Managing Res Infections

8/8/2019 Managing Res Infections

http://slidepdf.com/reader/full/managing-res-infections 1/24

Fbruar 2008

supplement to

Avaiab at www. jfi.com

Tis matria was submittd by ParmaWrit® and supportd by PRICARA®, Division o Orto-McNi-Janssn

Parmacuticas, Inc. It was ditd and pr rviwd by The Journal o Family Practice.

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http://slidepdf.com/reader/full/managing-res-infections 2/24S Vo 57, No 2 / Fbruar 2008 n s th Jra f Faiy pracic COPyRIghT © 2008 DOWDeN heAlTh MeDIA

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Cairman, had and Nck Institut

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Prossor o MdicinJrson Mdica Co

Piadpia, PnnsvaniaInctious Disass Consutant

Brn Mawr Mdica Spciaists AssociationBrn Mawr, Pnnsvania

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http://slidepdf.com/reader/full/managing-res-infections 3/24s th Jra f Faiy pracic n Vo 57, No 2 / Fbruar 2008 S

Tis publication reviews te callenges

aced by clinicians in te diagnosis and

management o bacterial respiratory tract

inection (RTI). It igligts patient actors tat

may be indicative o treatment ailure and pro-

vides recommendations to elp clinicians most

eectively manage teir patients wit RTIs.

Te articles are based on te proceedings o a

May 2006 meeting o a multispecialty working

group eld in Cicago. Participants included

inectious disease specialists, pulmonologists,

otolaryngologists, and primary care pysicians.

Te articles in tis supplement relect te par-

ticipants’ own conclusions and are based on

teir collective clinical experience and on cur-

rently available treatment guidelines.

Te participants noted tat a major cal-

lenge or clinicians is te seer number o pa-

tient visits rom September troug Marc,oten called “te respiratory season.” Inectious

diseases are among te most common reasons

patients consult teir ealt care proessionals,

accounting or more tan one it (21.2%) o

all nonroutine visits and approximately 129 mil-

lion visits annually.1 Between 1980 and 1990,

tese visits increased steadily (2.14% annually

[P = .006]),1 wit signiicant growt in te num-

ber o upper respiratory tract inections (URTIs)

( P = .02), owr rspiratory tract inctions (lRTIs),and inluenza ( P = .008).1 Coupled wit tis in-

creased volume o patient visits or inectious

diseases, and RTIs speciically, are conlicting

pressures suc as limited time or evaluating pa-

tients, managed-care eiciency requirements,

and complicated patient issues resulting rom

an aging and sicker population.

During te course o te group’s discus-

sion, te participants identiied 3 areas tat are

critical or improvement o patient outcomes in

te primary care setting:

n Reducing resisance o anibioics by ad-

herence o appropriae prescribing of hese

agens.2-4 As will be discussed in “Is it bacterial

or viral? Criteria or distinguising bacterial and

viral inections” ( see page S5 ), te irst callenge

or clinicians is to determine more accurately

weter te origin o an RTI is viral or bacterial.

Antibacterials, altoug ineective against viral

inections, are oten prescribed.5 National, re-

gional, and local resistance patterns must also

be careully considered, as will be discussed

in “Treatment recommendations or patients

wit common respiratory tract inections witvariables indicative o treatment ailure” ( see

page S19 ).

n Idenifying hose paiens wih RtIs wih

paien variables ha may be indicaive of

reamen failure and recognizing he con-

sequences of reamen failure for such pa-

iens. Wic patients are at increased risk? Do

tey ave underlying comorbid conditions or

social complications? Are tey arboring resis-tant patogens? Wic patients need a more

aggressive terapeutic approac? Te cal-

lenges o providing care or at-risk populations

are discussed in “Patient variables associated

wit treatment ailure in respiratory tract inec-

tions” ( see page S12 ).

IntRoDuCtIon By hANS h. lIU, MD

1

CONTINUeD

2


http://slidepdf.com/reader/full/managing-res-infections 4/24S Vo 57, No 2 / Fbruar 2008 n s th Jra f Faiy pracic

n Inerpreing and synhesizing reamen rc-

dai dd by ciay dica

cii fr riary car raciir. Spe-

cialty medical societies ave developed treatment

guidelines to elp guide clinicians in te care o

patients wit specifc RTIs, including acute bacte-

rial rinosinusitis, acute exacerbation o cronic

broncitis, and community-acquird pnumonia.6-9

however, tese guidelines are usually oriented

toward te needs o specialists and are typically

written using teir specialized terms. “Treatment

recommendations or patients wit common re-

spiratory tract inections wit variables indicative

o treatment ailure” ( see page S19 ) provides a

user-riendly interpretation and syntesis o avail-

able guidelines tat can be implemented in te

busy primary care setting.

W op tat tis pubication wi b o vau to

busy cinicians and wi p you idntiy patints

wos at pro and prsona circumstancs

rquir caru considration in ormuatin ap-

propriat tratmnt rimns or RTIs.

Te autors tank PRICARA®, Division o

Orto-McNeil-Janssen Parmaceuticals, Inc, or

providing te resources to old te meeting and

or unding te costs o tis supplement.

IntRoDuCtIon By hANS h. l IU, MD, FACP

1. ArmstrongGL,PinnerRW.OutpatientvisitsorinectiousdiseasesintheUnitedStates,1980

through1996.Arch Intern Med.1999;159:2531-2536.2. SlamaTG,AminA,BruntonSA,etal,ortheCouncilorAppropriateandRationalAntibioticTherapy.A clinician’sguideto theappropriateandaccurateuseoantibiotics:theCouncilorAppropriate and Rational Antibiotic Therapy(CARAT)criteria.Am J Med. 2005;118(suppl7A):1S-6S.3. Low DE. Antimicrobial drug use and re-sistance among respiratory pathogens in thecommunity.Clin Infect Dis. 2001;33(suppl 3):S206-S213.4. File TM Jr. Overview o resistance in the

1990s.Chest.1999;115(suppl):3S-8S.5. GonzalesR,MaloneDC,Maselli JH, etal.

Excessive antibiotic use or acute respiratoryinectionsintheUnitedStates.Clin Infect Dis.2001;33:757-762.6.NiedermanMS,MandellLA,AnzuetoA,etal,orthead-hocsubcommitteeotheAssemblyonMicrobiology,Tuberculosis, andPulmonaryIn-ections,AmericanThoracicSociety.Guidelinesorthemanagementoadultswithcommunity-acquired pneumonia: diagnosis, assessment oseverity,antimicrobial therapy,andprevention.Am J Respir Crit Care Med. 2001;163:1730-1754.7.Mandell LA, Wunderink RG, Anzueto A,et al. Inectious Diseases Society o America/

American Thoracic Society consensus guide-lines on the management o community-

acquiredpneumoniain adults.Clin Infect Dis.2007;44(suppl2):527-572.8. Anon JB, JacobsMR,PooleMD, etal,ortheSinusandAllergyHealthPartnership.Anti-microbialtreatmentguidelinesor acutebacte-rialrhinosinusitis.Otolaryngol Head Neck Surg.2004;130(suppl1):1-45.9. BalterMS,LaForgeJ,LowDE,etal,andtheChronicBronchitisWorkingGrouponbehalotheCanadianThoracicSocietyandtheCanadianInectiousDisease Society.Canadianguidelinesor themanagemento acuteexacerbations ochronicbronchitis.Can Respir J.2003;10(supplB):3B-32B.

3

Reerences




s th Jra f Faiy pracic n Vo 57, No 2 / Fbruar 2008 S

Muchdiscussioninthemedicalliteraturehasocusedontheconsequencesoinappropriateprescribingo

antibiotics,includingtheincreasedpotentialorad-

verseevents,highertreatmentcosts,andthedevelopmento

bacterialresistance.Whatactorscontributetoinappropriate

prescribing?Thisarticlereviewschallengesacingclinicians

andsuggestsstrategiestoaddresstheseproblems.

Managedhealthcaresystemsplacesignicanttimecon-

straints onprimary care practitioners. Prescribing behavior

maybeaectedinseveralways.Intheshorttimeavailableor

anocevisit,itcanbechallengingtodierentiateviralversusbacterialinectionsindiseasesthatsharesimilarclinicalsigns

andsymptoms.Insuchasetting,writingaprescriptionor

anantibioticcanbeperceivedasthequickestwaytoendthe

visit.1Additionally,patientsotenpressuretheircliniciansto

prescribeanantibiotic,whetherornotitisindicated,because

otheirimpatiencetoeelwellorbecauseopsychological

expectationsassociatedwithocevisits.1Theissueotime

(orlackoit)presentsanotherchallengeascliniciansstruggle

tokeepabreastolocalresistancetrendssotheycanselect

anappropriateantibioticwhenabacterialinectionhasbeendiagnosed.

Cliniciansmaynditeasiertocopewiththesepressures

itheycanmorecondentlydistinguishbetweenbacterialand

viral inections.This article seeks to providebusy primary

carepractitionerswithtoolstoquicklydeterminetheetiology

ocommonrespiratorytractinections(RTIs)suchasacute

I i bacria r ira?Criria fr diigihig bacriaad ira ifciMiche Benninger, MD • John Segreti, MD

Dicr: Dr Bnninr as discosd tat as rcivd rsarc support rom Narx Parma, Inc., and Novartis Parmacuticas; as

srvd as a consutant to Abbott laboratoris, Orto-McNi-Janssn Parmacuticas, Inc, and sanoi-avntis; and as srvd on t spakrs

burau o Abbott laboratoris. Dr Srti as discosd tat as srvd as a consutant to Pizr Inc, Orto-McNi-Janssn Parmacuti-

cas, Inc, and Wt Parmacuticas; as srvd on t spakrs burau o ean, Orto-McNi-Janssn Parmacuticas, Inc, Pizr Inc, andWt Parmacuticas; and is a stockodr o Pizr Inc.

K Points

o Dirntiation o bactria rom vira

inctions is ssntia or appropriat

tratmnt. Additiona, unncssar

us o antibactria prscriptions

can ad to incrass in advrs

ractions and tratmnt costs and

promotion o rsistant bactria.

o Inappropriat, xcssiv, and cost

antibiotic prscribin is o concrn:

k rspirator patons ar

bcomin incrasin rsistant to

common usd antibiotics suc as

pniciins and macroids.

o Currnt, t numbr o antibiotic

prscriptions ar surpasss

t numbr o actua bactria

inctions.

o Acut rinosinusitis, acut

xacrbation o cronic broncitis,

and communit-acquird pnumonia

ar 3 inctious disass common

ncountrd b cinicians.

o Most cass o rinosinusitis ar

vira in oriin, wras acut

xacrbation o cronic broncitis

and communit-acquird pnumonia

tpica rsut rom bactria

inction.



rhinosinusitis, acute exacerbation o chronic

bronchitis (AECB), and community-acquired

pneumonia (CAP), thus enabling clinicians to

treatthesediseasesappropriately.

