Embed Size (px)
DESCRIPTION
Staphylococcus pseudintermedius
Citation preview
The effectiveness of systemic antimicrobial treatment incanine superficial and deep pyoderma: a systematic review
Jennifer F. Summers*, David C. Brodbelt*, Peter J. Forsythe†, Anette Loeffler* and Anke Hendricks*
*Department of Veterinary Clinical Sciences, Royal Veterinary College, Hawkshead Lane, North Mymms, Hatfield, Hertfordshire AL9 7TA, UK
†The Dermatology Referral Service, 528 Paisley Road West, Glasgow G51 1RN, UK
Correspondence: Jennifer F. Summers, Department of Veterinary Clinical Sciences, Royal Veterinary College, Hawkshead Lane, North Mymms,
Hatfield, Hertfordshire AL9 7TA, UK. E-mail: [email protected]
Aim – To identify and evaluate existing evidence for the effectiveness of systemic antimicrobial treatments for
naturally occurring superficial and deep canine pyoderma.
Method – Electronic searches of PubMed, MEDLINE and CAB Direct were carried out (25 May 2011) without
date or language restrictions. Proceedings of ESVD ⁄ ECVD, AAVD ⁄ ACVD, NAVDF and WCVD annual congresses
were searched. Unpublished studies were sought via the Veterinary Dermatology discussion list and Veterinary
Information Network.
Results – Seventeen full-length, peer-reviewed controlled trials reporting clinical outcomes of systemic antimicro-
bial treatment for canine pyoderma were identified. Outcomes specific to superficial or deep pyoderma were
reported in nine and five studies, respectively. Five studies reported outcomes only for nondifferentiated pyoderma
depth. Heterogeneity of study designs and outcome measures made meta-analysis inappropriate. A good level of
evidence was identified supporting the high efficacy of subcutaneously injected cefovecin in superficial pyoderma
and for oral amoxicillin–clavulanic acid in deep pyoderma. A fair level of evidence was identified for moderate to
high efficacy of oral amoxicillin–clavulanic acid, clindamycin, cefadroxil, trimethoprim–sulphamethoxazole and sul-
fadimethoxine–ormetoprim in superficial pyoderma and oral pradofloxacin, oral cefadroxil and subcutaneously
injected cefovecin in deep pyoderma. Eleven trials reported observations of adverse effects in treated pyoderma
cases by intervention group; four dogs were withdrawn owing to the severity of adverse effects.
Conclusions – There is a need for greater numbers of adequately sized, blinded, randomized controlled trials
evaluating systemic antimicrobial interventions for canine pyoderma. Improved differentiation between superfi-
cial and deep pyoderma in outcome reporting, outcome measure standardization and association of outcomes
with causative bacterial species and their resistance patterns are required.
Introduction
Canine pyoderma represents a common group of skin
diseases characterized by bacterial infection of the skin.1
In the vast majority of cases, the causative organism is
Staphylococcus pseudintermedius (formerly Staphylococ-
cus intermedius2,3), though other staphylococcal species
may also be involved.4 Less common bacterial pathogens
known to cause pyoderma in the dog include Strepto-
coccus, Corynebacterium, Micrococcus, Proteus, Escheri-
chia coli and Pseudomonas aeruginosa.5,6 Staphylococcus
pseudintermedius is a normal resident of canine mucous
membranes and is thought to colonize the skin surface
transiently in healthy dogs.7 Clinical pyoderma lesions
usually develop secondary to some predisposing factor,
such as cutaneous damage, inflammatory skin disease
and primary conditions causing immune compromise. As
such, even following complete resolution pyoderma has a
tendency to recur if the underlying disease is not properly
addressed.8 A number of different clinical manifestations
of canine pyoderma are recognized based on lesion
type and distribution. Classification by lesion depth is
considered useful, because choice of antimicrobial ther-
apy may vary according to the cutaneous tissue layers
affected.8,9
Topical antimicrobial treatment may be effective as a
sole treatment for superficial pyoderma lesions,10 and is a
useful adjunct to systemic antibiosis in more extensive
Accepted 7 March 2012
Sources of Funding: As part of the doctoral studies of the first
author at the Royal Veterinary College this study was funded by
a Biotechnology and Biological Sciences Research Council
Collaborative Awards in Science and Engineering (BBSRC CASE)
studentship, with Pfizer Inc. as industrial partner.
Conflict of Interest: Jennifer Summers is undertaking doctoral
studies at the Royal Veterinary College, funded by a Biotechnol-
ogy and Biological Sciences Research Council Collaborative
Awards in Science and Engineering (BBSRC CASE) studentship
with Pfizer Inc. as industrial partner. Pfizer Inc. was not, how-
ever, directly involved in the conception, protocol design, imple-
mentation, analysis or final reporting of this systematic review.
Anke Hendricks has received consultancy fees and project
funding from Novartis Animal Health Inc. and was involved in
clinical trials funded by Phytopharm Plc and Pfizer Animal Health.
Anette Loeffler received funding from Defra and from the
PetPlan Charitable Trust for her PhD studies and from Leo
Animal Health, UK, for her residency. David Brodbelt and Peter
Forsythe declared no conflicts of interest.
ª 2012 The Authors. Veterinary Dermatology
ª 2012 ESVD and ACVD, Veterinary Dermatology, 23, 305–e61. 305
Vet Dermatol 2012; 23: 305–e61 DOI: 10.1111/j.1365-3164.2012.01050.x
superficial and deep pyodermas.11,12 It has also been
reported as an effective preventative measure in some
cases of recurrent pyoderma.13 However, systemic anti-
biotic treatment is generally considered necessary for the
resolution of forms of deep pyoderma and is also widely
used and recommended for treatment of superficial pyo-
derma.14 Although other therapeutic approaches have
also been suggested, this review considers systemic anti-
microbial interventions only.
A wide range of antimicrobial groups has been advo-
cated for treatment of staphylococcal pyoderma based
on their in vitro efficacy against S. pseudintermedius,
clinical experience of in vivo efficacy and clinical trial
results. These include sulfonamides, macrolides, lincosa-
mides, cefalosporins, b-lactamase-resistant penicillins
and fluoroquinolones.15 For some antibiotics, a wide
dosage range is licensed or recommended. The required
duration of antibiotic treatment for successful resolution
of pyoderma is also variable, although generally longer
treatment schedules are proposed for deep infections.
For certain recurrent forms of pyoderma, long-term man-
agement with antibiotic low-dose or pulse therapy has
been attempted with variable success.16
In light of emerging multidrug resistance and the asso-
ciated potential restriction of veterinary antimicrobial drug
use, the choice of agent ideally should be based on bacte-
rial culture and antimicrobial sensitivity testing of the
individual pathogens involved in each case [www.bva.
co.uk/public/documents/BVA_Antimicrobial_Guidance.pdf
(accessed 12 September 2011)]. However, empirically
chosen antibacterial treatment, where pathogen identity
and antimicrobial susceptibility profiling information
remain unknown, is common, particularly in the first-
opinion clinical setting.17 General recommendations for
empirically chosen systemic antimicrobial therapy are
difficult to make with reliability; rational choice (not
based on culture and sensitivity) of a suitable antimicro-
bial agent may be largely dependent on known regional
differences in the antibiotic susceptibility profile of rele-
vant bacterial populations, in addition to specific patient
and drug factors (e.g. drug availability, safety, practicality
of administration, cost and legal status). As such, the
remit of this systematic review is not to provide defini-
tive guidelines for empirical choice of systemic antimi-
crobial therapy in canine pyoderma cases. The review
aims to establish a useful basis for evidence-based treat-
ment recommendations by identification, summarization
and evaluation of the highest quality existing evidence
on clinical effectiveness of systemic antimicrobials for
treatment of superficial and deep canine pyoderma.
Methods
Search strategyThe literature search aimed to identify studies comparing in vivo,
systemic antimicrobial interventions for naturally occurring cases of
canine bacterial pyoderma in more than one dog, published in peer-
reviewed journals or major conference proceedings. The population
of interest was dogs with bacterial pyoderma diagnosed clinically
by a veterinarian and preferably confirmed by bacterial culture or
cytology.
Search strategies included use of electronic search engines for
publication databases, hand searching of the proceedings of rele-
vant scientific conferences and meetings, and direct approaches to
the specialist veterinary dermatology community to identify sources
of unpublished data. Electronic databases searched were Pub
Med (www.ncbi.nlm.nih.gov/PubMed) and CAB Abstracts (www.
cabdirect.org). Final electronic searches were carried out on 25 May
2011, with no date restrictions, by the primary author. The search
terms used in both search engines were as follows: (dog OR dogs
OR canine) AND (folliculitis OR impetigo OR furunculosis OR pyo-
derma OR overgrowth) OR [(skin OR cutaneous) AND infection*]
OR dermatitis) AND (bacterial OR staphylococc* OR intermedius
OR aureus OR pseudintermedius) AND (treat* OR intervention OR
therap*). Hand searching of major veterinary dermatology confer-
ence and meeting proceedings from 1990 to 2010 was carried
out by two authors (AH and PF). Conferences ⁄ meetings searched
were as follows: Annual Congresses of the European Society and
College of Veterinary Dermatology (ESVD ⁄ ECVD) and the American
Association and American College of Veterinary Dermatologists
(AAVD ⁄ ACVD), North American Veterinary Dermatology Forum
(NAVDF) meetings, World Congresses of Veterinary Dermatology
(WCVD) and Advances in Veterinary Dermatology volumes 3–5 (pub-
lished in 1998, 2002 and 2005). Unpublished studies were sought
by two authors (AH and PF) via correspondence on the Veterinary
Dermatology discussion list ([email protected]) and Veterinary
Information Network (VIN). Reference lists from published studies,
including secondary review articles, were examined to identify any
further studies of interest. All items returned by the search engines,
hand searches and correspondence were recorded and entered into
the screening process.
