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Canine superficial bacterial folliculitis: Current understanding of its etiology,
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Paul Bloom
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http://dx.doi.org/10.1016/j.tvjl.2013.11.014
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Please cite this article as: Bloom, P., Canine superficial bacterial folliculitis: Current understanding of its etiology,
diagnosis and treatment, The Veterinary Journal (2013), doi: http://dx.doi.org/10.1016/j.tvjl.2013.11.014
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Canine superficial bacterial folliculitis: Current understanding of its etiology, diagnosis
and treatment
Paul Bloom
Allergy, Skin and Ear Clinic for Pets, 31205 Five Mile Road, Livonia, Michigan 48154, USA
* Corresponding author. Tel.: +1 734 4228070.
E-mail address: [email protected] (P. Bloom).
Abstract
Superficial bacterial folliculitis (SBF) is more common in the dog than other
mammalian species. Until recently, a successful outcome in cases of canine SBF was possible
by administering a potentiated amoxicillin, a first generation cephalosporin or a potentiated
sulfonamide. Unfortunately, this predictable susceptibility has changed, because methicillin
resistant Staphylococcus pseudintermedius (MRSP) and Staphylococcus aureus (MRSA) are
becoming more prevalent in canine SBF cases. The increasing frequency of multidrug
resistance complicates the selection of antimicrobial therapy. Antimicrobial agents that were
once rarely used in cases of canine SBF, such as amikacin, rifampicin and chloramphenicol,
are becoming the drugs of choice, based on bacterial culture and susceptibility testing.
Furthermore, changes in antimicrobial susceptibility have helped to re-emphasize the
importance of a multimodal approach to treatment of the disease, including topical therapy.
Due to the increasing frequency of identification of highly resistant Staphylococcus spp.,
topical antimicrobial therapy, including the use of diluted sodium hypochlorite (bleach), is
becoming necessary to successfully treat some cases of canine SBF. Other important
antiseptics that can be used include chlorhexidine, benzoyl peroxide, ethyl lactate, triclosan
and boric acid/acetic acid. This review discusses the diagnostic and therapeutic management
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of canine SBF, with a special emphasis on treating methicillin resistant staphylococcal
infections.
Keywords: Staphylococcus; Pyoderma; Canine; Methicillin; Antimicrobial resistance
Introduction
Bacterial pyoderma is more common in the dog than other mammalian species. In
contrast to Staphylococcus aureus infections in human beings, virulence factors, such as
protein A, leukocidin, hemolysins and epidermolytic toxin, have not been shown to play a
role in the pathogenesis of canine pyoderma. Numerous studies have failed to identify any
differences in toxin profiles between Staphylococcus spp. from normal dogs and those from
dogs with pyoderma (Allaker et al., 1991). Since Staphylococcus pseudintermedius, the most
common organism that causes canine pyoderma, is a normal commensal of the dog, it appears
that abnormal ‘host factors’ are the primary cause of these infections. The most common
primary causes include hypersensitivities, ectoparasites, endocrinopathies and cornification
abnormalities. Long term success in treating canine bacterial pyoderma requires identifying
and treating the primary cause.
Bacterial pyoderma can be classified on the basis of the depth of the lesion(s). The
different classifications are (1) surface pyoderma (pyotraumatic dermatitis, mucocutaneous
pyoderma and skin fold dermatitis); (2) superficial bacterial folliculitis (SBF); and (3) deep
pyoderma, namely, deep folliculitis and furunculosis, and cellulitis (subcutaneous
involvement). This review article is focused on superficial bacterial infection of the hair
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follicle (folliculitis). It is beyond the scope of this article to completely review canine SBF
and the objective is to provide an update on the disease in dogs, especially in regards to
methicillin resistance.
Etiology
Historically, Staphylococcus intermedius had been the most commonly isolated
pathogen in dogs with SBF (Cox et. al., 1984; Medleau et. al., 1986). More recently,
microbiologists have shown that all the organisms identified in the past as S. intermedius were
really S. pseudintermedius (Devriese et al., 2005). This has been modified further, such that
there is now a Staphylococcus intermedius group (SIG) with members including S.
intermedius, S. pseudintermedius and S. delphini.
S. pseudintermedius remains the organism most commonly causing SBF in dogs
(Sasaki T et. al., 2007). However, for clinicians, these name changes have no bearing on the
medical management of the cases. What is important is to differentiate SIG from the
bacterium that causes human infections, i.e. S. aureus. SIG can be differentiated from S.
aureus based on a variety of different techniques, including phenotypic testing or molecular
identification using whole-cell fingerprinting by matrix-assisted laser desorption-ionization
(MALDI)-time-of-flight mass spectrometry (MS), biochemical features, DNA-DNA
hybridization and PCR (Dubois et al., 2010; Sasaki et al., 2010).
Staphylococcus schleiferi has also been associated with bacterial pyoderma. S.
schleiferi may be either coagulase positive (S. schleiferi coagulans) or coagulase negative (S.
schleiferi schleiferi) (Frank et al., 2003). In the past, coagulase negative staphylococci were
considered to be contaminants when found on a culture from a superficial lesion in a dog.
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However, coagulase negative S. schleiferi schleiferi is a pathogen that is potentially zoonotic.
For this reason, it is important that laboratories identify coagulase negative staphylococci
down to the species level (for example, to differentiate non-pathogenic S. epidermidis from
pathogenic S. schleiferi schleiferi).
