Background: The historical concept that topical treatments have to ‘sting, stain and stink’ in order to be effective has long been overhauled. A broad range of topical antibacterial products is now available, some as prescription-only medicines following efficacy and safety studies, others are accessible to owners without prescription and marketed as antibacterial. Now, with the emergence of multidrug-resistant bacteria to systemic therapies, the role of topical therapy has changed from supportive to mainstay in many infections. However, the outcome of topical therapy relies heavily on owner and patient compliance, and engaging owners in the process can be time-consuming and challenging for veterinary practitioners.
Aim of the article: This article summarises the latest evidence relating to topical antibacterial treatments for canine pyoderma, provides practical tips on how to maximise treatment success, and highlights where topical therapy can replace systemic antibiotics to support good antimicrobial stewardship.
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Siân-Marie Frosini qualified from the Royal Veterinary College (RVC), London in 2013. She then completed a PhD in 2018 and is currently a post-doctoral researcher at the RVC, investigating the transmission of multidrug-resistant bacteria between people and pets.
Anette Loeffler qualified from the University of Munich, Germany in 1994 and then spent six years in mixed practice in Cumbria. In 2001, she undertook a residency in veterinary dermatology followed by a PhD at the RVC. She is currently a reader in veterinary dermatology at the RVC and is the editor-in-chief of Veterinary Dermatology.
Key learning outcomes
After reading this article, you should understand:
The approach to deciding whether to use topical antibacterial therapy for canine pyoderma, based on clinical presentation;
The evidence base supporting topical antibacterial products licensed in the UK for canine microbial skin infections;
Which antimicrobial agents have demonstrated efficacy against methicillin-resistant staphylococci;
Practical tips to engage owners in the conversation surrounding topical antibacterial therapy;
The reasons why in vitro susceptibility test results are highly relevant for selecting antibacterial drugs for systemic but not for topical therapy.
Opportunity for good antimicrobial stewardship
In view of the major threat to human and animal health from antimicrobial resistance in bacterial pathogens, there is an urgent need to review, reduce and prioritise antimicrobial prescribing. For livestock, substantial reductions in antimicrobial use have been achieved in many countries over the past two decades through regulatory, educational and marketing efforts. In contrast, antimicrobial prescribing in small animal practice, at least in the UK, currently remains unregulated beyond medicine authorisation requirements and the legal flexibility of the Veterinary Medicines Directorate cascade, although promotion of good antimicrobial stewardship has recently been seen in advisory recommendations (Lloyd and Page 2018). This calls for self-motivated reflection and voluntary implementation of responsible prescribing practices.
Canine pyoderma, most commonly caused by Staphylococcus pseudintermedius, is a major reason for antimicrobial use in small animal practice, in most cases administered systemically. However, the skin is almost uniquely accessible for the direct application of drugs. This presents an exceptional opportunity to replace systemic with topical antibacterial therapy in many cases and new evidence has become available to support such a change in clinical decision making.
Indications for topical antibacterial therapy
The topical application of drugs is widely accepted and recommended for most eye, ear and superficial wound infections, and guidelines for these presentations suggest using systemic antibacterial therapy only if there is specific involvement of deeper structures (orbital abscessation, otitis media, bacterial cellulitis, signs of systemic illness).
For pyoderma, recommendations on antibacterial treatment are critically dependent on the depth of infection (Table 1). Systemic antibacterial therapy is always indicated for cases of deep pyoderma and topical antibacterial therapy is recommended as adjunctive treatment where suitable. For superficial pyoderma, the textbook dogma of three weeks of systemic antimicrobial therapy is being challenged based on new published evidence, as illustrated in recent small animal practice-specific antimicrobial use guidelines (BSAVA 2018, FECAVA 2018). These guidelines recommend topical antibacterial therapy, wherever suitable for the case, as the only antibacterial treatment modality, highlighting an opportunity for good antimicrobial stewardship in small animal practice. For surface pyodermas, topical therapy is intuitive and effective due to the location, and clinical efficacy has been demonstrated, although this often benefits from combination with topical glucocorticoid (Fig 1). Unfortunately, for superficial pyoderma few clinical studies have been done to prove efficacy or show superiority to systemic drugs.