Hw c i iarria

aibiic rcribig?Althoughviralinectionsdonotrespondtoanti-

biotics,prescriptionsortheseagentsexceedthe

numberoactualbacterialinections.Resultso

theNationalAmbulatoryMedicalCare Survey

(1991-1999)showthatviraldiseasessuchasvi-

ral rhinosinusitis, unspecied upper respiratorytract inections (URTIs), and acute bronchitis

accounted or 22% o adult prescriptions or

broad-spectrum antibiotics.2 A comparison o

1998 data underscores the extent o the prob-

lem.Apublishedstudyrevealedthatmorethan

hal o the 22.6 million antibiotics prescribed

oracuteRTIs, suchasbronchitisandunspeci-

edURTIs,wereusedorinectionsoprobable

nonbacterial origin.3 The cost o treatment o

acuteRTIstotaledapproximately$1.32billion;

othistotal,$726million(55%)was

spentoninappropriateantibioticpre-

scriptions.3 Although the estimated

bacterial prevalence o bronchitiswas10%,antibioticswereprescribed

or 59% o the 13 million patients

diagnosedwith bronchitis (FIGuRe).3

Clearly, inappropriateprescribing o

antibioticsoracuteRTIshasbecome

excessiveandcostly.4

In addition to incurring unnec-

essary treatment costs, inappropri-

ate antibiotic use has been shown

to decrease the utility o antibioticsbecause o resistance to commonly

prescribedagents.5-7Theuseoanti-

biotics and certain vaccines poses

uniquerisks:theyarethesolethera-

peuticclassesthatmayaectnotonly

individualpatientsbutalsotheiram-

ilies,coworkers,riends,andotherswithwhom

they come in contact, by potentially inecting

themwithresistantpathogens.1

Resistancetopenicillinandmacrolidesispar-ticularlyhigh.1,8-10Severalstudieshaveoundthat

ratesopenicillinresistance amongStreptococ-

cus pneumoniaerangerom9.8%to21.2%.9,10

Similarly,ratesomacrolide (azithromycin and

erythromycin)resistancehavebeenestimatedat

17.3%to40.4%.8,10Inaddition,overuseoanti-

bioticsislikelytoexacerbatetheresistanceprob-

lem1;decreasinginappropriateuseoantibiotics

shouldbeconsideredarststeptowardattempt-

ingtocontrolresistance.1

Rhiiii: I fr ciicia

Epidemioogy nd burden o disese

Virusesareresponsibleorthetraditional“com-

moncold”andrelatedacuteviralRTIs.In1997,

theannualincidenceoviralRTIsamongadults

intheUnitedStateswas2to3illnessesperper-

son.11,12Inthe1990s,itwasestimatedthatap-

proximately90%ocaseshadaconrmedviral

N u m b e r o f V i s i t s ( m i l l i o n s )

25

20

15

10

5

0

FIGURE

Primry cre ofce visits nd ntibiotic prescriptions

or cute respirtory inesses in the United Sttes

U R I

O t i t i s

M e d i a

R h i n o s i n u

s i t i s

P h a

r y n g i t

i s

B r o n

c h i t i s

nOic visits

n Antibiotic prscription

nBactria prvanc

Data rom t 1998 Nationa Ambuator Mdica Car Surv (Nationa

Cntr or hat Statistics).

URI, uppr rspirator inction.

ModiedwithpermissionromGonzalesR,MaloneDC,MaselliJH,SandeMA.ExcessiveantibioticuseoracuterespiratoryinectionsintheUnitedStates.Clin Inect Dis.2001;33:757-762.©2001TheUniversityoChicagoPress.

CRIteRIA FoR DIstInGuIsHInG BACteRIAl AnD vIRAl InFeCtIons



component.12Incontrast,acutebacterialrhinosi-

nusitis(ABS)occursinonly0.5%to2%othese

cases11,12;however,giventhelargenumberore-

spiratoryillnessesoccurringannually(>1billionas o 200412), that percentage translates to an

estimated20millioncases.

ThesocioeconomicburdenoURTIs,includ-

ingsinusitis,isconsiderable,inpartbecauseotheir

highprevalence.In1996,rhinosinusitistreatment

costs totaled $3.39 billion.13Work productivity

andqualityoliealsodeclined.Arandomsurvey

conductedbytheUniversityoPittsburghSchool

oMedicinein2004evaluated606sel-identied

recurrentchronicrhinosinusitisorbronchitispa-tients.Otheserespondents,25%reportedmiss-

ing3ormoreworkdaysbecauseoillness, 14and

another23%reportedmissing1to2workdays.In

all,sinusitismayaccountor>30millionsickdays

eachyear.14Inaddition,58%otherespondents

saidtheywerelikelytocurtailleisureactivitiesbe-

causeorhinosinusitisorbronchitis, 14suggesting

reducedqualityolieorthesepatients. 14

Limiteddataareavailabletoassesstheprev-

alenceoviraletiologyinacuterhinosinusitisbe-causeewsinusaspiratesaretestedorviruses.11

However,onestudyoaspiratesromadultpa-

tientswith rhinosinusitis identied the 3 most

commonviralpathogensasrhinovirus,infuenza

virus,andparainfuenzavirus.15

tABle 1liststhebacterialpathogenscommon-

lyassociatedwithRTIs.InABS,S pneumoniaeis

the most common pathogen ound (20%-43%

o cases), ollowed byHaemophilus infuenzae

(22%-35%), and Moraxella catarrhalis (2%-10%).12 A recentmeta-analysis o prospective,

randomized, controlled clinical trials in acute

bacterial rhinosinusitis suggests that Staphylo-

coccus aureus is amajorpathogen, accounting

or10%ocases.16Whetherornotthisrecent

identicationoS aureusasapathogeninacute

rhinosinusitiswillaltertreatmentguidelinesre-

mainstobeseen.Incontrast,anaerobesareless

commonlyimplicated,causingupto9%oacute

rhinosinusitisinadults.12

Dignosis o cute bcteri

versus vir rhinosinusitis

Sinuspuncturewithculture(maxillarysinustap)

isthediagnosticreerencestandardorABS.17As

an alternative, endoscopically directed middle

meatal (EDMM) culturesmay be considered.18

However, these tests are not practical routine

TaBlE 1

Pthogens commony ssocited

with bcteri RTIs

ABs

Streptococcus pneumoniae

Haemophilus infuenzae

Moraxella catarrhalis

Staphylococcus aureus

Anarobs

Streptococcus spp

ABeCB



Moraxella catarrhalisStaphylococcus aureus

Pseudomonas aeruginosa

Opportunistic ram-nativ bactria

Mycoplasma pneumoniae

CAp

tyica ahg



Moraxella catarrhalis

Staphylococcus aureus

Streptococcus pyogenes

Neisseria meningitides

Klebsiella pneumoniae and otr ram-nativ rods

Ayica ahg

Mycoplasma pneumoniae

Chlamydia pneumoniae

Legionella spp

ABeCB, acut bactria xacrbation o cronic broncitis;

ABS, acut bactria rinosinusitis; CAP, communit-acquirdpnumonia; RTI, rspirator tract inction.

AnonJB,etal.Otolaryngol Head Neck Surg.2004;130(suppl1):

1-45;BallP.Chest.1995;108:43S-52S;BartlettJG,etal.Clin Inect Dis.2000;31:347-382;RayNF,etal. J Allergy ClinImmunol.1999;103:408-414.



procedures but rather, invasive, endoscopic-

directedculturesthatrequirespecialequipment

and experience. Both are expensive. Thereore,

ABS is most commonly diagnosed by clinical

signsandsymptoms.tABle 2 lists the signs andsymptoms typi-

callyassociatedwithbacterialversusviralRTIs.

DiagnosisoABScanbemadeinthepresenceo

theollowing3clinicalcriteria,whichmayhave

moderatediagnosticsensitivityandspecicity17:

• Purulentnasaldischargewitheitherunilat-

eralorbilateralpredominance

•Localpainwithunilateralpredominance

•Presenceopusinthenasalcavity.

ABSmayalsobediagnosedinpatientswitha

viralURTIwhosesymptomshaveworsenedater

5to7daysorhavenotimprovedater10days

andareaccompaniedbysomeorallothesymp-

tomsshownintABle 2.12

Viral rhinosinusitis can cause the ollow-ingsymptoms:coughing, acial pain, everand

chills,muscleachesandjointpain,nasalconges-

tionanddischarge,sorethroat,andhoarseness.

Unlikebacterialrhinosinusitis,viralrhinosinus-

itisspontaneouslyresolvesin10to14daysandis

commonintheall,winter,andearlyspring.12,19

Although some clinical signs andsymptoms

obacterial andviral rhinosinusitisoverlap, an-

tibiotics should be reserved primarily or indi-

vidualswhose symptomspersist or 10days or


TaBlE 2

Cinic symptoms o RTIs o bcteri or vir etioogy

Acu rhino- Acu bronchii

ABs inuii (iral) ABeCB (iral) Bacrial CAp viral CAp

ABeCB, acut xacrbation o cronic broncitis; ABS, acut bactria rinosinusitis; CAP, communit-acquird pnumonia;RTI, rspirator tract inction; URTI, uppr rspirator tract inction.

AnonJB,etal.Otolaryngol Head Neck Surg. 2004;130(suppl1):1-45;AnthonisenNR,etal.Ann Intern Med. 1987;106:196-204;BalterMS,etal.CanRespir J.2003;10(supplB):3B-32B;FamilyPracticeNotebook.www.pnotebook.com/ENT189.htm.AccessedJan10,2008.

