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* This is the Veterinary Version. *

Antibacterials for Integumentary Disease

By Michael Shipstone, BVSc, FACVSc, DACVD, Queensland Veterinary Specialists

Most canine skin infections are caused by coagulase-positive Staphylococcus pseudintermedius (formerly S intermedius), which commonly produce β-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 seen in North America, with S pseudintermedius and S aureus showing more resistance than S schleiferi coagulans. Species identification requires molecular techniques such as PCR detection of species-specific thermonuclease genes (nuc) or 16S rDNA sequencing, because phenotypic differentiation is unreliable.

Occasionally, Proteus spp, Pseudomonas spp, and Escherichia coli are secondary invaders of the dermis. Pasteurella multocida and β-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.

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 β-lactam antibiotics, including penicillins, cephalosporins, and carbapenems) is the most important mechanism of resistance in staphylococci; the reported incidence of antimicrobial-resistant bacteria has increased markedly over the past 5–10 yr, 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 antibiotics), which makes clinical management, particularly empirical therapy, more difficult. Before the increase in incidence of resistant strains, if the exudative cytology showed the presence of an active infection with coccoid organisms, empirical antibiotic 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], International Society for Companion Animal Infectious Disease [www.iscaid.org]) on the appropriate use of antibiotics for case management. (See table: Dosages of Antistaphylococcal Antibiotics.)

Empiric therapy may still be appropriate in the case of first-time or previously untreated superficial infections in which positive exudative cytology (with coccoid bacteria) has been established. The following may be used as first-line antimicrobials: cephalexin, cephadroxil, amoxicillin-clavulanate, trimethoprim-sulfas, lincosamides, and cefovecin (if owner compliance is considered an issue). Culture and sensitivity testing should be performed in any of the following circumstances: infections that have not responded to appropriate empiric therapy, presence of deep infections (nodules, hemorrhagic bullae, draining tracts), rod-shaped or unusual organisms on cytology, recurrent or relapsing infection, history of previous courses (particularly multiple) of antibiotic therapy, nonhealing wounds, recent potential exposure of owner or affected animal to methicillin-resistant staphylococci in health care environments, or history of prior MRSP infections. Second-line antimicrobials should be used only if there is no sensitivity to first-line antimicrobials on culture and sensitivity testing. These antibiotics are not appropriate for empiric therapy and include cefovecin (except when owner compliance is an issue), cefpodoxime, and fluoroquinolones (difloxacin, enrofloxacin, marbofloxacin, orbifloxacin, pradofloxacin). Third-line antimicrobials should be used only in cases in which there is evidence of sensitivity, no sensitivity 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, the use of topical antiseptics has increased. They can be used as sole therapy 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.

Dosages of Antistaphylococcal Antibiotics

Drug

Dosage

Cephalosporins

Cephalexin

20–30 mg/kg, bid, PO

Cephadroxil

Dogs: 20 mg/kg, bid, PO

Cats: 20 mg/kg/day, PO

Cefaclor

10–25 mg/kg, bid, PO

Cefovecin

8 mg/kg, SC, every 14 days

Cefpodoxime

5–10 mg/kg/day, PO

Penicillins

Amoxicillin-clavulanate

13.75 mg/kg, bid, PO

Oxacillin

22 mg/kg, tid, PO

Fluoroquinolones

Enrofloxacin

5 mg/kg/day, PO

Marbofloxacin

2 mg/kg/day, PO

Orbifloxacin

2.5 mg/kg/day, PO

Difloxacin

5 mg/kg/day, PO

Pradofloxacin

3 mg/kg/day, PO

Sulfonamides

Trimethoprim-sulfadiazine

15–30 mg/kg, bid, PO

Trimethoprim-sulfamethoxazole

15–30 mg/kg, bid, PO

Macrolides

Erythromycin

15–30 mg/kg, tid, PO

Clindamycin

Dogs: 10–20 mg/kg, bid, PO

Cats: 12.5–25 mg/kg, bid, PO

Lincomycin

10–20 mg/kg, bid, PO

Azithromycin

10 mg/kg/day, PO

Others

Chloramphenicol

50 mg/kg, tid, PO

Rifampin

5–10 mg/kg, once or twice daily, PO

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

The potential for serious adverse effects when using either chloramphenicol or rifampin should be understood. Chloramphenicol can cause a dose-dependent bone marrow suppression (cats more sensitive), although GI 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 GI upset, hemolytic anemia, thrombocytopenia, and orange discoloration of body fluids. Liver enzymes should be monitored at least every 2 wk for the duration of therapy.

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* This is the Veterinary Version. *