Canine pyoderma: a tiered approach

Introduction

Pyoderma is a bacterial infection of the skin, generally divided into superficial and deep categories depending on the layer of the skin that is affected. Clinical lesions of superficial pyoderma include erythematous papules and pustules (Figure 1) which may be centered on hair follicles. Honey-to-brown colored crusts (Figure 2) are also often present on the skin and may be adhered to the hair shafts. Epidermal collarettes (Figure 3), which develop as an annular area of scale, may be noted as well. In more chronic cases, alopecia, hyperpigmentation and ulcerations are to be found (Figure 4). Deep pyoderma lesions are noted clinically by ulcers and draining tracts (Figure 5) 1.

Causative organisms

The bacteria associated with a pyoderma are basically an overgrowth of the animal’s normal flora; the most common bacteria identified in pyoderma are coagulase positive Staphylococcus species. Of these, S. pseudintermedius is the most common in dogs, whilst S. aureus, another coagulase positive organism, has also been identified as an offending bacteria, but is more prevalent in cats. S. schleiferi has been reported as the second most common bacteria in canine pyoderma, and a unique aspect of this organism is that it is a coagulase variable species; some reports identify it as coagulase positive, while others note it as coagulase negative 2. Historically, coagulase negative Staphylococcus spp. have been identified as being non-pathogenic, but newer reports are showing these bacteria (which include S. epidermidis, S. xylosus, and S. haemolyticus 1,3,4) can be pathogenic. Occasionally, Streptococcus canis, Pseudomonas aeruginosa, Corynebacterium auriscanis, Escherichia coli and Proteus spp. are identified as the causative bacteria in a pyoderma 1.

Antimicrobial resistance

Bacteria are constantly evolving and acquiring resistant mechanisms or genetic mutations, and Staphylococcus spp. are well-known for some of their genetic mutations to circumvent antimicrobials. A common one identified in 80-94% of S. pseudintermedius cases is the blaZ gene mutation, which is known for resistance to beta-lactams, hence amoxicillin, ampicillin, and penicillin are not effective. Amoxicillin still may be effective in these cases if it is potentiated, e.g., with amoxicillin-clavulanic acid 5,6. 

A bigger concern in veterinary medicine from a One Health perspective is the mecA gene mutation. This encodes for an altered penicillin-binding protein (PBP2a) with low affinity to all β-lactams, including penicillins, cephalosporins, and carbapenems, meaning that β-lactams cannot bind to the bacterial cell wall to kill the organism. This genetic mutation is referred to as methicillin-resistant staphylococcus (MRS), with the species noted afterwards; for example, methicillin-resistant Staphylococcus pseudintermedius (MRSP) and methicillin-resistant Staphylococcus aureus (MRSA) 2,7. A new generation of cephalosporins has been developed that are effective against MRSA, but these should be reserved for human medicine. It is common for MRS to express resistance to a combination of other drugs, including aminoglycosides, chloramphenicol, fluoroquinolones, lincosamide, tetracyclines, potentiated sulfonamides and rifampicin. These cases may then be considered multidrug-resistant (MDR) if they are resistant to two additional antimicrobial classes, or extensively drug-resistant (XDR) when they are resistant to all but two or fewer antimicrobial classes 2,7.

Prevalence and risk factors

MRSP was first identified in animals in 2005 in Belgium 8, and since then it has been identified in animals in most, if not all, countries. Its prevalence, however, shows considerable geographical variability, which may be due to different antimicrobial stewardship guidelines and antimicrobial restrictions. In 2011, rates of MRSP were reported from 0-4.5% in dogs in the community and up to 7% of dogs with skin disease. At that time, anywhere from 30-66% of S. pseudintermedius isolates were methicillin-resistant, depending on the country 9. A recent study in the United States showed that the prevalence of S. pseudintermedius isolates resistant to oxacillin (determinant for methicillin resistance) has statistically significantly increased between 2010 and 2021 10, whilst another US study showed an increase of MRSP from 28% in 2010 to 80% in 2020 11. The prevalence has seen a significant increase in the last 10 years worldwide.

In terms of risk factors, one study noted dogs with a history of being treated with antimicrobials within the last month have an increased risk of MRSP compared to methicillin-susceptible Staphylococcus pseudintermedius (MSSP) 5. Another study showed animals given antibiotics in the previous year had an increased risk of being multidrug-resistant 11. Development of MRSP has also been linked with previous fluoroquinolone exposure 12.

Diagnosis

Cytology

The easiest and most efficient way for a diagnosis of pyoderma is cytology of clinical lesions (pustules, crusts, epidermal collarettes). There are a variety of ways to do this, including direct impression, tape cytology, cotton-tipped applicator, and the slurry technique 13. The type of sampling method is based on the characteristics of the lesion to be sampled. For example, pustules and ulcerations are easily sampled with direct impression since exudate is present. Tape cytology may be a better option for crusts and epidermal collarettes due to their dry nature. Observance of inflammatory cells with associated bacteria (Figure 6) is supportive of a pyoderma, and when the inflammatory cells contain intracellular cocci (Figure 7), diagnosis is confirmed 1.