• Nasa draina

• Nasa constion

• Facia prssur/

pain (spciay

wn uniatra

and ocusd in

t rion o a

particuar sinus

roup)

• Purunt postnasa

drip

• hyposmia/anosmia

• Cou

• Fvr

• Fatiu

• Maxiary dnta

pain

• ear unss/

prssur

• URTI tat is

no bttr atr

10 days, or

worsns atr

5-7 days

• Nasa discar

• Nasa constion

• Facia prssur

• Cou

• Fvr and cis

• Musc acs and

joint pain

• Sor troat and

oarsnss

• Spontanousy

rsovs in 10-14days

• Common in t a,

wintr, and ary

sprin

• Primary symptoms:

– Increased dyspnea

– Increasedsputumvolume

– Increasedsputumpurulence

• May aso xibit:

– Sorethroat

and/ornasal

dischargewithin

past5days

– Feverwithout

othercause

– Increased

wheezing

–Increasedcough

– Elevated

respiratoryor

heartrate

• Dyspna

• Cou otn dry,

nonproductiv

• Cou may b

productiv o

variaby coord

sputum

• Cou onst witin

2 days in 85% o

acut broncitis

• Wzin

• Cst pain

• hoarsnss

• Constitutiona

symptoms:

–Fever

–Myalgia

–Fatigue

• Cou

• Purunt sputum

(nonproductiv in

atypica cass)

• Suddn onst

• Dyspna

• Tacypna

• Tacycardia

• Puritic cst pain

• I-apparin

patint, spciaywit:

–Fever

–Fatigue

–Abnormalbreath

sounds

–Crackles

• Nonproductiv

cou (ru out

atypica bactria

inction)

• gradua onst wit

prodrom (maais

and adac)

• Cst x-ray mor

imprssiv tan

xamination

• Onst in a or

wintr

• Wzin mor

common in vira

causs

• low-rad

tmpratur

(<101.3º F)

• Conjunctivitis



worsenater5to7days.12However,

antibioticscanbeusedorpatientswith

moderately severe symptoms regard-

lessoillnessdurationandorpatientswithseveresymptoms,suchaseveror

signicant pain or discomort.20 The

colorothemucusisnotauseuldis-

tinguishingeatureindeterminingian

inection isviral orbacterialbecause

discoloredmucusiscommoninboth

viralandbacterialrhinosinusitis. (Fur-

ther treatment recommendations are

discussed in “Treatment recommen-

dations or patients with commonrespiratory tract inections with vari-

ables indicative o treatment ailure”

on page S19.)

Ac bacria xacrbai

f chric brchii

Epidemioogy nd

burden o disese

Acute bacterial exacerbation ochronicbronchitis(ABECB)aectsan

estimated 13million Americans (ap-

proximately4%-6%oadults[1995

gures]).21Thesepatients experience

anaverageo3ABECBepisodesan-

nually,withonethirdeachhaving<3,3,and≥4

episodes.22 In the 1990s, these acute episodes

accountedorabout12millionocevisitsan-

nuallyandor$200millionto$300millionin

medicalcosts.21

Viral pathogens are associated with only

30% o all AECBs,23 including infuenza and

parainfuenza viruses, respiratory syncytial vi-

rus,rhinoviruses,andcoronaviruses.23Mostex-

acerbationsochronicbronchitisarebacterialin

nature, and 3 bacterial pathogens—H infuen-

zae, S pneumoniae, andM catarrhalis—account

or70%oallexacerbationsand85%to95%

obacterial exacerbations.23Arecentstudyby

KahnetalevaluatedpatientswithABECB.These

3pathogenswereoundin46.2%(147/318)o

patientswithlessseveresymptomsand41.9%

(143/341) o patientswithmore severe symp-

toms.24Theauthorsalsoreportedthatgram-neg-

ativeorganismswereoundin22%opatients(Enterobacteriaceae,14.4%;Pseudomonas spp,

7.6%),andS aureuswasoundin3.9%opa-

tients(tABle 3).24Thesendingsresemblethose

oearlierstudies.25,26

Diagnosis of acute bacterial exacerbation

of chronic bronchitis vs viral bronchitis

The Anthonisen classication system helps to

establishadiagnosisoABECB.Ituses3typeso

exacerbationstoidentiypatientslikelyinected

TaBlE 3

Bcteri pthogens isoted rom ptients with cute

bcteri excerbtion o chronic bronchitis

Kan t a habib t a

Patons (2007) N (%) (1998) N (%)

Typica ABeCB patons 290 (44.0) 89 (49)

- Streptococcus pneumoniae 71 (10.8) 17 (9)

- Haemophilus infuenzae 131 (19.9) 45 (25)

- Moraxella catarrhalis 88 (13.4) 27 (15)

gram-nativ oranisms o not 145 (22.0) 58 (32)

- entrobactriaca 95 (14.4) 34 (19)

- Pseudomonas spp 50 (7.6) 24 (13)

gram-positiv oranisms o not

- Tota Staphylococcus aureus 26 (3.9) 12 (7)

- Staphylococcus aureus (MSSA) 24 (3.6) —

- Staphylococcus aureus (MRSA) 2 (0.3) —

Otr 169 (25.6) —

- Haemophilus parainfuenzae 134 (20.3) 22 (12)

- Otr Haemophilus spp 26 (3.9) —

- Acinetobacter spp 9 (1.4) —

Otr ram-nativ spp 16 (2.4) —

Otr ram-positiv cocci 13 (2.0) —

ABeCB, acut xacrbation o cronic broncitis; MRSA, mticiin-rsistant Staphylococcus aureus; MSSA, mticiin-suscptib

Staphylococcus aureus.

BalterMS,etal.Can Respir J.2003;10(supplB):3B-32B;HabibMP,etal.Inect DisClin Pract. 1998;7:101-109;KahnJB,etal.Curr Med Res Opin.2007;23:1-7.


http://slidepdf.com/reader/full/managing-res-infections 10/24S10 Vo 57, No 2 / Fbruar 2008 n s th Jra f Faiy pracic

withbacterialpathogens,basedonthepresence

otheclinicalsymptomsoincreaseddyspnea,spu-

tumvolume,andsputumpurulence(tABle 2).26,27

InatypeIexacerbation,all3symptomsarepres-ent,whereasintypeIIandtypeIIIexacerbations,

2symptomsand1symptomarepresent,respec-

tively.26 The Anthonisen classication is also

helpulin predictingantibiotic response (typeI

beingmost predictive).26 Other symptomsmay

alsobepresent,suchassorethroatand/ornasal

dischargewithinthepast5days, everwithout

othercause,andincreasedwheezing,cough,and

elevatedrespiratoryorheartrate.26

Thepresenceogreen,purulentsecretionsisespecially predictive o a high bacterial load.26

As demonstrated by Balter et al, the presence

o these secretions was 99.4% sensitive and

77.0%specicorahighbacterialloadinpa-

tientswithahistoryochronicobstructivepul-

monarydisease.26

Patients with viral bronchitis present with

a wider range o signs and symptoms, includ-

ing dyspnea; a dry, nonproductive cough or a

cough that produces variably colored sputum;coughonsetwithin2days;wheezing;chestpain;

hoarseness;ever;myalgias;andatigue.19

Ciy-acqird

ia

Epidemioogy nd burden o disese

Pneumoniaisthesixthleadingcauseodeath

in the United States and ranks highest as the

causeodeathamonginectiousdiseases,28

withanestimated45,000deathsannually(1997g-

ure).29Theincreaseddeathraterompneumo-

niaobservedoverthepastewyearsmayresult,

inpart,romtheagingothepopulation;some

othehighermortalityrateisattributedtopa-

tients≥65yearsoage.29Signsandsymptoms

independentlyassociatedwithincreasedmortal-

ityincludedyspnea,chills,alteredmentalstatus,

hypothermia or hyperthermia, tachypnea, and

hypotension(diastolicandsystolic).29

CAP accounts or500,000hospitalizations

annually.29Anestimated5%to35%opatients

hospitalizedwithCAPhaveseveredisease,which

accountsor10%oallintensivecareunit(ICU)admissions.30In1998,Niedermanetalcalculat-

edthecostohealthcareresourceutilizationor

CAPtobe$4.8billionorpatients≥65yearsand

$3.6billionorpatients<65years. 31

CAPiscausedprimarilybybacterialpatho-

gens(tABle 1).S pneumoniaeisthemostcom-

moncauseoCAP(20%-60%oallepisodes),

ollowed by H infuenzae (3%-10% o all

episodes) (1990 gures).9,28 Atypical bacterial

pathogens, such as Mycoplasma pneumoniae,Chlamydia pneumoniae,andLegionellaspp,are

lessrequentlyimplicatedascausesoCAP.9The

percentageoviralCAP(1%intheUnitedStates)

is negligible.32 Because bacterial pathogens are

predominantinCAP,treatmentguidelinesrom

theAmericanThoracicSocietyandtheInectious

DiseasesSocietyoAmericarecommendantibi-

otictreatmentorallpatients.28,33

Dignosis o cute community-cquiredpneumoni

CAPisindicatedbytheonsetocough,sputum

production,and/ordyspneainnonhospitalized

patients.Feverandabnormalbreathsoundsand

cracklesonauscultationurthersupportadiag-

nosisoCAP.In immunosuppressedorelderly

patients,respiratory symptomsmaybe absent;

patientswithCAPmaypresentwithsymptoms

suchasconusion,malaise,ortachypnea.Stan-

dardposteroanteriorandlateralchestx-raysarestrongly recommended to confrm a diagnosis

oCAP.28 InbacterialCAP,coughingproduces

purulent sputum, whereas a nonproductive

coughismorecommoninviralCAPorinpneu-

monia caused by atypical pathogens, such as

M pneumoniae andLegionella spp.19 In addi-

tion, inbacterialCAPa sudden onset iscom-

mon, compared with a gradual onset in viral

CAP.19 Furtherdierentiating signsandsymp-

tomsareshownintABle 2.



http://slidepdf.com/reader/full/managing-res-infections 11/24s th Jra f Faiy pracic n Vo 57, No 2 / Fbruar 2008 S11

1. AvornJ,SolomonDH. Culturaland eco-nomic actors that (mis)shape antibiotic use:the nonpharmacologic basis o therapeutics.Ann Intern Med.2000;133:128-135.2. SteinmanMA,GonzalesR, Linder JA,etal.Changinguseoantibioticsincommunity-based outpatient practice, 1991-1999. AnnIntern Med.2003;138:525-533.3. GonzalesR,MaloneDC,MaselliJH,etal.Excessive antibiotic use or acute respiratoryinectionsintheUnitedStates.Clin Inect Dis.2001;33:757-762.

