Case Reports 2014
[45] P Seng S Bayle A Alliez F RomainD Casanova andA SteinldquoThe microbial epidemiology of breast implant infections in aregional referral centre for plastic and reconstructive surgery inthe south of Francerdquo International Journal of Infectious Diseasesvol 35 pp 62ndash66 2015
[46] D J Lane ldquo16S23S rRNA sequencingrdquo in Nucleic Acid Tech-niques in Bacterial Systematics E Stackebrandt and M Good-fellow Eds pp 115ndash175 John Wiley amp Sons Chichester UK1991
[47] J R Cole Q Wang J A Fish et al ldquoRibosomal DatabaseProject data and tools for high throughput rRNA analysisrdquoNucleic Acids Research vol 42 no 1 pp D633ndashD642 2014
[48] Clinical and Laboratory Standards Institute ldquoPerformancestandards for Antimicrobial Susceptibility Testing 25th infor-mational supplementrdquo Tech Rep M100-S25 Clinical and Lab-oratory Standards Institute 2015
[49] Canadian Institutes of Health Research Natural Sciences andEngineering Research Council of Canada and Social Sciencesand Humanities Research Council of Canada ldquoTri-CouncilPolicy Statement Ethical Conduct for Research InvolvingHumansrdquo December 2014
Submit your manuscripts athttpwwwhindawicom
Stem CellsInternational
Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014
Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014
MEDIATORSINFLAMMATION
of
Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014
Behavioural Neurology
EndocrinologyInternational Journal of
Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014
Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014
Disease Markers
Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014
BioMed Research International
OncologyJournal of
Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014
Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014
Oxidative Medicine and Cellular Longevity
Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014
PPAR Research
The Scientific World JournalHindawi Publishing Corporation httpwwwhindawicom Volume 2014
Immunology ResearchHindawi Publishing Corporationhttpwwwhindawicom Volume 2014
Journal of
ObesityJournal of
Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014
Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014
Computational and Mathematical Methods in Medicine
OphthalmologyJournal of
Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014
Diabetes ResearchJournal of
Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014
Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014
Research and TreatmentAIDS
Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014
Gastroenterology Research and Practice
Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014
Parkinsonrsquos Disease
Evidence-Based Complementary and Alternative Medicine
Volume 2014Hindawi Publishing Corporationhttpwwwhindawicom
Submit your manuscripts athttpwwwhindawicom
Stem CellsInternational
Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014
Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014
MEDIATORSINFLAMMATION
of
Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014
Behavioural Neurology
EndocrinologyInternational Journal of
Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014
Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014
Disease Markers
Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014
BioMed Research International
OncologyJournal of
Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014
Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014
Oxidative Medicine and Cellular Longevity
Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014
PPAR Research
The Scientific World JournalHindawi Publishing Corporation httpwwwhindawicom Volume 2014
Immunology ResearchHindawi Publishing Corporationhttpwwwhindawicom Volume 2014
Journal of
ObesityJournal of
Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014
Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014
Computational and Mathematical Methods in Medicine
OphthalmologyJournal of
Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014
Diabetes ResearchJournal of
Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014
Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014
Research and TreatmentAIDS
Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014
Gastroenterology Research and Practice
Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014
Parkinsonrsquos Disease
Evidence-Based Complementary and Alternative Medicine
Volume 2014Hindawi Publishing Corporationhttpwwwhindawicom