Study selectionNo restrictions based on earliest publication date or publication
language were imposed. Items not available in English were
assessed based on an English translation, initially produced using
translation software [Google Translate, Google Inc. (www.translate.
google.com)] and verified by a veterinarian fluent in the language of
publication.
A two-stage process of screening was used, first to identify stud-
ies of relevance to the systematic review questions (stage 1) and
then to select those likely to provide evidence of the highest available
quality reported in sufficient detail for outcome extraction and meth-
odological evaluation (stage 2). Stage 1 of the screening process
identified from the total search results studies of any report length
that fulfilled all of the following criteria: (i) published in a peer-
reviewed publication or major congress proceedings; (ii) Reporting
original research (review articles were excluded); (iii) reporting find-
ings related to effects of in vivo, systemic antimicrobial treatment
interventions in canine pyoderma cases (in vitro research, assess-
ments of combined topical ⁄ systemic or nonantimicrobial treatments
and studies concerning bacterial populations on the skin of healthy
dogs were excluded); and (iv) involving study group(s) selected for
treatment with the intervention(s) of interest (individual case reports
and case series were excluded).
Selection for full data extraction and inclusion in the review
required studies identified at stage 1 also to fulfil the following
stage 2 screening criteria: (i) controlled trial study design [blinded,
randomized controlled trial (RCT), open RCT or controlled trial with no
randomization] comparing outcomes in a systemic antimicrobial
treatment group with at least one alternative systemic antimicrobial
treatment group and ⁄ or untreated control group and ⁄ or group with
different pyoderma depth; and (ii) published as a full-length paper
with sufficient detail for outcome extraction and methodological
evaluation (abstracts only and short communication items were
excluded).
Items excluded at the stage 1 screening phase are reported no
further in this review. Citations for studies passing stage 1 but
excluded at stage 2 are listed (Table 1, citations not marked with an
asterisk) but not described in any further detail. Selected research
items (fulfilling all stage 1 and 2 criteria) were evaluated in detail in
terms of treatment outcomes and the quantity and quality of evi-
dence for clinical efficacy.
ª 2012 The Authors. Veterinary Dermatology
306 ª 2012 ESVD and ACVD, Veterinary Dermatology, 23, 305–e61.
Summers et al.
Data extractionEach selected study was reviewed for data extraction by two authors
(JS and either AH or AL) with the addition of a third author (DB) to
moderate in the event of significant discrepancies. Study findings
and design characteristics relevant to assessment of evidence quality
were recorded using a standardized, purpose-designed data extrac-
tion form (available on request). Reviewers were not blinded to
author names, institutions or publication titles. Extracted outcome
data and study design features were summarized in a standardized
tabular format.
Assessment of quality of evidenceStudy design was determined in each trial selected for review;
blinded RCTs were considered most likely to produce evidence of
good quality, followed by open RCTs then controlled trials with no
randomization.
Using extracted information on study design, implementation and
reporting, the reviewers used a pre-prepared system of evidence
quality assessment to indicate the strengths and weaknesses of
each study. This three-part system incorporated the following
assessments: (i) study group sizes; (ii) subject enrolment quality; and
(iii) overall risk of bias based on methodological quality, to provide an
indicator of confidence associated with the findings of each report
(Figure 1). A statement of evidence quality was formulated and
reported alongside the tabulated outcomes reported from each
study.
Study group sizes
This characteristic was categorized for each study using the following
system, derived from a recently published scheme assessing trial
quality based on trial sizes in the field of published veterinary (rather
than human) research18: (i) >50 subjects per group (‘good number’ of
subjects); (ii) 20–50 subjects per group (‘moderate’ number); (iii) 10–
19 subjects per group (‘small’ number); and (iv) <10 subjects per
group (‘very small’ number’)
Assessment of subject enrolment quality
Information on diagnostic inclusion criteria was used to assess the
quality of subject enrolment in each study as ‘well characterized’,
‘fairly characterized’ or ‘poorly characterized ⁄ unclear’. Where diag-
nostic or enrolment criteria were not described, this aspect of
the study was categorized as ‘not reported’. The grading system
described here was based structurally on one used in a recent
systematic review of canine atopic dermatitis treatments18 adapted
for assessment of canine pyoderma, as follows.
1 Well characterized, when criteria included clinical signs or test
results consistent with current standards for pyoderma diagno-
sis; specifically, the presence of papules and ⁄ or pustules, crusts
and ⁄ or collarettes (superficial pyoderma) and nodules and ⁄ or
furuncles and ⁄ or fistulae and ⁄ or erosion ⁄ ulceration (deep pyo-
derma) on clinical examination, and either signs consistent with
bacterial infection on lesion fluid ⁄ impression smear cytology or
culture and identification of bacterial species from lesion sam-
ples.
2 Fairly characterized, used for intermediate situations, and where
diagnosis was based on clinical lesions without confirmation of
bacterial aetiology.
3 Poorly characterized ⁄ unclear, when participant selection criteria
were vague (e.g. where clinical signs were not stated or insuffi-
cient details of diagnostic methods were provided.)
4 Not reported, when mention of diagnostic criteria for pyoderma
or enrolment criteria were not made in the report.
Assessment of methodological quality
Using the criteria for judging risk of bias in the Cochrane ‘risk of bias’
assessment tool,19 each of the following study components was
categorized as presenting a ‘high’, ‘low’, ‘moderate’ or ‘unclear’ risk
of introducing bias to the study findings: random sequence genera-
tion, allocation concealment, blinding of participants (owners), per-
sonnel and outcome assessors, completeness of outcome data,
selective reporting of outcomes and other sources of bias. Overall
risk of bias within each study was then estimated by combining the
bias risk grades assigned to study components using a defined
numerically based system (see Table S1). The findings of each study
Table 1. Citations for all 58 studies identified by the search strategy
which fulfilled stage 1 screening criteria (listed by ascending year of
publication); denoted with an asterisk are the 16 publications report-
ing 17 studies selected for full review on the basis of stage 2 screen-
ing criteria
Citations
Bywater RJ, Hewett GR, Marshall AB et al., 1985.43
Carlotti D, Ovaert P., 1988.44
Angarano DW, MacDonald JM., 1989.45
DeBoer DJ., 1990.46
Gravino AE, Cerundolo R, Agresti A., 1990.47
Paradis M, Lemay S, Scott DW et al., 1990.48
Wustenberg T, Rodenbeck H., 1990.49
Hove WV, Lettow E, Opitz M., 1992.50
Koch HJ, Peters S., 1992.51
Trailovic D, Nikolic V, Markovic B et al., 1992.52
*Frank LA, Kunkle GA., 1993.33
*Guaguere E, Salomon C, Maynard L., 1998.32
*Harvey RG, Noble WC, Ferguson EA., 1993.29
*Messinger LM, Beale KM., 1993.25
Prost C, Arfi L., 1993.53
Scott DW, Miller WH, Wellington JR., 1993.54
Scott DW, Miller WH Jr, Cayatte SM et al., 1994.55
Bell A., 1995.56
*Carlotti DN, Jasmin P, Guaguere E et al., 1995.31
Guaguere E, Maynard L, Salomon C., 1996.57
Harvey RG., 1996.58
Koch HJ, Peters S., 1996.59
Scott DW, Miller WH Jr, Rothstein SE et al., 1996.60
*Lloyd DH, Carlotti DN, Koch HJ et al., 1997.27
Rosser EJ Jr., 1997.61
Bettenay SV, Mueller RS, Dell’Osa D., 199862
Bourdeau P, Kwochka KW, Willemse T et al., 1998.63
Hummel PH, Kohne K, Weiskopf S., 1998.64
Carlotti DN, Guaguere E, Pin D et al., 1999.65
*Littlewood JD, Lakhani KH, Paterson S et al., 1999.24
Bloom PB, Rosser EJ., 2001.66
Paradis M, Abbey L, Baker B et al., 2001.67
Jaham CD., 2003.68
Bassett RJ, Burton GG, Robson DC., 2004.69
Blanco AL, Wolberg A., 2004.70
Chakrabarti A, Baksi S, Mukherjee A., 2004.71
*Horspool LJI, van Laar P, van den Bos R et al., 2004.30
Bensignor E, Guaguere E., 2005.72
*Seena VB, Kumari KN, Singari NA et al., 2005.34
Senturk S, Ozel E, Sen A., 2005.73
*Cherni JA, Boucher JF, Skogerboe TL et al., 2006.26
Hillier A, Alcorn JR, Cole LK et al., 2006.74
Hillier A, Pinchbeck LR, Cole LK., 2006.75
Horspool LJI, van Laar P, van den Bos R et al., 2006.76
*Perego R, Proverbio D, Spada E et al., 2006.35
Pin D, Carlotti DN, Jasmin P et al., 2006.77
Scott DW, Peters J, Miller WH Jr., 2006.78
Udayasree VJ, Pillai UN, Baby PG., 2006.79
Grommelt P., 2007.80
*Mueller RS, Stephan B., 2007.20
Sprucek F, Svoboda M, Toman M et al., 2007.81
*Stegemann MR, Coati N, Passmore CA et al., 2007.21
*Laago M., 2008.23
*Six R, Cherni J, Chesebrough R et al., 2008.22
*Toma S, Colombo S, Cornegliani L et al., 2008.28
Centeno Eizaguirre MI., 2009.82
Bhat UR, Bhagwat VG., 2010.83
Restrepo C, Ihrke PJ, White SD et al., 2010.84
ª 2012 The Authors. Veterinary Dermatology
ª 2012 ESVD and ACVD, Veterinary Dermatology, 23, 305–e61. 307
Systemic antimicrobials in canine pyoderma
were categorized accordingly as having ‘low’, ‘low ⁄ moderate’,
‘moderate’, ‘moderate ⁄ high’ or ‘high’ estimated overall risk of bias.