Clinical signs
Pruritus in dogs with SBF ranges from non-existent to intense. Clinically, SBF
presents differently in different breeds of dogs. Most dogs have multifocal areas of alopecia,
follicular papules or pustules, epidermal collarettes and serous crusts involving the trunk,
abdomen and axillary areas. Short-coated breeds often present with a ‘moth-eaten’ appearance
to the hair coat due to alopecic lesions associated with the folliculitis. Cocker spaniels have
their own special presentation, i.e. vegetative plaques, which are frequently mistaken for
seborrheic plaques associated with primary seborrhea of Cocker spaniels. Clinically and
histopathologically, they can be quite similar; therefore, if plaques are found on a Cocker
spaniel, the dog should be treated for a bacterial pyoderma before assuming that the dog has
‘idiopathic seborrhea’. The diagnosis of SBF is usually based on physical signs (i.e.
multifocal areas of alopecia, papules, pustules and epidermal collarettes), supported by
cytology and/or bacterial culture.
Diagnosis
Investigation of the underlying cause of the disease should be performed because
primary canine bacterial pyoderma does not occur. When a dog is presented for the first time
with SBF, only a limited number of diagnostic tests need to be undertaken. However, with
recurrent or chronic cases of SBF, or with any dog with a deep bacterial pyoderma, there is a
need for the underlying cause to be pursued aggressively.
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The predisposing causes of SBF include: (1) hypersensitivities (atopy, cutaneous
adverse food reactions, flea allergy dermatitis); (2) ectoparasites (e.g. Sarcoptes spp.); (3)
endogenous (hyperadrenocorticism) or exogenous exposure to corticosteroids; (4)
demodicosis (Demodex spp.); (5) hypothyroidism; (6) follicular dysplasias (e.g. color dilution
alopecia); (7) ectodermal dysplasia (e.g. Chinese crested dogs); and (8) cornification
abnormalities (sebaceous adenitis, ichthyosis) (Mason et al., 1989, Chesney, 2002).
Cutaneous cytological examination
Cutaneous cytology is an easy, inexpensive and rapid diagnostic test that should be
performed on any dog that is presented with skin lesions. There are a variety of methods to
collect cytology specimens (Mueller, 2000), with each method having advantages and
disadvantages. Cytology is used to identify the presence (and/or type) of: (1) bacterial or
fungal organisms (e.g. Malassezia); (2) neoplastic cells; (3) inflammatory cells; and (4)
abnormal cells (e.g. acantholytic keratinocytes associated with pemphigus foliaceus). When
evaluating cutaneous cytology specimens for infection, a semiquantitative scale ranging from
0 to 4+ should be used (Budach et al., 2012).
Bacterial culture
Bacterial culture may be necessary when managing a case of SBF. Before culturing a
lesion, cutaneous cytology should be performed on a representative lesion to confirm the
presence of bacterial infection (neutrophils with intracellular bacteria). Bacterial culture and
susceptibility (c/s) testing should always be performed in poorly responsive SBF cases, but is
not necessary in antimicrobial responsive but recurrent cases, since these cases will mostly
benefit from identifying and treating the primary cause only. Since Gram negative, rod shaped
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bacteria isolated from the skin are frequently resistant to many antibacterial agents (Petersen
et al., 2002), a bacterial culture should be submitted if neutrophils and rod-shaped bacteria are
identified on cutaneous cytology.
If a culture and susceptibility test is submitted, the minimum inhibitory concentration
(MIC) broth microdilution technique rather than the disc diffusion method should be used to
determine susceptibility. The disk-diffusion susceptibility test (DDST) is semiquantitative in
that the drug concentration achieved in the agar surrounding the disc can be roughly
correlated with the concentration achieved in the dog’s serum. It will only report the
organism’s susceptibility (susceptible, intermediate or resistant, SIR) based on an
approximation of the effect of an antimicrobial agent on bacterial growth on a solid medium.
Tube dilution (MIC) is quantitative, not only reporting SIR, but also the amount of drug
necessary to inhibit microbial growth. The MIC is reported as the lowest concentration of an
antimicrobial agent (in µg/mL) necessary to inhibit visible growth of the tested bacteria. This
allows a clinician to decide, not only susceptibility or resistance, but also the proper dosage
and frequency of administration of the antimicrobial agent. The MIC method can imply the
relative risk of emerging resistance and thus the need for a high treatment dose.
Samples from a pustule or intact nodule should be used for culturing, but if an intact
pustule or papule is not available, culturing an epidermal collarette has also been shown to be
reliable for sampling for SBF (White et al., 2005). Submitting a crust is also useful for a dog
with SBF if any of the classical lesions are not present; culture results from the crust are the
same as those from a macerated tissue punch biopsy sample (Vaughan and Lemarie, 2008).
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Systemic treatment
Recently, successful treatment of SBF could be accomplished predictably with a βlactam antibiotic (a first generation cephalosporin, such as cephalexin, or a potentiated
amoxicillin). However, increasingly methicillin resistant Staphylococcus spp. (MRS) are
being identified as causes of skin infections in dogs. MRS may be S. aureus (MRSA), S.
pseudintermedius (MRSP), S. intermedius (MRSI) or S. schleiferi (MRSS). No member of the
β-lactam family of antibiotics will be effective when MRS is identified.
The incidence of MRSP has been increasing over the last decade, rendering many
commonly used antibacterial agents ineffective (Jones et al., 2007). An additional
complication is that these bacteria are frequently multi-drug resistant (MDR). In a recent
study, >90% of MRSP were MDR, defined as being resistant to >4 antimicrobial drug classes
(Bemis et al., 2009).
