8/11/17 Introduction 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 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 Up to 5 members: $599/year 50-60 podcasts/year plus 30+ hours of webinars! $199/year 40+ hours of RACE-CE Up to 10 members: $999/year > 10 members: Ping us 1
8/11/17 VETgirl online veterinary CE video archives Download our VETgirl podcasts Find VETgirl on social media! How to get your VETgirl CE certificate! n n n n n Introduction Katrina Viviano, DVM, PhD, DACVIM, DACVCP Type in questions Emailed to you 48 hours after the webinar Active participation = no quiz Watching video later, must complete quiz n ELITE members only Email / contact with ANY questions n garret@vetgirlontherun.com n justine@vetgirlontherun.com Lecture Outline Current challenges use in CA Antibiotic stewardship Evidence-based prescribing Antibiotic Antimicrobial update 2
MDR Bacterial Isolates Current Challenges MRSP ESBL E. coli VRE Pseudomonas aeruginosa HUMAN and VETERINARY MEDICINE Harrison and Lederberg, 1998 Differences: Antibiotic Use Guardabassi and Prescott, 2015 Differences: Antibiotic Used Human Veterinary Human FQ SA Veterinary 80% 59% pen/ ceph. 8% 75% amox/clav/ 1 st gen.ceph. other other 10% FQ Weese et al, 2012 Ferran et al, 2016 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 UWVC ESBL Isolates Year Total ESBLs 2014 15 15/393 E. coli E. cloacae P. mirabilis P. aeruginosa 2015 13 10/401 2/81 1/92 2016 12 9/386 1/15 1/93 1/117 3
UWVC ESBL Isolates 11 yr old, FS, Am. Shorthair Year Urine ESBLs E. coli 2014 11 (15) 11/192 2015 9 (10) 9/192 2016 6 (9) 6/234 Dx pyelonephritis (hx CKD, IRIS stage III) Tx Clavamox 1/2017 UWVC 1/2017 BUN 221, creatinine 9, PO 4 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 Antibiotic use in CA Urine > 100,000 CFU/mL Enterococcus faecium Vancomycin resistant; susceptible nitrofurantoin Feels well with stable creatinine 2.3 Fowler et al, 2016 Gaps Antimicrobial Rx Vet Med Antimicrobial Rx Over-prescribing Documentation /Justification Inappropriate Selection Education 4
UWVC Antimicrobial Use 2009-2011 Antimicrobial Stewardship O CR C/S AS D 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) Weese, 2006 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 DVMs Attitudes - ASP AVMA, 2015 NCSU VMTH and AVMA members NCSU AVMA Concern ABX resistance 59% 45% Guidance - Choosing ABX - Duration tx Lack awareness guidelines 77% 83% 88% 5
Antibiotic Stewardship Education RATIONAL USE Evidence-Based Rxs Resources Documentation 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) Urinary Tract Infections Uncomplicated Dogs Westropp et al, 2012 Clare et al, 2014 UTI n=68; FS 57/MN 11 Bacterial cystitis n=38, FS Random/blinded Multicenter (5) Placebo-controlled Duration Therapy ABX enro x 3 d vs amox/clav x 14 d TMS x 3 d vs ceph x 10 d Cure rates 7 days post ABX 3 days; 4 and > 30 days post ABX E AC TMS C Microbiologic 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% 6
Bacterial Pneumonia Viitanen et al, 2017 Bacterial Pneumonia Viitanen et al, 2017 Dogs- bacterial pneumonia Dogs- bacterial pneumonia Died (1) Euthanized (1) N=19 Died (1) Euthanized (1) N=19 Tx ABX Tx ABX Tx ABX Tx ABX discretion clinician CRP normalized + 7 days discretion clinician CRP normalized + 7 days N=9 N=8 N=9 N=8 35 days Median Tx 21 days Monitor CRP, CXR, clinical signs Monitor CRP, CXR, clinical signs MOA inhibits topoisomerase II/IV PK/PD low MIC (FQ) Antimicrobial Update Cats Approval wounds/abscesses Lister et al, 2007 Hartmann et al, 2008 Cats: Bacteriuria LUTS Cats URI 30 25 20 15 10 Post Tx NG Post Tx Bacteriuria All cats resolved clinical signs Mycoplasma PCR neg. both gps Chlamydia - prado PCR positive (4) doxy prado 5 0 (n= 27) Amox/clav (n = 28) Doxycyline (n = 23) 7
Rhinitis HS cats Spindel et al, 2008 Amox 10/15 vs prado (low) 11/15 vs prado (high) 11/12 Dowers et al, 2009 Cats exp. infected M. haemofelis Cefovecin 3 rd 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 Litster et al, 2012 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 cefovecin A/C doxy 8
Lawrence et al, 2013 Lawrence et al, 2013 Cefovecin Cefovecin Healthy dogs (n=14) impact fecal flora Single 8 mg/kg SQ (n=7) vs no tx (n=17) E. coli Cefovecin-resistant E. coli Weese et al, 2013 KuKanich et al, 2014 Minocycline Similar spectrum activity doxycycline MRSP Inducible resistance assay/pcr Tet(M) R all tetracyclines Tet (K) no minocycline R Tetracycline R minocycline R Minocycline Side Effects Esophageal strictures? Bioavailability Dogs concurrent sucralfate Sig. reduction in PO bioavailability KuKanich and KuKanich, 2015 KuKanich et al, 2011 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 Nitrofurantoin Lower urinary antiseptic PK Half-life 20 minutes Peak urine conc. 20 min. 50% excreted unchanged in urine Poor tissue conc. 9
Hubuka and Boothe, 2011 Fukata et al. 2008 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 MIC 90 2 µg/ml; MIC 50 1 µg/ml 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 Bacteria/Antibiotic Resistance Drug Discovery Antibiotic Stewardship Education Bacteria Increasing rate of resistance to conventional antibiotics Development of novel-acting antibiotics Resources RATIONAL USE Documentation VETgirl Questions? 10
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