VETcpd - Vol 2 - Issue 2 - Page 37

Prescribing antimicrobials: How do we make the right decisions?Antimicrobial resistance is a rapidly developing problem in both the human and veterinary fields. The development of new agents is slow and it is clear that careful stewardship and rational prescribing of antimicrobial agents is going to be key in slowing the rate of bacterial resistance over the forthcoming decades. This article reviews the mechanisms by which antimicrobial resistance occurs and how we can optimise our therapy to be as effective as possible, limiting selection pressure for drug resistance to occur.

Key words: antimicrobials, mutation, antimicrobial resistance, minimum inhibitory concentration, mutant prevention concentration

Simon Tappin MA VetMB CertSAM DipECVIM-CA MRCVS

European and RCVS Recognised Specialist in Veterinary Internal Medicine

Hon. Assoc. Professor of Small Animal Medicine, University of Nottingham

Simon graduated from the University of Cambridge and after two years in small animal practice under took a residency at the University of Bristol in Small Animal Medicine and Intensive Care. He gained the European Diploma in Small Animal Medicine. He is currently working as a consultant in internal medicine at Dick White Referrals where he sees cases in all areas of internal medicine.

Dick White Referrals, The Six Mile Bottom Veterinary Specialist Centre, Station Farm, London Road, Six Mile Bottom, Suffolk, CB8 0UH

Email: st@dwr.co.uk

Tel: 01638 572012

actually necessary and secondly whether there might be an alternative.

Are antibiotics over-prescribed? Recent studies have shown that anti-microbial use in first opinion practice is high, with studies in the United King-dom revealing that antimicrobials were prescribed or administered to dogs and cats in between 33% and 48% of consulta-tions (Radford et al, 2011, Mateus et al, 2011), leading to the suggestion that some of these treatments may not have been needed. Investigating this further, Wayne and colleagues (2011) looked at antimicrobial administration at a large teaching hospital in the United States and concluded that in only 17% of instances where antimicrobials were administered there was a confirmed infection, in 45% there was a suspected infection and in 38% there was no documented evidence of infection. Whilst some of the antimicrobial use in this study is likely to relate to the caseload seen (e.g. metro-nidazole administration for its postulated immune-modulatory action rather than its antimicrobial action) these studies provide suggestive evidence that antimicrobials are being over used and administered inappro-priately in small animal practice.

Managing owner expectations Owner education regarding the need for antimicrobial therapy will help reduce client expectation for antibiotic administra-tion, which will reduce the inappropriate prescription of antimicrobials.

Alternatives to antibiotics In a straight forward viral infection or self-limiting disease, prescribing alterna-tive therapies will provide symptomatic relief and help improve patient welfare and client satisfaction. An example of this would be dogs with kennel cough, where

IntroductionThe discovery of penicillin by Sir Alexander Fleming in 1928 and sulphonamides by Gerhard Domagk in 1935,

revolutionised the treatment of bacterial disease in people and antimicrobials are now very commonly prescribed in veterinary medicine. Since the start of antimicrobial use, resistance has been noted and is increasing over time (Box 1).

“I would like to sound a note of warn-ing…It is not difficult to make microbes resistant to penicillin in the laboratory by exposing them to concentrations not sufficient to kill them and the same thing has occasionally happened in the body” Sir Alexander Fleming, Noble Lecture 1945

Box 1

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Antimicrobial use alone does not cause antimicrobial resistance, indeed in 2011 genes encoding resistance for β-lactams and tetracycline were identified in DNA derived from bacteria 30,000 years old, but antimicrobials do select for resistant strains.

Several new classes of antimicrobials have been discovered and refinements have been made to optimise their effectiveness, but development of new drugs is unlikely to keep up with the mounting pressure of antimicrobial resistance. As a result, rational prescribing of optimised therapy and careful stewardship of antimicrobial use in small animal practice is needed to minimise the development of resistance.

Identifying the needBefore prescribing antimicrobials we need to firstly consider if therapy is

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owners often expect administration of antimicrobial therapy. These infections usually have short, self-limiting courses and are associated with very low morbid-ity. The coughing that results will cause mild discomfort to the dog and, perhaps more marked frustration to the owner, however administration of antimicrobials is unlikely to significantly alter the clinical course of the disease. In these instances clinical improvement may be seen with other therapies such as cough suppressants or non-steroidal anti-inflammatory drugs.