4. FendrickAM,Monto AS,NightengaleB,etal.The economicburdeno non-infuenza-related viral respiratory tract inection in theUnited States. Arch Intern Med. 2003;163:487-494.5. NouwenJL.Controllingantibioticuseandresistance.Clin Inect Dis.2006;42:776-777.6. LivermoreDM.Minimisingantibioticresis-tance.Lancet.2005;5:450-459.7. BronzwaerSL,CarsO,BuchholzU, etal.AEuropeanstudyontherelationshipbetweenantimicrobialuseandantimicrobialresistance.Emerg Inect Dis.2002;8:278-282.8. SahmDF,BenningerMS,EvangelistaAT,etal.Antimicrobialresistancetrendsamongsinusisolates o Streptococcus pneumoniae in theUnitedStates (2001-2005).Otolaryngol Head

Neck Surg.2007;136:385-389.9. Brown SD, Rybak MJ. Antimicrobialsusceptibility o Streptococcus pneumoniae,Streptococcus pyogenes and Haemophi-lus infuenzae collected rom patients acrossthe USA, in 2001-2002, as part o thePROTEKTUSstudy. J Antimicrob Chemother.2004;54(suppl1):i7-15.10.Centers or Disease Control and Preven-tion.ActiveBacterialCoreSurveillance(ABCs)ReportEmergingInectionsProgramNetwork,Streptococcus pneumoniae. www.cdc.gov/ ncidod/dbmd/abcs/survreports/spneu03.pd.AccessedJan23,2008.11.Gwaltney JM Jr. Acute community-ac-quired sinusitis. Clin Inect Dis. 1996;23:1209-1225.

12.AnonJB,JacobsMR,PooleMD,etal,ortheSinusandAllergyHealthPartnership.An-timicrobialtreatmentguidelinesoracutebac-terial rhinosinusitis. Otolaryngol Head NeckSurg. 2004;130(suppl1):1-45.13.Ray NF, Baraniuk JN,Thamer M, et al.Healthcareexpendituresor sinusitis in1996:contributions o asthma, rhinitis, and otherairway disorders. J Allergy Clin Immunol.1999;103:408-414.14.Uhl J, Manko S. Sinusitis, bronchitisaccountormorethan30millionmissedwork-

days each year. www.medicalnewstoday.com/ articles/15277.php.AccessedJan16,2008.15.Hamory BH, SandeMA, Sydnor A Jr, etal.Etiologyandantimicrobialtherapyoacutemaxillarysinusitis. J Inect Dis.1979;139:197-202.16.Payne SC, BenningerMS. Staphylococcusaureus isa majorpathogen inacutebacterialrhinosinusitis:ameta-analysis.Clin Inect Dis.2007;45:e121-127.Epub2007Oct11.17.Agency or Health Care Policy and Re-search. Diagnosis and treatment o acutebacterialrhinosinusitis:summary.EvidenceRe-port/TechnologyAssessmentAHCPRPubNo.99-E015,1999.18.Benninger MS, Payne SC, Ferguson BJ,et al. Endoscopically directed middle meatal

culturesversusmaxillarysinustapsinacutebac-terialmaxillaryrhinosinusitis:ameta-analysis.Otolaryngol Head Neck Surg. 2006;134:3-9.19.FamilyPractice Notebook. Rhinosinusitis.www.pnotebook.com/ENT189.htm. Accessed Jan10,2008.20.Hickner JM,Bartlett JG,BesserRE,etal.Principles o appropriate antibiotic use oracuterhinosinusitisinadults:background. AnnIntern Med.2001;134:498-505.21.SethiS.Inectiousexacerbationochronicbronchitis:diagnosisandmanagement. J An-timicrob Chemother. 1999;43(suppl A):97-105.22.NiedermanMS.Antibiotic therapyo ex-acerbationsochronicbronchitis. Semin RespirInect. 2000;15:59-70.

23.Ball P. Epidemiology and treatment ochronicbronchitisanditsexacerbations.Chest.1995;108:43S-52S.24.KahnJB,KhashabAM,AmbruszM.Studyentry microbiology in patients with acutebacterial exacerbations o chronic bronchitisinaclinicaltrialstratiyingbydiseaseseverity.Curr Med Res Opin. 2007;23:1-7.25.HabibMP,GentryLO,Rodriguez-GomezG,etal.Multicenter,randomizedstudycompar-ingecacyandsaetyoorallevofoxacinandceaclorintreatmentoacutebacterialexacer-

bationso chronicbronchitis.Inect Dis ClinPract.1998;7:101-109.26.BalterMS,LaForgeJ,LowDE,etal.Ca-nadianguidelinesorthemanagementoacuteexacerbationsochronicbronchitis.Can Respir J.2003;10(supplB):3B-32B.27.AnthonisenNR,ManredaJ,WarrenCPW,et al. Antibiotic therapy in exacerbations ochronicobstructivepulmonarydisease.Ann In-tern Med.1987;106:196-204.28.Niederman MS, Mandell LA, Nanuet A,etal.Guidelinesorthemanagementoadultswithcommunity-acquiredpneumonia:diagno-sis,assessmentoseverity,antimicrobialthera-py,andprevention.Am J Respir Crit Care Med.2001;163:1730-1754.29.BartlettJG,DowellSF,MandellLA,etal.

Practiceguidelinesorthemanagementocom-munity-acquiredpneumoniainadults.Clin In-ect Dis.2000;31:347-382.30.deCastroFR,TorresA.Optimizing treat-mentoutcomes in severe community-acquiredpneumonia.Am J Respir Med.2003;2:39-54.31.NiedermanMS,McCombs JS,UngerAN,etal.Thecostotreatingcommunity-acquiredpneumonia.Clin Ther.1998;20:820-837.32.FileTM.Community-acquiredpneumonia.Lancet.2003;362:1991-2001.33.MandellLA,WunderinkRG, AnzuetoA,et al. InectiousDiseases SocietyoAmerica/ American Thoracic Society consensus guide-lines on the management o community-acquiredpneumoniainadults.Clin Inect Dis.2007;44(suppl2):527-572.

CciAcute rhinosinusitis,AECB,andCAPare com-

monlyencounteredinectiousdiseasesthatvary

intheincidenceoviralandbacterialorigin.Mostcasesorhinosinusitisareviralinorigin,whereas

AECBandCAPcommonlyresultrombacterial

inection. Cliniciansmust beable todierenti-

ateviralandbacterialRTIsbeoretheyreachor

theirprescriptionpads.Inappropriateantibiotic

prescribing leads to unnecessary drug-related

adverse events, excessivemedication costs, and

thedevelopmentoantibioticresistance.Practi-tionersmustresistthevariouspressuresplaced

onthemtoprescribeantibioticsinappropriately

andinsteaddeterminetheetiologyotheseRTIs

oroptimalpatientcare.n

Reerences




pai ariab aciadwih ra fair i riraryrac ifciHns H. liu, MD • Robert E. Siege, MD

K Points

o Witout ctiv antibiotic

tratmnt, bactria rspirator tract

inctions ma worsn and sprad,

rsutin in potntia srious at

consquncs and incrasd costs

to t patint.

o Patint variabs associatd

wit tratmnt aiur incud

comorbiditis and inction wit a

rsistant paton as w as ss

obvious socia actors tat ma

compicat t cours o disas.

o Tratmnt aiur ma subjct

patints to proond discomort,

tratmnt dissatisaction, missd

work, ospitaization, incrasd

costs rom additiona anti-inctiv

tratmnts, or otr nativ rsuts.

o Wn sctin antibiotic trap,

cinicians soud considr t

compt cinica and socia proi

o a patint wit rspirator tractinctions.

Certainactorspredisposesomepatientswithrespira-tory tract inections (RTIs) to treatment ailure. In

“Is it bacterial or viral? Criteria or distinguishing

bacterialandviralinections”(see page S5),theauthorsde-

scribedstrategiestodistinguishbacterialromviralRTIs—a

crucialstepinappropriateantibioticprescribing.Clinicians

alsoneedtobeawareoindividualpatientcircumstancesthat

maynegativelyaecttreatment.Thisarticleprovidesaclini-

calalgorithmbasedoncurrenttreatmentguidelinesandthe

combinedclinicalexperienceoamultidisciplinaryconsensus

group.Wehopethistoolwillhelpcliniciansto identiypa-tientswithclinicalandsocialactorsindicativeotreatment

ailure in commonbacterial RTIs, and avoid the potential

consequencesoinappropriaterst-linetreatment.

pai ariab ha affc rac

WhenapatientpresentswithanRTI,acompleteassessment

providestherststepinidentiyingvariablesthatmayaect

treatmentoutcomes.Someothemoreobviousquestionsthatshouldbeposedinclude:

•Does the patient look“toxic” or have abnormal vital

signs?Iso,isthepatientmedicallyunstable,indicating

theneedorhospitalization?

•Does the patient have comorbidities such as diabetes,

human immunodeciency virus (HIV), cardiovascular

Dicr: Dr liu as discosd tat is on t spakrs burau o Avntis Parmacuticas, Bar hatCar Parmacuticas, Bristo-

Mrs Squibb Compan, Cubist Parmacuticas, gaxoSmitKin, Mrck & Co., Inc., Orto-McNi-Janssn Parmacuticas, Inc, Pizr Inc,

Purdu Parma, Oscint Parmacuticas Corporation, and Wt Parmacuticas. Dr Si as discosd tat as srvd as a consutant

or and on t spakrs burau o Borinr Inim, gaxoSmitKin, Orto-McNi-Janssn Parmacuticas, Inc, and Pizr Inc.



disease,chronicobstructivepulmonarydisease

(COPD),orunderlyingmalignancy,whichare

likelytoaectthecourseotheRTI?

•Doesthepatientsmokeorabusealcohol? •Isthepatientolderthan65yearsand/orhave

poorunctionalstatus?

Acompletepatientprolerequiresurtherprob-

ingandhistorytaking,especiallyornewpatients.

Cinic ctors

tABles 1-3 list the clinical variables associated

with treatment ailure specic to patientswith

3 common RTIs: acute bacterial rhinosinusitis

(ABS), acute bacterial exacerbation o chronicbronchitis (ABECB), and community-acquired

pneumonia (CAP). Some variables overlap in

all3RTIs,suchasrecentantibioticuseandan

immunosuppressive illness or treatment with

an immunosuppressive agent (FIGuRe 1). Other

variablesoverlapin2RTIs:inABECBandCAP,

advancedage isanimportantclinical indicator

otreatmentailure;andinABSandCAP,malig-

nanciesandcontactwithchildrenindaycarecan

complicatetreatment.Othervariablesarespecictotheindividualdisease.