Bacterial culture

When there is a lack of response to empirical antimicrobial therapy, bacterial culture and susceptibility are necessary to determine the appropriate systemic antimicrobial. It is never wrong to culture a pyoderma, but there are criteria when it is highly recommended. Current recommendations for bacterial culture and susceptibility include the following:

1. less than 50% reduction of lesions within 2 weeks of appropriate systemic antimicrobial therapy; 
2. emergence of new clinical lesions (papules, pustules, epidermal collarettes, crusts) two or more weeks after appropriate antimicrobial therapy with a cytological diagnosis of pyoderma; 
3. presence of clinical lesions after six weeks of antimicrobial therapy alongside a diagnosis of pyoderma based on cytology; 
4. intracellular rod-shaped bacteria identified on cytology; 
5. a prior history of multidrug-resistant infection in the animal or a household animal 1. 

Pustules are the ideal lesion to sample, as they can be lanced and sampled with the culturette swab. Sampling with the culturette swab under crusts is also a good option if there is purulent exudate present. If the lesion is completely dry, such as a crust or an epidermal collarette, an ideal method to use is saturating the culturette swab with saline prior to rubbing the skin. This method has been shown to obtain a higher number of bacteria compared to a dry swab 14. None of the above sampling methods requires any surface disinfection. However, if planning to biopsy the skin for tissue culture, it is recommended to clean the surface to remove contaminants 1.

Treatment

Treatment of a superficial pyoderma can be accomplished with either topical or systemic therapy, or a combination of both. With the increase in antimicrobial resistance, there has been a push to use more topicals in place of systemic antimicrobials 10. One study demonstrated no difference when canine superficial pyoderma was treated with a systemic antimicrobial (amoxicillin-clavulanic acid) or a topical chlorhexidine shampoo and solution over a 4-week period 15. 

Topical therapy

Topical therapy has historically been underutilized for treating superficial pyoderma 1, but it has the benefit of achieving a higher concentration of drug compared to what can be delivered systemically. Additionally, since the therapy is applied directly to the skin, drug concentration is not decreased via metabolism. When deciding to use topical therapy, two decisions are necessary; 

1. what active ingredient to use, and 
2. which formulation would be ideal for the situation. 

In terms of active ingredients, chlorhexidine is widely accessible, and the most common agent used. It is available in a variety of concentrations (2-4%) and some products will combine it with an antifungal, such as miconazole, ketoconazole or climbazole. There are studies available showing the concentration of chlorhexidine does not directly correlate to efficacy; for example, a 4% chlorhexidine shampoo is not superior to a 2% chlorhexidine/2% miconazole shampoo. Chlorhexidine has been shown to be equally successful in treating MRSP and MSSP, and while resistance to chlorhexidine is a common concern, there is no evidence to suggest that this is a clinically relevant problem 16.

Benzoyl peroxide and ethyl lactate are the next most common active ingredients after chlorhexidine. Benzoyl peroxide has been shown to be effective in treating superficial pyoderma, but the formulations available are significantly limited. Some reports have shown variable results regarding its success, but it should be noted that in-vivo studies are necessary to show the true activity of benzoyl peroxide – the reason being that the interaction with the skin will produce highly reactive oxygen radicals, which are very potent against bacteria. Ethyl lactate is similar to benzoyl peroxide in multiple aspects, but again formulations are limited, and again in-vivo studies are necessary to show the true activity of this ingredient, because of the necessary skin interaction that hydrolyzes it into ethanol and lactic acid 16. 

Some of the newer active ingredients that have shown success in treating superficial pyoderma include sodium hypochlorite, accelerated hydrogen peroxide, silver compounds, and essential oils or plant extracts. Diluted bleach, which has the active ingredient of sodium hypochlorite, has previously been shown to be effective against S. pseudintermedius 16, and it also appears to be tolerated on the skin when diluted down to 0.005% in healthy dogs 17. Sodium hypochlorite is available in combination with salicylic acid in a shampoo formulation in some countries. Accelerated hydrogen peroxide has also been shown to be effective and comes in a shampoo. Silver compounds are an attractive active ingredient when used in combination with other products such as chlorhexidine, with several formulations available. Some essential oils and plant extracts have been added to topical products to aid in the resolution of pyoderma or help in prevention 16.

The variety of formulations available for topical therapy include shampoos, sprays, wipes, mousses, rinses, conditioners, gels, creams and ointments. One way to decide which formulation may be preferred is the extent of the disease, whether generalized, localized or focal. For generalized disease; shampoos, sprays, mousses, rinses, and conditioners would be ideal. For localized or focal lesions, wipes, gels, creams and ointments are good options. Shampoos are by far the most common formulation available with the widest variety of active ingredients. Typical regimen for shampoos, sprays and mousses includes 2-3 times weekly until 7 days past resolution, with shampoos allowed a contact time of 10 minutes prior to rinsing. Wipes, gels, creams, and ointments should be used daily 1.

