01/03/2022, 10:28 How I Treat Methicillin-Resistant Staphylococcal Pyoderma - WSAVA 2014 Congress - VIN

How I Treat Methicillin-Resistant Staphylococcal Pyoderma

World Small Animal Veterinary Association World Congress Proceedings, 2014

Valerie A. Fadok, DVM, PhD, DACVD
North Houston Veterinary Specialists, Spring, TX, USA

Staphylococcal infections in dogs are not as simple to treat since the emergence of
methicillin resistance. Most infections in dogs are caused by methicillin resistant
Staphylococcus pseudintermedius (MRSP). We can also see methicillin resistant S.
schleiferi (MRSS) and less commonly, S. aureus (MRSA), the human pathogen. In
most dogs with methicillin resistance, a history of repetitive courses of antibiotics for
treatment of pyoderma is obtained.
Methicillin resistance in the staphylococcal bacterium is mediated by the acquisition
of a mobile gene cassette (staphylococcal chromosome cassette/SCCmec)
containing the mec gene, most often mecA, which encodes for an abnormal penicillin
binding protein, PBP2a gene. This protein's conformation is different, and it cannot
bind beta-lactam antibiotics. Higher doses of antibiotics cannot overcome this
mutation, thus beta-lactams are no longer effective. The SSCmec can also carry
other genes that mediate resistance to additional classes of antibiotics, and therefore
many MRSP are multidrug resistant as well.
The first step in treating methicillin resistant staphylococcal pyoderma is to
recognize its presence. Indications that methicillin resistant infections could be
present include a failure to respond to antibiotics previously used successfully, and a
failure to response to all beta-lactam antibiotics. If a dog fails to respond to an
injection of cefovecin then either the infection is methicillin resistant, or the lesions
are not caused by staphylococci. Failure to respond to cephalexin given twice daily is
suspicious but not diagnostic for MRS, as at least in some parts of the world,
cephalexin used twice daily is not always successful. Failure to respond to other
classes of antibiotic implies that the organism could also be multidrug resistant. It is
very important not to try to pick antibiotics empirically when we suspect MRS. We
need to collect samples for culture and sensitivity and we need to be sure that our
laboratories tell us what species of Staphylococcus is involved, so we can advise our
clients about any potential zoonotic hazards.
Topical therapy is a critical part of treatment. Published evidence suggests that the
most effective shampoos are those containing 2–4% chlorhexidine. As we wait for
culture and sensitivity, owners can bathe daily with this shampoo, or at least 3 times
that week, using sprays or rinses in between. Bathing is a powerful tool. It removes
the crusts laden with the staph, it soothes the skin, and it makes the dogs look, feel,
and smell better more quickly. In fact, should culture and sensitivity reveal a multidrug
resistant bug, daily bathing can be used to resolve the infection without antibiotics.
Even if antibiotics can be used, bathing frequently will shorten the course of therapy.
For example, we have had excellent results using rifampin for 2 weeks, with 3 x
weekly bathing with chlorhexidine. Accelerated hydrogen peroxide offers substantial
antistaphylococcal activity and it can be used for the environment as well as on
animals. Bleach has been recommended; it is not clear what concentration is optimal.
Dilutions range from 1:64 to 1:250, with no evidence yet for which is most efficacious.
With the loss of beta-lactams, we can consider choosing other classes if they are
reported as sensitive.
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Here are some tips for using these antibiotics successfully:
Macrolides: Most dermatologists advocate for the use of clindamycin. If
clindamycin is considered, it is important to look at the sensitivity to
erythromycin and other macrolides/lincosamides. Staphylococci can contain a
resistance gene called the clindamycin inducible resistance factor. The
presence of this factor is suggested when erythromycin is reported as
resistant and clindamycin as sensitive. Under these circumstances
erythromycin should not be used as it will likely result in a treatment failure.
Tetracyclines: While most S. pseudintermedius are resistant to tetracyclines,
they can be used if indicated by sensitivity testing. It is important to note that
the breakpoints used to predict sensitivity to doxycycline are not correct, and
result in some resistant bacteria being called sensitive. Until these breakpoints
are revised, if doxycycline is reported as sensitive, have a look at the MIC. If it
is greater than 0.5 microgram/ml, we can predict a therapeutic value.
Potentiated sulfas: Potentiated sulfas can be extremely helpful for pyoderma.
Ormetoprim-sulfadimethoxine (Primor, Zoetis) can be used once daily. Sulfa
antibiotics have the potential to cause side effects, including arthropathy in
Doberman pinschers, exacerbation of keratoconjunctivitis sicca, a lowering of
thyroid hormone levels and drug eruptions including urticarial. The incidence
of side effects is low but owners should be counseled to look out for them.
Fluoroquinolones: There is some concern about using fluoroquinolones for
methicillin resistant staphylococcal infections, because it is possible that
resistance might develop during treatment. This seems particularly true when
older fluoroquinolones (enrofloxacin, ciprofloxacin) are used at doses that will
achieve less than the mutant prevention concentration in tissue. Ciprofloxacin
is not recommended because 20% of dogs don't absorb it well, and because it
may not be possible to achieve a mutant prevention concentration in the
tissue. This author has used marbofloxacin successfully at 5.5 mg/kg/day,
which appears to be the mutant prevention concentration.
Chloramphenicol: Chloramphenicol can be used successfully in some cases. It
must be given every 8 hours and side effects of nausea, loss of appetite, and
vomiting are common. In addition, some dogs have developed a rear limb
paresis, the pathogenesis of which is not known. It resolves when treatment is
stopped. Chloramphenicol can cause aplastic anemia in humans; while it has
never been shown that handling the capsules results in this side effect, we
recommend that clients wear gloves when handling this drug.
Amikacin: Amikacin is less likely to cause renal problems than gentamicin, and
so it is preferred for treating pyoderma when an aminoglycoside is needed. It
seems to work better for deep pyodermas than superficial pyodermas, in my
experience. It can be dosed at 15 mg/kg subcutaneously every 24 h. Because
of the potential for renal toxicity, monitoring is recommended. For an otherwise
healthy dog, a urinalysis once weekly can be used to check for casts,
proteinuria, and changes in specific gravity. Urinalysis is more sensitive than
assessment of BUN or creatinine levels. Some clinicians advocate for the use
of subcutaneous fluids when using amikacin. We have no evidence that this
will reduce renal toxicity, and I am not comfortable with putting large volumes
of fluids in the subcutaneous space of a dog with a resistant skin infection.
Rifampin: Rifampin is an older antibiotic often used in combination with other
antimicrobials in the treatment of human tuberculosis. Contrary to what we
have been taught, rifampin can be and has been used as monotherapy for
methicillin resistant staphylococcal infections in dogs. Because it has the
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potential to cause hepatotoxicity, liver enzyme levels should be monitored
before treatment, and every 10–14 days during treatment. By keeping the total
daily dose at 10 mg/kg, we seem to get very good response with minimal
toxicity. Owners should be cautioned to watch for appetite loss and vomiting. I
have found that by combining bathing 3 x weekly with rifampin orally, we can
resolve most superficial pyodermas within 2 weeks.
Table of antibiotic doses for canine pyoderma