Soci ctors

In addition tomedical considerations, the clini-

cian’s complete assessment may discover less-

obvious patient variables, such as complicating

socialactors.Theseactorsmayaectthecourse

otheRTIandinfuencetheclinician’streatment

decisions(FIGuRe 2).Forexample,thosewholive

alone(especiallythosewithpoorunctionalstatusorelderlypatients),maynditdiculttoadhere

tooutpatienttreatments;theyalsomaynothave

asucientamilyorsocialnetworktomeettheir

needsduringanillness.Suchpatientsmaybelost

to urtherollow-up, andappropriateinitialan-

tibiotictherapyisespeciallyimportantorthem.

Thealternativetreatmentoptionorthesepatients

isotenhospitaladmission. 1

Patientsmayalsohavestressulworksched-

ulesandmaytravelrequently.Theymaynotbe

abletoaordmissedworkdays,withthepoten-

tialconsequenceso lostpay,misseddeadlines,

andanincreasedworkloadwhentheyeventually

returntowork.Inaddition, patientsmayhaveamilyresponsibilities,suchasthecareoyoung

childrenorelderlyamilymembers,ortheymay

havebusysociallivesthattheyareunwillingto

curtailorlong.Thesepatientsrequirerapidres-

olutiono theirsymptoms through appropriate

rst-linetherapy,bothormedicalreasonsandto

accommodatetheirliestyles.

acute bcteri rhinosinusitis

Clinical risk actors identied in therhinosinus-itisguidelinesocusonanticipatingantibiotic-re-

sistantpathogens(tABle 1).2-4Patientswhohave

receivedantibioticswithintheprior4to6weeks

areespeciallyatriskoacquiringresistantpatho-

gens.2Onesmallstudy(N=20)evaluatedpatients

withABSwhohadbeentreatedwithantibiotics

asearlyas6monthspriortodiagnosis.Follow-up

showedasignicantlyhigherrecoveryoresistant

organismsromthesepatients.4Penicillin-nonsus-

ceptible pneumococcal inections are associatedwith comorbid conditions such as organ trans-

plantation,HIVinection,asplenia,malignancies,

andsicklecelldiseaseinpatientswhoreceivepeni-

cillinprophylaxis.3Inaddition,inpatientswithsi-

nusitis,smokinghasbeenidentiedasariskactor

orinectionwithresistantstrains. 4

Otherpatientsatriskotreatmentailureor

ABShavemoderateorseveredisease.Moderate

disease is characterized by more severe symp-

toms,butthisremainsaclinicaljudgment.Symp-tomsassociatedwithABSincludenasaldrainage

andcongestion,acialpainorpressure,postna-

saldrip,ever,cough,andatigue,amongothers.

Thesepatientsaremorelikelytoexperiencedis-

comortandmayalsohaveareducedtolerance

ortreatmentailure.2

acute bcteri excerbtion o chronic

bronchitis nd tretment iure

In ABECB, variables associated with treatment



ailuremaybelooselycategorizedasthoserelat-

ingtoclinicalissues(eg,inectionwitharesistant

pathogen) or those resulting in increased costs.

Although therationalesbehind the2 categories

aredierent,manysimilarvariablesarepresentin

bothcategories(tABle 2).

Similar to ABS, variables associated with

treatment ailure inABECB includerecentanti-

bioticuseandsignicantcomorbidities, such as

cardiac disease, which can increase the risk o

pAtIent vARIABles In RtI tReAtment FAIluRe

FIGURE 1

Where compicting ptient vribes overp in disese sttes

ABs: Rik facor for rian

organim

• Smokin

• Svrity o symptoms (mor discomort)

associatd wit rducd toranc or

tratmnt aiur

CAp: Rik facor forrian ahogn

• Acooism

• Mutip mdica conditions

• Immunosupprssiv inss

• Contact wit cidrn in day car

CAp: Incrad rik facor for a

comlicad cour of CAp

• Tmpratur >38.3ºC

• hi-risk tioois ( S pneumoniae, S aureus,

ntric ram-nativ bactria, P aeruginosa )

• Incrasd risk or mortaity

— At ast 2 o t oowin:

- Rspiratory rat ≥30/minut- Bood ura nitron ≥7.0 mmo/l

(>19.1 m/dl)

- Diastoic bood prssur ≤60 mm h

- Mnta conusion

ABs and CAp

• Contact wit

cidrn in

day car

• Mainancis

ABs, ABeCB,

and CAp

• Rcnt antibiotic us

• Immunosupprssiv

inss/tratmnt*

ABeCB: Rik facor

for ramn failur or

rian ahogn

• >4 xacrbations/yar

• Cardiac disas

• history o prvious

pnumonia

• Us o om oxyn

• FeV1

<50% prdictd

ABeCB: Facor ha incra h

co of ramn failur

• Cardiac disas

• Sinicant comorbidity• Cronic corticostroid administration

• Frqunt purunt xacrbations o COPD

• Manutrition

• Svry impaird undryin un unction

• Cronic mucous yprscrtion

• Us o suppmnta oxyn

• gnraizd dbiity

CAp and ABeCB

• Advancd a/odr

patints (>65 yars

o a)

*Recent systemic corticosteroid therapy or cancer chemotherapy, chronic oral steroid use, sickle cell disease, HIV infection, or asplenia.

ABeCB, acut bactria xacrbation o cronic broncitis; ABS, acut bactria rinosinusitis; CAP, communit-acquird

pnumonia; COPD, cronic obstructiv pumonar disas; FeV1, orcd xpirator voum in 1 scond; hIV, umanimmunodcinc virus.

AnonJB,etal.Otolaryngol Head Neck Surg. 2004;130(suppl1):1-45; BalterMS,etal.Can Respir J. 2003;10(supplB):3B-32B; BrookI,etal.AnnOtol Rhinol Laryngol.1999;108:645-647; BruntonS,etal.Am J Manag Care. 2004;10:689-696; deCastroFR,etal.Am J Respir Med.2003;2:39-54; GrossmanRF.Chest.1997;112:310S-313S; GrossmanRF.Semin Respir Inect. 2000;15:71-81; JacobsMR.Am J Med. 2004;117(suppl3A):3S-15S; MandellLA,etal.Clin Inect Dis.2003;37:1405-1433; NiedermanMS.Semin Respir Inect.2000;15:59-70; NiedermanMS,etal.Am J Respir Crit Care Med.2001;163:1730-1754.



• Prolonged suffering

• Similar consequences to other groups

• Dissatisfaction, missed work, etc.

• Extended treatment course with antibiotic leads to unrecognized

treatment failure because doctor believes patient needs

repeated antibiotic course• Patient exposed to further development of bacterial resistance

• Missed opportunities (work, family, special events)

• Frustration level increases (will patient be able to make follow-upappointment; will it be a follow-up by phone call?)

• Patient may go to urgent care center (increased cost, inconvenience,

relationship between doctor and patient suffers)

• If follow-up by phone call, missing important facts such as allergies,

drug interactions, etc, doctor may order an inappropriate medication

• Hospitalization

• Disease progression

• Need for ICU/ventilator

• Exacerbation of underlying disease

• Sepsis (eg, phlebitis at IV site)/bacteremia

• If admitted, potential for nosocomial infection

(eg, Clostridium difficile )

Consequences of inappropriate treatment

FIGURE 2

assessment o ctors tht my ect RTI disese course

nd consequences o inpproprite tretment o RTIs

A ai/ia ig

Rik facr fr dia rgri r?• Siniicant comorbidity

–Uncontrod diabts, hIV, undryin mainancy,

COPD/mpysma, cardiovascuar disas/art

aiur, immunosupprssion

• Ciartt smokin

• Acoo abus

• Poor unctiona status

• A >65

moDeRAte (AtrISk)

lk ick (“xic”) /abra ia

ig/hiaizai rqird

Hiaizaiuab

oai

Hahy

n

Cicaig cia facr r?

• May b ost to oow-up

• Patint wo ivs aon• Patints wit critica jobs

• Patints wo trav

• Patints wit amiy obiations

(, carivrs or cidrn or dry prsons)

n

A rik fr ifci wih a ria ahg?

• Prvious antibiotic us

• exposur to cidrn in day car (CAP)

n

Y

Y

Y

mIlD



CAP, communit-acquird pnumonia; COPD, cronic obstructiv pumonar disas; hIV, uman immunodcinc virus;

ICU, intnsiv car unit; RTI, rspirator tract inction.

BalterMS,etal.Can Respir J.2003;10(supplB):3B-32B;BrookI,etal.Ann Otol Rhinol Laryngol. 1999;108:645-647;deCastroFR,etal.Am J RespirMed.2003;2:39-54;GrossmanRF.Semin Respir Inect.2000;15:71-81;JacobsMR.Am J Med.2004;117(suppl3A):3S-15S;NiedermanMS,etal.Am J Respir Crit Care Med. 2001;163:1730-1754.