The cause of the increased frequency of MRSP has not been clearly established, but
one of the many risk factors for MRSA and MDR Staphylococcus spp. is the administration of
fluoroquinolones. Reducing the use of antimicrobial agents and, particularly,
fluoroquinolones and third generation cephalosporins, may help to prevent persistent carriage
of MRSA in human beings (Monnet et al., 1998; Muto et al., 2003). Fukatsu et al. (1997)
reported MRSA outbreaks in human beings in a hospital that were correlated with the overuse
of third generation cephalosporins for prolonged periods; the incidence of these outbreaks
decreased by restricting the use of these antibiotics.
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In the past, oxacillin was used in antimicrobial sensitivity testing panels to identify
MRS. If the Staphylococcus sp. was an MRS, then it would be resistant to all of the β-lactams
(Weese et al., 2010). Currently, the protocol for identifying MRSA in vitro is to use cefoxitin
as the surrogate, since certain strains of MRSP may be falsely identified as methicillin
susceptible if the laboratory uses cefoxitin susceptibility as the indicator (it is unknown if this
applies to other members of the SIG) (Schissler et al., 2009; Weese et al., 2009). In order to
avoid mislabeling MRSP as susceptible, a new lower breakpoint (reduced from 2.0 to 0.5
g/mL for oxacillin when testing S. pseudintermedius) should be used. If culture and
sensitivity testing is performed by a laboratory more familiar with human specimens, the
laboratory may not be aware of these important differences and changes. To avoid these
errors, a veterinary laboratory that uses Clinical and Laboratory Standards Institute (CLSI)1 or
the European Committee on Antimicrobial Susceptibility Testing (EUCAST) guidelines2
should perform the tests.
Recently the effectiveness of clindamycin against MRSA has been questioned (Rich et
al., 2005). Two genes (msrA and erm) are responsible for the resistance of S. aureus to
macrolides (e.g. erythromycin). The msrA gene accounts for the resistance only to macrolides,
while the erm gene encodes for macrolide and lincosamide (lincomycin and clindamycin)
resistance. The erm gene can be expressed constitutively and the culture will report resistance
to clindamycin; this gene can also be inducible, in which case the MRSA will be susceptible
initially to clindamycin (and therefore reported as sensitive).
When MRSA has the inducible gene, resistance to clindamycin will develop during
treatment. Since the pattern of susceptibility to clindamycin of MRSA isolates possessing the
1
2
See: http://www.clsi.org/standards/micro/ (accessed 9 November 2013).
See: http://www.eucast.org/antimicrobial_susceptibility_testing/ (accessed 9 November 2013).
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msrA gene (truly susceptible to clindamycin) or the inducible erm gene (inducibly resistant)
are the same, it is important to distinguish between these phenotypes. This is accomplished by
an additional culture technique, the double disc diffusion D-test, which will detect the
occurrence of the inducible erm gene. Since commercial veterinary laboratories currently are
not performing this additional culture, resistance to erythromycin may be used as a surrogate
to indicate the presence of this inducible gene. This is because the msrA gene and the erm
gene both encode staphylococcal resistance to erythromycin. Therefore, if the Staphylococcus
sp. is resistant to erythromycin, there is a potential for the inducible erm gene to be present.
Rich et al. (2005) found that that 97.3% of erythromycin-resistant isolates of MRSA
were truly resistant to clindamycin, even though only 25.5% demonstrated clindamycin
resistance on routine laboratory testing. On the basis of this study, it would be prudent to
avoid clindamycin for all S. aureus infections that report resistance to erythromycin. Concern
about this inducible gene being present in MRSP was investigated in a recent report by Faires
et al. (2009), in which inducible clindamycin-resistance was present only in MRSA isolates
and not, for example, in MRSP. The authors concluded that, since inducible resistance was
not identified in any of the MRSP, the use of clindamycin was a reasonable option for MRSP
infections. Unfortunately, subsequent work questioned this conclusion, since the inducible
clindamycin gene was identified in two strains of MRSP (Perreten et al., 2010). An additional
report also found this inducible gene in methicillin susceptible Staphylococcus spp. (MSSP)
and methicillin susceptible S. aureus (MSSA) (Rubin et al., 2011). For this reason, it is
recommended that clindamycin should be avoided in any Staphylococcus spp. infection,
regardless of the species and strain, if the organism is reported to be resistant to erythromycin.
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Resistance of Staphylococcus spp. to tetracycline is mediated by two genes, tet(K) and
tet(M) (Trzcinski et al., 2000; Schwartz et al., 2009). Resistance to tetracycline, but not
doxycycline or minocycline, is mediated by tet(K), while tet(M) will confer resistance to all
three members of the tetracycline family. However, it is different in the case of MRSA. If an
MRSA isolate has the tet(K) gene, exposure to either tetracycline or doxycycline can induce
doxycycline, but not minocycline, resistance. It is currently unknown whether this is true for
members of SIG that are methicillin resistant. This is a problem, because the results of culture
will have suggested that the Staphylococcus sp. isolate is susceptible to doxycycline, but in
vivo resistance will occur. If the isolate is MSSA the tet(K) gene will confer resistance only to
tetracycline. In cases of MRSA infection the tet(K) gene will also induce doxycycline
resistance, leading to clinical failure if using doxycycline. This has led to the recommendation
that MRSA infections that are resistant to tetracycline should be considered to be resistant to
doxycycline regardless of the in vitro test result. In cases of tetracycline resistant MRSA
infections, minocycline should be tested since, if the tet(M) gene is present, minocycline will
be ineffective, but if the tet(K) gene is present, minocycline will be effective (Schwartz et al.,
2009).
