Antimicrobial use and resistance
in companion animals
Michele Anholt DVM PhD
Manager One Health at UCalgary
Office of the VP (Research)
Danny Joffe DVM Dipl. ABVP Emeritus Canine and Feline PracticeVice president, Medical Operations
VCA Canada
October 6, 2020
Presenter Disclosure
Michele and Danny have no potential conflicts of interest.
Michele Anholt, [email protected]
Danny Joffe, [email protected]
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
beds
Dogs (18%) and cats (30%) sleep on beds
Cats (45%) allowed to jump onto kitchen
sink
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
Cost
Principles of AM 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
Cost
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
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
Cost
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.
0.1
.2.3
.4.5
Pro
port
ion o
f e
nte
ric c
ases
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)
AMP, ampicillin; FOT, cefataxime; TAZ, ceftazidime; MERO, meropenem; CIP, ciprofloxacin;
NAL, nalidixic acid; AZI; azithromycin; CHL, chloramphenicol; COL, colistin; GEN, gentacimin;
SMX, sulfamethoxazole; TMP, trimethoprim, TET, tetracycline, TGC, tigecycline
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)
AMP, ampicillin; FOT, cefataxime; TAZ, ceftazidime; MERO, meropenem; CIP, ciprofloxacin;
NAL, nalidixic acid; AZI; azithromycin; CHL, chloramphenicol; COL, colistin; GEN, gentacimin;
SMX, sulfamethoxazole; TMP, trimethoprim, TET, tetracycline, TGC, tigecycline
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
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
Antimicrobial use in a new era
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)
IF…
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 use in a new era
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 in a new era
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
Pet
Characteristics
Current and past clinical situation
Owner
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
Time
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?