Assessment of outcome measuresStudy outcomes of interest to the systematic review were primarily
measures of treatment success, ideally the number of animals from
the total treated group considered ‘recovered ⁄ cured ⁄ resolved’ by
the end of a stated treatment period. Where presented, 95% confi-
dence intervals (CIs) for treatment group recovery rates were
reported or were calculated by the authors where sufficient data
were available. Outcomes of secondary interest included assess-
ment of relapse occurrence (group figures with stated assessment
periods, with 95% CI for rates where possible), duration of systemic
antimicrobial treatment required (mean or median number of days of
treatment required in each group to attain clinical resolution; standard
deviations for means were reported where possible) and summariza-
tion of the nature and frequency of any adverse effects reported in
treated animals during the study period.
Presentation of quantitative resultsFor all studies selected at stage 2, summaries of the design charac-
teristics, evidence quality assessment and clinical outcomes relevant
to the systematic review are presented in tabular form.
Presentation of qualitative resultsBlinded RCTs with good numbers of study animals, low overall risk
of bias and specifying outcomes specific to superficial and ⁄ or deep
pyoderma throughout were considered to provide the highest avail-
able quality of evidence in each intervention category. Based on evi-
dence specific to deep or superficial pyoderma, statements of
recommendation for the use of individual systemic antimicrobial
treatment strategies in each pyoderma category were allocated
according to the following system (modified from that described by
Olivry and Mueller in 2003):18 ‘good’ evidence ‘for’ recommending
use of the drug, when more than one study, including at least one
blinded RCT, supported the high efficacy of the drug tested specifi-
cally for superficial ⁄ deep pyoderma; ‘fair’ evidence ‘for’ recom-
mending use of the drug, when at least one blinded RCT supported
medium to high efficacy of the drug investigated specifically for
superficial ⁄ deep pyoderma; ‘insufficient’ evidence ‘for ⁄ against’ rec-
ommending the use of the drug, when blinded RCTs were not avail-
able or when multiple studies yielded controversial evidence of
treatment effect or when available blinded RCTs reported outcomes
with no differentiation between superficial and deep pyoderma
cases; ‘fair’ evidence ‘against’ recommending the use of the drug,
when at least one blinded RCT provided evidence of lack of efficacy
or when efficacy is associated with common harmful events; and
‘good’ evidence ‘against’ recommending the use of the drug, when
at least one blinded RCT supported the lack of efficacy of the
medication tested, or supported any efficacy but with unacceptable
adverse effects.
Results
Description of studies
By the 25 May 2011, the search strategy had identified a
total of 1128 unique citations; 1103 from the electronic
searches of PubMed MEDLINE and CAB Abstracts and 25
from hand searching of major conference proceedings
(see Data S1). No relevant items were identified via other
search strategy methods. Fifty-eight published items ful-
filled stage 1 screening criteria (Table 1). Of these, 17 indi-
vidual studies reported in 16 papers (published between
1993 and 2008) also fulfilled stage 2 selection criteria and
were thus selected for review (Figure 2).
Study designs represented were blinded RCT (eight
studies20–27), open RCT (three28–30), RCT with blinding
unconfirmed (five31–34) and one controlled trial using pair-
matching to allocate dogs to treatment groups.35 Twelve
studies were published in English, three in French,31,32
one in Italian35 and one in Swedish.23 Nine studies
reported relevant outcomes specific to superficial pyo-
derma (Table 2) and five studies reported similar out-
comes for deep pyoderma (Table 3). Seven studies
reported at least one outcome from a group combining
superficial and deep pyoderma cases (Table 4); in five of
these, no treatment outcomes were reported separately
for animals in each diagnostic category,26,27,30,33,34 while
two studies reported outcomes from a combined diagno-
sis group in addition to outcomes specific to deep and ⁄ or
superficial pyoderma.23,31 Where possible, the numbers
and proportions of randomized and evaluated dogs with
deep and superficial pyoderma in each treatment group,
or overall as a minimum, were also presented when sum-
marizing studies on pyoderma. However, findings from
treatment groups (or whole studies) enrolling dogs with
either superficial or deep pyoderma but not reporting out-
comes separately for superficial and deep cases could not
contribute to the formulation of treatment recommenda-
tion statements specific to pyoderma type.
Summaries of all individual trials with respect to overall
design quality, aspects of methodology affecting quality
of design, numbers of study subjects recruited and evalu-
ated, treatment intervention details and results for out-
come measures of interest to the systematic review in
each treatment group are presented in Tables 2–4.
Disease definitions
According to the described grading system for subject
enrolment quality, 16 studies enrolled treatment groups
of well-characterized deep and ⁄ or superficial pyoderma
cases, involving diagnosis both by clinical assessment
and by lesion cytology or culture. In one trial, cases were
considered only fairly characterized, because the specific
lesions required for diagnosis were unclear.33
Trial size
Of 17 selected studies, 15 reported the overall number of
recruited dogs (range, 18–245 dogs; median, 70 dogs). All
17 reported the total number of dogs evaluated (range,
18–228 dogs; median, 68 dogs). Six of the nine studies
Overall grade for quality of
evidence produced
Treatment group size category
Quality of subject enrolment
Combined assessment of the risk of bias within
each study
Figure 1. Formulation of overall evidence quality assessment for the
findings of each reviewed study.
ª 2012 The Authors. Veterinary Dermatology
308 ª 2012 ESVD and ACVD, Veterinary Dermatology, 23, 305–e61.
Summers et al.
reporting outcomes specific to superficial pyoderma
reported total numbers of recruited dogs (range, 20–95
dogs; median, 45 dogs) and all nine reported total evalu-
ated dogs (range, 20–129 dogs; mean, 64 dogs; median,
50 dogs). Of the five studies reporting outcomes specific
to deep pyoderma, only two reported total numbers of
recruited dogs (range, 70–135 dogs; mean ⁄ median, 103
dogs), but all five reported total evaluated dogs (range,
43–107 dogs; mean ⁄ median, 68 dogs).
Six of the selected studies evaluated more than 50 dogs
per treatment group,20–22,26,30,31 10 studies evaluated
10–50 dogs in all treatment groups,23–25,27–29,32,33,35 and a
single study34 evaluated fewer than 10 dogs per treat-
ment group. Individual outcomes specific to pyoderma
depth came either from studies recruiting only cases of a
given depth, or on subgroups derived from studies enroll-
ing dogs with either deep or superficial pyoderma. In
those studies reporting outcomes specific to superficial
pyoderma, evaluated treatment groups (or subgroups)
consisted of more than 50 dogs in one study22 and at least
10 dogs in the remaining eight. Likewise, of the five
studies reporting outcomes specific to deep pyoderma,
treatment groups evaluated consisted of more than 50
and at least 10 dogs in one20 and four trials, respectively.
Signalment and baseline characteristics of study
subjects
Baseline characteristics (such as breed, age, sex and
underlying primary condition) of total enrolled dogs were
reported to some extent for all 17 trials. However, some
trials enrolling dogs with a variety of diagnoses did not
report these characteristics for pyoderma cases alone,
and other studies did not report them specifically for indi-
vidual treatment groups. Clear presentation of statistical
comparison of intervention groups with respect to signal-
ment and baseline disease characteristics pretreatment
was rarely encountered.
In all trials reporting baseline data, the recruited dogs
represented multiple breeds, both sexes and a wide range
of ages. Three studies excluded dogs below a minimum
age because of adverse effects on cartilage of growing
dogs previously described for fluoroquinolones.20,30,31
Types of interventions
Overall, the 17 selected studies reported systemic antimi-
crobial interventions with 12 different agents from five
antimicrobial classes (Tables 2–4). No trial included an
untreated or placebo-only treatment group. All antimicro-
bial interventions were orally administered except for
cefovecin, which was injected subcutaneously in two tri-
als.21,22. Three studies enrolled cases exclusively from
referral-level dermatology clinics,24,27,33 three exclusively
from first-opinion clinics22,23,30 and two from a combina-
tion of first-opinion and referral settings.20,28 In nine
studies, the clinical scenario from which subjects were
enrolled was unclear or not specified.21,25,26,29,31,32,34,35
Pooling of outcome data from multiple studies investi-
gating similar treatment interventions was not possible
owing to heterogeneity of study designs and reported
outcome measures.