Indications that are unfortunately gaining importance worldwide are those skin infections that involve meticillin-resistant S pseudintermedius (MRSP) or Staphylococcus aureus (MRSA). For such cases, topical therapy has been shown to be effective not only in the treatment of infection, but also in limiting the risk of zoonotic transmission of multidrug-resistant staphylococci between pets and people during close contact and via environmental contamination. Such general cleaning and cosmetic benefits of topical antibacterial therapy were reviewed by Curtis (1998), but have now become particularly relevant for their decontaminating effect on MRSP or MRSA.
Efficacy against MRSP and MRSA infections
Multidrug-resistant bacteria, specifically MRSP and MRSA for pyoderma, have added extra complexity to the management of canine bacterial skin infections (Table 2). Although MRSP and MRSA are typically resistant to most or all clinically relevant systemically used antibacterials, this resistance does not extend to topical antibacterial therapy. In vitro studies have consistently shown low minimum inhibitory concentrations (MICs) for antibacterial agents in products licensed for topical use in canine pyoderma. Several clinical studies, although they only include a small number of dogs, have indicated good efficacy of chlorhexidine and fusidic acid products applied topically for the treatment of MRS superficial pyoderma and, at least in the short term, for elimination of MRS carriage using the same regimens as for infections caused by meticillin-susceptible staphylococci (Loeffler and others 2011a, Borio and others 2015) (Fig 2).
Which active ingredients are best for treating canine pyoderma?
A multitude of licensed and over-the-counter topical products is marketed as antibacterial, using various words with similar interpretations (Box 1). However, evidence for clinical efficacy specifically for canine pyoderma is currently only available for a small number of active ingredients (Mueller and others 2012), and even fewer agents have gone through efficacy and safety testing leading to a product authorisation in the UK (Table 3). Authorised products should always be first choice when starting treatment as this will ease assessment of suitability and compliance. The frequency of the application of these products should be governed by the datasheet recommendation (often twice weekly for shampoo products), although higher frequencies (up to daily applications of spray or mousse products) have been safely implemented in some clinical studies. If a licensed product with proven efficacy fails despite appropriate prescription and good compliance, then other factors may be involved, and alternatives need to be considered.
Selected terminology describing the inhibitory or destructive effect of a product against bacteria (± other microorganisms)
Antibiotic – substance derived from a microorganism
Antiseptic – substance applied to living tissue (eg, skin)
Biocide – diverse group of substances, sometimes including disinfectants, but also pest control products and preservatives
Disinfectant – substance used on inanimate objects
In addition, the same active ingredient may also be available in over-the-counter products or in medicines authorised for other indications or for people (ie, off-license use if administered to pets). Usually there will be some differences in product formulation with unknown effects on clinical efficacy. For example, chlorhexidine is available as (di)gluconate in 2 per cent or 3 per cent shampoos authorised for canine pyoderma (Table 3) or as 4 per cent in the antimicrobial skin cleanser Hibiscrub (Mölnlycke) or in a 4 per cent spray or shampoo (Clorexyderm; Vetruus).
Other active ingredients for which efficacy against staphylococci has been shown, at least in vitro, but where no product formulations are licensed in the UK for dogs include several well-known compounds, such as:
Acetic and boric acid;
Silver sulfadiazine; and
Sodium hypochlorite (bleach).
However, there is no strong in vivo veterinary evidence to support these ingredients and further clinical studies are needed. For example, sodium hypochlorite (bleach), at a concentration of 2.5 µl/ml, has been suggested in human medicine to be suitable as a bleach bath for killing MRSA based on in vitro data (this extrapolates to 30 ml of 8 per cent household bleach in 1 l of water; Fisher and others 2008), but little veterinary evidence exists to support its use, with only a single, open-label, combination-shampoo pilot study which has assessed its use (Fadok and Irwin 2019).
Lastly, owners are increasingly exposed to a wide range of products or ‘care’ formulations on pet shop or supermarket shelves, through the internet or even in veterinary practice waiting areas. Many of these claim antibacterial properties due to herbal or chemical ingredients, such as eucalyptus oil in Green Veterinary Salve (Easi-Vet Supplies) or chloroxylenol, found in both Coatex (VetPlus) and Dettol (Reckitt Benckiser); however, evidence for clinical efficacy is not always available through peer-reviewed publications.
