Antimicrobial use and resistance in companion animals · Research examining companion AMR Search of...

transcript

Antimicrobial use and resistance

in companion animals

Michele Anholt DVM PhD

Manager One Health at UCalgary

Office of the VP (Research)

rmanholt@ucalgary.ca

Danny Joffe DVM Dipl. ABVP Emeritus Canine and Feline PracticeVice president, Medical Operations

VCA Canada

Daniel.Joffe@vca.com

October 6, 2020

Presenter Disclosure

Michele and Danny have no potential conflicts of interest.

Michele Anholt, rmanholt@ucalgary.ca

Danny Joffe, Daniel.Joffe@vca.com

One Health and AMU/AMR in companion animals

The human- animal bond

Mutually beneficial and dynamic

relationship between people and animals

that is influenced by behaviours essential

to the health wellbeing of both (AVMA)

59% households owned pets in US (2018)

Dogs (38%), Cats (25%)

Positive aspects for people and animals

Negative aspects

Zoonoses

Bacteria, viruses, fungi, and parasites1

Imported exotic animals and imported

abandoned pets2

Potential reservoirs of antimicrobial resistant

bacteria or their resistance genes

Generally considered low overall but ~2/3 are

not reportable diseases so poor

understanding of frequency

Increased risk in young, elderly, pregnant

women, and immunocompromised

Opportunities for transmission

Dogs (45%) and cats (60%) allowed on

Dogs (18%) and cats (30%) sleep on beds

Cats (45%) allowed to jump onto kitchen

40% to 50% owners allow face licking

Allowing pets to lick human wounds

Bites and scratches

13/19 dogs tested were positive for

Enterobacteriaceae on fur or footpads1

1. Overgauw PA, et al. https://doi.org/10.1016/j.vetpar.2009.03.044

AMR and AMU Surveillance in Pets

Surveillance is the ongoing, systematic collection,

analysis, and interpretation of health-related data essential

to planning and implementation (CDC)

Most of non-human AMU and AMR monitoring is focused on

food-producing animals

Greater recognition that all uses of antimicrobials exert

selective pressure on bacteria and transmission possible

between the environment and animal and human

populations

However, there is no AMR surveillance of pets anywhere in

the world and variable levels of AMU surveillance1

Research examining companion AMR

Search of English articles published in Web of Science past 5 years:

Companion animals and antimicrobial resistance, returned 242 articles

47 articles examined AMR of skin, wound and soft tissue pathogens

Staph. aureus; Staph. intermedius; Streptococcus species

22 articles focused on methicillin-resistant strains of Staph. spp.

98 articles examined Enterobacteriaceae family

Commensals, especially E. coli = good indicator species for the effects of

selective pressure of AMU on the microbiome in general and pathogenic

bacteria in particular

Klebsiella pneumoniae (11 articles) and Acinetobacter spp. (4 articles)

Ubiquitous organisms able to acquire MDR and spread easily1, 2

Important nosocomial infections in companion animal hospitals

Studies of AMU in Pets

Understanding clinical management of common problems necessary to:

Provide exposure information to understand AMR trends

Identify problems in prescribing practices

Identify clinical presentations where evidence-based practice guidelines would

be beneficial

Currently our understanding of AMU in pets is based on surveys or

medical record extraction

Little ongoing monitoring of AMU by companion animal veterinarians

In Canada data collected by Canadian Animal Health Institute, not divided by

species

Weight of active substance, not defined daily dosages animal (DDDA)

What do we know about AMU in

Companion Animals?

Studies in companion animals have shown high use of

broad-spectrum antibiotics and antibiotics important for

human medicine

Especially with the following presentations:

Skin and soft tissue

Gastrointestinal

Urinary tract

Respiratory tract

Principles of antimicrobial prescribing

Patient

Known or likely causative organism

Risk of bacterial resistance with repeated courses

Pharmacology

Bacteriostatic vs bactericidal – life threatening / immune

competency of patient

Spectrum of activity – narrow to avoid super infection

Dose and route → convenience

Potential for side effects/interactions

Principles of AM prescribing

Patient

Known or likely causative organism???

Pharmacology

12 companion animal practices in Calgary

Extracted 447,658 medical records dated 1/1/2007 to

12/31/2010

Text mining to identify 15,928 cases of diarrhea

How were these cases managed?