Methodological quality of included studies
Based on the criteria outlined in the review protocol, the
findings of two,24,25 three,20–22 eight23,26,27,30–33 and
four28,29,34,35 studies were considered to be at low, low
to moderate, moderate and moderate to high overall risk
of bias, respectively (Tables 2–4; details of individual
study assessments are provided as online supplementary
material) (Table S1). None of the studies presented a for-
mal assessment of compliance by owners administering
oral antimicrobial courses.
Randomization
Overall, all but one study (which allocated matched pairs
of similar dogs, one to each treatment group35) used
some form of randomization to assign dogs to interven-
tion groups. However, only nine of these reported enough
detail to confirm that the method of randomization used
was appropriate.20,22,23,26,28,30–32
Blinding of outcome assessment
Outcome assessment blinding was clearly described in
eight studies,20–27 was not applied in four,28–30,35 and in
five studies31–34 was unconfirmed either way based on
study methodology reporting.
Handling of losses between enrolment and evaluation
Four studies presented outcome data from all enrolled
dogs in the treatment group to which they were originally
allocated.28,32,34,35 Across the remaining 13 trials, the pro-
portion of total recruited dogs excluded from data analy-
sis was extractable from 11n studies and ranged from
2.233 to 30.6%.27 In two studies, it was not possible to
calculate overall or treatment group attrition rates for pyo-
derma cases distinct from other skin infections in the
total study group.21,22 One study (involving only deep pyo-
17 studies (reported in 16 published research papers) selected for data extrac on and
evidence quality assessment
Research items fulfilling stage 1 selection criteria
58
Unpublished research
0
From electronic databases
1262
Research items excluded at stage 1 screening
1070
Total unique research items
identified 1128
Duplicated research items 159
From proceedings hand search
25
Research items also fulfilling stage 2 selection criteria
17
58 relevant cita ons listed (Table 1)
Figure 2. Flowchart representing results of the screening process
for items identified by the literature search strategy.
ª 2012 The Authors. Veterinary Dermatology
ª 2012 ESVD and ACVD, Veterinary Dermatology, 23, 305–e61. 309
Systemic antimicrobials in canine pyoderma
Tab
le2.
Sum
maries
of
stu
die
sre
port
ing
syste
mic
antim
icro
bia
ltre
atm
ent
outc
om
es
indogs
with
superfi
cia
lpyoderm
a
Refe
rence
Tom
aet
al.
28
Littlew
ood
et
al.
24
Harv
ey
et
al.
29
Six
et
al.
22
Ste
gem
ann
et
al.
21
Messin
ger
and
Beale
25
Carlott
iet
al.
31
Guaguere
et
al.
32
Pere
go
et
al.
35
Qualit
yof
evid
ence:stu
dy
findin
gs
have
….
Modera
te⁄h
igh
estim
ate
d
overa
llrisk
of
bia
sand
are
derived
from
a
stu
dy
usin
gw
ell-
chara
cte
rize
d
but
only
sm
all
to
modera
te
num
bers
of
cases
Low
estim
ate
d
overa
llrisk
of
bia
sand
are
derived
from
a
stu
dy
usin
g
modera
te
num
bers
of
well-
chara
cte
rize
d
cases
Modera
te⁄h
igh
estim
ate
dovera
ll
risk
of
bia
sand
are
derived
from
astu
dy
usin
g
well-
chara
cte
rize
d
but
only
sm
all
num
bers
of
cases
Low
⁄modera
te
estim
ate
dovera
ll
risk
of
bia
sand
are
derived
from
astu
dy
usin
ga
good
num
ber
of
well-
chara
cte
rize
d
cases
Low
⁄modera
te
estim
ate
dovera
ll
risk
of
bia
sand
are
derived
from
a
stu
dy
usin
gfa
irto
good
num
bers
of
well-
chara
cte
rize
d
cases
Low
estim
ate
d
overa
llrisk
of
bia
sand
are
derived
from
a
stu
dy
usin
gw
ell-
chara
cte
rize
d
but
only
sm
all
num
bers
of
cases
Modera
te
estim
ate
dovera
ll
risk
of
bia
s.They
are
derived
from
astu
dy
usin
g
modera
te
num
bers
of
well-
chara
cte
rize
d
cases
Modera
te
estim
ate
dovera
ll
risk
of
bia
s.They
are
derived
from
astu
dy
usin
g
modera
teto
good
num
bers
of
well-
chara
cte
rize
d
cases
Modera
te⁄h
igh
estim
ate
dovera
ll
risk
of
bia
s.They
are
derived
from
a
stu
dy
usin
gsm
all
num
bers
of
well-
chara
cte
rize
d
cases
Stu
dy
desig
nO
pen
RC
TB
linded
RC
TO
pen
RC
TB
linded
RC
TB
linded
RC
TB
linded
RC
TR
CT
(blin
din
g
unconfirm
ed)
RC
T(b
lindin
g
unconfirm
ed)
Pair-m
atc
hed
contr
olle
dtr
ial
Random
allo
cation
genera
tion
Adequate
Uncle
ar
Uncle
ar
Adequate
Uncle
ar
Uncle
ar
Adequate
Adequate
Not
used
Random
allo
cation
concealm
ent
Not
used:open
stu
dy
Adequate
Not
used:open
stu
dy
Adequate
Adequate
Uncle
ar
Uncle
ar
Uncle
ar
Not
used
Maskin
gof
outc
om
e
assessor
Not
used:open
stu
dy
Adequate
Not
used:open
stu
dy
Adequate
Adequate
Adequate
Uncle
ar
Uncle
ar
Uncle
ar
Inte
ntion-t
o-t
reat
analy
sis
Not
required
Not
pre
sente
dN
ot
pre
sente
dN
ot
pre
sente
dN
ot
pre
sente
dN
ot
pre
sente
dN
ot
pre
sente
dN
ot
required
Not
required
Tota
ldogs
ente
red
intr
ial
40
59
33
Not
report
ed
Not
report
ed
50
Not
sta
ted
95
20
Tota
ldogs
com
ple
ting
tria
l
40
56
30
129
114
43
50
95
20
Length
of
tria
lTx
⁄assessm
ent
period
(min
⁄max):
28–56
days
Tx
⁄assessm
ent
period
(min
⁄ max):
21–42
days
Tx
⁄assessm
ent
period
(min
⁄max):
21–42
days
Tx
period
(min
⁄m
ax):
14–28
days.
Assessm
ent
period
(min
⁄max):
28–42
days
Tx
dura
tion:
14–56
days.
Assessm
ent
tim
e:
28–70
days
Tx
⁄assessm
ent
period
(min
⁄max):
21
⁄63
days
Tx
⁄assessm
ent
period
(min
⁄max):
5–40
days
Tx
period
(min
⁄m
ax):
18–60
days.
Assessm
ent
period
(min
⁄max):
8–60
days
Tx
period
(min
⁄m
ax):
30
days.
Assessm
ent
period
(min
⁄max):
15–30
days
Antim
icro
bia
l
inte
rvention
(Tx)
1(n
o.of
dogs
intr
eatm
ent
gro
up:ente
red
⁄evalu
ate
d)
Cefa
lexin
,30
(40
or
60)†
mg
⁄kg,
once
daily
,p.o
.
(20
⁄20)
Clin
dam
ycin
,
5.5
mg
⁄kg,
twic
edaily
,
p.o
.(3
0⁄2
9)
Lin
com
ycin
,
22
mg
⁄kg,tw
ice
daily
,p.o
.
(Unknow
n⁄1
4)
Cefo
vecin
,
8m
g⁄k
g,every
14
days,s.c
.
inje
ction
(+daily
ora
lpla
cebo)
(Unknow
n⁄6
2)
Cefo
vecin
,
8m
g⁄k
g,every
14
days,s.c
.
inje
ction
(Unknow
n⁄8
3)
TM
PS
,30
mg
⁄kg,
once
daily
,p.o
.
(16
⁄13)
Marb
ofloxacin
,
2m
g⁄k
g,once
daily
,p.o
.
(Unknow
n⁄2
4)
Cefa
lexin
,15
mg
⁄kg,
twic
edaily
,p.o
.
(42
⁄42)
Marb
ofloxacin
,
2m
g⁄k
g,once
daily
,p.o
.(1
0⁄1
0)
Antim
icro
bia
l
inte
rvention
(Tx)
2(n
o.of
dogs
intr
eatm
ent
gro
up:ente
red
⁄evalu
ate
d)
Cefa
lexin
,15–30
mg
⁄kg,tw
ice
daily
,p.o
.(2
0⁄2
0)
Am
oxic
illin
+
cla
vula
nic
acid
,
10
mg
⁄kg
+
2.5
mg
⁄kg,
twic
edaily
,
p.o
.(2
9⁄2
7)
Clin
dam
ycin
,
11
mg
⁄kg,once
daily
,p.o
.
