How to win the war with skin infections: Part I (Proceedings)

Bacterial skin infections represent a common condition affecting the canine and is often recurrent. The infective organism most frequently isolated is Staphylococcus intermedius although other species of staphylococcus may be involved. Most recently Staphyloccus schleiferi has been cultured from dogs with chronic recurrent pyoderma often demonstrating resistance to cephalexin and other cephalosporins.

Factors Related to Pyoderma

In general, canine pyodermas are secondary. Factors that are probably involved with the development or recurrence/perpetuation of the infection are multifactorial. They include the following: 1. The bacterial characteristics and pathogenic properties 2. underlying disease and its relationship towards decreasing the protective mechanisms of the skin and the permissive effects on host defense 3. The inflammatory response (or lack of) by the host.

The identification of the underlying/predisposing disease(s) become a predominant focus point in the treatment of the clinical case since this is an area of major concern in the evolvement of the disease but also it is one of the few areas we can do something about. Changing the bacterial characteristics is not possible and modifying the host response has proven to be of minimal value in eliminating the recurrent infection. Recognizing and treating the underlying disease(s) is of primary relevance although the problem may not always be easily determined and in some cases cannot be identified.

In the southeastern United States (and other geographic regions) allergic dermatitis is the most common predisposing factor. Atopy, flea allergy, food allergy and rarely allergic contact allergy. This is further complicated by the length of coat, amount of oiliness, scaliness or crusts (seborrhea) and the pets habits (environmental factors). Other disease considerations include ectoparasites (demodex, scabies, cheyletiella, fleas, etc.), and endocrinopathies (hypothyrodism, hyperglucocorticoidism or sex hormone disturbance), metabolic abnormalities (keratnization defects, idiopathic seborrheic dermatitis), hair follicle dysplasias and immunological incompetencies. A major predisposing factor of recurrent pyoderma in the dog is the administration of glucocorticoid compounds, particularly when given chronically or when long acting products are used. Therapeutic failures are most often a result of incomplete recognition and treatment of underlying factors. A chronic relapsing pyoderma is most likely secondary. The most common reason for therapeutic ineffectiveness or chronic/recurrent pyodermas is a failure to eliminate or control predisposing factors or the inability to identify coexisting disease (idiopathic pyoderma).

Initial Troubleshooting the Relapsing Pyoderma

The following questions should represent a check list for evaluation of the dog with chronic recurrent pyoderma. Was the proper antibiotic selected? Was the drug dosed & administered properly? Was the animal reevaluated during treatment to determine the end point? Was the antibiotic used for sufficient duration? Were skin scrapings acquired? Was the animal pruritic and did the pruritus persist after the pyoderma had cleared? The approach to the clinical management of these cases include several objectives. The first is to acquire a detailed history and perform a com;ete clinical examination to lead toward the development of a differential diagnosis and diagnostic plan for the underlying disease as well as the symptoms of the pyoderma. The second is to formulate a plan to treat the underlying disease and also eliminate the current active infection. The final objective is to develop a plan that will reduce the recurrence of the pyoderma until the underlying/predisposing factors can be maximally controlled.

All cases with lesions suggestive of bacterial pyoderma should be skin scraped for evidence of ectoparasites (demodicosis). Lesions with suspicion of cutaneous malassezia should be should be evaluated by microscopic inspection of specimens obtained from the surface of the skin for the presence of yeast. Pustules should be evaluated by microscopic inspection of the pus carefully obtained from the lesion placed on a microscopic slide and stained. Bacterial cultures are not routinely performed on superficial pyoderma but may be indicated in the evaluation of deep pyoderma. Bacterial cultures should never be obtained without performing susceptability testing. Biopsies are often indicated for culture and susceptibility testing as well as histopathologic evaluation in refractory or recurrent cases.