For treatment of canine SBF, an antibacterial agent should be administered for at least
21 days, or 7-14 days past a physical examination that has determined that the infection has
resolved, whichever is longer. In SBF, glucocorticoid therapy should be withheld when the
pruritus is only at the site of the lesions or when the pruritus in non-lesional areas is only
mild. If a dog with a SBF has intense pruritus in non-lesional areas, then a tapering 21 day
course of prednisone may be dispensed. Using glucocorticoids in the presence of a pruritic
pyoderma makes interpretation of response to therapy impossible, since it is uncertain
whether the glucocorticoid or the antibacterial therapy/antifungal therapy was responsible for
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the resolution of the pruritus. Treatment with glucocorticoids may also have a negative effect
on the response to antibacterial agents.
A consensus statement titled ‘Guidelines for use of antibacterial drugs for superficial
bacterial folliculitis in dogs’ will soon be released (Hillier and Lloyd, 2012). In this
publication, the steps involved in the proper selection of antibacterial agents for canine SBF
will be reviewed. These guidelines, like the previous guidelines published concerning
antibiotic use for treating urinary tract infections in dogs and cats (Weese et al., 2011), are the
result of a committee consisting of veterinary internists, pharmacologists, microbiologists and
dermatologists. The key points are: (1) identify and treat the underlying cause of SPF; (2)
perform skin scrapings to determine if Demodex spp. are present; (3) perform cytology to
confirm a bacterial component; and (4) if possible, use disinfectants and/or topical
antimicrobials as the sole treatment; if this is not possible, at least use topical therapy to
shorten the length of time that systemic antibiotics need to be used; and (5) empirical therapy
can be used in non-recurrent cases or recurrent cases that have successfully responded to
previous treatment; drugs should be selected from the list of first tier medications.
In cases that fail to respond to appropriate treatment (dose and frequency) using a first
tier antibiotic, bacterial culture should be performed. When selecting an antibiotic based on a
culture result, a sensitive second tier antibiotic should only be used if the organism is resistant
to all first tier antibiotics, if the animal cannot tolerate any of the first tier drugs or if the
owner is unable to administer them.
In regards to second tier antibiotics, when appropriate, a veterinary fluoroquinolone
should be administered rather than ciprofloxacin. This recommendation is based on a study
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showing that there is a large variation in absorption of oral ciprofloxacin in dogs; to obtain
appropriate blood levels it would be necessary to administer 12-52 mg/kg ciprofloxacin orally
(Papich, 2012). Since this dosage was for highly susceptible bacteria (i.e. with low MIC),
larger doses may be required for organisms with high MICs.
When administering rifampicin, a dosage of 5-10 mg/kg once daily should be
prescribed for a maximum of 21 days due to potential hepatotoxicity (Papich, 2007). To
prevent rapid onset of resistance when treating S. aureus in human beings, Liu et al. (2011)
suggested that rifampicin should not be used as the only systemic therapy. However, this
recommendation is contrary to a review of clinical trials in which rifampicin was effective
against S. aureus whether administered as monotherapy or in combination (Falagas et al.,
2007). In dogs with MRSP, resistance to rifampicin may occur during therapy whether used
as a monosystemic drug or in combination (Kadlec et al., 2011). The author has successfully
used rifampicin as monosystemic therapy.
Concern about using third generation cephalosporins is shared by numerous groups
and agencies. The BSAVA Guide to the Use of Veterinary Medicines discusses the prudent use
of antimicrobial agents; with respect to third generation cephalosporins, and also for any
fluoroquinolones, the guide states ‘that in all species fluoroquinolones and third- and fourthgeneration cephalosporins should be used judiciously and never considered as first-choice
options’3.
The European Medicines Agency (EMA) is also concerned about the use of third
generation cephalosporins and fluoroquinolones and states that ‘It is prudent to reserve third
3
See: http://www.bsava.com/LinkClick.aspx?fileticket=Pik2rSpsRWA%3D&tabid=372 (accessed 9 November
2013).
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generation cephalosporins for the treatment of clinical conditions, which have responded
poorly, or are expected to respond poorly, to other classes of antimicrobials or first
generation cephalosporins’ and ‘use of the product should be based on susceptibility testing
and take into account official and local antimicrobial policies’4.
In Sweden, guidelines were published in 2009 concerning the use of antimicrobial
agents in the treatment of dogs and cats; these guidelines state that third generation
cephalosporins should only be used to treat infections where there are no other suitable
options 5. The guidelines also state that injections with long-acting antimicrobial agents
should not normally be used to treat a pyoderma and, specifically, that cefovecin should only
be used if the treatment is ‘of the utmost importance’ for the animal and where administration
of other medications is not possible.
Cefovecin (Convenia, Zoetis) is a parenterally administered third generation
cephalosporin that has tremendous value when used properly (selectively). The author
reserves this drug for cases where the owner is unable to orally medicate the dog or cat, or the
animal cannot tolerate oral antibiotics. The concern about using this antibiotic is that, after the
first injection, therapeutic drug concentrations (above MIC) are only maintained for 7-14
days, depending on the infectious agent, while tissue levels persist for up to 65 days. An
unanswered question is whether this prolonged subtherapeutic blood (or tissue) level will put
selective pressure on the bacteria such that the incidence of MRS will increase. Will there be
an increase in the incidence of extended spectrum β-lactamase (ESBL)-producing bacterial
4
See: http://www.ema.europa.eu/docs/en_GB/document_library/EPAR__Product_Information/veterinary/000098/WC500062067.pdf (accessed 9 November 2013).
