Time to act on antimicrobial resistance in canine pyoderma

Antimicrobial resistance is a major health threat of our time. Concerted efforts towards reducing inappropriate use of antimicrobials in the livestock sector started decades ago, but similar efforts in small animal medicine are lagging behind.

The overall consumption of antimicrobials in small animal practice may be low compared to farming and human medicine. However, the often very close contact between people and their pets adds an extra zoonotic dimension and the recent reports of increasing multi-drug resistance (MDR) in small animal pathogens can no longer be ignored.

Antibiotics and skin disease

Bacterial skin infections are among the most common presentations in small animal practice and canine pyoderma has been reported as one of the most common reasons for antibiotic prescribing in UK and European surveys (De Briyne et al, 2014; Mateus et al, 2011).

In the past, Staphylococcus pseudintermedius (previously S intermedius), the predominant pathogen involved in canine pyoderma, has been susceptible to most antibacterial agents on our shelves.

Its UK resistance pattern during the 1980s and 1990s was probably best reflected by two large screening studies of more than 3,000 clinical isolates in total submitted to the diagnostic services of the veterinary laboratories of the universities of Glasgow and London (Lloyd et al, 1996; Normand et al, 2000).

Resistance tended to be high (30% to 80%) to penicillin and the tetracyclines – antimicrobials that would be unlikely choices for empirical treatment of canine pyoderma – while lower levels of resistance of around 10% to 30% were seen to clindamycin, lincomycin, erythromycin and to potentiated sulphonamides.

None or less than 5% of S pseudintermedius isolates were resistant to amoxicillin-clavulanate, cephalexin and to the fluoroquinolones in those days, no trends of increasing resistance over the respective nine and 16-year time periods were found and no multidrug-resistant staphylococci, such as methicillin-resistant S aureus (MRSA) and methicillin-resistant S pseudintermedius (MRSP) were isolated. Thus, treatment of canine bacterial skin infections rarely presented a clinical challenge provided owner and patient compliance was good.

What has changed?

The first dark clouds appeared on the horizon in 2011, when a letter to the Veterinary Record announced isolation of the first MRSP in the UK by a veterinary diagnostic laboratory. MRSP can be considered as the small animal counterpart of MRSA, one of the most troublesome multidrug-resistant nosocomial pathogens in human hospitals, as they share many epidemiological, microbiological and clinical characteristics.

Later, another UK survey, almost a sequel to the two preceding studies from Glasgow and London, confirmed the arrival of MRSP and identified most of the isolates as belonging to MRSP ST71, the lineage spreading successfully in small animal practices in continental Europe over the past few years (Beever et al, 2015).

Most importantly though, this survey highlighted a new trend of increasing antimicrobial resistance to clinically relevant antimicrobials among S pseudintermedius.

The survey, the largest published of its kind, had included more than 13,000 isolates (mostly from canine infections seen in first opinion practice) submitted to a veterinary diagnostic laboratory in the north of England, and more than 1,200 isolates from dogs submitted to the RVC diagnostic laboratory from its referral hospital between 2006 and 2012.

Resistance overall had remained below 10% for amoxicillin-clavulanate, cephalexin, cefovecin and the fluoroquinolones, but the increasing trend in resistance over time, both in first opinion and in referral isolates, was new and had not been identified in the previous surveys. MRSP accounted for 0.7% of the first opinion isolates and for 2.6% of referral submissions – still low rates compared with the 20% to 30% MRSP reported from continental Europe and up to 50% from areas in North America and Asia.

Time to act now

Even though many UK small animal practices may not yet have seen their first case of MRSP or any other MDR pathogens, these warning signs warrant action. History has shown stopping a contagious organism in its tracks is feasible, cost-effective and most successful when measures are employed early while prevalence is low.

The emergence and spread of MRSA in UK human hospitals illustrates what can happen when action is delayed. MRSA was recognised in the UK in 1961, initially causing difficult, but limited, outbreaks in individual hospital wards. It only started to spread epidemically 20 years later during the 1980s and 1990s and since then, major efforts have been required to turn the tide and reduce prevalence again.

Limiting the spread of MDR pathogens boils down to reducing antimicrobial use to “as little as possible, as much as necessary” and employing rigorous hygiene measures. Both strategies require effort, awareness, and sometimes behavioural changes – and all without an immediate reward. On the positive side, plenty of guidelines exist on responsible use of antimicrobials (Table 1) – and on infection control measures – and adopting and possibly adapting them for practice should be straightforward.

Antimicrobials in pyoderma

To implement the guidelines, patients with skin disease have an advantage. In contrast to other diseased organs, the skin is right under our eyes and hands, which helps to answer some important questions prior to antimicrobial use.

Is this really a bacterial infection?

Skin lesions will help to suggest a pyoderma and determine its depth, for example, are there papules, pustules and epidermal collarettes suggestive of superficial pyoderma or haemorrhagic crusts and fistula in a deep pyoderma.

The involvement of bacteria (and inflammatory cells) can then be confirmed by cytology, a still largely underused in-house test that can be performed in less than five minutes. Impression smears from moist lesions or tape strip impressions from dry lesions are easy to take, quick to stain with any Romanowsky-type stain and cheap. What should not be cheap though is the microscope as only good, clear ×100 lenses used with immersion oil will reveal the diagnostic features (Figure 1).