Fow cart sowin variabs associatd wit tratmnt aiur and t potntia consquncs o inappropriat tratmnt orcommon rspirator inctions

sab



treatmentailuremorethan2-old.5,6Forpatients

withABECB,theseverityotheunderlyinglung

disease—as indicated by use o home oxygen,

FEV1level,numberoexacerbationsperyear,orhistoryopneumonia—andchronicoralsteroid

usearealsoimportantriskactorsortreatment

ailure.5-10

TreatmentailureinABECBhasbeenshown

toresultinincreaseduseohealthcareresources

causedbyadditionalphysicianvisits,urtherdiag-

nostictests,andrepeatedantibiotictreatments.5,6

Signicantcomorbidity,suchascardiacdisease,

chronic corticosteroid administration, severely

impairedunderlyinglungunction,useosupple-mentaloxygen,requentpurulentexacerbations

oCOPD,malnutrition, advancedage, general-

izeddebility,andchronicmucoushypersecretion

(tABle 2) all increase the costs associatedwith

treatmentailureandhospitalization.5,6

Community-cquired pneumoni:

Resistnt pthogens nd other ctors

Because the prognosis o CAP can range rom

rapidsymptomaticrecoverywithout unctionalimpairmenttoseriousmorbidcomplicationsand

death, it is especiallyimportant to identiy pa-

tientswhoareatriskotreatmentailure.11As

withotherRTIs,acquisitionoresistantpatho-

gensinCAPisanimportantpredictorotreat-

mentailure.Additionalpredictorsotreatment

ailureinCAP,stratiedbyleveloimportance,

areshownintABle 3.3,11-15

AsseeninABSandABECB,oneothemost

important risk actors or inection with a re-sistant organism is recent antibiotic therapy,

including β-lactam therapy within the past 3

months.4,12,13 Other modiying actors that in-

crease the risk o inectionwith drug-resistant

pneumococciincludeage>65years,alcoholism,

immunosuppressive illness requiring long-term

corticosteroids, multiple medical comorbidities,

and exposure to a child in day care.12 Finally,

organtransplantation,HIV,asplenia,andmalig-

nanciesarecomorbidconditionsassociatedwith


TaBlE 2

Vribes ssocited with

tretment iure in aBECB

Rik facr fr ra fair

• Rcnt antibiotic us (in t past 3 monts)

• Cardiac disas

• Svr undrin un disas

– Us o om oxn

– FeV1

<50% prdictd

– ≥4 xacrbations/ar

– histor o prvious pnumonia

• Cronic ora stroid us

Facr ha icra h c f ra fair

• Sinicant comorbidit

– Cardiac disas

• Cronic corticostroid administration

• Svr impaird undrin un unction

• Us o suppmnta oxn

• Frqunt purunt xacrbations o COPD• Manutrition

• Advancd a

• gnraizd dbiit

• Cronic mucous prscrtion

ABeCB, acut bactria xacrbation o cronic broncitis;COPD, cronic obstructiv pumonar disas; FeV

1,

orcd xpirator voum in 1 scond.

BalterMS,etal.Can Respir J.2003;10(supplB):3B-32B;BruntonS,etal.Am J Manag Care.2004;10:689-696;DewanNA,etal.Chest.2000;117:662-671;GrossmanRF.Chest.1997;112(6suppl):310S-313S;GrossmanRF.Semin Respir Inect.2000;15:71-81;NiedermanMS.Semin Respir Inect.2000;15:59-70.

TaBlE 1

Vribes ssocited with

tretment iure in aBS

Rik facr fr ria ahg


• Oran transpantation, hIV inction, aspnia,

mainancis, and sick c disas in patints wo

rciv pniciin propaxis

• Smokin

Rdcd rac fr ra fair

• Mor svr smptoms (mor discomort)

ABS, acut bactria rinosinusitis; hIV, umanimmunodcinc virus.

AnonJB,etal.Otolaryngol Head Neck Surg.2004;130(suppl1):1-45;BrookI,etal.Ann Otol Rhinol Laryngol.1999;108:645-647;JacobsMR.Am J Med.2004;117(suppl3A):3S-15S.



pneumococcalinectionsthatarenotsusceptible

topenicillin.3

Alimitedbutsignicantnumberopatients

initiallybelievedtohavemildpneumoniawilldevelopmoresevereCAPandwillrequirehos-

pitalization.RiskactorsorcomplicatedCAP

includeage>65years,comorbidillnesses,tem-

perature>38.3ºC,immunosuppressiondueto

continuouscorticosteroiduseorcancerchemo-

therapy,andthepresenceohigh-risketiologies

suchasStaphylococcus aureusorentericgram-

negativebacteria.14

Numerousprognosticactorsordeathrom

CAPhavebeenidentied.14Theriskotreatmentailureincreasesproportionallywiththenumbero

riskactorsthepatienthas. 14Signsandsymptoms

thatareindependentlyassociatedwithincreased

CAPmortalityaredyspnea,chills,alteredmental

status,hypothermiaorhyperthermia, tachypnea,

anddiastolicorsystolichypotension.14,16Therisk

odeathmayalsobesignicantlyassociatedwith

theidentityo the inectingpathogen;mortality

wasoundtobehighestorpatientswithpneumo-

niacausedbyPseudomonas aeruginosa,Klebsiellaspecies,Escherichia coli,orS aureus.15,16

ponial conqunc of ramn

fair i ai wih RtI

Treatment ailure in patientswith comorbidi-

tiesotenleadstoexacerbationoanunderly-

ingdiseasestate,suchasdiabetes,orworsening

otheinectiontothepointthathospitalization

isrequired.AlthoughABSrarelyleadstohospi-talization,severelowerRTIssuchasABECBor

CAPcanbecomeseriousenoughthatthepatient

mustbehospitalized,which inturncan intro-

duceurtherchallenges.5,12,13

Amultidisciplinary group investigating the

consequences o antibiotic treatment ailure in

RTIsoundthatapproximately10%opatients

withRTIsailedtreatmentwithamacrolidean-

tibiotic.17Thisresultedinincreasedhealthcare

utilization,includinghospitalizations,emergency

department visits, andadditionalocevisits.17

Repeatedcoursesoantibioticsorhospitalized

patientsalsoputthesepatientsatahigherrisk

oinectionwithresistantorganisms,asituation

thatcanhavesocioeconomicaswellasclinical

consequences.

TaBlE 3

Risk ctors or tretment iure in CaP

Rik facr fr ria ahg


• Odr patints (a >65 ars)

• Contact wit cidrn in da car

• Acooism

• Mutip mdica comorbiditis

• Immunosupprssiv inss

• Incrasd risks or rsistant S pneumoniae incud

mainancis, hIV inction, aspnia, and patints wit

sick c disas wo rciv pniciin propaxis

Icrad rik fr a cicad cr f CAp

• A >65 ars

• Comorbid inss

• Tmpratur >38.3ºC

• Immunosupprssion (rcnt sstmic corticostroid

trap or cancr cmotrap)

• hi-risk tioois ( S pneumoniae, S aureus, ntric

ram-nativ bactria, P aeruginosa )

Icrad rik fr raiy

• At ast 2 o t oowin:

- Rspirator rat ≥30/minut

- Bood ura nitron >7.0 mmo/l (>19.1 m/dl)

- Diastoic bood prssur ≤60 mm h

• Dspna

• Cis

• Atrd mnta status

• hpotrmia or prtrmia

• Tacpna

• Diastoic or sstoic potnsion

• hi-risk tioois ( P aeruginosa, Klebsiella spp ,

E coli, or S aureus )

CAP, communit-acquird pnumonia; hIV, uman

immunodcinc virus.

BartlettJG,etal.Clin Inect Dis. 2000;31:347-382;deCastroFR,etal.Am J Respir Med.2003;2:39-54;FineMJ,etal. JAMA.1996;275:134-141;JacobsMR.Am J Med. 2004;117(suppl3A):3S-15S;MandellLA,etal.Clin Infect Dis.2003;37:1405-1433;NiedermanMS,etal.Am J Respir Crit Care Med.2001;163:1730-1754.



CciRTI is one o themost common reasons that

patients seek medical attention.When patients

presentwithvariablesassociatedwithtreatmentailure, the clinician should take extra care to

reducetheimpactotheseinectionsonpatients’

healthandnormalunctioning.

Ater theclinician hasdetermined that the

etiology o the RTI is bacterial and not viral,

treatment with an appropriate antimicrobial

agentmayleadtoanimprovedclinicaloutcome.

Itmayalsoreducetheoverallcostsotreatment,

particularly when it prevents complications

o the inection, respiratory ailure, and hos-pitaladmission.6Itisthereorecrucialtoiniti-

ateappropriateempiricantibiotic therapyina

timelyashion.Treatmentrecommendationsor

patientsatriskotreatmentailurearepresented

inthenextarticleinthissupplement,byBasriet

al(see page S19).n

1. Marrie TJ,Huang JQ.Low-riskpatientsadmittedwith community-acquired pneumo-nia.Am J Med.2005;118:1357-1363.2. AnonJB,JacobsMR,PooleMD,etal,ortheSinusandAllergyHealthPartnership.An-

timicrobialtreatmentguidelinesoracutebac-terial rhinosinusitis.Otolaryngol Head NeckSurg.2004;130(suppl1):1-45.3. Jacobs MR. Streptococcus pneumoniae:epidemiology andpatternso resistance.Am J Med .2004;117(suppl3A):3S-15S.4. BrookI,GoberAE.Resistancetoantimi-crobialsusedortherapyootitismediaandsinusitis:eectopreviousantimicrobialther-apyandsmoking.Ann Otol Rhinol Laryngol.1999;108:645-647.5. Balter MS, La Forge J, Low DE, et al.Canadian guidelines or the management oacute exacerbations o chronic bronchitis.Can Respir J .2003;10(supplB):3B-32B.6. GrossmanRF. Cost-eective therapy oracute exacerbations o chronic bronchitis.Semin Respir Inect.2000;15:71-81.

7. GrossmanRF.Guidelinesorthetreatmentoacuteexacerbations o chronicbronchitis.Chest. 1997;112:310S-313S.8. Brunton S, Carmichael BP,Colgan R, etal.Acuteexacerbationo chronicbronchitis:

a primary care consensus guideline. Am J Manag Care.2004;10:689-696.9. Niederman MS. Antibiotic therapy oexacerbations o chronic bronchitis. SeminRespir Inect.2000;15:59-70.10.Dewan NA, Raque S, Kanwar B, etal.Acute exacerbation o COPD: actors asso-ciated with poor treatment outcome.Chest.2000;117:662-671.11.Bartlett JG, Dowell SF, Mandell LA, etal.Practiceguidelinesorthemanagementocommunity-acquired pneumonia in adults.Clin Inect Dis.2000;31:347-382.12.NiedermanMS,MandellLA,AnzuetoA,etal.Guidelinesorthemanagementoadultswith community-acquired pneumonia: diag-nosis, assessment o severity, antimicrobialtherapy,andprevention.Am J Respir Crit Care

Med.2001;163:1730-1754.13.MandellLA,BartlettJG,DowellSF,etal.Updateopracticeguidelinesorthemanage-ment o community-acquired pneumonia inimmunocompetent adults. Clin Inect Dis.

2003;37:1405-1433.14.deCastroFR,TorresA.Optimizingtreat-mentoutcomesinseverecommunity-acquiredpneumonia.Am J Respir Med. 2003;2:39-54.15.Fine MJ, Smith MA, Carson CA, et al.Prognosisandoutcomesopatientswithcom-munity-acquiredpneumonia:ameta-analysis. JAMA.1996;275:134-141.16.Ball P. Epidemiology and treatment ochronic bronchitis and its exacerbations.Chest. 1995;108:43S-52S.17.Wu JH, Howard DH, McGowan JE Jr,etal.Patternsohealthcareresourceutilizationatermacrolide treatment ailure:results roma large, population-based cohort with acutesinusitis, acute bronchitis, and community-acquired pneumonia. Clin Ther. 2004;26:2153-2162.