5
See:
http://svf.se/Documents/S%C3%A4llskapet/Sm%C3%A5djurssektionen/Policy%20ab%20english%2010b.pdf
(accessed 9 November 2013).
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infections, as has been reported with other third generation cephalosporins (Colodner et al.,
2004)? ESBLs are capable of conferring bacterial resistance to the penicillins, as well as first,
second and third generation cephalosporins. Will adverse reactions require prolonged
treatment due to the longer systemic drug clearance? What are the long term effects at
injection sites, especially in cats? Most of these questions have not been answered.
An additional concern about both fluoroquinolones and third generation
cephalosporins is that they are both independent risk factors for development of ESBLproducing bacterial infections (Colodner et al., 2004). ESBLs are a concern in human
medicine because they are frequently MDR, not only to β-lactam antibiotics, but also to other
antimicrobial agents, such as aminoglycosides, fluoroquinolones, tetracyclines,
chloramphenicol and sulfamethoxazole-trimethoprim. This wide ranging resistance greatly
limits effective treatment options. The genes encoding this resistance are mediated by
plasmids and/or mobile elements, allowing horizontal transfer between the same and different
species of bacteria (Vaidya, 2011). In contrast to fluoroquinolones and third generation
cephalosporins, first generation cephalosporins have not been reported to be a risk factor for
such resistance (Colodner et al., 2004).
Additional concerns about using fluoroquinolones are that, according to information
from the Centers for Disease Control and Prevention (CDC) website, ‘none of the
fluoroquinolones are Federal Drug Administration approved for the treatment of MRSA
infections. A major limitation of fluoroquinolones is that resistant mutants can be selected
with relative ease, leading to relapse and treatment failure’.6 MRSA strains are especially
adept at developing fluoroquinolone resistance and such resistance is already found among
MRSA isolated from human beings with community-associated MRSA infections. In
6
See: http://www.cdc.gov/mrsa/pdf/MRSA-Strategies-ExpMtgSummary-2006.pdf (accessed 9 November 2013).
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addition, there is a significant association between total fluoroquinolone use in human
hospitals and the proportion of S. aureus isolates that are MRSA, as well as between total
fluoroquinolone use in the community and the percentage of E. coli isolates that are
fluoroquinolone resistant (MacDougall et al., 2005). There is an association between the use
of fluoroquinolones against mec(A) positive S. aureus and an increase in the resistance index
for methicillin resistance (Venezia et al., 2001). There is also an association between the use
of fluoroquinolones and the occurrence of clinically significant MRSA (Crowcroft et al.,
1999; Polk et al., 2004).
Topical treatment
Systemic therapy for canine pyoderma is becoming more problematic because of the
increasing incidence of MRS (Morris, et al., 2006; Loeffler et al., 2007; Jones, et al., 2007).
To help address this problem, topical therapy, either as monotherapy or as part of
polypharmacy, has become an essential component of managing SPF. Topical therapy may
decrease the length of time administering, or eliminate the need for, systemic antibiotics.
Since dogs with SBF frequently have atopic dermatitis, bathing will also remove problematic
allergens, in addition to bacteria, from the skin. The limitations of using topical therapy
include time constraints of the owner, patient cooperation (especially with baths) and, if
treating a large area, possibly cost.
Shampoo ingredients that are effective for treating bacterial pyoderma include
chlorhexidine, benzoyl peroxide, ethyl lactate, triclosan and boric acid/acetic acid.
Chlorhexidine was found to be the most effective ingredient in shampoos (Loeffler et al.,
2012; Young et al., 2012). However, the widespread use of chlorhexidine in human beings
has resulted in reports of reduced chlorhexidine susceptibility (Noguchi et al., 2006). This
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resistance is of concern, since chlorhexidine is used for decolonizing human beings with
MRSA. Adding to this concern is circumstantial evidence of horizontal transfer of plasmids
carrying these resistance genes. Whether or not the use of chlorhexidine in veterinary
medicine will add additional resistance pressure on methicillin resistant members of SIG is
unclear at this time.
Bleach baths have been reported to be effective for the treatment and prevention of
MRSA in young children with atopic dermatitis (Huang et al., 2009). The author has seen
very good responses in cases of MDR MRSP in dogs using a 0.06-0.12% solution as a soak 24 times weekly. These soaks are followed by a moisturizer or humectants.
Topical therapy with mupirocin is effective for treating localized lesions (Mueller et
al., 2012). An advantage of mupirocin is its unique mechanism of action; as a consequence,
cross-resistance with other antibacterial agents is very uncommon. However, there have been
disturbing reports of mupirocin-resistant MRSA strains (Deshpande et al., 2002; Loeffler et
al., 2008). As with chlorhexidine, this resistance is plasmid-mediated and spreads
horizontally. Since mupirocin is used for decolonizing human beings with MRSA, restricted
use has been advised (Simor, 2007). It is currently unknown whether this resistance will occur
in methicillin resistant members of SIG.
The anti-fungal agent miconazole also possesses antibacterial properties against some
Gram positive bacteria, including MRSA and MRSP in vitro (Weese et al., 2012). Whether
miconazole proves to have the same in vivo effect is unknown. Silver sulfadiazine has
traditionally been used for infections associated with Gram negative bacteria, especially
16
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Pseudomonas spp. (Hillier, 2006). However, it is also effective against some Gram positive
bacteria, including S. aureus. Its effectiveness on S. pseudintermedius infection is unknown.
