Risk Factors for Colonisation with Antimicrobial-Resistant Bacteria

Introduction

Antimicrobial resistance (AMR) is an increasing threat to modern human and veterinary healthcare. This is a one-health problem - humans and animals are intimately associated, and we're exposed to the same drugs, bacteria and resistance genes. Medical staff, veterinary staff, the public and animal owners all have a role in limiting AMR and maintaining the efficacy of these drugs.

Antibiotics and Antibiotic Resistance

AMR genes are widespread as organisms use antibiotics to compete. These are probably in evolutionary balance. Therapeutic use, in contrast, results in abrupt exposure to high antibiotic concentrations and systemic use leads to whole microbiome exposure. This favours survival of AMR bacteria. Horizontal transfer allows AMR genes to spread within and between bacterial populations.

Antimicrobial-Resistant Organisms of Concern

Meticillin-resistant staphylococci (MRS) are of most concern. MRSP was first recognised in 2004, and has spread worldwide. In the UK, MRSA isolates have been relatively stable while MRSP isolates have increased. MRSP isolates tend to have a wider resistance spectrum than MRSA. Other bacteria with increasing AMR include multi-drug resistant (MDR) Pseudomonas, Salmonella and Streptococcus, and extended-spectrum beta-lactamase (ESBL) and AmpC producing E. coli and Klebsiella.

Antibiotic Resistance in Healthy Animals

AMR bacteria are readily isolated from healthy animals; nearly 40% of healthy horses and 18–29% of healthy dogs carry MDR E. coli, and 29% of horses and 6–40% of dogs carry MRS. Fortunately, more clinically significant AMR bacteria are less common. ESBL E. coli are only carried by 6.3% of horses and 4% of dogs, and AmpC E. coli, MRSA and MRSP by less than 1% of animals.

Does Antibiotic Use Select for Resistance?

Antibiotic use is the biggest factor driving the emergence and spread of resistance. Resistance to penicillins was seen shortly after their introduction; for example, meticillin was introduced in 1959 and MRSA first isolated in 1961. The first companion animal MRSA isolates were also reported in 1961, with multiple case series emerging in the 1990s. The same pattern has been seen with other antimicrobial classes. Levels of resistance correlate with antibiotic prescribing rates in human healthcare and reducing prescribing is associated with lower levels of resistance. Glycopeptides, cephalosporins, and fluoroquinolones are specifically associated with selection for MRSA in humans.

Animal data are not quite as clear, although multiple antibiotic courses are associated with AMR. Systemic treatment in dogs increases the prevalence of AMR among staphylococci and E. coli, and the effects last for three months. However, evidence that specific antimicrobials select for resistance is less clear. There is some evidence that cephalosporins, 3rd-generation cephalosporins and fluoroquinolones may select for resistance among staphylococci and E. coli, but clindamycin may have less effect on resistance.

Antimicrobial Stewardship

We need to reduce systemic antimicrobial use. Studies of prescribing behaviour in the UK have shown that 17–39% of vet-visiting dogs, cats and horses get antimicrobials. The most common problems are pruritus, diarrhoea and respiratory conditions, and it is likely that many cases did not require systemic broad-spectrum antimicrobials.

Drivers for Antimicrobial Use in Practice

Antimicrobial use can be influenced by practice expectations (real or imagined). The three most important drivers are vet prescribing behaviours, interactions with clients and practice norms.

Antimicrobial Use Guidelines

A variety of guidelines are available. However, implementation varies from mandatory (e.g., in Denmark and Sweden) to professional responsibility (e.g., in the UK) or voluntary. The challenge is to improve engagement and adherence. Peer discussion of treatment protocols, but these should be evidence-based, follow current recommendations and take into account the resources available.

Veterinary Contact and Antimicrobial-Resistant Bacteria

Colonisation with AMR bacteria increases with veterinary contact. For example, MRS have been isolated from 0.5% to 10% of vet-visiting animals and clinical samples in Europe and Canada. The prevalence was 46% among canine in-patients in Japan, and in the US they have been found in 15–38% of dogs with pyoderma and up to 20% of clinical samples. Some 7–13% of veterinary staff are colonised with MRS, which reflect their area of work. MRS can also be isolated from up to 10% of veterinary practice samples, particularly hand touch sites. Fluoroquinolone-resistant, ESBL and AmpC E. coli have been found in 5–10% of faecal and environmental samples from UK veterinary hospitals, particularly ward floors, tables and keyboards.

Specific risk factors include:

• Multiple antibiotic courses
• Postoperative infections
• Nosocomial (healthcare-acquired) infections
• Prolonged hospitalisation (especially in ICUs)
• Surgical or nursing implants (e.g., catheters and feeding tubes)

Zoonotic Colonisation and Infection

AMR bacteria and genes can be transferred between humans and animals in both directions. This varies — MRSP is fairly animal specific but MRSA seem to move between species more readily, and gene transfer is more frequent among Gram-negative bacteria. The risk of infection is very low as these are mostly commensal opportunists. Nevertheless, owners of animals with AMR colonisation or infections should be asked about risk factors for infections and be given appropriate hygiene advice. Whether animals belonging to owners with recent hospital contact are at greater risk of AMR carriage is less clear, but it would be prudent to check.

Raw Food Diets

These diets are more often contaminated with potential pathogens (e.g., Salmonella, Campylobacter or Listeria) or AMR bacteria compared to dry foods. Raw meat is a risk factor for carriage of AMR bacteria (e.g., ESBL-producing E. coli) and shedding of pathogens.

Environmental Exposure

Early studies have suggested that contamination of the environment by antibiotic-treated dogs and farm animals may facilitate dissemination of AMR in communities. Other sources of environmental contamination include sewage and effluent from farms, hospitals and veterinary premises.

Conclusions

We have clear responsibilities in reducing antimicrobial use and infection control. We must encourage owners to expect less antibiotic treatment and to treat effectively. Finally, we can work with policy makers to develop effective guidelines and regulation.

Further Resources

1.  British Veterinary Association - www.bva.co.uk/public/documents/bva_antimicrobials_poster.pdf

2.  British Small Animal Veterinary Association - www.bsava.com/Advice/PracticePack/PROTECTPoster/tabid/1500/Default.aspx

3.  www.bsava.com/Resources/MRSA

4.  British Equine Veterinary Association - www.beva.org.uk/Home/Resources-For-Vets/Guidance (VIN editor: link was modified on 5-18-18)

5.  Responsible Use of Medicines in Agriculture (RUMA) - www.ruma.org.uk

6.  Federation of European Companion Animal Veterinary Associations (FECAVA) - www.fecava.org (VIN editor: link was modified on 12-22-17)

7.  International Society for Companion Animal Infectious Diseases (ISCAID) - www.iscaid.org

8.  Bella Moss Foundation - www.thebellamossfoundation.com (VIN editor: link was modified on 12-22-17)

9.  Antibiotic Action and Guardian campaigns - http://antibiotic-action.com/ & http://antibioticguardian.com/