Reerences




s th Jra f Faiy pracic n Vo 57, No 2 / Fbruar 2008 S1

Forpatientswithrespiratorytractinections(RTIs),anti-microbial treatmentisprescribed todecreasethebacte-

rialburden,returnthepatienttobaselinecondition,and

reducetheriskothepatientprogressingtoamoreseverein-

ection.1Althoughagentsromseveralantimicrobialclassesare

approvedtotreattheseinections,certainpatientandpathogen

actorswilllimittheselectionoappropriatetherapy.Itiscriti-

callyimportanttoidentiyriskactorsthatmayputpatientsat

riskotreatmentailurebecausethesepatientsmayrequiremore

aggressivetherapytoachievethedesiredtreatmentoutcomeand

tominimizethepotentialdevelopmentoseverecomplications.In“Patient variablesassociatedwith treatmentailurein

respiratorytractinections”(see page S12),LiuandSiegeliden-

tiedvariablesassociatedwith treatment ailure,whichplay

criticalrolesinselectionoantimicrobialtherapy.Primarycare

practitionerstypicallyprovideempiricalRTItreatment;there-

ore,theoptimalagentshouldprovidecoverageorallpoten-

tialpathogens.Thebacterialspeciesmostcommonlyisolated

rom patients with RTIs includeStreptococcus pneumoniae,

Haemophilus infuenzae,andMoraxella catarrhalis.Inpatients

with acute bacterial rhinosinusitis (ABS) andacute bacterialexacerbationochronicbronchitis(ABECB)(tABle 1),these3

pathogensaccountorapproximately80%ocases,although

various other gram-positive and gram-negative species can

playanimportantrole.2-5Inpatientswithcommunity-acquired

pneumonia (CAP), studies o sputum cultures indicate that

S pneumoniaeinectionspredominate,althoughinectionwith

tra rcdai fr ai

wih c rirary rac ifci wih

ariab idicai f ra fair

Rymond S. Bsri, MD • Dvid a. Weind, MD • Greg l. ledgerwood, MD

K Points

o Tratmnt wit an appropriat

antimicrobia ant siniicant

dcrass t bactria burdn

and rducs t risk o a patint

prorssin to a mor svr

inction.

o Wn vauatin t us o

antibiotics, practitionrs soud

considr suc actors as t oca

rsistanc pattrns o common

rspirator patons, t

ikiood o inction wit a

rsistant oranism, and t

potntia or tratmnt aiur.

o Rcnt antibiotic us is a risk actor

or tratmnt aiur.

o For patints wit risk actors

prdictiv o tratmnt aiur,

β-actams (usua in combination

wit a β-actamas inibitor or a

macroid) and uoroquinoons

ar most common rcommndd.

Dicr: Dr Basri is a consutant or and srvs on t spakrs burau o Daiici-Sanko, Kin Parmacuticas, Novartis Parmacuticas,

Orto-McNi-Janssn Parmacuticas, Inc, Pizr Inc, and sanoi-avntis; is a sarodr o gnntc, Inc, Kin Parmacuticas, Mrck &

Co., Inc., Orto-McNi-Janssn Parmacuticas, Inc, Pizr Inc, Novartis Parmacuticas, and Scrin-Pou. Dr Wiand as srvd as a

consutant or and is on t spakrs burau o Abbott laboratoris, Orto-McNi-Janssn Parmacuticas, Inc, Pizr Inc, and sanoi-avntis. Dr

ldrwood as srvd as a consutant or Acon, AlTANA Parma, Astra-Znca, gaxoSmitKin, MdPoint, Inc, and Orto-McNi-JanssnParmacuticas, Inc; and is on t spakrs’ burau o Acon, Astra-Znca, and gaxoSmitKin.



Staphylococcus aureus, H infuenzae, and other

entericgram-negativesisalsocommon(tABle 1).

Atypicalpathogens,suchasMycoplasma pneumoni-

ae, Chlamydia pneumoniae,andLegionella pneu-

mophila, canalsoplayasignicantroleincausing

CAP.6,7

SelectionoappropriateempirictherapyorRTIsthereorerequiresagentswithactivityagainst

avarietyogram-positive,gram-negative,andatyp-

icalpathogensoradequatecoverage.

Local patterns omicrobial resistancemust

alsobeconsidered.Thisinormationmaybeavail-

able rom local hospital antibiograms or rom

surveillance studies.TheTrackingResistance in

theUS Today (TRUST) program is a continu-

ous surveillance program covering 10 consecu-

tiveyearsorespiratorypathogensintheUnited

States. Results rom this study have

shownasequentialincreaseinpenicil-

lin-andazithromycin-resistantS pneu-

moniae over successive respiratoryseasons.In2004and2005,28.8%o

S pneumoniaeisolateswereresistantto

azithromycin comparedwith23%in

1998and1999.8 Penicillin resistance

(minimum inhibitory concentration

[MIC]≥2mcg/mL) inS pneumoniae

has also remained at elevated levels,

with 15.6% o isolates exhibiting

high-levelresistanceand19.3%exhib-

iting intermediate resistancein2004-2005.8Resistancetolevofoxacinhas

beenrareandsporadicovertheyears,

withmorethan99%oS pneumoniae

isolates remaining susceptible to this

agentin2005.8Amongothercommon

respiratorytractpathogens,H infuen-

zae andM catarrhalis are requently

resistanttoβ-lactams,suchasampicil-

lin.9 Fortunately, these pathogens re-

main susceptible to other commonlyused agents, such as the macrolides

and fuoroquinolones. Nonetheless,

thesendingsemphasize thatantimi-

crobialresistancerates,particularlyor

S pneumoniae,areelevatedorcertainagentsand

mayaectappropriatetherapeuticselection.

Gidi ad rcdai

fr raPrimarycareprovidersacemanychallengesto

providingqualitycare,includingapatientpopu-

lationthatliveslongerbutotenexperienceslong-

termmanagementocomplicatedconditionsand

multiplecomorbidities.Theelevatedratesoan-

timicrobialresistancecanalsocomplicatetreat-

mentdecisions.Toimproveoverallpatientcare,

itisnecessarytoidentiypatientswithriskac-

tors that may predict treatment ailure and to

optimize treatment or these patients. Current

tReAtment FoR RtI pAtIents pRone to tReAtment FAIluRe

TaBlE 1

Bcteri distribution ssocited with RTIs

Paton ABS ABeCB CAP

Streptococcus pneumoniae 20-43 3-25 20-60

Haemophilus infuenzae 22-35 14-36 3-10

Moraxella catarrhalis 2-10 7-21 —

Staphylococcus aureus 0-8 3-20 3-5

Streptococcus spp 3-9 — —

Anarobs 0-9 — —

Pseudomonas spp — 1-15 —

Haemophilus parainfuenzae — 2-28 —

entrobactriaca spp — 5-33 —

Mycoplasma pneumoniae — — 1-6

Chlamydia pneumoniae — — 4-6

Legionella spp — — 2-8

gram-nativ bactria — — 3-10

pralnc (%)

ABeCB, acut bactria xacrbation o cronic broncitis; ABS, acutbactria rinosinusitis; CAP, communit-acquird pnumonia. RTI,rspirator tract inction.

AnonJB,etal.Otolaryngol Head Neck Surg.2004;130(suppl1):1-45;BalterMS,etal.Can Respir J.2003;10(supplB):3B-32B;BartlettJG,etal.N Engl J Med.1995;333:1618-1624;MandellLA,etal.Clin Infect Dis.2007;44(suppl2):S27-S72;NiedermanMS,etal.Am J Respir Crit Care Med.2001;163:1730-1754.



management guidelinesprovide some direction

inidentiyingtheseat-riskpatientsandoerrec-

ommendationsorantimicrobialselection.

liiai f aiicrbia

gidi rcdaiTheantimicrobialtreatmentrecommendationsre-

portedinthisarticleandsummarizedintABle 2

aretakenromguidelinesdevelopedbyconsen-

suscommitteesophysiciansconvenedbypro-

essional organizations interested in the study

andtreatmentoABS,ABECB,andCAP.Where

possible, these recommendations are based on

dataromrandomizedcontrolledtrials,butthey

also take into account inormation available

romsmalleropentrials(inABECBandCAP).In

addition, some recommendations arebased on

TaBlE 2

Synthesis o tretment recommendtions or aBS, aBECB, nd CaP

in ptients with vribes ssocited with tretment iure

low risk At risk low risk At risk low risk At risk

Rik

tramn

ABs ABeCB CAp

Mid disas and

no rcnt

antimicrobia us

Mid disas

wit rcnt

antimicrobia us

or

mid disas

and worsnin

atr 72 on

antibiotics, or

modrat disas

Mid to modrat

impairmnt o

un unction,

<4 xacrbations

pr yar, no

sinicant cardiac

disas

Poor undryin

un unction,

sinicant

comorbidity

(iscmic

art disas,

constiv art

aiur),

≥4 xacrbations

pr yar, us o

om oxyn,cronic ora

stroid us,

antibiotic us in

t past 3 monts

Prviousy

aty, no

risk actors or

dru-rsistant

S pneumoniae

Prsnc o

comorbiditis

(cronic art,

un, ivr, or rna

disas), diabts

mitus, acooism,

mainancis,

aspnia, immuno-

supprssant

conditions or us

o immunosupprs-sin drus. Us o

antimicrobias witin

prvious 3 monts,

a (< 2 or >65 yr),

xposur to cid in

a day-car cntr.

Amoxiciin,

amoxiciin/

cavuanat,

or cpaosporin

(cpodoxim,

curoxim,

cdinir),TMP-SMX,†

doxycycin,†

macroid,† or

titromycin†

Rspiratory

fuoroquinoon,*

amoxiciin/

cavuanat,

ctriaxon, or

combination o

ts drus.Rspiratory

fuoroquinoon†

or combination

o riampicin pus

cindamycin†

Macroid,

cpaosporin,

amoxiciin,

doxycycin, or

TMP-SMX

Fuoroquinoon

or β-actam/

β-actamas

inibitor

Macroid or

doxycycin

β-actam pus

a macroid,

or doxycycin,

or antipnumo-

cocca fuoro-

quinoon‡

ABeCB, acut bactria xacrbation o cronic broncitis; ABS, acut bactria rinosinusitis; CAP, communit-acquird pnumonia;TMP-SMX, trimtoprim-suamtoxazo.