Conclusions
If a dog is presented with lesions consistent with SBF, such as papules, pustules and/or
epidermal collarettes, skin cytology and a deep skin scraping should be performed. A fungal
culture and/or bacterial culture should be considered, depending on the history, physical signs
and cytological results. In cases of SPF, if cocci are seen on cytology and the lesion is focal,
treatment with an antimicrobial shampoo, with or without a residual spray or cream, may be
effective. If the infection is more widespread and there has not been a recent history of
antibiotic use, a first tier antibiotic may be prescribed. A re-examination should be performed
after 14-21 days to assess the response to therapy. Lastly, there should be an attempt to find
and treat the underlying primary cause of the SBF.
Treating SBF requires both symptomatic treatment and identifying and treating the
primary cause; however, if only symptomatic treatment is given, recurrence is likely to occur.
In view of increasingly resistant bacteria involved in SBF, it is becoming essential to include
topical therapy as a part of the symptomatic treatment of SBF. In addition it is necessary to be
more restrictive in dispensing second tier antibiotics to reduce the selection pressure these
drugs apply to bacteria. Even though using antimicrobial agents may not harm an individual
animal, excessive usage has led to the spread of resistant bacteria, both in human beings and
veterinary species. Hopefully, this disturbing trend can be disrupted with good stewardship of
the use of antimicrobial agents.
17
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Conflict of interest statement
The author of this paper has no financial or personal relationship with other people or
organisations that could inappropriately influence or bias the content of the paper
References
Allaker, R.P., Lamport, A.I., Lloyd, D.H., Noble, W.I., 1991. Production of virulence factors
by Staphylococcus intermedius isolated from cases of canine pyoderma and healthy
carriers. Microbial Ecology in Health and Disease 4, 169-73.
Bemis, D.A., Jones, R.D., Frank, L.A., Kania, S.A., 2009. Evaluation of susceptibility test
breakpoints used to predict mecA-mediated resistance in Staphylococcus
pseudintermedius isolated from dogs. Journal of Veterinary Diagnostic Investigation 21,
53-58.
Budach, S.C., Mueller, R.S., 2012. Reproducibility of a semiquantitative method to assess
cutaneous cytology. Veterinary Dermatology, 23, 426-480.
Chesney, C.J., 2002. Food sensitivity in the dog: A quantitative study. Journal of Small
Animal Practice 43, 203-207.
Colodner, R., Rock, W., Chazan, B., Keller, N., Guy, N., Sakran, W., Raz, R. 2004. Risk
factors for the development of extended-spectrum beta-lactamase-producing bacteria
in nonhospitalized patients. European Journal of Clinical Microbiology and Infectious
Diseases 23, 163-167.
Cox, H.U., Newman, S.S., Roy, A.F., Hoskins, J.D., 1984. Species of Staphylococcus isolated
from animal infections. Cornell Veterinary Magazine74, 124-135.
Crowcroft, N.S., Ronveaux, O., Monnet, D.L., Mertens, R., 1999. Methicillin-resistant
Staphylococcus aureus and antimicrobial use in Belgian hospitals. Infection Control and
Hospital Epidemiology 20, 31-36
Deshpande, L.M., Fix, A.M., Pfaller, M.A., Jones, R.N., Group, S.A.S.P.P., 2002. Emerging
elevated mupirocin resistance rates among staphylococcal isolates in the SENTRY
Antimicrobial Surveillance Program (2000): Correlations of results from disk diffusion,
Etest and reference dilution methods. Diagnostic Microbiology and Infectious Disease
42, 283-290.
Devriese, L.A., Vancanneyt, M., Baele, M., Vaneechoutte, M., De Graef, E., Snauwaert, C.,
Cleenwerck, I., Dawyndt, P., Swings, J. et al., 2005. Staphylococcus pseudintermedius
sp. nov., a coagulase-positive species from animals. International Journal of Systematic
and Evolutionary Microbiology 55, 1569-1573.
18
资料来自互联网，仅供科研和教学使用，使用者请于24小时内自行删除
Dubois, D., Leyssene, D., Chacornac, J.P., Kostrzewa, M., Schmit, P.O., Talon, R., Bonnet,
R., Delmas, J., 2010. Identification of a variety of Staphylococcus species by matrixassisted laser desorption ionization-time of flight mass spectrometry. Journal of Clinical
Microbiology 48, 941-945.
Faires, M.C., Gard, S., Aucoin, D., Weese, J.S., 2009. Inducible clindamycin-resistance in
methicillin-resistant Staphylococcus aureus and methicillin-resistant Staphylococcus
pseudintermedius isolates from dogs and cats. Veterinary Microbiology 139, 419-420.
Falagas, M.E., Bliziotis, I.A., Fragoulis, K.N., 2007. Oral rifampin for eradication of
Staphylococcus aureus carriage from healthy and sick populations: A systematic review
of the evidence from comparative trials. American Journal of Infection Control 35, 106114.
Frank, L.A., Kania, S.A., Hnilica, K.A., Wilkes, R.P., Bemis, D.A.2003. Isolation of
Staphylococcus schleiferi from dogs with pyoderma. Journal of the American Veterinary
Medical Association 222, 451-454.
Fukatsu, K., Saito, H., Matsuda, T., Ikeda, S., Furukawa, S., Muto, T., 1997. Influences of
type and duration of antimicrobial prophylaxis on an outbreak of methicillin-resistant
Staphylococcus aureus and on the incidence of wound infection. Archives of Surgery
132, 1320-1325.
Hillier, A., Alcorn, J.R., Cole, L.K., Kowalski, J.J., 2006. Pyoderma caused by Pseudomonas
aeruginosa infection in dogs: 20 cases. Veterinary Dermatology 17, 432-439.
