Skin infections, MRSI, perpetuating factors,topicals, antibiotics and more (Proceedings)

Skin infections with bacteria (pyoderma) or yeast (Malassezia dermatitis) often are found in dogs secondary to other diseases such as seborrhea, endocrine diseases and allergic diseases. Many of these cases have abnormalities in skin barrier function or desquamation and even when the primary disease is controlled if this defect is not corrected the dog may still be prone to recurrent infections though episodes may be less severe or less frequent. In chronic or recurrent infections other factors may develop which are referred to as perpetuating factors. The most common bacteria to cause skin infections in dogs is Staphylococcus pseudintermedius which used to be called Staph intermedius. However in some cases other bacteria such as Enterococcus, Corynebacteria, E. coli, and Pseudomonas may be pathogenic. The diagnosis of a skin infection is simple if the lesions are recognized and sampled for cytology.

Success treating skin infections requires appropriate antimicrobial therapy and this has been the main emphasis of veterinarians for many years. Topical therapy though considered helpful can actually be essential to successful therapy and in some cases with resistant bacteria such as methicillin resistant Staph (MRS) may become the main or sole method to eliminate the infection. MRSI in dogs presents the same as other methicillin susceptible Staph and is only suspected due to failure to respond to normally effective antimicrobials such as cephalosporins. In general these have not been a zoonotic risk of disease to humans though the same is not true when dogs have MRSA. Successful long term management will require that underlying primary diseases are identified and managed and predisposing factors are eliminated or controlled. Additionally any pathologic changes in the normal anatomy or physiology of the skin that occur because of the inflammation from the infection need to be reversed or controlled. If any part of these components are not addressed then more antimicrobial therapy will be required and success will be limited.

DIAGNOSIS

The diagnosis of pyoderma requires a skin lesion that has neutrophils with bacteria present which are preferably found intracellular within inflammatory cells. If cocci are seen then most commonly the pyoderma is due to Staphylococcus though definitive identification requires a culture. Bacterial overgrowth is diagnosed when no inflammatory cells are present but bacteria are present in abnormally high numbers. The author utilizes greater the one cocci or 0.5 rods per OIF (1,000X) based on work by Dr Colombo. lHistopathology is also helpful in diagnosing pyoderma though bacteria are not often seen. Histopathology is also used to identify primary diseases as well as perpetuating factors. Most suppurative folliculitis and perifolliculitis occur because of pyoderma. The presence of bacteria in a crust or the stratum corneum is also significant. Histopathology is not a good way to diagnose Malassezia though when any yeast are seen the diagnosis should be strongly considered.

The real key to diagnosing pyoderma and Malassezia is to make sure multiple sights and types of lesions are cytologically evaluated. There are many cases where one site may reveal on diagnosis while another site on the same patient and visit may reveal something else. This means it is important to recognize all the lesions that may be seen with these diseases.

THE LESIONS SUGGESTIVE OF -

Pyoderma

The classic primary lesions of pyoderma are: Pustules, furuncles, fistula. Other lesions suggestive or compatible with pyoderma include: Crusts, papules, nodules, lichenification. The spreading ring of scale (epidermal collarette) associated with some erythema, exudate or crusting is also very typical of pyoderma.

The lesions of pyoderma most commonly affect the ventrum, groin and axilla, interdigital and occasional dorsal and lateral thorax. Ventral cervical lesions and anterior elbow are also common sites, especially in atopic dogs.

PERPETUATING FACTORS

Chronic recurrent pyoderma may lead to pathologic changes that become self perpetuating. This helps to explain why some allergic dogs that have their allergies well controlled may still get recurrent pyodermas for a period of time. Infections induce pathology in the skin and this may also contribute to the difficulty in eliminating the infection. Folliculitis can stimulate follicular hyperkeratosis and dilation altering the follicular ostia. Bacteria have greater access to these abnormal follicles and antimicrobial therapy may be required until these pathologic changes can normalize. Folliculitis may result in furunculosis and the released keratin and hair shafts stimulate a foreign body reaction. Though normally this material is broken down and eventually eliminated some cases develop persistent hair shaft sequestrum that appears to be associated with chronic or recurrent cases. In others it may not be hair shafts but remnants of corneocytes are found in the center of microabcesses or scars and the possibility of cocci which may adhere to corneocytes being protected inside a folded or rolled up corneocyte is another possible site for sequestering bacteria and protecting them from tissue levels of antibiotics or the body's immune defenses. Abscess or granuloma formation may alter the ability of some antimicrobials to effectively reach or kill the microorganisms. Another pathologic change that may be less apparent is fibrosis unless it occurs grossly. Fibrosis more often occurs at the microscopic and not the gross level. The fibrosis may be perifollicular or more diffuse throughout the dermis. Certain breeds (Doberman pinscher, bull and Staffordshire terriers, Rottweiler) seem more predisposed to excessive scarring that appears to make resolution of the pyoderma more difficult.

THERAPY OPTIONS FOR THE MICROBES

Cleaning the skin and topical therapy

Cleaning the skin promotes desquamation which removes surface bacteria and yeast as well as irritants and allergens. In some cases ingredients may be used to normalize keratinization or improve barrier function. Inflammation may be decreased by addition of anti inflammatory ingredients or just the use of cool water. This along with moisturizing and cooling the skin will also decrease pruritus. Cleansing the skin is most readily accomplished by bathing the pet and is also the most effective way to topically treat large body areas. Bathing also lends itself to the use of rinses after the bath that may contain topical antimicrobials. In general the more frequent the bathing the better and in some cases 2-3 times a week is very effective in preventing recurrent pyoderma and bacterial overgrowth. In addition to cleaning topical antibacterial ingredients may be incorporated into the shampoo or used following and in between bathing as sprays, lotions, leave on conditioners and gels. These are particularly useful for more localized areas such as the chin, paws and fold areas. Topical wipes have become very popular for these localized areas. For MRS daily therapy is needed and generally is best with shampoos but sprays and rinses may also be effective. The most common active antimicrobial ingredients used in veterinary medicine are: benzoyl peroxide, chlorhexidine, ethyl lactate, mupirocin, neomycin, polymyxin, phytosphingosine, salicylic acid, and sulfur. If the primary disease is not controlled and barrier function not returned then long term therapy will be required. Even when those are controlled and the infection is resolved longer therapy may be required until perpetuating factors have resolved.