(Unknow
n⁄1
6)
Cefa
dro
xil,
22
mg
⁄kg,tw
ice
daily
,p.o
.+
(1·
pla
cebo
s.c
.
inje
ction)
(Unknow
n⁄6
7)
Am
oxic
illin
+
cla
vula
nic
acid
,
10
mg
⁄kg
+
2.5
mg
⁄kg,tw
ice
daily
,p.o
.
(Unknow
n⁄3
1)
TM
PS
,30
mg
⁄kg,
twic
edaily
,p.o
.
(17
⁄14)
Am
oxic
illin
+
cla
vula
nic
acid
,
10
mg
⁄kg
+
2.5
mg
⁄kg,
twic
edaily
,p.o
.
(Unknow
n⁄2
6)
Am
oxic
illin
+
cla
vula
nic
acid
,
10
mg
⁄kg
+
2.5
mg
⁄kg,tw
ice
daily
,p.o
.(5
3⁄5
3)
Am
oxic
illin
+
cla
vula
nic
acid
,
10
mg
⁄kg
+
2.5
mg
⁄kg,tw
ice
daily
,p.o
.(1
0⁄1
0)
ª 2012 The Authors. Veterinary Dermatology
310 ª 2012 ESVD and ACVD, Veterinary Dermatology, 23, 305–e61.
Summers et al.
Tab
le2.
(Continued)
Refe
rence
Tom
aet
al.
28
Littlew
ood
et
al.
24
Harv
ey
et
al.
29
Six
et
al.
22
Ste
gem
ann
et
al.
21
Messin
ger
and
Beale
25
Carlott
iet
al.
31
Guaguere
et
al.
32
Pere
go
et
al.
35
Antim
icro
bia
l
inte
rvention
(Tx)
3(n
o.of
dogs
intr
eatm
ent
gro
up:ente
red
⁄evalu
ate
d)
——
——
—TM
PO
,55
mg
⁄kg
on
day
1,th
en
27.5
mg
⁄kg
there
aft
er,
once
daily
,p.o
.(1
7⁄1
6)
——
—
Tre
atm
ent
success
rate
(s)
[successes
⁄dogs
treate
d;%
(95%
confidence
inte
rval),Tx
period]
Tx
gro
up
1:
4⁄2
0;20.0
%
(7.5
–42.2
%),
14
days;
15
⁄20;75.0
%
(52.8
–89.2
%),
28
days.
Tx
gro
up
2:
6⁄2
0;30.0
%
(14.3
–52.1
%),
14
days;
16
⁄20;80.0
%
(57.8
–92.5
%),
28
days
Tx
gro
up
1:
17
⁄29
dogs;
58.6
%
(40.7
–74.5
%),
21
days.
Tx
gro
up
2:
8⁄2
7dogs;29.6
%
(15.7
–48.7
%),
21
days
(as
assessed
usin
g
tota
lscore
for
lesio
ns)
Tx
gro
up
1:
10
⁄14
dogs;71.4
%
(45.0
–88.7
%),
21
days;
13
⁄14
dogs;92.9
%
(66.5
–>
99.9
%),
42
days.
Tx
gro
up
2:
13
⁄16
dogs;81.3
%
(56.2
–94.2
%),
21
days;
15
⁄16
dogs;93.8
%
(69.7
–>
99.9
%),
42
days
Tx
gro
up
1:
57
⁄62
dogs;91.9
%
(82.1
–96.9
%),
28
or
42
days.
Tx
gro
up
2:
60
⁄67
dogs;89.6
%
(79.7
–95.1
%),
28
or
42
days
Tx
gro
up
1:
82
⁄83;98.8
%
(92.8
–>
99.9
%),
28
days.
Tx
gro
up
2:
28
⁄31;90.3
%
(74.3
–97.4
%),
28
days
Tx
gro
up
1:
5⁄1
3dogs,38.5
%
(17.6
–64.6
%),
21
days;
10
⁄13
dogs,76.9
%
(49.1
–92.5
%),
42
days.
Tx
gro
up
2:
8⁄1
4dogs,57.1
%
(32.6
–78.7
%),
21
days;
11
⁄14
dogs,78.6
%
(51.7
–93.2
%),
42
days.
Tx
gro
up
3:
12
⁄16
dogs,75.0
%
(50.0
–90.3
%),
21
days;
16
⁄16
dogs,100%
(77.3
–100.0
%),
42
days
Tx
1:23
⁄24;
95.8
%(7
8.1
–
>99.9
%*),
by
day
40
of
stu
dy.
Tx
2:15
⁄26;
57.7
%(3
8.9
–
74.5
%*),
by
day
40
of
stu
dy
Tx
1:39
⁄42;92.9
%
(80.3
–98.2
%*),
aft
er
maxim
um
60
days
of
Tx.
Tx
2:40
⁄53;75.5
%
(62.3
–85.2
%*),
aft
er
maxim
um
60
days
of
Tx
Tx
1:10
⁄10;100%
(67.9
–100%
*),
aft
er
30
days
of
Tx.
Tx
2:9
⁄10;90.0
%
(57.4
–>
99.9
%*),
aft
er
30
days
of
Tx
Sta
tistical
com
parison
(test,
P-v
alu
e)
No
sig
nifi
cant
diffe
rences
betw
een
treatm
ent
gro
ups
at
either
tim
e
poin
t(F
isher’
s
exact,
P=
0.3
6
and
P=
0.2
0,
respectively
)
Diffe
rences
betw
een
treatm
ent
gro
ups
did
not
quite
reach
sta
tistical
sig
nifi
cance
(v2
test,
P=
0.0
56)
No
sig
nifi
cant
diffe
rences
betw
een
treatm
ent
gro
ups
at
either
tim
e
poin
t(F
isher’
s
exact
test,
P=
0.6
75
and
P=
1.0
0,
respectively
)
Str
ong
evid
ence
for
nonin
feriority
of
cefo
vecin
com
pare
dw
ith
the
cefa
dro
xil
thera
py
usin
ga
15%
thre
shold
(90%
CI
for
the
diffe
rence
insuccess
rate
s:
)5.9
9to
10.7
6,
P=
0.0
01).
Cefo
vecin
dem
onstr
ate
d
nonin
feriority
com
pare
dw
ith
am
oxic
illin
⁄cla
vula
nic
acid
usin
ga
15%
thre
shold
(90%
CI
for
the
diffe
rence
insuccess
rate
s:
)3.4
0to
25.2
5,no
report
ed
P-v
alu
e)
No
sig
nifi
cant
diffe
rences
betw
een
treatm
ent
gro
ups
at
either
tim
e
poin
t(v
2,P
=0.1
4
and
P=
0.0
92,
respectively
).
Str
ong
evid
ence
for
truly
superior
‘cure
’ra
tein
marb
ofloxacin
Tx
gro
up
com
pare
d
with
gro
up
giv
en
am
oxic
illin
⁄cla
vula
nic
acid
(Fis
her’
sexact*
,
P=
0.0
02)
Som
eevid
ence
for
truly
superior
‘cure
’
rate
incefa
lexin
Tx
gro
up
com
pare
d
with
gro
up
giv
en
am
oxic
illin
⁄cla
vula
nic
acid
(v2,P
=0.0
25)
Auth
ors
sta
teth
ere
was
no
sig
nifi
cant
diffe
rence
betw
een
treatm
ent
gro
ups
(but
test
used
was
uncle
ar
and
no
P-v
alu
epre
sente
d)
ª 2012 The Authors. Veterinary Dermatology
ª 2012 ESVD and ACVD, Veterinary Dermatology, 23, 305–e61. 311
Systemic antimicrobials in canine pyoderma
Tab
le2.
(Continued)
Refe
rence
Tom
aet
al.
28
Littlew
ood
et
al.
24
Harv
ey
et
al.
29
Six
et
al.
22
Ste
gem
ann
et
al.
21
Messin
ger
and
Beale
25
Carlott
iet
al.
31
Guaguere
et
al.
32
Pere
go
et
al.
35
Tre
atm
ent
dura
tion
required
for
clin
ical
rem
issio
n
(avera
ge)
Tx
gro
up
1:
28
days
(95%
CI:
23.2
–32.8
)
(media
n).
Tx
gro
up
2:
28
days
(95%
CI:
23.5
–32.5
)
(media
n)
Not
assessed
Not
assessed
No.of
dogs
‘cure
d’
aft
er
sin
gle
14
day
treatm
ent
cours
e:
Tx
gro
up
1:50
⁄62;
80.6
%(9
5%
CI:
69.0
–88.7
%).
Tx
gro
up
2:47
⁄67;
70.1
%(9
5%
CI:
58.3
–79.8
%)
Not
assessed
Not
assessed
Not
pre
sente
dand
unable
to
calc
ula
tebased
on
availa
ble
data
Tx
1:29.7
days
(mean).