Principles of AM prescribing

Patient

Known or likely causative organism

Pharmacology

7400 (46.5%) of the diarrhea cases had

antimicrobials administered or prescribed Category I (Very High Importance)

3rd and 4th generation cephalosporins (1.7%)

Fluorquinolones (2.7%) TOTAL CATEGORY I = 87.1%

Nitroimidazoles (78.6%)

Penicillin B-lactam inhibitors (1.9%)

Category II (High Importance)

1st and 2nd generation cephalosporins

Lincosamides (5.8%)

Macrolides(1.0%) TOTAL CATEGORY II = 20.5%

Penicillins (10.9%)

Trimethoprim-Sulpha (1.1%

Category III (Medium importance)

Chloramphenicol (0.1%)

Sulphonamides (0.8%) TOTAL CATEGORY III = 1.0%

Tetracycline (0.1%)

Time series of the proportion of enteric cases treated with

any antimicrobial, nitroimidazole class and penicillin class.

January 2007 January 2008 January 2009 January 2010

All antimicrobials Nitroimidazoles Penicillins

p = 0.012

p = 0.002

p = 0.004

A more recent study…

Buckland EL, et al. (2016) Characterisation of AMU in cats and dogs

attending UK primary care companion animal practices, Vet Record

Medical record extraction from 374 practices using VetCompass for 2

years (2012-2014)

Records from 963,463 dogs and 594,812 cats

25% of dogs and 21% of cats had at least on antimicrobial prescription

In dogs, 60.3% of prescriptions were agents classified by WHO1 as critically

important AM agents (CIA’s) to human medicine; 6.4% were of highest

importance

In cats, 80.9% of prescriptions were agents classified by WHO1 as critically

important AM agents (CIA’s) to human medicine; 34.6% were of highest

importance

Cross-sectional study

Veterinarians contacted in Belgium, Italy, and Netherlands

50 dogs and 50 cats were randomly selected in each country

Criteria: Healthy, 1 pet/owner, no enteric symptoms, able to provide AMU for the previous year

Treatment Incidence = treatment duration/number of days at risk (365) X LA factor (treatment

interval) X100 AAR

Fresh fecal sample from each animal

Antimicrobial resistance proportion (%) among E. Coli isolates from 93% of fecal samples,

n = 137 cats and 148 dogs

AMP, ampicillin; FOT, cefataxime; TAZ, ceftazidime; MERO, meropenem; CIP, ciprofloxacin;

NAL, nalidixic acid; AZI; azithromycin; CHL, chlamphenicol; COL, colistin; GEN, getacimin;

SMX, sulfamethoxazole; TMP, trimethoprim, TET, tetracycline, TGC, tigecycline

Antimicrobial resistance proportion (%) among E. coli isolates from fecal samples,

n = 137 cats and 148 dogs (E. coli was isolated from 93% of fecal samples)

NAL, nalidixic acid; AZI; azithromycin; CHL, chloramphenicol; COL, colistin; GEN, gentacimin;

OR of finding a resistant E.coli in the treated vs untreated = 1 (95% CI: 0.5 – 1.0)

Antimicrobial resistance proportion (%) among E. coli isolates from fecal samples,

n = 137 cats and 148 dogs (E. coli was isolated from 93% of fecal samples)

NAL, nalidixic acid; AZI; azithromycin; CHL, chloramphenicol; COL, colistin; GEN, gentacimin;

OR of finding a resistant E.coli in the treated vs untreated = 1 (95% CI: 0.5 – 1.0)

What reasons may there be that the researchers did not find an association

between exposure and outcome?

Harold—5 year old M(N) Boxer

Chin Pyoderma—2008

Cephalexin 30 mg/kg BID for two weeks

Rechecked in 14 days, minimal improvement

Dispensed enrofloxacin 5 mg/kg BID

Missed recheck appointment 2 weeks later, lost contact with client

Harold—5 year old M(N) Boxer

Chin Pyoderma—2020

Do cytology of pustule to confirm bacterial disease

Would treat topically with chlorhexidine scrub 5-10 min contact time

daily for a week then every third day

Recheck 2 weeks later—100% cure

Antimicrobial resistance is the new

reality

Antibiotic use is a privilege

In Alberta, the Veterinary Prescribing Act allows

veterinarians to prescribe, dispense, compound and sell

pharmaceutical.

A very broad scope

This is a privilege

Abuse of lack of vigilance could put this privilege at risk

Bacterial infections are

seen daily in general

veterinary practice

Pyoderma

Otitis

Cystitis

Bite wounds

Respiratory infections

GIT infections

Treating bacterial infections

“Olden Days’

Repeated courses of treatment

“Big guns”

Combinations of antimicrobials

together

Rarely performed cultures

Treating bacterial infections

We need to rethink our approaches to antibiotic usage

“One Health-One Medicine”

Antimicrobial resistance in the new reality

What can we do??