Are systemic antimicrobials required?

With pyoderma confirmed, antibacterial therapy is indicated. However, the question whether this needs to be by the systemic route deserves new attention in the light of increasing drug resistance.

For surface infections such as “hot spots” or lip fold problems, it is intuitive to use topical treatment only, and for deep pyoderma, systemic antimicrobial treatment will be required. For superficial pyoderma (bacterial folliculitis) though, the old text book dogma of systemic antibiotic therapy has been challenged and topical treatment alone has been shown to be effective in cases where owners are able and willing to wash their dogs two to three times weekly.

Resolution of pyoderma lesions may take a little longer than with systemic therapy and so will the necessary “owner talk” to explain how treatment is to be done. However, topical therapy can replace systemic antimicrobials in some cases. It will be effective in MDR staphylococcal infections – as good in vitro and clinical efficacy has already been demonstrated against MRSP – and it will give owners a degree of control over their animal’s disease that can be beneficial, especially in some chronic cases.

Right drug for right bug

What is “the right drug for the right bug” when systemic treatment is required? For deep pyoderma, the choice should always be based on bacterial culture and sensitivity test results. For the more common superficial pyoderma, empirical choice of drug remains appropriate, with knowledge of the local resistance pattern as stated in recent consensus guidelines (Hillier et al, 2013).

In superficial pyoderma, we know “the bug” since S pseudintermedius is involved in more than 90% of cases. And we have a good idea of its resistance pattern in the UK, based on the survey described previously.

In summary, along the lines of narrow versus broad spectrum, clindamycin would be a good choice for “first-time offenders” or animals that have not received repeated courses of antimicrobials. Resistance to clindamycin tends to be higher in cases of recurrent pyoderma where this drug is therefore less reliable.

Cephalexin should be effective against the vast majority of S pseudintermedius skin infections, while amoxicillin-clavulanic acid, frequently recommended as a first choice drug for superficial pyoderma, performs well in vitro, but efficacy in clinical trials have been less convincing.

The fluoroquinolones and the third generation cephalosporin, cefovecin, should be reserved for cases where bacterial culture has yielded unusual bacterial pathogens or resistance patterns. The data sheets state these agents are only indicated when the “clinical condition has responded poorly, or is expected to respond poorly, to other classes of antimicrobials or first generation cephalosporins”.

For canine superficial pyoderma in the UK, this would be extremely unlikely because S pseudintermedius is the pathogen isolated from more than 90% of canine superficial pyodermas and susceptibility to narrower spectrum agents such as cephalexin and amoxicillin-clavulanate was recently confirmed in more than 90% of UK S pseudintermedius isolates.

Why did the dog get pyoderma?

This still leaves the most difficult question though, which is why the dog got pyoderma in the first place.

Pyoderma in dogs is always secondary to an underlying primary trigger and identification and successful management of such underlying disease is the key to success and to reducing the need for antimicrobial therapy.

Although occasionally described as “idiopathic”, this term is more likely to reflect our inability to identify a cause rather than a true absence of a cause. Ectoparasite infestations, endocrinopathies or, more problematically, allergic skin disease are among the most common triggers and owners need to be aware just treating the “rash” is relatively easy, but actually stopping it from coming back is the challenging task. Cutaneous signs that remain once the pyoderma has been resolved will help to diagnose the primary disease.

Recurrent pyoderma

For cases where a cause cannot be identified or “fixed”, management of recurrences is often tricky. Although generally considered safe by owners, repeated courses of systemic antimicrobials are highly likely to select for MDR and once a dog has acquired MRSP, management will become labour intensive (often only achievable with topical therapy); risky (unlicensed, more toxic antimicrobials are frequently the only alternative for systemic therapy); and expensive (heightened infection control measures required to avoid nosocomial spread).

Prevention is preferable, but the list of alternatives for pyoderma management is short. It consists of repeated efforts to find and treat underlying causes, prophylactic topical antibacterial therapy and, at least, for superficial pyoderma, immunomodulation.

Pulse therapy or low-dose, long-term antimicrobials can no longer be recommended. In addition, recurrent pyoderma or repeated antibiosis should never be due to a lack of good flea control.

Of these alternatives, topical therapy requires a substantial commitment from owners, typically in the form of whole body washes two to three times a week with a 10-minute contact time, although for localised disease, washing may be limited to affected areas only.

Chlorhexidine-based shampoos (2% to 3%, also in combination with miconazole) and topical fusidic acid-containing products are recommended, as numerous studies have shown good in vitro and clinical efficacy against staphylococci, including MDR strains (Mueller et al, 2012).

For immunomodulation, either autogenous S pseudintermedius bacterin or a commercially produced S aureus “vaccine” have been used in dogs. Although little is known about how and whether immunomodulation works in dogs, these treatments may deserve renewed attention at a time when antibiotic efficacy is under threat.

Conclusion

On a canine pyoderma timeline, the past was good, the present is becoming of concern, the future is in our hands. Or, more specifically, the future is “topical” and in the hands of dog owners who are applying topical medications. Systemic antibiotics will, hopefully, continue to play a role in the management of bacterial skin disease in dogs, but they will need to be prescribed with the care they deserve.

While limiting the spread of MDR through responsible use of antimicrobials and rigorous hygiene measures may not be the most attractive tasks to implement in practice, they are the best we have at the moment.