Tx
2:32.3
days
(mean)
Not
assessed
Sta
tistical
com
parison
(test,
P-v
alu
e)
No
sig
nifi
cant
diffe
rence
betw
een
the
treatm
ent
gro
ups
(logra
nk
test,
P=
0.7
4)
——
No
sig
nifi
cant
diffe
rence
betw
een
treatm
ent
gro
ups
(Fis
her’
sexact
test,
P=
0.2
21)
——
—A
uth
ors
sta
teno
sig
nifi
cant
diffe
rence
betw
een
Tx
gro
ups
(Stu
dent’
st-
test,
P-v
alu
enot
giv
en)
—
Rela
pse
rate
(s)in
dogs
achie
vin
g
resolu
tion
(tim
e
post-
treatm
ent
cessation)
Not
assessed
Not
assessed
Not
assessed
Not
assessed
Not
assessed
Not
assessed
Not
report
ed
specifi
cally
for
superfi
cia
l
pyoderm
acases
Not
assessed
Not
assessed
Sta
tistical
com
parison
(test,
P-v
alu
e)
——
——
——
——
—
Advers
eeff
ects
Tx
gro
up
1:
vom
itin
gor
dia
rrhoea
(five
dogs).
Tx
gro
up
2:
dia
rrhoea
(one
dog)
Sta
tes
that
none
report
ed
Sta
tes
that
none
report
ed
Not
report
ed
for
pyoderm
acases
separa
tely
from
oth
er
skin
infe
ctions
Report
ed
overa
ll
but
not
specifi
cally
for
superfi
cia
l
pyoderm
acases
Tx
gro
up
1:sta
tes
that
none
report
ed.
Tx
gro
up
2:
haem
atu
ria,
hepato
toxic
osis
(one
dog
each).
Tx
gro
up
3:S
eiz
ure
(one
dog)
Not
report
ed
specifi
cally
for
superfi
cia
l
pyoderm
acases
Report
ed
only
in
com
bin
ation
with
the
para
llel,
deep
pyoderm
a
stu
dy
gro
up
als
ore
port
ed
inG
uaguere
(1998)3
2
Sta
tes
that
none
observ
ed
Sta
tistical
com
parison
(test,
P-v
alu
e)
No
sig
nifi
cant
diffe
rence
betw
een
the
treatm
ent
gro
ups
(Fis
her’
sexact
test,
P=
0.9
0)
——
——
Not
com
pare
d—
——
Abbre
via
tions:C
I,confidence
inte
rval;
p.o
.,per
os
⁄ora
lly;R
CT,ra
ndom
ized
contr
olle
dtr
ial;
s.c
.,subcuta
neous;TM
PO
,sulfadim
eth
oxin
e–orm
eto
prim
;TM
PS
,tr
imeth
oprim
–sulfadia
zine;Tx,tr
eatm
ent.
*P
erf
orm
ed/c
alc
ula
ted
by
the
syste
matic
revie
wauth
ors
.
†D
ose
varies
inth
ete
xt.
ª 2012 The Authors. Veterinary Dermatology
312 ª 2012 ESVD and ACVD, Veterinary Dermatology, 23, 305–e61.
Summers et al.
Tab
le3.
Sum
maries
of
stu
die
sre
port
ing
syste
mic
antim
icro
bia
ltre
atm
ent
outc
om
es
indogs
with
deep
pyoderm
a
Refe
rence
Muelle
rand
Ste
phan
20
Ste
gem
ann
et
al.
21
Carlott
iet
al.
31
Guaguere
et
al.
32
Laago
23
Qualit
yof
evid
ence:stu
dy
findin
gs
have
…Low
⁄modera
teestim
ate
dovera
ll
risk
of
bia
s.They
are
derived
from
astu
dy
usin
ga
good
num
ber
of
well-
chara
cte
rize
d
cases
Low
⁄modera
teestim
ate
dovera
ll
risk
of
bia
s.They
are
derived
from
astu
dy
usin
gfa
irto
good
num
bers
of
well-
chara
cte
rize
d
cases
Modera
teestim
ate
dovera
llrisk
of
bia
s.They
are
derived
from
a
stu
dy
usin
gm
odera
tenum
bers
of
well-
chara
cte
rize
dcases
Modera
teestim
ate
dovera
llrisk
of
bia
s.They
are
derived
from
a
stu
dy
usin
gm
odera
tenum
bers
of
well-
chara
cte
rize
dcases
Modera
teestim
ate
dovera
llrisk
of
bia
s.They
are
derived
from
a
stu
dy
usin
gsm
all
tom
odera
te
num
bers
of
well-
chara
cte
rize
d
cases
Stu
dy
desig
nB
linded
RC
TB
linded
RC
TR
CT
(blin
din
gunconfirm
ed)
RC
T(b
lindin
gunconfirm
ed)
Blin
ded
RC
T
Random
allo
cation
genera
tion
Adequate
Uncle
ar
Adequate
Adequate
Adequate
Random
allo
cation
concealm
ent
Adequate
Adequate
Uncle
ar
Uncle
ar
Uncle
ar
Maskin
gof
outc
om
e
assessor
Adequate
Adequate
Uncle
ar
Uncle
ar
Adequate
Inte
ntion-t
o-t
reat
analy
sis
‘Last-
valu
e-c
arr
ied-f
orw
ard
’
analy
sis
Not
pre
sente
dN
ot
pre
sente
dN
ot
pre
sente
dN
ot
pre
sente
d
Tota
ldogs
ente
red
intr
ial
135
Not
sta
ted
Not
sta
ted
70
Not
sta
ted
Tota
ldogs
com
ple
ting
tria
l107
71
52
68
43
Length
of
tria
lM
axim
um
Tx
period:63
days
Maxim
um
assessm
ent
period:
77
days
Tx
dura
tion:14–56
days
Assessm
ent
tim
e:28–70
days
Tx
dura
tion:5–40
days
Assessm
ent
tim
e:5–40
days
Tx
dura
tion:28–56
days
Assessm
ent
tim
e:30–90
days
Tx
⁄assessm
ent
period
(min
⁄max):
21
days
Antim
icro
bia
lin
terv
ention
(Tx)
1(n
o.of
dogs
in
treatm
ent
gro
up)
Pra
dofloxacin
,3
mg
⁄kg,once
daily
,ro
ute
not
sta
ted
(66
dogs
ente
red,56
evalu
able
)
Cefo
vecin
,8
mg
⁄kg,every
14
days,s.c
.in
jection
(unknow
n
num
ber
of
dogs
ente
red,
50
evalu
ate
d)
Marb
ofloxacin
,2
mg
⁄kg,once
daily
,p.o
.(u
nknow
nnum
ber
of
dogs
ente
red,27
evalu
ate
d)
Cefa
lexin
,15
mg
⁄kg,tw
ice
daily
,p.o
.(2
2dogs
ente
red,21
evalu
ate
d)
Cefa
dro
xil,
20
mg
⁄kg,tw
ice
daily
,
p.o
.(u
nknow
nnum
ber
of
dogs
ente
red,18
evalu
ate
d)
Antim
icro
bia
lin
terv
ention
(Tx)
2(n
o.of
dogs
in
treatm
ent
gro
up)
Am
oxic
illin
+cla
vula
nic
acid
,
10
mg
⁄kg
+2.5
mg
⁄kg,tw
ice
daily
,ro
ute
not
sta
ted
(69
dogs
ente
red,51
evalu
ate
d)
Am
oxic
illin
+cla
vula
nic
acid
,
10
mg
⁄kg
+2.5
mg
⁄kg,tw
ice
daily
,p.o
.(u
nknow
nnum
ber
of
dogs
ente
red,21
evalu
ate
d)
Am
oxic
illin
+cla
vula
nic
acid
,
10
mg
⁄kg
+2.5
mg
⁄kg,tw
ice
daily
,p.o
.(u
nknow
nnum
ber
of
dogs
ente
red,25
evalu
ate
d)
Cefa
lexin
,30
mg
⁄kg,tw
ice
daily
,p.o
.(2
4dogs
ente
red,24
evalu
ate
d)
Cefa
dro
xil,
40
mg
⁄kg,once
daily
,
p.o
.(u
nknow
nnum
ber
of
dogs
ente
red,25
evalu
ate
d)
Antim
icro
bia
lin
terv
ention
(Tx)
3(n
o.of
dogs
in
treatm
ent
gro
up)
——
—A
moxic
illin
+cla
vula
nic
acid
,
20
mg
⁄kg
+5
mg
⁄kg,tw
ice
daily
,p.o
.(2
4dogs
ente
red,
23
evalu
ate
d)
—
Tre
atm
ent
success
rate
(s)
[successes
⁄dogs
treate
d;
%(9
5%
CI)
,Tx
period]
Tx
1:48
⁄56
dogs;85.7
%
(74.0
–92.8
%),
7–63
days.
Tx
2:37
⁄51
dogs;72.6
%
(59.0
–83.0
%),
7–63
days
Tx
1:47
⁄50;94.0
%(8
3.2
–
98.6
%*),
aft
er
28
days
of
Tx
Tx
2:18
⁄21;85.7
%(6
4.5
–
95.9
%*),
aft
er
28
days
of
Tx
Tx
1:18
⁄27;66.7
%(4
7.7
–
81.5
%*),
by
day
40
of
stu
dy.
Tx
2:16
⁄25;64.0
%(4
4.4
–
79.8
%*),
by
day
40
of
stu
dy
Tx
1:15
⁄21;71.4
%(4
9.8
–86.4
%*),
aft
er
maxim
um
90
days
of
Tx.
Tx
2:20
⁄24;83.3
%(6
3.5
–93.9
%*),
aft
er
maxim
um
90
days
of
Tx.