Systemic therapy is usually necessary at least in the initial therapy of pyoderma and Malassezia. Only topical therapy is usually limited to recurrent cases to try to prevent recurrences or for very focal small number of lesions. Initially a choice of antibiotic is made empirically based on the results of cytology, and history of any previous antibiotic use and response. Cocci are most often treated initially with cephalosporin's, clavulanic acid and amoxicillin , and potentiated sulfa drugs. Clindamycin is used in some cases with scarring. Culture and sensitivity is indicated when there has been poor response to empiric therapy, chronic, partial antibiotic responsive disease, or no bacteria on cytology or unusual findings in what is suspected to be a pyoderma. Recently MRSI has become more of a problem and will often not be sensitive to most commonly used empirical choices and often requires doxycycline, minocycline, trimethoprim sulfa, chloramphenicol or amikacin. In rare cases no systemic alternative is available and aggressive topical therapy may be the treatment of choice. When mixed infections are seen then most specialists recommend treating based on both organisms or when Staphylococcus is present treating for just that and see if the others resolve with it. The antibiotic selected must be prescribed at an adequate dose for an appropriate duration. Often cases require weeks of therapy which does not always reflect how long it takes to eliminate the bacteria but also to allow skin time to develop normal defense mechanisms again. Dose ranges are often given for antibiotic and in general only mid to high dose ranges should be used. The deeper the infection is then the higher dose should be prescribed. Also scarred lesions, foreign bodies or abscesses that may inhibit vascular perfusion should have higher doses prescribed. The duration is determined by the pet's response as treatment should always be continued beyond resolution of the pyoderma, at least one week for superficial infections and 2 weeks for deep infections. With superficial infections this may be as short as two weeks though most clinicians now start with three weeks of therapy so they do not have to rely on clients to assess if they need a refill after two weeks. Deep folliculitis and furunculosis often requires 4-6 weeks and scarred granulomatous lesions can require up to 6 months. As long as a lesion is improving it should not be considered healed even though subtle changes in long term treated lesions may reflect remodeling and not resolution of residual pyoderma. The nodular, scarred lesions and some resistant or mixed infections may respond best to combinations of antibiotics. The two combinations used by the author's the most are cephalosporin and fluoroquinolone or rifampin with cephalosporin.

Long term antibiotic therapy may be required in some situations when underlying disease cannot be controlled or determined or the pathologic changes are slow to resolve. When long term therapy is elected there are 3 methods most commonly utilized. Intermittent therapy is the use of the antibiotics following the recurrence of the pyoderma lesions. This is most appropriate for cases that recur infrequently, two or three times a year. Pulse therapy is the method that has been evaluated and utilizes the normal dose and frequency but given at a set interval that is less frequent than the relapse rate.[4] Examples of common intervals are 2-7 days on antibiotics and 5-32 days off. Cephalexin is considered the best antibiotic for pulse and low dose therapy. Low dose is the slow tapering of antibiotics usually from q12h to q24h then to half dose q24h. Some cases will be tapered even further.

This type of therapy should be reserved for cases where it is essential as there is some concern this may be contributing to the development of MRSI infections. This has not been documented but the emergence of these resistant strains has occurred in recent years. This type of therapy may contribute to resistance though prior survey with cephalosporins did not show this. Pulse therapy should not be done with other antibiotics unless absolutely essential.

THERAPY OPTIONS FOR REVERSING PATHOLOGIC CHANGES

Some treatments may need to be directed at reversing pathologic changes or long term therapy may be required until the body naturally remodels or reverses those changes. Long term antibiotic therapy is the initial approach in most cases. This may also be the case in some allergic dogs that have had a lot of glucocorticoids leading to recurrent pyoderma even after the allergy is controlled. In others surgical correction or removal of localized fibrotic or granulomatous lesions can be an effective and cost saving procedure. Long term pentoxifylline may help to reverse scarring in some cases with widespread lesions not amenable to surgical therapy. Glucocorticoids have been used in some cases with residual granulomas but this should only be done after antibiotic therapy has eliminated the bacteria and the granulomas are sterile based on culture of ground up tissue samples.

References

Plant, J.D., W. Rosenkrantz, and C.E. Griffin, Factors associated with the presence of high Malassezia pachydermatis numbers on dog skin. J Am Vet Med Assoc, 1992. 201: p. 879-895.

Negre, A., E. Bensignor, and J. Guillot, Evidence-based veterinary dermatology: a systematic review of interventions for Malassezia dermatitis in dogs. Vet Derm, 2009. 20(1): p. 1-12.

White, S., et al., Evaluation of aerobic bacteriologic culture of epidermal collarette specimens in dogs with superficial pyoderma. J Amer Vet Med Assoc, 2005. 226(6): p. 904-908.

Carlotti, D., et al., Evaluation of cephalexin intermittent therapy (weekend therapy) in the control of recurrent idiopathic pyoderma in dogs: a randomized, double-blinded, placebo-controlled study. Vet Dermatol, 2004. 15(s): p. 9.