ASNP17vgwn - VETgirl
Transcript of ASNP17vgwn - VETgirl
8/11/17
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Antimicrobials: An UpdateKatrina Viviano, DVM, PhD, DACVIM, DACVPVETgirl WebinarAugust 17, 2017
GarretPachtinger,VMD,DACVECC
COO,VETgirl
Introduction
JustineA.Lee,DVM,DACVECC,DABTCEO,VETgirl
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Katrina Viviano, DVM, PhD, DACVIM, DACVCP
Introduction Lecture Outline
�Current challenges�Antibiotic use in CA�Antibiotic stewardship�Evidence-based prescribing
�Antimicrobial update
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Current Challenges
MDR Bacterial Isolates
�MRSP�ESBL E. coli�VRE�Pseudomonas aeruginosa
HUMAN and VETERINARY MEDICINE
Differences: Antibiotic Use
Human Veterinary
80%
Harrison and Lederberg, 1998
Differences: Antibiotic Used
Human SA Veterinary
other
pen/ceph.
FQ
amox/clav/1st gen.ceph.
other
FQ
75%59%
8%
10%
Guardabassi and Prescott, 2015
MRSP� Dogs
� Link between antimicrobial therapy within 30 days and MSRP infections
� S. psuedintermedius� In vitro susceptibility may not be reflective of
susceptibility if organisms present at biofilm
Weese et al, 2012Ferran et al, 2016
UWVC – ESBL Isolates
Year TotalESBLs
E. coli E. cloacae P. mirabilis P. aeruginosa
2014 15 15/393
2015 13 10/401 2/81 1/92
2016 12 9/386 1/15 1/93 1/117
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UWVC – ESBL Isolates
Year Urine ESBLs E. coli
2014 11 (15) 11/192
2015 9 (10) 9/192
2016 6 (9) 6/234
11 yr old, FS, Am. Shorthair� Dx – pyelonephritis (hx CKD, IRIS stage III)
� Tx – Clavamox 1/2017
� UWVC 1/2017� BUN 221, creatinine 9, PO4 24.6� Urine > 100,000 CFU/mL Proteus mirabilis� Rx – marbofloxacin� Culture neg. on ABX (~10 days) – creatinine 2.5
11 yr old, FS, Am. Shorthair� Urine > 100,000 CFU/mL MRSP
� Following a 4 wk course of marbofloxacin� Rx chloramphenicol� Clinically ill with increasing creatinine 3.9� Urine culture neg. on ABX (~ 3 wks)
� Urine > 100,000 CFU/mL Enterococcus faecium� Susceptible – gentamicin, nitrofurantoin, tetracycline� Clinically doing well with stable creatinine 2.6
� Urine > 100,000 CFU/mL Enterococcus faecium� Vancomycin resistant; susceptible – nitrofurantoin� Feels well with stable creatinine 2.3
Antibiotic use in CA
Gaps Antimicrobial Rx – Vet Med
�Over-prescribing�Documentation /Justification �Inappropriate Selection�Education
Antimicrobial Rx
Fowler et al, 2016
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UWVC – Antimicrobial Use2009-2011
O CR C/S AS D
Antimicrobial Stewardship
Antimicrobial Stewardship�Reduce inappropriate use
�Develop guidelines for prescribers�Max health benefits�Maintain clinical efficacy�Min. resistance�Adverse effects
ASP – Veterinary Medicine
�2013 AVMA committee�Dev. resources/programs ASP
�Not widely adapted/used
SA VMTH (Guelph)
� Antibiotic use/impact antimicrobial guidelines
� Dogs/cats Rx antibiotics – 1995-2004� Introduction ABX guidelines 2001� Post-guidelines – overall decrease antibiotic use
� Decrease – pen./ceph. and FQ� Decrease in carapenems
Weese, 2006
DVMs Attitudes - ASP
�NCSU VMTH and AVMA members
AVMA, 2015
NCSU AVMAConcern ABX resistance 59% 45%Guidance- Choosing ABX- Duration tx
77%83%
Lack awareness guidelines 88%
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Antibiotic Stewardship
Resources
Education
Documentation
RATIONAL USE Evidence-Based Rxs
Evidence-Based Rx
�Evidence bacterial infection�Site of Infection�Understanding Drugs�C/S testing�Patient specific factors
Consensus Guidelines
�General – antibiotic use dog/cats
�UTI (2011)�Superficial pyoderma (2014)�Respiratory tract (2017)�MRSP (2017)
Duration Therapy
Urinary Tract InfectionsWestropp et al, 2012 Clare et al, 2014
UncomplicatedDogs
UTI n=68; FS 57/MN 11
Bacterial cystitis n=38, FS
Random/blinded Multicenter (5) Placebo-controlled
