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8/11/17 1 Antimicrobials: An Update Katrina Viviano, DVM, PhD, DACVIM, DACVP VETgirl Webinar August 17, 2017 Garret Pachtinger, VMD, DACVECC COO, VETgirl Introduction Justine A. Lee, DVM, DACVECC, DABT CEO, VETgirl Introduction VETgirl…on the run! The tech-savvy way to get RACE-approved, online veterinary CE! A subscription-based podcast and webinar service offering veterinary RACE-approved CE 50-60 podcasts/year plus 30+ hours of webinars! $199/year 40+ hours of RACE-CE Up to 5 members: $599/year Up to 10 members: $999/year > 10 members: Ping us

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8/11/17

1

Antimicrobials: An UpdateKatrina Viviano, DVM, PhD, DACVIM, DACVPVETgirl WebinarAugust 17, 2017

GarretPachtinger,VMD,DACVECC

COO,VETgirl

Introduction

JustineA.Lee,DVM,DACVECC,DABTCEO,VETgirl

Introduction VETgirl…on the run!� Thetech-savvywaytogetRACE-approved,onlineveterinaryCE!

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Upto10members:$999/year

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8/11/17

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VETgirl online veterinary CE video archives

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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?

VETgirl

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