Therapy

Specific therapy should be directed at treating the underlying disease(s) in addition to systemic antibiotics. Antibiotics chosen for the management of canine pyodermas should have a known spectrum of activity against S. intermedius. In situations of known immune incompetency, bactericidal antibiotics should be used. Antibiotics that should never be used include penicillin, ampicillin, amoxicillin, tetracycline and sulfa drugs without potentiation. All antibiotics should be dosed on the basis of actual body weight determination. Antibiotics should be administered for a minimum of 21-30 consecutive days or 10 days beyond apparent remission. Deep pyodermas may require 812 weeks or even longer. Pyogranulomatous lesions (acral lick dermatitis) have taken as long as 4-6 months of continuous antibiotic treatment. It is not necessary to change antibiotics if they are still effective. One should watch for discrepancy between in vivo responsiveness and in vitro susceptability. Antibiotic responsiveness may change. Recognition of resistance patterns is essential. Proper dosing may make the difference between response and failure.

Problems Associated with Antibiotic Therapy

The response is obviously predicated on the proper identification of a bacterial pyoderma realizing there are a number of nonbacterial and nonseptic conditions that will mimic the clinical appearance of pyoderma. Coexisting or underlying diseases will affect the responsiveness to antibiotic therapy but are more likely to have the most dramatic influence on the relapse rate and remission interval. Recurrence of the pyoderma may be observed within several days of the cessation of antibiotic therapy. The effectiveness of an antibiotic is related to the previous use of that particular antibiotic and the chronicity of the problem and therapy.

"First round" antibiotics such as used early in the treatement regimen (lincomycin, clindamycin, clavuanic acid potentiated amoxicillin, potentiated sulfas, etc.) may have limited or minimal effect on the chronic casebut should always be considered in the early cases of bacterial infection. Increased observations of refractoriness of the pyoderma to antibiotics previously considered the "second round" or the highly effective drugs (cephalosporins) are commonly being observed. Most of these are "methicillin resistant" staph. organisms. Seeking an alternative in these instances may be more difficult and predictably more expensive, The use of cephalosporins has conventionally been used in the event of failure recognized with more conservative antibiotics. Failure of cephalexin leaves few realistic choices. Methicillin resistant Staphylococcal bacteria will be resistant to ALL betalactam antibitioitcs and often will have resistance to fluoroquinolone antibiotics. Ideally, dogs with cephalosporin refractory pyoderma should be evaluated by sterile biopsy acquisition and submitted for culture and suscepatbility. The availability of minimum inhibitory concentrations (MIC's) may enhance the antibiotic choice and be helpful to the dosing of the selected antibiotic. Older, conventional drugs such as potentiated sulfas, clindamycin and chloramphenicol have been helpful in controlling infection caused by methicillin resistant staph. Multiple bacteria infections are observed in chronic, deep pyoderma in the dog, particularly when affecting the feet and face. Gram negative organisms may be found in addition to the Staphylococcal infection and usually represent opportunistic infection secondary to the staph. Pseudomonas aeroginosa, Proteus mirabilis, Eschericia coli are more commonly identified. Fluoroquinolones are often required in these instances for systemic therapy.

Commonly Used Antibiotics for the Treatment of Pyoderma in the Dog

Antibiotic choices for first-occurrence pyoderma

Amoxicillin trihydrate with clavulanate potassium...........14-22 mg /kg bid

Lincomycin....................22 mg/kg bid

Erythromycin....................10-15 mg/kg tid

Ormetoprim-sulfadimethoxine....................28 mg/kg qd

Trimethoprim-sulfadiazine or trimethopirm

sulfamethoxizole....................20-30 mg/kg qd-bid

Antibiotic choices for refractory, recurrent or resistant pyoderma

Cephalosporins

Cephalexin....................22 mg/kg tid or 33 mg/kg bid

Cefpodoxime....................5-10 mg/kg qd

Antibiotic choices for refractory, recurrent or resistant pyoderma

Cefadroxil ....................22 mg/kg bid

Clindamycin....................5.5-11.0 mg/kg bid (11mg/kg qd)

Oxacillin....................22 mg/kg tid

Chloramphenicol....................50 mg/kg bid - tid

Enrofloxacin

Superficial pyoderma....................5 mg/kg qd - bid

Deep pyoderma....................10-15 mg/kg qd

Marbofloxacin....................5 mg/kg once daily

Orbifloxacin....................2.5 - 7.5 mg/kg once daily;

Difloxacin....................5 - 10 mg/kg once daily;

