Superficial bacterial folliculitis (SBF) is one of the most common dermatologic problems diagnosed in dogs. The infecting organism is usually a Staphylococcus spp. In the recent past, successful treatment could be accomplished with a beta lactam antibiotic [cephalosporins (specifically cephalexin) or a potentiated amoxicillin]. Increasingly methicillin-resistant Staphylococcus (MRS) is being identified as a cause of skin infections in dogs. The MRS may belong to the species aureus (MRSA), pseudintermedius (MRSP), intermedius (MRSI) or schleiferi (MRSS). No member of the beta-lactam family will be effective when a MRS is identified. In addition, many of the MRS are also multi-drug resistant (MDR), meaning that it is resistant to at least 4 other classes of antibiotics. A report in 2009 by Bemis et al.¹ reported that more than 90% of the MR isolates of S. pseudintermedius were resistant to ≥ 4 other classes of antibiotics. The purpose of this lecture is to help stem the rising incidence of MRS in our cases of canine pyoderma.

Culture and susceptibility (c/s) testing should be performed on poorly responsive (not recurrent) SBF. If a deep pyoderma has exclusively rods on cytology, has been treated with antibiotics recently or the dog is systemically ill, then a culture and susceptibility test should be performed on the first visit. If a c/s is submitted, the minimum inhibitory concentration (MIC) (broth microdilution technique) method should be used to determine the susceptibility rather than the disc diffusion method (Kirby-Bauer). The disk-diffusion susceptibility test (DDST) is semi quantitative in that the drug concentration achieved in the agar surrounding the disc can be roughly correlated with the concentration achieved in the patient's serum. It will only report the organism's susceptibility (susceptible, intermediate or resistant) based on an approximation of the effect of an antibiotic on bacterial growth on a solid medium. Tube dilution (MIC) is quantitative, not only reporting results of susceptible, intermediate or resistant (SIR), but also the amount of drug necessary to inhibit microbial growth. It is reported as the lowest amount (concentration) of antibiotic (in µg/ml) necessary to inhibit visible growth of bacteria. This allows determination of both susceptibility (or resistant) and how susceptible a bacterium is to a given antibiotic. This information can then be used to determine the proper dosage and frequency of administration of the antibiotic.

To interpret and use a susceptibility test based on MIC requires the following information:

1.  MIC of the antibiotic in relationship to the organism. This is reported on your culture results.

2.  Breakpoint MIC or in other words at what concentration are the bacteria considered susceptible (if the MIC is lower than this value) or resistant (if the MIC is higher than this value). This value should be available from your laboratory. Currently MSU's DCPAH website has a breakpoint chart available (see below for chart or go to www.dcpah.msu.edu/sections/bacteriology/WEBCD.BACT.REF.011.pdf)

3.  You, then, look at the culture results and list all the antibiotics that are reported as ≤ X, where X is the listed MIC for each antibiotic.

4.  For the next step, you need to be aware that within a population of susceptible bacteria, there is a mixture of strains (heterogeneity). Some of the strains are very sensitive to a given antibiotic, while others are less susceptible. The less susceptible ones would be the ones with the MIC closer to the breakpoint (resistant MIC level). From the list you made in step 3, you need to rank the antibiotics based on which have the most susceptible bacteria. You do this by calculating the efficacy ratio. This number is the breakpoint of the antibiotic divided by the MIC of the bacteria. The higher the number, the more susceptible the bacteria are to that antibiotic.

5.  You will need to take the list from step 4 and decide which antibiotic fulfills your needs based on

a.  High efficacy ratio

b.  Ability to penetrate the infected tissue

c.  Side effects of the drug

d.  Ease of administration (consider both route and frequency required)

e.  Cost of the medication

6.  If there are no antibiotics with ≤ X, or the ones that do are either too toxic or too expensive, you should then list the remaining antibiotics that are reported as susceptible. From this list, you need to calculate the efficacy ratio. Remember this number is the breakpoint of the antibiotic divided by the MIC of the bacteria. The higher the number, the more susceptible the bacteria are to that antibiotic. For example, you have Staph bacteria that have a MIC of 1 µg/ml to enrofloxacin and have a MIC of 4 µg/ml to cephalexin. Which antibiotic is the population of bacteria most susceptible to? To determine this, you take the breakpoint of enrofloxacin (4) and divide it by the MIC (1) and the efficacy ratio is 4. Doing the same for cephalexin you get (32/4) 8. Remember the higher the number, the more susceptible the bacteria are to that antibiotic. So cephalexin would have the highest number of susceptible bacteria.

7.  With this list of antibiotics and their efficacy ratio, apply the criteria listed in step 5 to determine the most appropriate antibiotic.

In the past, oxacillin was used to identify all species of methicillin-resistant Staphylococcus.² If the Staphylococcus was resistant to methicillin (MRS), then it would be reported as resistant to all of the beta-lactams. In humans, the most common MRS organism is Staphylococcus aureus (MRSA). The new protocol for humans is to use cefoxitin to identify MRSA.³ The problem for veterinarians is that in animals Staphylococcus infections usually belong to the Staphylococcus intermedius group (SIG) (S. intermedius, S. pseudintermedius, and S. delphini) and certain strains of methicillin-resistant S. pseudintermedius (maybe any in the Staphylococcus intermedius group?) may be falsely identified as methicillin-susceptible (MS) if the laboratory uses cefoxitin susceptibility as the indicator.⁴ How is this clinically important? If you are using a human laboratory, they may not be aware of this difference between Staphylococcus aureus and SIG testing and therefore use cefoxitin for testing for MRS. Because of this, the author recommends using a veterinary laboratory that uses Clinical and Laboratory Standards Institute (CLSI) guidelines and is aware of and has current knowledge of veterinary pathogens.