Hillier A., Lloyd D.H., 2012. Guidelines for use of antibacterial drugs for superficial bacterial
folliculitis in dogs from the International Society for Companion Animal Infectious
Disease Antimicrobial Guidelines Working Group. Proceedings of the Continuing
Education Programme, 7th World Congress of Veterinary Dermatology, World
Association for Veterinary Dermatology, Vancouver, Canada, 24-28 July 2012, pp. 158162.
Huang, J.T., Abrams, M., Tlougan, B., Rademaker, A., Paller, A.S., 2009. Treatment of
Staphylococcus aureus colonization in atopic dermatitis decreases disease severity.
Pediatrics 123, e808-e814.
Jones, R.D., Kania, S.A., Rohrbach, B.W., Frank, L.A., Bemis, D.A., 2007. Prevalence of
oxacillin- and multidrug-resistant staphylococci in clinical samples from dogs: 1,772
samples (2001-2005). Journal of the American Veterinary Medical Association 230,
221-227.
Kadlec, K., van Duijkeren, E., Wagenaar, J.A, Schwarz, S., 2011. Molecular basis of
rifampicin resistance in methicillin-resistant Staphylococcus pseudintermedius isolates
from dogs. Journal of Antimicrobial Chemotherapy 66, 1236-1242.
Liu, C., Bayer, A., Cosgrove, S.E., Daum, R.S., Fridkin, S.K., Gorwitz, R.J., Kaplan, S.L.,
Karchmer, A.W., Levine, D.P., Murray, B.E.J., et al., 2011. Clinical practice guidelines
by the Infectious Diseases Society of America for the treatment of methicillin-resistant
19
资料来自互联网，仅供科研和教学使用，使用者请于24小时内自行删除
Staphylococcus aureus infections in adults and children: Executive summary. Clinical
Infectious Diseases 52, 285-292.
Loeffler, A., Linek, M., Moodley, A., Guardabassi, L., Sung, J.M., Winkler, M., Weiss, R.,
Lloyd, D.H., 2007. First report of multiresistant, mecA-positive Staphylococcus
intermedius in Europe: 12 cases from a veterinary dermatology referral clinic in
Germany. Veterinary Dermatology 18, 412-421.
Loeffler, A., Baines, S.J., Toleman, M.S., Felmingham, D., Milsom, S.K., Edwards, E.A.,
Lloyd, D.H., 2008. In vitro activity of fusidic acid and mupirocin against coagulasepositive staphylococci from pets. Journal of Antimicrobial Chemotherapy 62, 1301-304
Loeffler, A., Cobb, M.A., Bond, R., 2011. Comparison of a chlorhexidine and a benzoyl
peroxide shampoo as sole treatment in canine superficial pyoderma. Veterinary Record
169, 249.
MacDougall, C., Powell, J.P., Johnson, C.K., Edmond, M.B., Polk, R.E., 2005. Hospital and
community fluoroquinolone use and resistance in Staphylococcus aureus and
Escherichia coli in 17 US hospitals. Clinical Infectious Diseases 41, 435-440.
Medleau, L., Long, R.E., Brown, J., Miller, W.H.,1986. Frequency and antimicrobial
susceptibility of Staphylococcus species isolated from canine pyodermas. American
Journal of Veterinary Research 47, 229-231.
Monnet, D.L., 1998. Methicillin-resistant Staphylococcus aureus and its relationship to
antimicrobial use: Possible implications for control. Infection Control and Hospital
Epidemiology 19, 552-559.
Morris, D.O., Rook, K.A., Shofer, F.S., Rankin, S.C., 2006. 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). Veterinary Dermatology 17, 332-337.
Mueller, R.S., 2000. Specific tests in small animal dermatology, In: Dermatology for the Small
Animal Practitioner. Teton NewMedia, Jackson, Wyoming, USA, pp. 21-26.
Mueller, R.S., Bergvall, K., Bensignor, E., Bond, R., 2012. A review of topical therapy for
skin infections with bacteria and yeast. Veterinary Dermatology 23, 330-341, e362.
Muto, C.A., Jernigan, J.A., Ostrowsky, B.E., Richet, H.M., Jarvis, W.R., Boyce, J.M., Farr,
B.M.; Society for Healthcare Epidemiology of America (SHEA), 2003. SHEA guideline
for preventing nosocomial transmission of multidrug-resistant strains of Staphylococcus
aureus and enterococcus. Infection Control and Hospital Epidemiology 24, 362-386.
Noguchi, N., Nakaminami, H., Nishijima, S., Kurokawa, I., So, H., Sasatsu, M., 2006.
Antimicrobial agent of susceptibilities and antiseptic resistance gene distribution among
methicillin-resistant Staphylococcus aureus isolates from patients with impetigo and
staphylococcal scalded skin syndrome. Journal of Clinical Microbiology 44, 2119-2125.
20
资料来自互联网，仅供科研和教学使用，使用者请于24小时内自行删除
Papich, M.G., 2007. Saunders Handbook of Veterinary Drugs: Small and Large Animal, 3rd
Edn. Elsevier-Saunders, St Louis, Missouri, USA, 730 pp.
Papich, M.G., 2012. Ciprofloxacin pharmacokinetics and oral absorption of generic
ciprofloxacin tablets in dogs. American Journal of Veterinary Research 73, 1085-1091.
Perreten, V., Kadlec, K., Schwarz, S., Gronlund Andersson, U., Finn, M., Greko, C.,
Moodley, A., Kania, S.A., Frank, L.A., Bemis, D.A., et al., 2010. Clonal spread of
methicillin-resistant Staphylococcus pseudintermedius in Europe and North America:
An international multicentre study. Journal of Antimicrobial Chemotherapy 65, 11451154.
