Staphylococcal skin diseases–an update (Proceedings)

Much has changed in the management of bacterial skin diseases in veterinary patients since the recognition of methicillin resistant (β-lactam antibiotic resistant) staphylococcal skin infections and their significance in both the human and veterinary medical communities. Awareness and responsible use of antibiotic medications is a must when dealing with these emerging pathogens.

Bacterial flora of the skin: an overview

Normal canine and feline skin is host to various species and strains of bacteria that are considered normal inhabitants. Traditionally, these organisms have been considered resident transient organisms based on their ability to replicate on normal skin and hair. While resident bacteria are in fact capable of multiplication on normal skin, transient organisms are acquired from the environment and are not capable of multiplying on the normal skin of most animals. Thus transient organisms are not considered pathogenic unless isolated from lesional skin. In addition, a nomadic population also exists. Nomads are capable of brief adherence and colonization and their isolation is thought to reflect environmental contamination. Thus the current classification scheme identifies residents as those organisms that are isolated >75% of the time the skin is cultured, nomads are isolated <75% but >25% of the time, and transients can only be isolated <25% of the time the skin is cultured. An alternative method of classification involves the number of colonies isolated. One method utilized defined resident organisms as those with ≥10 colonies isolated from a specimen and transient organisms as those with <10 colonies per specimen. This method however, is more restrictive in that species that are consistently isolated with high frequency from multiple sites, regardless of the colony count, should be considered to have colonized the individual. By evaluating colony count only, less common but important species may not be considered relevant. Therefore both frequency and persistence of isolation should be considered when differentiating normal inhabitants from those organisms causing secondary colonization or contamination rather than secondary infections. This differentiation is crucial in generating an effective therapeutic plan for the appropriate pathogenic organism based on culture and sensitivity data, especially when multiple organisms are reported.

Frequently, additional organisms may be cultured from the skin. Upon isolating one such organism from the skin of a patient with skin disease, the clinical picture may become confused. The significance of the isolation of a transient organism must be questioned as a pathogen unless it is involved with a pathologic process as a secondary invader. Therefore, although it may not be the expected organism, when it is present in high numbers in a relatively pure culture, it is important to evaluate the site of culture as well as the method of collection. A culture obtained from the surface of the skin in an area that is pruritic or painful to the patient, for example, will be expected to contain transient contaminant organisms from the oral cavity as the animal licks or chews that site. However, if the lesion was a closed pustule or nodule, the result may be accurate. It has been demonstrated that culturing an epidermal collarette is also a reliable method if performed correctly.

Colonization of the skin

It is well documented that the oral, nasal and anal mucocutaneous sites serve as a reservoir for S. pseudintermedius colonization in the dog. In addition, the ear is another site where S. pseudintermedius can be frequently isolated. These locations appear to serve as carrier sites for seeding the rest of the skin and hair through normal grooming activity. It is not clear however, why some dogs become resident carriers of S. pseudintermedius with higher numbers of bacteria than others. Puppies of dogs that had been classified as resident carriers also had significantly higher populations of S. pseudintermedius, and it appeared that a dominant strain was consistently isolated from both the adult dogs and their puppies. This continued transfer of strains of S. pseudintermedius between generations has been suggested as a potential reservoir for retention of genes for staphylococcal antibiotic resistance. This concept needs to be investigated further as exchange and acquisition of new strains occurs between dogs with normal daily contact. Animals receiving antibiotic therapy may be especially at risk for acquisition of resistant organisms as this situation may in fact encourage the transfer of organisms via reduction of the normal resident population of staphylococcus.

Coagulase-negative staphylococci

Coagulase-negative staphylococci (CoNS) have long been considered resident organisms that are non-pathogenic in both small animals and humans. Because of their relatively low virulence and ubiquitous nature, they typically have not been speciated by most human and veterinary laboratories but reported simply as CoNS. However, with the emergence of nosocomial infections linked to CoNS in Europe and now in the United States, the current recommendation is to identify clinically significant CoNS to the species level. While some CoNS isolates remain true contaminants it is especially valid to speciate a CoNS including an antibiotic susceptibility profile when repeated cultures are obtained or no other isolate is identified in patients with clinical disease.

According to past reports, the most numerous coagulase-negative staphylococcus isolated from dogs is S. epidermidis, while S. simulans is isolated from cats (Table 1). More recently, both the coagulase-negative subspecies of S. schleiferi as well as S. sciuri have also been isolated from dogs.