Pradofloxacin....................5 mg/kg

Other Antibiotic Choices

Macrolide antibiotics have been utilized in the treatment of bacterial pyoderma for many years (e.g. erythromycin). Other variations include azithromycin (Azithromax; Pfizer, NY, NY), and Clarithromycin (Biaxin; Abbott Laboratories, Abbott Park). They may demonstrate efficacy against Staphylococci sp. particularly early in the course of a recurrent pyoderma. Azithromycin dosage in dogs is 10 mg/kg administered every 24 hours. The feline dosage is 5 mg/kg every 24 hours. Azithromycin should be administered before feeding providing 2 hours for absorption before allowing the animal to eat. The dose of clarithromycin in dogs and cats is 2.5 mg-10 mg/kg administered orally every 12 hours. Side effects include gastrointestinal (diarrhea and vomiting) as in humans who also describe abdominal pain and headaches. Clarithromycin is contraindicated with concomitant use of terbinafine, cisapride or pimozide. Tylosin is also a macrolide commonly used in veterinary medicine. It has demonstrated good efficacy and negligible side effects when used to treat dogs with superficial bacterial pyoderma using a dosage of 20 mg/kg orally bid for 21-28 days. Lower dosages have been used. Beta-lactam antibiotics adopted for veterinary application include imipenem-cilastin (Primaxin; Merck). It is useful for pyoderma that is refractory to conventional antibiotics but very expensive and a parenteral drug.. They are somewhat resistant to staphylococcal beta-lactamase. Imipenem-cilastin has broader spectrum of activity and may be considered in a combined staphylococcal and Pseudomonas infection. Primaxin is administered intravenously or intramuscularly at a dose of 3-10 mg/kg every 6-8 hrs for dogs only, and should be stored under refrigeration for 24 hour stability after reconstitution. Intravenous administration should be performed slowly to avoid nausea. A major limitation of imipenem-cilastin is the pain experienced upon intramuscular administration and local reaction (neurovascular damage) when the medication has been deposited outside the vein. Lidocaine has been reported to relieve discomfort when administered concurrently in intramuscular administration.

Fluoroquinolone antibiotic therapy should be reserved for combined Gram negative infections or staphylococcal pyoderma that has become refractory to cephalosporin antibiotic therapy. They are commonly employed in the treatment of otitis media which typically includes Gram negative bacteria (Pseudomonas sp.). While there are some variations in susceptibility of bacteria and tissue drug levels the mechanism of action is comparable among fluoroquinolones. Orbifloxacin has demonstrated lower skin penetration and higher minimal inhibitory concentrations than enrofloxacin and difloxacin. Enrofloxacin (Baytril, Bayer Corp) has flexible dosing (2.5-10 mg/kg once or twice daily) but is conventionally used at 5 mg/kg once daily where a lower dosage demonstrates decreased efficacy. Enrofloxacin has been shown to have higher tissue levels in inflamed skin in contrast to normal un-inflamed skin as a consequence of antibiotic concentration in white blood cells. Marbofloxacin has been useful for chronic otitis externa and otitis media and is an excellent choice for deep pyoderma with Gram negative organisms or cephalosporin resistant Staphylococcus spp. Cost factors may restrict the use in large dogs. Side effects of fluoroquinolones are relatively uncommon but should not be used in young dogs due to the concern for articular cartilage defects. Recommendations have been cited to exclude fluoroquinolones in dogs less than 1 year of age and less than 18 months in giant breed dogs. Higher dose enrofloxacin may (will?) cause retinopathy and lead to blindness in cats.

Failure of antibiotic therapy should be followed by more aggressive diagnostics and attempt to discover underlying or coexisting diseases. Macerated tissue cultures from biopsy specimens collected following a surgical scrub and submitted for bacteria isolation and susceptibility testing is important to include in the evaluation with the likelihood of antibiotic resistance developing. Treatment of the chronic relapsing case may result in the utilization of combined therapy or more aggressive treatment techniques. Among the options include chronic use of antibiotics, pulse therapy, subinhibitory antibiotic therapy and immunotherapy. Persistent use of antibiotics is tolerated well by most dogs but poses heavy financial burdens to the owner. Gastrointestinal disorders may occur.