Twenty years of pyodermas: How antimicrobial resistance has changed the way I practice

He was a routine dermatology patient: a senior neutered male Jack Russell terrier referred for chronically relapsing superficial pyoderma. He was presented with widespread superficial bacterial folliculitis; epidermal collarettes and crusts with abundant cocci on skin surface cytology (examples of these lesions are shown in Figures 1 and 2). He was moderately pruritic, and other than his skin disease, very healthy. I prescribed oral cephalexin and scheduled a recheck examination after 3 wk to investigate underlying causes for the pyoderma. But at the recheck, his infection remained stubbornly unchanged.

Figure 1.

Epidermal collarettes.

Figure 2.

Widespread superficial folliculitis resembling urticaria. Both dogs responded to topical antimicrobial therapy and treatment for the underlying condition. Photo credit: Kinga Gortel.

I treated this patient during my veterinary dermatology residency in the late 1990s, when pyoderma typically presented few therapeutic challenges. This dog’s refractory infection was highly unusual and thus memorable. But things were beginning to change. I encountered increasing numbers of similar cases as a newly minted dermatologist and see them frequently today.

Resistant staphylococcal infections are now common enough that the term “methicillin-resistant” is well-known to veterinarians. This term identifies a broad resistance to beta-lactam drugs including the potentiated penicillins and cephalosporins typically prescribed for skin infections. Methicillin-resistant staphylococci (MRS) can express co-resistance to any combination of other drug classes and this makes antibiotic therapy very difficult to nearly impossible for some strains (1). The prevalence of methicillin resistance in Staphylococcus pseudintermedius, the organism typically involved in canine pyoderma, had increased to > 30% of isolates in dogs from the United States within a decade of being reported in 1999 (2,3). In the last decade, the prevalence of methicillin-resistant isolates from Canadian dogs with pyoderma has ranged from 12.1% of all staphylococcal species in primary practice (4), to 45% of coagulase-positive staphylococci in a referral practice (5).

How did they become so common? Staphylococci comprise part of the normal skin and mucosal microbiota, with several species serving dual roles as commensals and opportunistic pathogens (1). Staphylococcus pseudintermedius is part of the commensal skin microbiota of most dogs and the most common species causing infections, followed much less frequently by S. aureus and the coagulase-variable S. schleiferi (1,6,7). Commensal bacteria are subjected to selection pressure any time their host is treated with systemic antibiotics, regardless of whether they are the target of treatment. Resistant strains of staphylococci are not created de novo when an animal is treated with an antibiotic. Rather, treatment can obliterate the existing susceptible commensal populations and allow re-colonization by a strain resistant to these drugs. Over the last 2 decades, this lateral transmission has allowed MRS to spread through canine populations (1,5). Unfortunately, even after successful treatment of pyoderma caused by MRS, these organisms can continue to colonize dogs (5) and cause future resistant infections.

The emergence of MRS in dogs is not surprising, as decades earlier S. aureus trod the same path in humans. The role of anti-microbial use as a risk factor was well-known. More surprising is how long it has taken our approach to pyoderma to change. I was far from alone in relying on systemic antibiotics as a key treatment. A study of UK primary care practices showed that 92% of canine pyoderma cases received systemic antimicrobials, over half without concurrent topical therapy. Fewer than 5% of dogs were treated with topical therapy alone (8). Due to the high frequency of pyoderma in dogs, skin infections are the primary reason for antibiotic treatment in this species and account for up to 30% of prescriptions (6,9). The lengthy courses of therapy used for skin infections compound the large number of doses used worldwide.

The toll of antimicrobial resistance (AMR) on humans and health care systems is already staggering (10). In veterinary medicine, the principles of antimicrobial stewardship and the One Health Initiative have gained prominence as we recognize that efforts to combat AMR must encompass all species. Three key approaches recommended for limiting AMR include preventing disease occurrence, reducing overall antimicrobial drug use, and improving antimicrobial drug use (11). In small animal practice, one of the most practical and frequent opportunities to practice antimicrobial stewardship is in the management of canine pyoderma.

As a result of AMR, my approach to pyoderma has changed since I treated this terrier more than 20 years ago. Some of the key points are listed here, and published guidelines with more detailed recommendations are included below.