Which formulation should I use: shampoo, cream, foam or wipe?
Efficacy of topical antibacterial therapy depends not only on appropriate product choice and correct prescribing, but also on good compliance from owners. Although the wide range of product formulations now offered may feel overwhelming, it provides opportunities for a tailor-made treatment plan to suit the type of patient, the type of infection and the owner’s lifestyle and budget (Table 4). While clinical studies will have been conducted for a specific indication (eg, canine superficial pyoderma), some formulations are available for different purposes with subtle differences in application.
How to get owners on board and improve compliance
Convincing owners to put our recommendations for topical therapy into action may be challenging, particularly since systemic alternatives are likely to be less labour intensive and more convenient. Similarly, there may be perceptions that owners expect to be prescribed systemic antibiotics for their pets. However, newer studies in veterinary and human medicine have also shown the opposite. Some owners (or patients) report a perceived pressure towards systemic antibiotics from the prescriber, and would be interested in exploring alternatives in light of the increasing media attention on antimicrobial resistance. Thus, topical therapy might be more acceptable to owners than we assume. Conversational ‘nuggets’ that might be helpful in this context include:
Comparison with something familiar: topical therapy is widely used in human medicine for bacterial skin infections.
Safety: drugs will only be used on the diseased organ (skin) or even only on affected areas.
Antimicrobial resistance: reduced risk of drug-resistant bacteria causing infections in the future (risk to dog) and potentially spreading to owners (risk to in-contact people through transmission).
More control for owners: as for all prescription drugs, treatment will need to be applied as prescribed, but topical therapy provides more opportunity to tailor treatment to the patient’s needs.
Value-added: antibacterial shampoos will help to remove dirt and improve coat condition and smell, properties often desired by owners who frequently wash their dogs for cosmetic reasons. Additional benefits may include mechanical disruption of biofilm (eg, in lip folds) and reduction of pruritus.
The risk of poor compliance is likely higher with topical therapy compared to systemic treatment and extra consultation time may be needed to explain the merits and correct application of topical products. Supporting owners in making topical treatment work should contribute to long-term success, particularly for cases of chronically recurrent superficial pyoderma, and veterinary nurses will be well placed to enhance this process, give practical advice and monitor compliance.
Do we need to worry about resistance to topically used antibacterials?
In the context of topical antibacterial therapy, it is important to differentiate between clinical resistance (ie, treatment failure) and in vitro measurements reported by the laboratory (MICs or ‘resistant/susceptible’ interpretations).
Individual cases of suspected failure of topical antibacterial agents are anecdotally reported and vigilance is always necessary. However, MICs to topically used antibacterial agents, including those for MRSP and MRSA from dogs, have so far remained consistently low, and convincing treatment failures of appropriately applied topical therapy have not been described for canine pyoderma. Often, other factors potentially contributing to poor response to treatment such as compliance, comorbidities or product formulation need to be considered.
Regarding the predictive value of ‘resistant/susceptible’ results reported by laboratories, these rely on the availability of clinical breakpoints that take into account pharmacokinetic and pharmacodynamic factors (specific to bacterium, agent, host and site of infection). Such breakpoints have not yet been defined for topical application and laboratory results will only be relevant to systemic therapy.
With topical treatment, the active ingredient is expected to reach the site of infection directly, bypassing the metabolic effects of the liver and avoiding any dilution effects related to blood perfusion. This concept of high concentrations reaching the site of infection with topical application has recently been supported by measuring fusidic acid concentrations at the level of the canine hair follicle infundibulum. After direct application to skin, concentrations exceeded the highest MICs described for S pseudintermedius in vitro (Frosini and others 2017).
In the past 20 years, the threat from multidrug-resistant bacterial pathogens and the need for responsible antimicrobial prescribing have become urgent. For skin infections, topical antibacterial therapy presents a valuable opportunity to help with both of these issues. Many different products are available for use in practice and while an element of ‘trial and error’ remains with some products, due to the paucity of evidence, more data are becoming available to support our clinical decision making. The increased effort of topical therapy will be compensated for by preventing multidrug-resistant infections through the practice of good antimicrobial stewardship.
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Competing interests The authors have received funding from Dechra Veterinary Products in support of laboratory research and clinical teaching of undergraduate and postgraduate students.
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