Petersen, A.D., Walker, R.D., Bowman, M.M., Schott, H.C., Rosser, E.J., 2002. Frequency of
isolation and antimicrobial susceptibility patterns of Staphylococcus intermedius and
Pseudomonas aeruginosa isolates from canine skin and ear samples over a 6-year
period (1992-1997). Journal of the American Animal Hospital Association 38, 407413.
Polk, R.E., Johnson, C.K., McClish, D., Wenzel, R.P., Edmond, M.B., 2004. Predicting
hospital rates of fluoroquinolone-resistant Pseudomonas aeruginosa from
fluoroquinolone use in US hospitals and their surrounding communities. Clinical
Infectious Diseases 39, 497-503.
Rich, M., Deighton, L., Roberts, L., 2005. Clindamycin-resistance in methicillin-resistant
Staphylococcus aureus isolated from animals. Veterinary Microbiology 111, 237-240.
Rubin, J.E., Ball, K.R., Chirino-Trejo, M., 2011. Antimicrobial susceptibility of
Staphylococcus aureus and Staphylococcus pseudintermedius isolated from various
animals. Canadian Veterinary Journal 52, 153-157.
Sasaki, T., Tsubakishita, S., Tanaka, Y., Sakusabe, A., Ohtsuka, M., Hirotaki, S., Kawakami,
T., Fukata, T., Hiramatsu, K., 2010. Multiplex-PCR method for species identification of
coagulase-positive staphylococci. Journal of Clinical Microbiology 48, 765-769.
Schissler, J.R., Hillier, A., Daniels, J.B., Cole, L.K., Gebreyes, W.A., 2009. Evaluation of
Clinical Laboratory Standards Institute interpretive criteria for methicillin-resistant
Staphylococcus pseudintermedius isolated from dogs. Journal of Veterinary Diagnostic
Investigation 21, 684-688.
Schwartz, B.S., Graber, C.J., Diep, B.A., Basuino, L., Perdreau-Remington, F., Chambers,
H.F., 2009. Doxycycline, not minocycline, induces its own resistance in multidrugresistant, community-associated methicillin-resistant Staphylococcus aureus clone
USA300. Clinical Infectious Diseases 48, 1483-1484.
Simor, A.E., Stuart, T.L., Louie, L., Watt, C., Ofner-Agostini, M., Gravel, D., Mulvey, M.,
Loeb, M., McGeer, A., Bryce, E., et al., 2007. Mupirocin-resistant, methicillin-resistant
Staphylococcus aureus strains in Canadian hospitals. Antimicrobial Agents and
Chemotherapy 51, 3880-3886
21
资料来自互联网，仅供科研和教学使用，使用者请于24小时内自行删除
Trzcinski, K., Cooper, B.S., Hryniewicz, W., Dowson, C.G., 2000. Expression of resistance to
tetracyclines in strains of methicillin-resistant Staphylococcus aureus. Journal of
Antimicrobial Chemotherapy 45, 763-770.
Vaidya, V.K., 2011. Horizontal transfer of antimicrobial resistance by extended-spectrum β
lactamase-producing Enterobacteriaceae. Journal of Laboratory Physicians 3, 37-42.
Vaughan, D.F., Lemarie, S.L., 2008. Comparison of culture and susceptibility results of
superficial versus biopsy specimens in dogs with superficial pyoderma. 23rd
Proceedings of the North American Veterinary Dermatology Forum, Denver, Colorado,
USA, 9-12 April 2008, p. 182.
Venezia, R.A., Domaracki, B.E., Evans, A.M., Preston, K.E., Graffunder, E.M., 2001.
Selection of high-level oxacillin resistance in heteroresistant Staphylococcus aureus by
fluoroquinolone exposure. Journal of Antimicrobial Chemotherapy 48, 375-381
Weese, J.S., Faires, M., Brisson, B.A., Slavic, D., 2009. Infection with methicillin-resistant
Staphylococcus pseudintermedius masquerading as cefoxitin susceptible in a dog.
Journal of the American Veterinary Medical Association 235, 1064-1066.
Weese, J.S., van Duijkeren, E., 2010. Methicillin-resistant Staphylococcus aureus and
Staphylococcus pseudintermedius in veterinary medicine. Veterinary Microbiology
140, 418-429.
Weese, J.S., Blondeau, J.M., Boothe, D., Breitschwerdt, E.B., Guardabassi, L., Hillier, A.,
Lloyd, D.H., Papich, M.G., Rankin, S.C., Turnidge, J.D., et al., 2011. Antimicrobial use
guidelines for treatment of urinary tract disease in dogs and cats: Antimicrobial
Guidelines Working Group of the International Society for Companion Animal
Infectious Diseases. Veterinary Medicine International 2011, 263768.
Weese, J.S., Walker, M., Lowe, T., 2012. In vitro miconazole susceptibility of meticillinresistant Staphylococcus pseudintermedius and Staphylococcus aureus. Veterinary
Dermatology 23, 400-e474.
White, S.D., Brown, A.E., Chapman, P.L., Jang, S.S., Ihrke, P.J., 2005. Evaluation of aerobic
bacteriologic culture of epidermal collarette specimens in dogs with superficial
pyoderma. Journal of the American Veterinary Medical Association 226, 904-908.
Young, R., Buckley, L., McEwan, N., Nuttall, T., 2012. Comparative in vitro efficacy of
antimicrobial shampoos: A pilot study. Veterinary Dermatology 23, 36-40.
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