Tx
3:17
⁄23;73.9
%(5
3.2
–87.7
%*),
aft
er
maxim
um
90
days
of
Tx
Tx
1:13
⁄18;72.2
%(4
8.8
–87.8
%*),
aft
er
21
days
of
Tx.
Tx
2:12
⁄25;48.0
%(3
0.0
–66.5
%*),
aft
er
21
days
of
Tx
ª 2012 The Authors. Veterinary Dermatology
ª 2012 ESVD and ACVD, Veterinary Dermatology, 23, 305–e61. 313
Systemic antimicrobials in canine pyoderma
Tab
le3.
(Continued)
Refe
rence
Muelle
rand
Ste
phan
20
Ste
gem
ann
et
al.
21
Carlott
iet
al.
31
Guaguere
et
al.
32
Laago
23
Sta
tisticalc
om
parison
(test,
P-v
alu
e)
No
evid
ence
for
true
diffe
rence
betw
een
Tx
gro
ups
(Fis
her’
s
exact*
,P
=0.1
01)
Cefo
vecin
dem
onstr
ate
d
nonin
feriority
com
pare
dw
ith
am
oxic
illin
⁄cla
vula
nic
acid
accord
ing
toa
15%
poin
t
thre
shold
for
the
diffe
rence
betw
een
success
rate
s(9
0%
CI
from
)3.4
0to
25.2
5)
No
evid
ence
for
true
diffe
rence
betw
een
Tx
gro
ups
(v2*,P
=0.8
40)
Auth
ors
sta
teth
at
there
isno
evid
ence
for
true
diffe
rence
betw
een
Tx
gro
ups
(v2,P
-valu
e
not
giv
en)
Auth
ors
pre
sent
little
evid
ence
for
true
diffe
rence
betw
een
Tx
gro
ups
(v2,P
=0.0
53)
Tre
atm
ent
dura
tion
required
for
clin
icalr
em
issio
n
(avera
ge)
Tx
1:49
days
(media
n).
Tx
2:35
days
(media
n)
Not
assessed
Not
pre
sente
dand
unable
to
calc
ula
tebased
on
availa
ble
data
Tx
1:44.5
days
(mean).
Tx
2:45.5
days
(mean).
Tx
3:49.0
days
(mean)
Not
assessed
Sta
tisticalc
om
parison
(test,
P-v
alu
e)
No
evid
ence
for
true
diffe
rence
betw
een
Tx
gro
ups
(logra
nk
test,
P=
0.8
47)
——
Auth
ors
sta
teno
sig
nifi
cant
diffe
rence
betw
een
Tx
gro
ups
(Stu
dent’
st-
test,
P-v
alu
enot
giv
en)
—
Rela
pse
rate
(s)in
dogs
achie
vin
gre
solu
tion
(tim
e
post-
treatm
ent
cessation)
Tx
1:0%
;0
⁄48
dogs
(14
days).
Tx
2:16.2
%;6
⁄37
dogs
(14
days)
Not
assessed
Report
ed
overa
llbut
not
specifi
cally
for
deep
pyoderm
a
cases
Not
assessed
Not
assessed
Sta
tisticalc
om
parison
(test,
P-v
alu
e)
Pyoderm
are
curr
ence
within
2w
eeks
of
treatm
ent
com
ple
tion
occurr
ed
sig
nifi
cantly
less
oft
en
inth
e
pra
dofloxacin
gro
up
(Fis
her’
s
exact
test,
P<
0.0
1)
——
——
Advers
eeff
ects
Tx
1:poly
uria
⁄poly
dip
sia
(one
dog),
dia
rrhoea
(one
dog).
Tx
2:dia
rrhoea
and
vom
itin
g(o
ne
dog),
vom
itin
g(o
ne
dog)
Report
ed
overa
llbut
not
specifi
cally
for
deep
pyoderm
a
cases
Report
ed
overa
llbut
not
specifi
cally
for
deep
pyoderm
a
cases
Report
ed
only
in
com
bin
ation
with
the
para
llel,
superfi
cia
lpyoderm
a
stu
dy
gro
up
als
ore
port
ed
in
inG
uaguere
(1998)3
2
Report
ed
overa
ll,but
not
specifi
cally
for
deep
pyoderm
a
cases
Sta
tisticalc
om
parison
(test,
P-v
alu
e)
Not
com
pare
d—
——
—
Abbre
via
tions:C
I,confidence
inte
rval;
p.o
.,per
os
⁄ora
lly;R
CT,ra
ndom
ized
contr
olle
dtr
ial;
s.c
.,subcuta
neous;Tx,tr
eatm
ent.
*P
erf
orm
ed/c
alc
ula
ted
by
the
syste
matic
revie
wauth
ors
.
ª 2012 The Authors. Veterinary Dermatology
314 ª 2012 ESVD and ACVD, Veterinary Dermatology, 23, 305–e61.
Summers et al.
Tab
le4.
Stu
die
sre
port
ing
outc
om
es
of
syste
mic
antim
icro
bia
ltre
atm
ent
where
som
eor
all
outc
om
es
are
not
report
ed
separa
tely
for
dogs
with
deep
and
superfi
cia
lpyoderm
a
Refe
rences
Hors
poole
tal.
30
Chern
iet
al.
26
Fra
nk
and
Kunkle
33
Seena
et
al.
34
Llo
yd
et
al.
27
Laago
23
Carlott
iet
al.
31
Qualit
yof
evid
ence:
stu
dy
findin
gs
have
…..
Modera
teestim
ate
d
overa
llrisk
of
bia
s.
They
are
derived
from
astu
dy
usin
g
good
num
bers
of
well-
chara
cte
rize
d
cases
Modera
teestim
ate
dovera
ll
risk
of
bia
s.They
are
derived
from
astu
dy
usin
ggood
num
bers
of
well-
chara
cte
rize
dcases
Modera
teestim
ate
d
overa
llrisk
of
bia
s.
They
are
derived
from
astu
dy
usin
gsm
all
num
bers
of
fairly
chara
cte
rize
dcases
Modera
te⁄h
igh
estim
ate
dovera
llrisk
of
bia
s.They
are
derived
from
astu
dy
usin
gvery
sm
all
num
bers
of
well-
chara
cte
rize
dcases
Modera
teestim
ate
d
overa
llrisk
of
bia
s.They
are
derived
from
a
stu
dy
usin
gm
odera
te
num
bers
of
well-
chara
cte
rize
dcases
Modera
teestim
ate
d
overa
llrisk
of
bia
s.
They
are
derived
from
astu
dy
usin
g
modera
teto
good
num
bers
of
well-
chara
cte
rize
dcases
Modera
teestim
ate
d
overa
llrisk
of
bia
s.They
are
derived
from
astu
dy
usin
ggood
num
bers
of
well-
chara
cte
rize
d
cases
Stu
dy
desig
nO
pen
RC
TB
linded
RC
TR
CT
(blin
din
g
unconfirm
ed)
RC
T(b
lindin
g
unconfirm
ed)
Blin
ded
RC
TB
linded
RC
TR
CT
(blin
din
g
unconfirm
ed)
Random
allo
cation
genera
tion
Adequate
Adequate
Uncle
ar
Uncle
ar
Uncle
ar
Adequate
Adequate
Random
allo
cation
concealm
ent
Adequate
Adequate
Uncle
ar
Uncle
ar
Uncle
ar
Uncle
ar
Uncle
ar
Maskin
gof
outc
om
e
assessor
Not
used;open
tria
lA
dequate
Uncle
ar
Uncle
ar
Adequate
Adequate
Uncle
ar
Inte
ntion-t
o-t
reat
analy
sis
Not
pre
sente
dN
ot
pre
sente
dN
ot
pre
sente
dN
ot
required
Not
pre
sente
dN
ot
pre
sente
dN
ot
pre
sente
d
Tota
ldogs
ente
red
in
tria
l(no.w
ith
superfi
cia
l⁄deep
pyoderm
a)
245
(uncle
ar)
157
(uncle
ar)
45
(uncle
ar)
18
(13
⁄5)
98
(not
report
ed)
117
(uncle
ar)
111
(not
report
ed)
Tota
ldogs
com
ple
ting
tria
l(%
superfi
cia
l⁄deep
pyoderm
a)
228
(60.1
%⁄3
9.9
%)
129
(uncle
ar)
44
(75%
⁄25%
)18
(72.2
%⁄3
8.5
%)
68
(69.1
%⁄3
0.9
%)
101
(57.4
%⁄4
5.6
%)
102
(49%
⁄51%
)
Length
of
tria
lTre
atm
ent
dura
tion
(min
,m
ax):
21
days,
unspecifi
ed.
Assessm
ent
dura
tion
(min
,m
ax):
7days,
unspecifi
ed
Tre
atm
ent
⁄assessm
ent
dura
tion
(min
,m
ax):
28,42
days
Tre
atm
ent
dura
tion
(min
,m
ax):
21,
42
days.
Assessm
ent
dura
tion
(min
,m
ax):
21,
63
days
Tre
atm
ent
dura
tion
(min
,m
ax):
7days,
unspecifi
ed.