1. Topical therapies are now my first-line treatments for pyoderma. The World Association for Veterinary Dermatology recommends that “topical therapy should be used as the sole on-animal antibacterial treatment for surface and superficial infections whenever a pet and owner can be expected to be compliant” (1). This works because most cases of canine pyoderma are indeed superficial, limited to the epidermis and superficial portion of the hair follicles. A “deeper” treatment with systemic antibiotics is usually not necessary and in my practice, it is now the exception. Topical monotherapy was previously recommended chiefly for localized infections. But when using shampoos, does it really matter if the patient has 1 lesion, or a few dozen? Various topical therapies have been studied and found to be effective for pyoderma. The best evidence exists for the use of chlorhexidine shampoos (1,9). Chlorhexidine has a broad spectrum of antibacterial activity and there is a relative lack of resistance to this drug despite more than 60 years of use in health care settings. It is nonirritating, rarely sensitizing, and can remain bactericidal for many days after application (12). Chlorhexidine-based products can be as effective as systemic antibiotics in dogs with superficial pyoderma: the efficacy of twice-weekly 4% shampoo (with 3 to 5 minutes of contact time) and daily 4% solution was equal to 4 weeks of oral antibiotics in 1 study, whether infection was caused by methicillin-susceptible or methicillin-resistant staphylococci (13). This is a common protocol that I use for active infections, with reduced frequency for prevention. In the last 5 years, the selection of chlorhexidine-based products available in Canada has grown substantially and includes 2% to 4% chlorhexidine shampoos, sprays, mousses, solutions, and wipes. In addition to an antiseptic effect, shampooing removes organisms and debris from the skin surface and improves the dog’s odor and appearance. It also spares bystander organisms in other organ systems unnecessary exposure to antimicrobial drugs, reducing the risk of selecting for resistant strains (9).

2. I help clients implement topical therapies effectively. This means providing a topical therapy handout, and instructions on the frequency, volume, and duration of application of prescribed products.

3. I still prescribe systemic antibiotics for pyoderma when necessary. This includes dogs with deep or severe pyoderma, dogs responding poorly to topical therapy within 3 to 4 weeks, or when patient or client factors make topical therapy impractical. Follow-up is key for assessing the efficacy of treatments for infection. I aim to re-examine patients (including cytologic examination) within 2 weeks if using systemic antibiotics, and within 2 to 4 weeks if using only topical therapy. I base my decision about whether to use systemic antibiotics on clinical and patient/client factors, rather than on whether the isolate is resistant or susceptible on culture. Methicillin-resistant S. pseudintermedius (MRSP) are no more virulent than susceptible strains and the disease they cause is clinically indistinguishable. It is only when we use systemic antibiotics that a difference becomes apparent. Thus the mere isolation of MRSP on culture should not prompt an escalation to systemic therapy.

4. When selecting systemic therapy, I rely on culture and susceptibility testing whenever MRS is suspected. Empirical antibiotic selection is contraindicated in these cases due to the high prevalence of multidrug resistance among these strains (1). In addition to severe infections, I collect cultures from patients with recurrent infections and when empirical therapy fails to resolve an infection as expected. Practically, I might collect a bacterial culture from a patient with superficial pyoderma while commencing topical therapy and treating the primary condition with the aim of adding a systemic antibiotic, if needed, once results are reported. A follow-up call to the client to relay the culture results often indicates sufficient improvement that antibiotics are not prescribed (I call this the “antibiotic cooling-off period”). When interpreting cultures, it is critical to evaluate not just the antimicrobial resistance pattern but also the species isolated. Notably, the significance of the uncommonly pathogenic coagulase-negative staphylococci (aside from S. schleiferi) should be interpreted with caution, even if methicillin-resistant (1). Key indications and techniques for bacterial culture and susceptibility testing are available in open-access resources (9,14) along with guidelines for culture interpretation (1).

