Antibacterials for Integumentary Disease in Animals

Most canine skin infections are caused by coagulase-positive Staphylococcus pseudintermedius (formerly S intermedius), which commonly produce beta-lactamase. Other staphylococcal species have been described, including S aureus, S schleiferi, and S hyicus. There does not appear to be any difference in the disease patterns or clinical signs produced by the different species, although species-specific differences in antimicrobial resistance profiles have been observed in North America, with S pseudintermedius and S aureus showing more resistance than S schleiferi coagulans. Because phenotypic differentiation is unreliable, species identification requires molecular techniques such as PCR assay detection of species-specific thermonuclease genes (nuc) or 16S rDNA sequencing.

Occasionally, Proteus spp, Pseudomonas spp, and Escherichia coli are secondary invaders of the dermis. Pasteurella multocida and beta-hemolytic streptococci are the most common bacteria isolated from the epidermis of cats. Actinomycetes and mycobacteria are rare opportunistic invaders in dogs and cats. Bactericidal drugs expected to be effective against these bacteria should be used when treating the first occurrence of pyoderma in an animal.

For uncomplicated surface and superficial pyoderma, it may be sufficient to use topical antimicrobial treatment (iodophors or 1%–4% chlorhexidine) to successfully treat the infection, so long as the animal and owner compliance allows adequate application.

Topical medication is the key to successful treatment of otitis externa, as this is an infection within the lumen of the canal and there is no transport mechanism that will transport systemically administered medications across the canal wall in high enough concentration to control the bacterial infection. The canal must be free of exudate before the medication is applied to allow full penetration of the entire canal length.

The choice of the antimicrobial is usually made empirically, based on cytologic evaluation of the canal exudate; however, culture should be considered in chronic cases where a number of therapies have already been used.

Bacterial skin disease in large animals may be caused by Dermatophilus congolensis, staphylococci, Corynebacterium spp, Actinomyces, and rarely Bacillus spp or Pseudomonas spp. Draining tracts or abscesses in the skin of sheep or goats may be caused by Corynebacterium pseudotuberculosis. Fusobacterium spp and Bacteroides spp are the primary invaders in interdigital necrobacillosis (footrot). The spirochete Borrelia suilla is a secondary invader of skin lesions caused by sarcoptic mange or ear biting in swine. Clostridial diseases in cattle and erysipelas in swine are disorders that involve the integumentary system and cause serious economic losses.

Methicillin resistance (a marker for resistance to all beta-lactam antimicrobials, including penicillins, cephalosporins, and carbapenems) is the most important mechanism of resistance in staphylococci; the reported incidence of antimicrobial-resistant bacteria has increased markedly since the early 2010s, although this varies depending on the geographic location. For example, a 2010 Japanese study reported the incidence of methicillin-resistant S pseudintermedius (MRSP) at 66.7%. Many methicillin-resistant isolates are also multidrug resistant (resistant to more than three classes of antimicrobials), which makes clinical management, particularly empirical treatment, more difficult. Before the increase in incidence of resistant strains, if cytologic evaluation of the exudate showed an active infection with coccoid organisms, empirical antimicrobial treatment could begin. The rise of antimicrobial resistance has led to the development of guidelines by several organizations (British Veterinary Association [www.bva.co.uk], Federation of European Companion Animal Veterinary Associations [www.fecava.org], and International Society for Companion Animal Infectious Disease [www.iscaid.org]) on the appropriate use of antimicrobials for case management. ( See table: Dosages of Antistaphylococcal Antimicrobials.)

Empirical treatment may still be appropriate in the case of first-time or previously untreated superficial infections in which cytologic evaluation has confirmed infection with coccoid bacteria. The following may be used as first-line antimicrobials: cephalexin, cefadroxil, amoxicillin-clavulanate, trimethoprim-sulfas, lincosamides, and cefovecin (if owner compliance is considered an issue).

Bacteriologic culture and antimicrobial susceptibility testing should be performed in any of the following circumstances: infections that have not responded to appropriate empirical treatment, deep infections (nodules, hemorrhagic bullae, or draining tracts), rod-shaped or unusual organisms on cytologic evaluation, recurrent or relapsing infection, history of previous courses (particularly multiple) of antimicrobial treatment, nonhealing wounds, recent potential exposure of owner or affected animal to methicillin-resistant staphylococci in healthcare environments, or history of prior MRSP infections.