ABX enro x 3 d vsamox/clav x 14 d
TMS x 3 d vsceph x 10 d
Cure rates 7 days post ABX 3 days; 4 and > 30 days post ABX
E AC TMS CMicrobiologic 77% 81% 4d post 59% 36%
> 30d post 44% 20%Clinical 89% vs. 88% 3d 89% 94%
4d post 85% 72%> 30d post 50% 65%
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Bacterial Pneumonia
Dogs- bacterial pneumonia
Tx ABX discretion clinician
Tx ABX CRP normalized + 7 days
N=19
N=9
Monitor – CRP, CXR, clinical signs
N=8
Viitanen et al, 2017
Died (1)Euthanized (1)
Bacterial Pneumonia
Dogs- bacterial pneumonia
Tx ABX discretion clinician
Tx ABX CRP normalized + 7 days
N=19
N=9
Monitor – CRP, CXR, clinical signs
N=8
Median Tx 35 days 21 days
Died (1)Euthanized (1)
Viitanen et al, 2017
Antimicrobial Update
Pradofloxacin
�MOA – inhibits topoisomerase II/IV�PK/PD – low MIC (FQ)
�Cats�Approval wounds/abscesses
Pradofloxacin
�Cats: Bacteriuria LUTS
Lister et al, 2007
0
5
10
15
20
25
30
Pradofloxacin (n= 27) Amox/clav (n = 28) Doxycyline (n = 23)
Post Tx NG Post Tx Bacteriuria
Pradofloxacin
Cats URI� All cats resolved
clinical signs� Mycoplasma PCR
neg. both gps� Chlamydia - prado
PCR positive (4)
Hartmann et al, 2008
pradodoxy
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PradofloxacinRhinitis – HS cats � Amox 10/15 vs prado (low) 11/15 vs prado (high) 11/12
Spindel et al, 2008
Pradofloxacin�Cats – exp. infected M. haemofelis
Dowers et al, 2009
PradofloxacinCefovecin�3rd generation cephalosporin
�Poor – P. aeruginosa, �None – Enterococcus spp.
�Half-live 7 days� Tx conc. urine and skin – 14 days
�Approved tx�Pyoderma, wounds, abscesses�Urinary tract
Cefovecin
�Murphy et al, 2012� Reported uses in cats� Sig. use in tx lower UTI and URI� URI – Mycoplasma, Bordetella, Chlamydia
�Burke et al, 2016� UK cats – describe clinical use of cefovecin� Skin (48%); Urinary (14%); Respiratory (10%)
Cefovecin� URI shelter cats – doxy. amox/clav. had
higher efficacy to cefovecin
Litster et al, 2012
doxy
A/C
cefovecin
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Cefovecin� Healthy dogs (n=14)– impact fecal flora� Single 8 mg/kg SQ (n=7) vs no tx (n=17)
Cefovecin-resistant E. coliE. coli
Lawrence et al, 2013
Cefovecin
Lawrence et al, 2013
Minocycline
�Similar spectrum activity doxycycline
�MRSP� Inducible resistance assay/PCR
�Tet(M) – R all tetracyclines�Tet (K) – no minocycline R
�Tetracycline R ≠ minocycline R
Weese et al, 2013
Minocycline �Side Effects
� Esophageal strictures?
� Bioavailability� Dogs – concurrent
sucralfate� Sig. reduction in
PO bioavailability
KuKanich et al, 2014
Chloramphenicol
�Use based on C/S testing – MDR isolates� MRSP, prostatitis, recurrent UTI
�CYP 450 enzyme inhibition (CYP2B11)� Healthy greyhounds � Significant increase methadone PO
�AUC: 90-fold�Cmax: 8-fold
� Others - propofol
KuKanich and KuKanich, 2015KuKanich et al, 2011
Nitrofurantoin
�Lower urinary antiseptic
�PK�Half-life 20 minutes�Peak urine conc. 20 min.�50% excreted unchanged in urine
�Poor tissue conc.
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Fosfomycin
�Broad spectrum antibacterial activity
�Low MW, water soluble, low protein binding� Good penetration tissues/fluids
� In vitro susceptibility E. coli� Urinary isolates - dogs and cats� MIC90 2 µg/mL; MIC50 1 µg/mL
Hubuka and Boothe, 2011
Fosfomycin�Nephrotoxicity
�Young cats�Increased BUN/creatinine
�Young and adult cats�Renal bx – tubular necrosis�Glomerular and basement membrane normal�Neither group – systemically ill
�Dogs - no biochem or morphological changes
Fukata et al. 2008
Bacteria/Antibiotic Resistance
Increasing rate of resistance to conventional
antibiotics
Development of novel-acting
antibiotics
Bacteria
Drug Discovery
Antibiotic Stewardship
Resources
Education
Documentation
RATIONAL USE
Questions?
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