*T rspirator fuoroquinoons incud mifoxacin, vofoxacin, and moxifoxacin.†In β-actam–aric individuas.‡Fuoroquinoon wit activit aainst S pneumoniae, incudin mifoxacin, vofoxacin, and moxifoxacin.

AnonJB,etal.Otolaryngol Head Neck Surg. 2004;130(suppl1):1-45;BalterMS,etal.Can Respir J.2003;10(supplB):3B-32B;MandellLA,etal.Clin Infect Dis.2007;44(suppl2):S27-S72;NiedermanMS,etal.Am J Respir Crit Care Med.2001;163:1730-1754.



the bacteriologicandclinicalecacyoantibi-

otics derived rom the mathematical modeling

o the disease using actors such as pathogen

distribution, resolution rates in the absence otreatment,andinvitromicrobiologicactivity(in

ABS).Assuch,datawerenotalwaysavailablein

amannerthatallowedorthecalculationothe

numberneededtotreat(NNT).

Ac bacria rhiiiiAntibiotic therapy or ABS seeks to eradicate

bacterial pathogens rom the site o inection,

helpingtodecreasesymptomdurationandallow-ingpatientstoquicklyresumenormaldailyactivi-

ties.3 Eradicationo bacterial pathogens returns

the sinuses to health, prevents severe complica-

tions,suchasmeningitisandbrainabscess,and

decreasesthelikelihoodochronicdisease. 3

Whenabacterialpathogenissuspected,theSi-

nusandAllergyHealthPartnershipGuidelinessug-

gestantimicrobialtherapybasedonthepatient’s

historyorecentantibioticuse,stratiyingpatients

accordingtoantibioticexposurewithintheprevious4to6weeks.3Diseaseseverityshouldbeassessed.3

Patientswithmilddiseaseandnorecent antimi-

crobial exposurecanbetreatedwithamoxicillin

(±clavulanate)oracephalosporin.However,pa-

tientswhohavemoderatedisease,orthosewith

milddiseasewhohavehadarecentcourseoanti-

biotics,shouldbetreatedwitharespiratoryfuoro-

quinolone(levofoxacinormoxifoxacin),high-dose

amoxicillin/clavulanate,orcetriaxone,asindicat-

edintABle 2.3,10

Patientswithcomplicatingactors,suchasanimmunodeciencyorapotentialinec-

tion with penicillin-resistant S pneumoniae, can

alsobetreatedwithhigh-dose(4g/day)amoxicillin

(±clavulanate,250mg/day)(tABle 2).3

Ithepatientdoesnotrespondtotheantimi-

crobialtherapyater72hours,re-evaluationora

switchtoanalternateantimicrobialtherapyisin-

dicated.Theclinicianshouldconsiderthecover-

agelimitationsotheinitialagent.3Patientswho

continue to be symptomatic ater appropriate

antibiotictherapyneedurtherevaluationinaddi-

tiontoantibiotictherapy.Acomputedtomography

scan,beropticsinusendoscopy,orsinusaspira-

tionorculturemaybenecessary.3

Ac bacria xacrbai f

chric brchiiChronicobstructivepulmonarydisease(COPD)is

characterizedbypotentiallypathogenicbacteria,

withtitersthatincreaseexponentiallyduringan

exacerbation.4 Treatment with appropriate an-

tibiotics signicantly decreases bacterial airway

burden,suggestingthatappropriateantibioticusecanreducethesymptomsoABECBanddecrease

the risk o progression to amore severe inec-

tion.1A pivotal studybyAnthonisen illustrated

thatABECB patients presenting withat least 2

o3symptoms(increasedsputumproduction,in-

creasedsputumpurulence,andincreaseddyspnea)

benetedromantimicrobialtherapy.11

TheCanadianThoracicSocietyandtheCana-

dian InectiousDisease Societydevelopedguide-

lines using clinical eatures to identiy high-riskpatientsandguideantibioticchoicesorthoseat

riskotreatmentailure.12Low-riskpatientswho

requireantibiotic therapy typicallypresentwith

increasedcoughandsputum, sputumpurulence,

andincreaseddyspneabutdonothaveadditional

risk actors ortreatment ailure.Thesepatients

maybetreatedwithavarietyorst-lineagents,in-

cludingmacrolides,amoxicillin,orcephalosporins

(tABle 2).10,12High-riskABECBpatientscommon-

lypresentwithadditionalriskactors,suchaspoorunderlyinglungunction(FEV

1<50%predicted)

orcardiacdisease,experience4ormoreexacerba-

tionsperyear,usehomeoxygen,takeoralsteroids

chronically,orhavetakenanantibioticinthepast

3months.Forthesepatients,treatmentshouldbe

directedagainstpotentialresistantorganismsand

should includea respiratoryfuoroquinolone or

amoxicillin/clavulanate(tABle 2).10,12Inaddition,

orthosewhoailinitialtherapy,itmaybeadvis-

abletochangetheclassoantibiotic.12

tReAtment FoR RtI pAtIents pRone to tReAtment FAIluRe



Ciy-acqird iaCAPisacommonandseriousillness.Inpatients

with severe disease who require hospitaliza-

tion,mortalityratesrangerom14%to22%.7,13S pneumoniaeisthemostcommonpathogenin

patientswithCAP,ollowedbyH infuenzaeand

M catarrhalis.6,13TheAmericanThoracicSociety

and the Inectious Diseases Society o America

havedevelopedjointguidelinesorthetreatment

o CAP outpatients, including management o

high-risk patients and patients with variables

indicativeotreatmentailure.6,14Amacrolideor

doxycyclineisrecommendedorotherwisehealthy

patientswholackcomorbidconditionsandwhohave not received antibiotic therapy in the last

3months. Forpatients with previousantibiotic

exposureorwithpotentialexposuretoresistant

pathogens, the guidelines recommend treatment

witharespiratoryfuoroquinolonealone,orex-

ample, levofoxacin,gemifoxacin,ormoxifoxa-

cin,*oranadvancedmacrolide(azithromycinor

clarithromycin)plusaβ-lactamsuchashigh-dose

amoxicillin(±clavulanate),alternativestowhich

includecetriaxone,cepodoxime,andceuroxime(tABle 2).6,10,14,15 Either an advanced macrolide

plusaβ-lactamorarespiratoryfuoroquinolone

isrecommendedorpatientswithadditionalrisk

actors or poor outcomes, including comorbid

conditionssuchasCOPD,diabetes,renalailure,

orcongestiveheartailure(tABle 2).14,15

CciRespiratorytract inectionsinpatientsatrisko

poor outcomes are unlikely to resolve without

treatment, or to tolerate treatment ailure well.

Treatmentwithanappropriateantimicrobialagent

signicantly decreases the bacterial burden, and

mayreducetheriskothepatientprogressingto

amoresevereinection.1Whenmakingtreatmentchoices,itisimportantorpractitionerstoconsid-

erthemostcommonlyencounteredpathogensas

wellasthepotentialorresistancetoensurethat

theappropriateantimicrobialisprescribed.

Treatment guidelines rom several specialty

societies provide recommendations or initial

treatmentselectionorthemostcommonRTIs.

Forpatientswithcomplicationsthatincreasethe

probabilityotreatmentailure,β-lactams(usu-

allyincombinationwithaβ-lactamaseinhibitorand/oramacrolide)andrespiratoryfuoroquino-

lonesaremostcommonlyrecommended.3,6,12,14n

1. AdamsSG,AnzuetoA.Antibiotictherapyin acute exacerbations o chronic bronchitis.

Semin Respir Inect.2000;15:234-247.2. Jacobs MR. Streptococcus pneumoniae:epidemiology and patterns o resistance. Am J Med.2004;117(suppl3A):3S-15S.3. AnonJB,JacobsMR,PooleMD,etal,ortheSinusandAllergyHealthPartnership.An-timicrobialtreatmentguidelinesoracutebac-terial rhinosinusitis.Otolaryngol Head NeckSurg.2004;130(suppl1):1-45.4. SethiS.Inectiousexacerbationo chronicbronchitis:diagnosisandmanagement. J Anti-microb Chemother.1999;43(supplA):97-105.5. Ball P. Epidemiology and treatment ochronicbronchitisanditsexacerbations.Chest.1995;108:43S-52S.6. Niederman MS, Mandell LA, AnzuetoA, et al. Guidelines or the management oadults with community-acquired pneumonia:

diagnosis,assessmento severity,antimicrobialtherapy,andprevention.Am J Respir Crit Care

Med.2001;163:1730-1754.7. Bartlett JG,DowellSF,MandellLA,etal.Practiceguidelinesorthemanagementocom-munity-acquired pneumonia in adults. ClinInect Dis.2000;31:347-382.8. Ortho-McNeil,Inc.TRUST9.Dataonle.Raritan,NJ:2005.9. Brown SD, Farrell DJ. Antibacterial sus-ceptibility among Streptococcus pneumoniaeisolatedrompaediatricandadultpatientsaspartothePROTEKTUSstudyin2001-2002. J Antimicrob Chemother. 2004;54(suppl 1):i23-i29.10.BruntonS,CarmichaelB,FitzgeraldM,etal. Community-acquired bacterial respiratorytractinections. J Fam Pract. 2005;54:255-262.11.AnthonisenNR,ManredaJ,WarrenCPW,et al. Antibiotic therapy in exacerbations o

chronic obstructive pulmonary disease. AnnIntern Med.1987;106:196-204.

12.Balter MS, La Forge J, Low DE, et al.Canadian guidelines or the management oacuteexacerbationsochronicbronchitis.CanRespir J.2003;10(supplB):3B-32B.13.Mandell LA. Community-acquired pneu-monia: etiology, epidemiology, and treatment.Chest. 1995;108:35S-42S.14.MandellLA,WunderinkRG, AnzuetoA,et al. InectiousDiseases SocietyoAmerica/ American Thoracic Society Consensus guide-linesonthemanagementocommunity-aquiredpneumoniainadults.Clin Inect Dis.2007;44(suppl2):S27-S72.15. MandellLA,BartlettJG,DowellSF,etal.Updateo practiceguidelinesorthe manage-ment o community-acquired pneumonia inimmunocompetent adults. Clin Inect Dis.2003;37:1405-1433.

Reerences

*Currnt uidins do not incud atifoxacin bcaus toxicit issus av promptd witdrawa o tis ant rom t markt.



Fbruar 2008

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