Clinical infection control program

Clean AND DISINFECT tables, kennels, stethoscopes

KuKuanich KS, et al. JAVMA 2012

70% of stethoscopes cultured positive for enterococci

50% of DVM’s said never or rarely cleaned stethoscope

Murphy CP, et al. CVJ Sept 2020

100 Ontario veterinary clinics

Cultured tables, kennels, runs, floors, phones, keyboards,

stethoscopes, otoscope tips, thermometers

9% MRSA, 7%MRSP

92% E. coli, 58% C. difficile, 2% Salmonella spp.

Clinical infection control program

Barrier protection – wear gloves

Change gloves!!

Wash hands!!

Or alcohol based sanitizers!!

AND … be vigilant with antibiotic use!

Antimicrobial choices

Culture every infection?

Not realistic in veterinary medicine

Real world vs ideal world

SO……what to do??

Antimicrobial use in a new era

Confirm presence of bacteria if possible

Do more cytology

Cytology results: Neutrophils with cocci

Urinalysis

Swenson L, et al. Evaluation of Modified Wright Staining of dried urinary

tract sediment as a method for accurate detection of bacteruria in cats

Vet Clin Path, Vol 40, 2011

Diff-Quick stain of sediment is much better to evaluate for presence of

bacteria than “wet-mount”

Can confirm if a bacterial UTI

Canine Infectious Respiratory Disease

Complex (CIRDC)

Respiratory signs in a dog – is bacteria the cause?

Joffe, D., et al. (2016) Factors associated with development of

CIRDC in dogs in five Canadian small animal clinics. CVJ.

86 dogs, 5 clinics (BC, AB, ON x 3)

Samples collected June 2013 – February 2014

Performed Antech Lab’s Respiratory Pathogen PCR Test

CIRDC, is bacteria the cause?

10.9% bacterial

89.1% viral

Confirm presence of bacteria if possible

Logical empirical first choice

Appropriate drug for condition

As narrow a spectrum as possible

Appropriate dose

Appropriate duration

(Try to) Ensure client compliance

Recheck

Don’t use ‘big guns’ as ‘first line’

Topical therapy when appropriate (dermatology)

No response to appropriate therapy, or

If infection recurs

→ Culture and sensitivity

Keep eyes open for MRS and MDR bacteria

Do Not Create New Resistance

Raw Food Diets

E. coli that produce AmpC B-lactamase are very resistant to

cefoxitin, ceftriaxone, and amoxicillin-clavulanic acid

Increasing incidence in at risk (hospitalized,

immunosuppressed) human patients

Study of pet visitation found visitation to not be a risk factor

for carrying AmpC B-lactamase+ E. coli, but feding raw food

was strongly associated (p < 0.001)

Lefebvre SL, et al. (2009) JAVMA

Raw food diets

Significant risk factors for carriage of antimicrobial resistant

Salmonella spp. and E. coli in dogs

Feeding home-made diets

Feeding raw diets

Adding raw food into a diet

Feeding raw chicken in the last week

Leonard EK (2015) AJVR

Raw food diets

73 raw food-fed Labrador Retrievers that had never visited a

veterinarian and never received antibiotics

Commensal E. coli:

63% showed antimicrobial resistance

30% demonstrated multi-drug resistance (resistance to 3 or

more antimicrobial families)

Schmidt VM (2015)

Antimicrobial resistance is the New Reality

Prevent infections and their spread in your practice

Confirm a bacterial infection

If no response to the first appropriate antimicrobial therapy

of if infection recurs → Culture and Sensitivity

Antimicrobial use is a privilege

The playing field is changing and CA vets need to be vigilant

and change habits with new information and changing times

Abuse or lack of vigilance of the changing microbial

landscape could put this privilege at risk

We must protect this privilege by changing our AMU ‘habits’

Patient-related factors

Characteristics

Current and past clinical situation

Owner demands

Owner convenience and costs

Treatment-related factors

Alternative treatment options (supportive

care, topical therapy)

Good response last time used?

Owner needs convincing?

Bathing a big, hairy dog is hard

Antimicrobial-related factors

Classification, spectrum, route, duration of

effect

Ease of use

Contextual factors

Professional interactions within clinic

Clinic policies or protocols

Influence / expectation of (more senior) owner veterinarian

Influence of younger veterinarian

Professional interactions between clinics

Owners will go to neighboring clinic to get Rx

Diagnostics

Cytology, culture and sensitivity

Availability

Commercial drivers

Veterinary-related factors

Personal beliefs, experiences, and habits

Use of guidelines

To help guide their decision-making

Convince owner to accept alternatives

Knowledge of infectious diseases, antimicrobials

Value of literature and CE

Perceived risks of non-treatment and treatment

Fear of complications

Fear of AMR

The quick fix

Discussion:

Mitigation of AMR in CA Practice

1. What is the role of AMU and AMR surveillance in mitigation?

2. What do you see as some of the challenges to effective

surveillance?

3. How may improved surveillance help to change behaviours?

Questions?

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