8 mg/kg subQ; repeat in 2 weeks if

Cefovecin (Convenia)*
necessary

Cefpodoxime (SIMPLICEF)* 5–10 mg/kg QD (higher doses best)

Cephalexin* 22–30 mg/kg TID

Lincomycin (Lincocin) 20 mg/kg BID

Clindamycin 11 mg/kg QD to BID

Amoxicillin-clavulanate (Clavamox)* 20 mg/kg BID to TID

Ormetoprim-sulfadimethoxine
27.5–30 mg/kg QD
(Primor)

TMP-sulfa 20–30 mg/kg BID

Doxycycline (if sensitive) 10 mg/kg BID

Minocycline (if sensitive) 5–10 mg/kg BID

Marbofloxacin (Zeniquin) 5.5 mg/kg QD

Enrofloxacin (Baytril) 20 mg/kg QD

Ciprofloxacin (not recommended) 30 mg/kg QD***

Chloramphenicol 50 mg/kg TID

Amikacin 15 mg/kg subQ QD

Rifampin 5–10 mg/kg QD****

* Not for use in methicillin resistant infections

*** Ciprofloxacin, while inexpensive, is a second generation fluoroquinolone with less activity
against gram-positive bacteria than we would like. It has been shown in 2 different studies to
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be very inconsistent in absorption. If used, use at the high dose. It may be helpful to crush the
tablets to help promote absorption but we really don't know as much about this antibiotic in
dogs as we would like. (This from data provided by Dr. Mark Papich, NCSU.)
****Keep dose at a max of 10 mg/kg/day to reduce risk of hepatic damage, including necrosis
and death.

Most dogs with recurrent pyoderma have an unresolved underlying cause. Once
methicillin resistant staphylococcal infections are diagnosed, there is a 50% chance
that subsequent infections will be MRS as well. Culture and sensitivity may need to
be performed with each subsequent infection. The goal is to prevent relapse.
Long term maintenance for dogs will include management of the underlying cause,
regular bathing, skin barrier repair, and in some cases, the use of Staphage Lysate
(SPL). I have found that many atopic dogs with recurrent pyoderma are allergic to
staphylococcal proteins, as indicated by intradermal testing and/or serum testing for
IgE against Staphage Lysate. Thus it is possible that the SPL is acting as allergen
specific immunotherapy for these dogs. It can be used as a sole agent, or mixed into
injection or sublingual immunotherapy vaccines.
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Valerie A. Fadok, DVM, PhD, DACVD
North Houston Veterinary Specialists
Spring, TX, USA

URL: https://www.vin.com/doc/?id=7054870

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