Prophylactic use of antibiotics The prescription of antimicrobials is not a substitute for good surgical technique, as prophylactic antibacterials are not needed for all routine surgeries and should be reserved for patients at increased risk – for example immunocompromised patients or those undergoing prolonged surgery, as it has been shown that infection rates double for every hour a surgery is prolonged (Table 1). It has also been shown that in uncomplicated procedures a single pre-emptive one-off intravenous antimicrobial treatment given preoperatively is as effec-tive in reducing infection as a 5-day course of postoperative antimicrobials (Bray 2011).

It is also important to remember that the presence of fever or an elevation in white blood cell count, suggests an inflammatory reaction, which may be driven by viral infection or a sterile inflammatory process and does not always imply the presence of a bacterial infection, requiring antimicro-bial therapy. Even some bacterial infections may not require antimicrobials for them to resolve, the well cat with a cat bite abscess that has been lanced and cleaned, does not need systemic antimicrobial therapy.

Choosing an agentTo try to limit the emergence of antimicrobial resistance, therapy should ideally only be used when infection is documented. Where infection is an expected complication or suspected, but culture is pending, it is useful to have a small number of front line antimicrobials for routine use. Practice policies such as that outlined by the SAMSoc / BSAVA PROTECT scheme (see Appendix), allows local and optimised choices for the empirical prescribing of antimicrobials to be developed. These policies take account of the most likely bacterial agents and provide a rational, progressive approach through prescribing antimicrobials, without culture and sensitivity data.

Surgical category Surgical category Are antimicrobials needed?

Clean • Elective, non-traumatic procedure

• No entry into urinary, gastrointestinal or respiratory tract

• No break in asepsis

• Not warranted for healthy animals undergoing procedure less than 90 minutes in length

Clean-contaminated • Entry into a hollow organ viscus with no significant spillage and no infection present

• Minor break in asepsis during a clean procedure

• Need should be assessed on a patient by patient basis, considering the potential numbers and virulence of bacteria at the surgical site, and the status of the patient and its immune system

Contaminated • Spillage during a clean-contaminated surgery from a hollow viscus

• Entry into a hollow viscus with the presence of infection

• Recent traumatic wounds (less than 6-8 hours old)

• Major break in asepsis during a clean procedure

• Antimicrobial are needed in most cases, given the likely presence of high numbers of contaminating organisms

• Meticulous lavage / debridement and cleaning will help reduce bacterial numbers at contaminated surgical sites

Dirty • Infected surgical site or purulent discharge present

• Older traumatic wounds (untreated of more than 6-8 hours)

• Antimicrobials will be required and should be chosen on the basis of the likely agents and site of infection

• Where possible culture and sensitivity results should be used to guide antimicrobial therapy

Table 1: Classification of surgical wounds and appropriate antimicrobial management

Culture and sensitivity testingWhenever possible a bacterial culture, with sensitivity testing should be per-formed. This allows the use of narrow spectrum agent, where possible avoid-ing the general use of broad spectrum antimicrobials, and can limit the effects on the normal flora. For example, taking a Clostridium perfringens isolate that is susceptible to both metronidazole and potentiated amoxicillin, and assuming no other influencing factors were present, metronidazole would be the better choice as it would spare the normal aerobic enteric flora and reduce selection pressure for resistance, as it is effective only against anaerobic bacteria.

Antimicrobial sensitivity testing is per-formed by using disks impregnated with the expected serum concentration of the antimicrobial at a standard dose (Kirby Bauer or disk diffusion method, Figure 1).

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It is semi-quantitative as, depending on the area of inhibited growth around the disk, the organism can be classified as sensitive or resistant to the antimicrobial.

Minimum inhibitory concentration Measurement of the minimum inhibitory concentration (MIC) provides a quantita-tive assessment of antimicrobial sensitivity by determining the minimum concentra-tion of antimicrobial needed to inhibit bacterial growth. This is usually performed when sensitivity testing by disc diffusion has not elicited a clear choice in therapy and allows comparison between agents and the effect of antimicrobial concentration. The MIC is determined by incubating a defined density of bacteria (105 colony forming units/ml) with various anti-microbial concentrations, which is then extrapolated to expected serum concentra-tions at standard doses and the bacteria are classified as sensitive or resistant to the antimicrobial (Figure 2).