Emerging pathogens

Coagulase-negative staphylococcus

Coagulase-negative Staphylococcus species (CoNS) caused 27 to 27.9% of nosocomial blood stream infections in hospitals participating in surveillance programs in the early 1990's. In addition, based on data obtained during this assessment, coagulase-negative Staphylococcus species are among the five most commonly reported pathogens isolated from these same hospitals. Why is this important? How does this relate to veterinary medicine? The answer is progressively more relevant as the rate of nosocomial and community-acquired infections with coagulase-negative staphylococci species (CoNS) continues to increase in both human and veterinary health care settings. In human hospitals, immunocompromised patients, as well as hospitalized patients with implant devices such as intravenous catheters or pacemakers have been overrepresented as they are the population most susceptible to such infections. The significance of the problem in the veterinary field has also grown with the increase in numbers of immunocompromised patients as well as advancements and demands for sophisticated veterinary health care. The increased incidence of CoNS infections coincides with the development of more invasive medical procedures and advancements in medicine for both humans and animals, allowing for opportunistic infection to occur.

In spite of this growing concern, very little is known about the true incidence of infections caused by CoNS in veterinary patients. Historically clinical microbiologists as well as clinicians discounted the presence of CoNS as contaminants in clinical specimens because they are considered less virulent and for the reason that they comprise a significant component of the resident microflora of both humans and animals. Differentiating pathogenic from contaminant strains therefore, has and still does pose a large problem. In the human health field anything other than S. aureus, which is coagulase-positive, was simply not reported or was reported as CoNS. Unfortunately this approach continues today and has perpetuated in veterinary microbiology laboratories as well. Therefore as a result of the lack of concern with the pathogenicity of CoNS in the human health field, the same trend has existed within the veterinary health field until the most recent changes that have occurred in regards to CoNS.

Staphylococcus schleiferi

In the early 1990's, Staphylococcus schleiferi, a coagulase variable organism, was recognized as a human as well as a veterinary pathogen. Two subspecies were initially identified and isolated from patients: a coagulase negative subspecies, S. schleiferi schleiferi from humans in 1988 and a coagulase positive subspecies, S. schleiferi coagulans in 1990 from the external auditory meatus of dogs with otitis externa. In human medicine both subspecies have been associated with wound infections, endocarditis, osteomyelitis, bacteremia, urinary tract infections and meningitis. In the veterinary literature, S. schleiferi coagulans has been associated with pyoderma as well as otitis externa in dogs. Both S. schleiferi schleiferi and S. schleiferi coagulans were isolated from dogs with pyoderma in the most recent veterinary study. This was the first report to associate S. schleiferi schleiferi with canine pyoderma, as well as demonstrate the presence of methicillin-resistant variants.

S. schleifericoagulans was first identified in 1988, but only recently has this subspecies been reported as a pathogen in human and veterinary medicine. Prior to that, the most recent reclassification of Staphylococcus species isolated from domestic animals occurred in 1976, when S. intermedius was differentiated from S. aureus. Thus, it is likely this organism is under-reported by automated staphylococcal identification systems because S. schleiferi coagulans is phenotypically similar to S. aureus, and therefore is similar to S. pseudintermedius. In addition the (CoNS) have historically been considered nonpathogenic and all staphylococcal organisms other than S. aureus were reported simply as CoNS in human medicine. Based on this information, it is expected that the coagulase-negative subspecies, S. schleiferi schleiferi has also been under-reported.

Staphylococcus species identification

Consistently, S. pseudintermedius has been reported as the most frequently isolated coagulase-positive Staphylococcus species associated with canine pyoderma since it was reported in the 1970's. How do we know that this is true? How can we be sure these isolates were actually S. pseudintermedius? Prior to the initial report differentiating S. pseudintermedius from S. aureus, the literature reported all coagulase-positive isolates as S. aureus. Since then, when referring to older publications, newer reports have assumed that isolates reported, as S. aureus were actually S. pseudintermedius. Now, with the newly reported S. schleiferi coagulans also associated with pyoderma, it is likely that some of these isolates were misidentified previously as S. pseudintermedius as most laboratories do not perform the extra steps required to differentiate the species. While the frequency of isolation of S. schleiferi coagulans has been low in both the human and veterinary literature, the true incidence is unknown.

S. schleiferi is indistinguishable from S. pseudintermedius based on standard colony characteristics and biochemical tests. Colonies typical of both species appear as opaque, off-white colonies that are ≥ 1mm in diameter after 24 hours of incubation and are surrounded by a double zone of hemolysis on blood agar medium. In addition, both species display positive catalase and coagulase test results and no or delayed fermentation of maltose and mannitol. Additional carbohydrate fermentation tests are thus required in order to differentiate between the 2 species. While positive results are obtained from fermentation of trehalose and lactose for S. pseudintermedius, these tests are typically negative for S. schleiferi. Also, when performing the Voges-Proskauer (VP) test, which is the production of acetoin from glucose or pyruvate, S. pseudintermedius typically demonstrates a negative result and S. schleiferi has a positive result. The subspecies of S. schleiferi are then differentiated based on the result of the tube coagulase test. S. schleiferi coagulans is coagulase positive, whereas S. schleiferi schleiferi is coagulase negative.