5. I attempt to address the cause of pyoderma, knowing that repeated antibiotic therapy is likely to become ineffective. Preventing disease is arguably the most important component of antimicrobial stewardship and one that is often overlooked (11). Staphylococcal pyoderma in dogs is secondary to an underlying condition and addressing this is critical to preventing recurrences. Allergic skin disease tops the list of underlying conditions and may be responsible for 74% to 90% of cases (5,15). Despite their complex and chronic nature, allergies in most dogs can be successfully managed. Interventions including systemic and topical therapies to reduce inflammation and pruritus, allergen-specific immunotherapy, dietary and topical treatments to improve the skin barrier, and elimination diet trials can all be useful in preventing infections. It may take some time to find a regimen that is most effective for each dog, particularly now that we have many choices for antipruritic/anti-inflammatory therapies. The use of bacterins and other preventative therapies warrants further investigation. Staphage lysate (SPL) (Delmont Laboratories, Swarthmore, Pennsylvania, USA) bacterin injections can be considered for dogs with recurrent pyoderma that is idiopathic, or continues despite treatment of the primary disease (16,17).

6. I try to be more patient with skin infections. Unlike with sepsis or pneumonia, we can delay starting systemic antibiotics with most cases of superficial pyoderma, and we can tolerate a more gradual improvement. Since pyoderma represents a dysbiosis, rather than infection with an external pathogen, complete eradication of the causative organism is unlikely even using aggressive systemic therapy (5). Treatment should thus aim to restore a more balanced microbiota. This takes time. Treating the dog’s pruritus allows for an acceptable quality of life as we strive to return the skin to a more normal state.

7. I recognize the potential for inter-animal transmission of resistant staphylococci. Although pyoderma is not considered “contagious,” the lateral movement of resistant strains, especially within a clinic setting, is possible and impacts how I examine patients. Recommendations for hand hygiene, personal protective equipment, and cleaning/disinfection are discussed in published guidelines (1).

8. I am careful with how I present information about resistant infections to clients. I avoid the term “superbug” and the erroneous label “MRSA” (methicillin-resistant S. aureus) when speaking about MRSP. I reiterate that topical therapy is usually very effective for treating these infections. I discuss the low potential for zoonotic transmission and provide a balanced client handout.

Some of the questions that remain to be answered pertain to the appropriate duration of systemic antibiotic therapy. These questions are particularly relevant when treating resistant infections with drugs that carry a considerable risk of serious adverse effects (e.g., rifampin or amikacin). A 21- to 28-day course of systemic therapy, extending at least 1 week past the resolution of lesions, is a standard recommendation for treating superficial bacterial folliculitis in order to prevent relapses (11,12). This is based on experience but not yet on a scientific foundation, and the effect of concurrent topical therapy on treatment duration has not been explored. Since administering antibiotics for longer than is necessary can increase the risk of resistance, evidence-based recommendations in human and veterinary medicine have often moved to shorter courses of therapy than were previously prescribed (11,18). In light of the quantities of antibiotics prescribed to dogs with pyoderma, it is critically important to re-examine treatment duration for pyoderma using clinical trials.

When I recall patients like this Jack Russell terrier, what seems most surprising is that his treatment was once considered standard or appropriate. As you can imagine, I would treat him quite differently today. This is partly due to an improved selection of treatments to control his underlying disease, but largely as a response to antimicrobial resistance. A silver lining of the dissemination of MRS has been learning that we can and should treat skin infections differently, providing a key opportunity for antimicrobial stewardship in small animal practice.

Resources:

• Guidelines for the diagnosis and antimicrobial therapy of canine superficial bacterial folliculitis (Antimicrobial Guidelines Working Group of the International Society for Companion Animal Infectious Diseases). Open Access: https://doi.org/10.1111/vde.12118

• Recommendations for approaches to meticillin-resistant staphylococcal infections of small animals: Diagnosis, therapeutic considerations and preventative measures.: Clinical Consensus Guidelines of the World Association for Veterinary Dermatology. This comprehensive document addresses many questions including less frequently isolated species, such as MRSA. Open Access: https://doi.org/10.1111/vde.12444

• CVMA Guidelines for Veterinary Antimicrobial Use: https://www.canadianveterinarians.net/AMU-UAM

• The Canadian Academy of Veterinary Dermatology website contains open access and member resources including clinical guidelines, client handouts, and lists of topical therapies available in Canada: www.cavd.ca

• Client handouts for MRSP and MRSA: www.wormsandgermsblog.com