Second-line antimicrobials should be used only if there is no susceptibility to first-line antimicrobials on culture and antimicrobial susceptibility testing. These antimicrobials are not appropriate for empirical treatment and include cefovecin (except when owner compliance is an issue), cefpodoxime, and fluoroquinolones (eg, difloxacin, enrofloxacin, marbofloxacin, orbifloxacin, and pradofloxacin).

Third-line antimicrobials should be used only in cases in which there is evidence of susceptibility, no susceptibility to first or second-line antimicrobials, and topical antiseptics are not feasible or effective. Third-line antimicrobials include aminoglycosides, azithromycin, chloramphenicol, clarithromycin, imipenem, rifampin, and ticarcillin.

With the increase in methicillin- and multidrug-resistant strains of staphylococci, use of topical antiseptics has increased. They can be used as sole treatment for mild to moderate superficial infections and can reduce the treatment duration in more severe infections. There is little evidence that even multidrug-resistant staphylococci are not susceptible to topical antiseptics.

Duration of treatment varies with the type of infection; however, it should continue until the clinical lesions have resolved and findings on cytologic evaluation are normal. In general, superficial infections should be treated for 7 days beyond surface healing (commonly 3–4 weeks); deep infections should be treated 7–21 days beyond resolution, which may require treatment durations of 8–12 weeks if continued improvement is evident. Clinical resolution of MRSP infections may take longer than methicillin-susceptible S pseudintermedius infections; however, this is most likely due to infection chronicity and secondary changes of the skin rather than to any inherent virulence of the bacterial strain.

There is potential for serious adverse effects when using either chloramphenicol or rifampin. Chloramphenicol can cause a dose-dependent bone marrow suppression (cats are more sensitive), although gastrointestinal irritation, inappetence, and weight loss are the most common. Rifampin may cause hepatic enzyme induction and increase in hepatic enzyme activity, particularly alkaline phosphatase. Some dogs may develop a fatal hepatotoxicity. Other adverse effects include gastrointestinal upset, hemolytic anemia, thrombocytopenia, and orange discoloration of body fluids. Liver enzyme activity should be monitored at least every 2 weeks for the duration of treatment.

Gram-negative bacterial species causing cutaneous infections (superficial to deep) or otitis (externa, media and interna) in dogs and cats include:

• Enterobacteriaceae (Proteus spp, E coli, Klebsiella spp): non-spore forming, non-acid fast, anaerobic, gram-negative rods that are natural inhabitants of the intestinal tract

• Non-enterobacteriaceae (Pseudomonas spp): ubiquitous bacteria found in soil, decaying vegetation, and animals

The gram-negative cell wall confers some inherent resistance, and acquired resistance is common. Thus, sample collection for bacteriologic culture and antimicrobial susceptibility testing is recommended to identify and select the appropriate systemic antimicrobial. Patients with non–life-threatening infections can be empirically treated with either amoxicillin-clavulanate or first- or second-generation cephalosporins until culture results are known. Patients with life-threatening bacteremia should be treated with either enrofloxacin, amikacin, or a third-generation cephalosporin until culture results are known.

Pasteurella spp are frequently found in infections of bite wounds from dogs and cats. The infection may be treated with the penicillins, tetracyclines, trimethoprim-sulphonamides, quinolones, and second- and third-generation cephalosporins.

Gram-positive bacterial infections in dogs and cats include Streptococcus spp, which may be treated with penicillin G, penicillin V, erythromycin, chloramphenicol, or cephalexin.

Bacterial species causing cutaneous infections in horses include Streptococcus spp, Corynebacterium spp, and Dermatophilus congolensis.

Streptococcus spp may cause folliculitis, furunculosis, and abscesses. Most are susceptible to penicillin, ampicillin, erythromycin, enrofloxacin, cephalosporins, or trimethoprim-sulphonamides.

Corynebacterium spp are gram-positive pleomorphic bacteria that may cause folliculitis, furunculosis, and subcutaneous abscess formation. Infections may be treated with penicillin, erythromycin, trimethoprim-sulphonamides, and cephalosporins.

Dermatophilus congolensis is responsible for a common superficial, pustular, and crusting dermatitis in horses. Moisture and some form of skin damage are necessary for the infection to develop. Most lesions are self-limiting if the horse can be kept dry. Treatment involves removal of the scale and crust, treatment with a topical antiseptic (iodophors, 2–5% lime sulphur, or 1–4% chlorhexidine), and in severe, generalized, or chronic infections, systemic antimicrobials (penicillin, erythromycin, or trimethoprim-sulphonamides) may be used.