Adjustments in laboratory protocols are required for the future. New techniques to simplify the identification of CoNS are available and evaluated in the literature. Laboratories must agree to adopt consistent methods of precise identification, such as accurate commercial test kits and additional carbohydrate fermentation tests, to reliably identify CoNS as well as the newer coagualse-positive species, which are very similar to each other using conventional methods of identification.

Bacterial infections

The more recent literature classifies bacterial skin infections based on the depth of skin involvement rather than lesion distribution or underlying primary disease process. Because this manuscript focuses on emerging pathogens the diseases were classified based on causative organism rather than clinical presentation.

Staphylococcal pyoderma

Staphylococcus species have been associated with surface, superficial and deep pyoderma. Pyotraumatic dermatitis, skin-fold pyoderma (intertrigo) and mucocutaneous pyoderma are types of surface pyoderma with secondary Staphylococcus spp. involvement. These infections typically respond favorably to topical therapy but recurrence is frequent if a primary disease process cannot be identified and controlled. Superficial infections are commonly diagnosed in clinical practice and include impetigo, superficial bacterial folliculitis (pyoderma) and superficial spreading pyoderma. Typically caused by Staphylococcus species, it is now recognized that other species of staphylococcus can also serve as pathogens. Treatment is tailored for the expected organism as well as the severity of the disease. Impetigo is recognized in young dogs and is characterized by subcorneal pustules that do not involve hair follicles. Skin that is thinly haired is more commonly affected and the lesions are not typically pruritic. Antibiotics are rarely required as the lesions often resolve without treatment, however topical therapy with an appropriate dose and duration of oral antibiotic therapy may be required if concurrent superficial folliculitis is present. Superficial folliculitis is a very common clinical presentation in dogs, but is not common in cats. It is defined as inflammation of the superficial portion of the hair follicle and inflammatory papules are the hallmark lesion. Pruritus is routinely reported. Pyoderma is frequently secondary to an underlying primary process and recurrence is likely without control of the predisposing disease. Empirical therapy is often chosen for treatment of uncomplicated cases of superficial folliculitis, however with recurrence of lesions in the face of an appropriate dose and duration of therapy, culture and sensitivity should be considered and treatment adjustments made based on results. Deep bacterial infections are less commonly appreciated and are more serious in nature. Deep folliculitis, furunculosis and cellulitis typically require longer courses of treatment and scarring may complicate treatment. These lesions may be painful and organisms in addition to Staphylococcus species, such as Pseudomonas spp., Escherichia coli, or Proteus spp. may be involved. Culture of purulent material expressed from a non-draining lesion or macerated tissue culture obtained via sterile biopsy technique may be required in order to identify the causative agent and/or pattern of antibiotic resistance, especially if multiple abbreviated courses of treatment have failed previously.

Pseudomonas pyoderma

Little information exists in the veterinary literature describing reports of bacterial skin infections associated with Pseudomonas aeruginosa. Recently 15 cases of Pseudomonas pyoderma were described with deep infections comprising the majority of cases. While less numerous, cases of superficial pyoderma were also reported. Folliculitis associated with Pseudomonas aeruginosa has been described in humans in association with hot tubs or whirlpools and similar type cases of P. aeruginosa have been anecdotally reported in association with self -service dog grooming facilities. While these cases in humans tend to be self-limiting and the veterinary cases respond to antibiotic therapy, it is important to recognize that unexpected organisms beyond the standard coagulase-positive staphylococcus may serve as the causative agent in some instances.

Zoonotic concerns

Staphylococcus aureus and Staphylococcus pseudintermedius

Evidence of zoonotic transmission between pets and owners has been described for both S. aureus and S. pseudintermedius. A methicillin-resistant strain of S. aureus was isolated from a patient's wound as well as the dog in the household with asymptomatic nasal carriage. S. pseudintermedius was identified as the pathogenic organism in a healthy patient with otitis externa and was also isolated from the ear, back and chest of the dog in the household.

Staphylococcus schleiferi

Both subspecies of S. schleiferi have been isolated from normal and diseased humans and dogs. S. schleiferi has been reported as part of the normal human preaxillary flora and carnivores have been implicated as the normal host, however this information in the literature is poorly documented. The true incidence of isolation of S. schleiferi from humans or dogs is unknown and investigation into the role of this organism as a pathogen has only begun.