MRSA may have an inducible resistance to clindamycin; thus, the report will say susceptible but resistance develops during therapy. Resistance to erythromycin may be used to ID this strain of MRSA. If the MRS is erythromycin resistant, clindamycin sensitive, at least for MRSA, there is an inducible clindamycin resistant gene present. So, when selecting an antibiotic for a MRSA (other MRS?), it is best to avoid clindamycin if the culture reports resistance to erythromycin.

This inducible gene problem also affects the tetracycline family. There is an inducible gene for doxycycline, so that the culture may report susceptible to doxycycline, but develop resistance during therapy. There is not, at the present time, a minocycline inducible gene, so it is best to test minocycline in addition to tetracycline and doxycycline. Systemic therapy for canine pyoderma is becoming more problematic because of the increasing incidence of methicillin-resistant Staphylococcus.^4-7 Topical therapy, either as a monotherapy or as part of polypharmacy, is becoming even more important than it was in the past. Topical therapy may not only decrease or eliminate the need for systemic antibiotics, but since many of the dogs with SBF have atopic dermatitis, bathing will remove antigens from the skin, which can be useful in managing the allergies.

Topical therapy with mupirocin is very useful. Note, if the Staphylococcus is reported as resistant to clindamycin, there is a nine-fold increase in the incidence of resistance to mupirocin.⁸

Silver sulfadiazine has traditionally been used for gram-negative bacterial infections, especially Pseudomonas. It can be useful in SBF because it is effective against some gram-positive bacteria including MRSA.⁹

When treating a dog with a SBF, an antibiotic should be administered for at least 21 days, or 14 days past your clinical examination that has determined the infection has resolved, whichever is longer. For dogs with deep pyoderma, treat for at least 6 weeks or 21 days beyond clinical resolution, whichever is longer. In cases of SBF, don't use glucocorticoids (GC) when the pruritus is only at the lesions or when the pruritus is only mild at the nonlesional areas. If a dog with a SBF has intense pruritus at nonlesional areas, then a 21 days tapering course of prednisone may be dispensed. Using GC in the presence of a pruritic pyoderma makes interpretation of response to therapy impossible. Never use GC in cases of deep pyoderma!

In regards to systemic antibiotics, there are many effective first-line antibiotics. The author, the British Small Animal Veterinary Association (BSAVA), the Swedish Veterinary Medical Association and the European Medicines Agency strongly believe that 3rd-generation cephalosporins and fluoroquinolones should not be included in that list. It is beyond the scope of the lecture to go in depth concerning this statement; however, all the previously named groups believe you should be very selective when dispensing any fluoroquinolones and all the third- and fourth-generation cephalosporins in the treatment of canine bacterial pyoderma.

References

1.  Bemis DA, Jones RD, Frank LA, et al. Evaluation of susceptibility test breakpoints used to predict mecA-mediated resistance in Staphylococcus pseudintermedius isolated from dogs. J Vet Diagn Invest. 2009;21:53–58.

2.  Bemis DA, Jones RD, Hiatt LE, et al. Comparison of tests to detect oxacillin resistance in Staphylococcus intermedius, Staphylococcus schleiferi, and Staphylococcus aureus isolates from canine hosts. J Clin Microbiol. 2006;44: 3374–3376.

3.  Fernandes CJ, Fernandes LA, Collignon P. Cefoxitin resistance as a surrogate marker for the detection of methicillin-resistant Staphylococcus aureus. J Antimicrob Chemother. 2005;55(4):506–510.

4.  Weese JS, Faires M, Brisson BA, et al. Infection with methicillin-resistant Staphylococcus pseudintermedius masquerading as cefoxitin susceptible in a dog. J Am Vet Med Assoc. 2009; 235( 9):1064–1066.

5.  Morris DO, Rook KA, Shofer FS, Rankin SC. Screening of Staphylococcus aureus, Staphylococcus intermedius, and Staphylococcus schleiferi isolates obtained from small companion animals for antimicrobial resistance: a retrospective review of 749 isolates (2003–04). Vet Dermatol. 2006;17:332–337.

6.  Loeffler A, Linek M, Moodley A, et al. First report of multiresistant, mecA-positive Staphylococcus intermedius in Europe: 12 cases from a veterinary dermatology referral clinic in Germany. Vet Dermatol. 2007;18:412–421.

7.  Jones RD, Kania SA, Rohrbach BW, et al. Prevalence of oxacillin- and multidrug-resistant staphylococci in clinical samples from dogs: 1,772 samples (2001–2005). J Am Vet Med Assoc. 2007; 30:221–227.

8.  Fulham KS, Lemarie SL, Hosgood G, Dick HLN. In vitro susceptibility testing of methicillin-resistant and methicillin-susceptible staphylococci to mupirocin and novobiocin. Vet Dermatol. 2011;22:88–94.

9.  Loh JV, Percival SL, Woods EJ, et al. Silver resistance in MRSA isolates from wound and nasal sources in humans and animals. Int Wound J. 2009;6:32–38.