Finally, fluorescent light energy is a newer technology that has been used recently for both deep and superficial pyoderma. This technology combines fluorescent light along with chromophores present in a gel to produce photons at different wavelengths to penetrate deeper in the skin to influence biological activity, promote cutaneous repair, and increase antimicrobial activity. It has been shown to be successful as monotherapy for superficial pyoderma when compared to systemic antimicrobials for resolution of clinical lesions and to decrease the treatment time required 18.

Systemic therapy

Systemic antimicrobial therapy for superficial pyoderma is currently recommended to be 21 days or 1 week past resolution of clinical lesions, whilst deep pyodermas are recommended to be treated for 6 weeks or 2 weeks past clinical resolution. These recommendations are being evaluated further and may change in the future. Deep pyoderma necessitates systemic therapy, since topical therapy is unlikely to reach the infected area. Since antimicrobial stewardship is a major focus, guidelines regarding antimicrobial selection for superficial pyoderma have been developed, divided into tiers (Table 1). First-tier antimicrobials are recommended as empirical therapy when culture has not been performed. Third-generation cephalosporins are placed into a gray area of first/second tier, due to the concerns of increased selection of antimicrobial resistance of gram-negative microbes at distant sites. Second-tier antimicrobials should not be used unless a culture has been undertaken, with susceptibility that shows it would be an appropriate choice. Third-tier antimicrobials should not be used unless there is no other option for treating the infection, as they are reserved for human medicine. Since superficial pyodermas can be treated topically, third-tier antimicrobials are not recommended in this situation; deep pyoderma, which requires systemic therapy, would be the only situation where these may be applicable 1.

One study looked at the temporal changes of antimicrobial resistance between 2010 and 2021 in the United States. They found a significant increase in resistance to clindamycin, amoxicillin-clavulanic acid, oxacillin, cefoxitin, cefpodoxime, tetracycline, chloramphenicol, erythromycin, marbofloxacin, and gentamicin. The only two antimicrobials evaluated which did not show an increase over that period were cephalothin and sulfonamides 10. This shows the need to follow antimicrobial stewardship guidelines and use systemic antimicrobials judiciously, as noted in the tier structure.

Table 1. Systemic antimicrobial tiers.

Carrier status 

When pyoderma has been resolved, it is important to note that there is a high chance that the normal flora will then be the same organism that was treated; one study reported almost half (45.2-47.6%) of dogs with a pyoderma due to MRSP then had MRSP detected either on the skin or carriage sites after resolution of the infection 19. Almost as alarming is when dogs with pyoderma due to MSSP were treated successfully, 38.3% had MRSP detected on the skin or carriage sites afterwards 19. Trying to decolonize dogs infected with MRSP, as is performed in humans with MRSA, is not successful. Additionally, asymptomatic in-contact dogs have been shown to be positive at a similar frequency as dogs infected with MRSP (67.4% vs. 66.7%), demonstrating the transmission potential of bacteria with in-contact dogs in the house 20. Carrier status of MRSP was noted intermittently up to 10 months afterwards in this study, justifying the reason to culture an animal infected with a pyoderma if it has a history of MRSP within the last year. 

Preventing recurrent pyoderma

Pyoderma is a secondary disease in most cases, so the primary disease must be evaluated and controlled to prevent recurrence of pyoderma 1. Atopic dermatitis is a common primary precursor for pyoderma in dogs, and in such cases treatment should shift to control the atopy in order to prevent excessive use of antimicrobials. An Australian study looked at dogs with atopic dermatitis which were treated with oclacitinib; when compared to control dogs, fewer antimicrobial courses were prescribed in the oclacitinib treated dogs 21. Diet can also be beneficial to prevent pyoderma and lessen recurrence and severity of clinical signs from atopic dermatitis; one study in affected dogs fed an appropriate diet showed a significant decrease in signs of atopic dermatitis over a 9-month period 22.

Zoonotic concern

When managing any pyoderma, a common concern of owners is the zoonotic potential. There is a definite risk of bacteria being transferred from a pet to the owner and vice versa 1. A study in Taiwan showed an increased risk of owners being colonized with S. pseudintermedius when they have three or more dogs, and if they allow the dog to lick the owner’s face 5. If the owners are colonized with MRSP from the animal, the genetic mutation from the MRSP could then be transferred to the owner’s normal Staphylococcus spp. flora, which could mean that they are then at risk for MRS infections 7.

Conclusion

Bacterial resistance is significantly increasing with pyoderma. Therefore, topical therapy should be considered as the first line of treatment to prevent further pressure on the bacteria to develop resistance to systemic antimicrobials. If systemic antimicrobials are necessary, following the tier system is crucial; Tier 1 antimicrobials are ideal for empirical therapy, but Tier 2 antimicrobials should only be used when a culture indicates susceptibility.