Assessm
ent
dura
tion
(min
,m
ax):
4days,
unspecifi
ed
Tre
atm
ent
⁄assessm
ent
dura
tion:84
days
Tx
⁄assessm
ent
period
(min
⁄max):
21
days
Tx
⁄assessm
ent
period
(min
⁄max):
5–40
days
Antim
icro
bia
l
inte
rvention
(Tx)
1
(no.of
dogs
evalu
ate
din
treatm
ent
gro
up:
%superfi
cia
l⁄%
deep
pyoderm
a)
Ibafloxacin
,15
mg
⁄kg,
once
daily
,p.o
.(1
13
dogs:61%
⁄39%
)
Cefp
odoxim
e,5
mg
⁄kg,
once
daily
,p.o
.[7
8
dogs
enro
lled,63
evalu
ate
d:(u
ncle
ar)
]
Cefa
dro
xil,
22–35
mg
⁄kg,tw
ice
daily
,
p.o
.(1
5dogs:
unspecifi
ed)
TM
PS
,30
mg
⁄kg,
twic
edaily
,by
unspecifi
ed
route
(six
dogs:unspecifi
ed)
Am
oxic
illin
+cla
vula
nic
acid
,10
mg
⁄kg
+2.5
mg
⁄kg,tw
ice
daily
,p.o
.
(31
dogs:64.5
%⁄3
5.5
%)
Cefa
dro
xil,
20
mg
⁄kg,
twic
edaily
,p.o
.(4
9
dogs:63.3
%⁄3
6.7
%)
Marb
ofloxacin
,2
mg
⁄kg,
once
daily
,p.o
.(5
1
dogs:47.1
%⁄5
2.9
%)
Antim
icro
bia
l
inte
rvention
(Tx)
2
(no.of
dogs
evalu
ate
din
treatm
ent
gro
up:
%superfi
cia
l⁄%
deep
pyoderm
a)
Marb
ofloxacin
,2
mg
⁄kg,
once
daily
,p.o
.(1
15
dogs:59%
⁄41%
)
Cefa
lexin
,26.4
mg
⁄kg,
twic
edaily
,p.o
.[7
9
dogs
enro
lled,66
evalu
ate
d:(u
ncle
ar)
]
Cefa
lexin
(‘generic’)
,
22–35
mg
⁄kg,tw
ice
daily
,p.o
.(1
5dogs:
unspecifi
ed)
Lin
com
ycin
,22
mg
⁄kg,
twic
edaily
,by
unspecifi
ed
route
(6
dogs:unspecifi
ed)
Am
oxic
illin
+cla
vula
nic
acid
,20
mg
⁄kg
+5
mg
⁄ kg,tw
ice
daily
,p.o
.
(37
dogs:73.0
%⁄2
7.0
%)
Cefa
dro
xil,
40
mg
⁄kg,
once
daily
,p.o
.(5
2
dogs:51.9
%⁄4
8.1
%)
Am
oxic
illin
+cla
vula
nic
acid
,10
mg
⁄kg
+2.5
mg
⁄kg,tw
ice
daily
,
p.o
.(5
1dogs:51.0
%⁄
49.0
%)
ª 2012 The Authors. Veterinary Dermatology
ª 2012 ESVD and ACVD, Veterinary Dermatology, 23, 305–e61. 315
Systemic antimicrobials in canine pyoderma
Tab
le4.
(Continued)
Refe
rences
Hors
poole
tal.
30
Chern
iet
al.
26
Fra
nk
and
Kunkle
33
Seena
et
al.
34
Llo
yd
et
al.
27
Laago
23
Carlott
iet
al.
31
Antim
icro
bia
l
inte
rvention
(Tx)
3
(no.of
dogs
evalu
ate
din
treatm
ent
gro
up:
%superfi
cia
l⁄%
deep
pyoderm
a)
n.a
.n.a
.C
efa
lexin
(‘pro
prieta
ry’)
,
22–35
mg
⁄kg,tw
ice
daily
,p.o
.(1
5dogs:
unspecifi
ed)
Cefa
lexin
,25
mg
⁄kg,
twic
edaily
,by
unspecifi
ed
route
(six
dogs:unspecifi
ed)
n.a
.n.a
.n.a
.
Tre
atm
ent
success
rate
(s)[s
uccesses
⁄dogs
treate
d;
%(9
5%
CI)
,Tx
period]
Tx
gro
up
1:95
⁄113
dogs;
84.1
%(7
6.1
–89.8
%),
7–21
days.
Tx
gro
up
2:98
⁄115
dogs
85.2
%(7
7.5
–90.7
%)
7–21
days
By
change
inclin
ical
score
(28
or
42
days):
Tx
gro
up
1:61
⁄63;
96.8
%(8
8.5
–99.8
%).
Tx
gro
up
2:62
⁄66;
93.9
%(8
5.0
–>
98.1
%).
By
investigato
rs’overa
ll
finali
mpre
ssio
n(2
8or
42
days):
Tx
gro
up
1:62
⁄63;
98.4
%(9
0.7
–>
99.9
%).
Tx
gro
up
2:62
⁄66;
93.9
%(8
5.0
–>
98.1
%)
Overa
ll,fo
rall
Tx
gro
ups:31
⁄45
dogs;
68.9
%(5
4.3
–0.5
%),
21
days.
37
⁄45
dogs;82.2
%
(68.4
–91.0
%),
42
days
Tx
gro
up
1:4
⁄6dogs;
66.7
%(2
9.6
–90.8
%),
unspecifi
ed
Tx
tim
e.
Tx
gro
up
2:5
⁄6dogs;
83.5
%(4
1.8
–98.9
%),
unspecifi
ed
Tx
tim
e.
Tx
gro
up
3:6
⁄6dogs;
100%
(55.7
–100%
),
unspecifi
ed
Tx
tim
e
Tx
gro
up
1:28
⁄31
dogs;
90.3
%(7
4.3
–97.4
%),
84
days.
Tx
gro
up
2:32
⁄37
dogs;
86.5
%(7
1.6
–94.6
%),
84
days
Tx
gro
up
1:33
⁄49
dogs;
67.3
%(5
3.3
–78.9
%*),
21
days.
Tx
gro
up
2:31
⁄52
dogs;
59.6
%(4
6.1
–71.9
%*),
21
days
Tx
gro
up
1:49
⁄51
dogs;
96.0
%(8
6.0
–99.7
%*)
by
day
40
of
stu
dy.
Tx
gro
up
2:38
⁄51
dogs;
74.5
%(6
1.0
–84.6
%*)
by
day
40
of
stu
dy
Sta
tisticalcom
parison
(test,
P-v
alu
e)
No
sig
nifi
cant
diffe
rence
betw
een
treatm
ent
gro
ups
aft
er
7–21
days
thera
py
(Fis
her’
sexact,
P=
0.8
56)
Evid
ence
for
nonin
feriority
of
the
cefp
odoxim
e
regim
ecom
pare
dw
ith
the
cefa
lexin
treatm
ent
(90%
CIfo
rth
e
diffe
rence
insuccess
rate
s:)
4.7
to10.5
%,no
report
ed
P-v
alu
e)
No
sta
tistical
com
parisons
were
made
by
the
auth
ors
,
and
insuffi
cie
nt
raw
data
were
report
ed
to
make
these
calc
ula
tions
independently
No
sta
tistical
com
parisons
were
made
by
the
auth
ors
,
and
the
very
sm
all
stu
dy
gro
up
siz
es
make
sta
tistical
analy
sis
inappro
priate
No
sig
nifi
cant
diffe
rence
betw
een
the
responses
achie
ved
by
the
two
dose
rate
s(F
isher’
s
exact,
P=
0.4
8)
Auth
ors
report
no
sig
nifi
cant
diffe
rence
betw
een
treatm
ent
gro
ups
with
respect
to
clin
ical‘
cure
’ra
tes
aft
er
21
days
treatm
ent
(v2,P
=0.3
08)
Consid
ering
‘cure
s’and
‘mark
ed
impro
vem
ents
’
togeth
er
as
‘very
good
results’,
som
eevid
ence
for
atr
uly
hig
her
rate
of
‘good
results’in
the
marb
ofloxacin
Tx
gro
up
(Mante
l–H
aentz
elt
est,
P=
0.0
2)
Tre
atm
ent
dura
tion
required
for
clin
ical
rem
issio
n(a
vera
ge)
Tx
gro
up
1:41
±26
days
(mean,S
D).
Tx
gro
up
2:38
±21
days
(mean,S
D)
Tx
gro
up
1:48
⁄61
(76.2
%)re
quired
28
days
treatm
ent,
13
⁄61
dogs
(20.6
%)re
quired
42
days
treatm
ent.
Tx
gro
up
2:53
⁄62
(80.3
%)re
quired
28
days
treatm
ent,
9⁄6
2(1
3.6
%)
required
42
days
treatm
ent
Tx
gro
up
1:27
±12
days
(mean).
Tx
gro
up
2:26
±11
days
(mean).
Tx
gro
up
3:28
±13
days
(mean)
Tx
gro
up
1:14
days
(media
n).
Tx
gro
up
2:14
days
(media
n).
Tx
gro
up
3:21
days
(media
n)
See
Table
s1
and
2fo
r
this
outc
om
ein
separa
tedeep
and
superfi
cia
lpyoderm
a
gro
ups
Not
assessed
Cum
ula
tive
perc
enta
ge
of
dogs
att
ain
ing
‘cure
’
sta
tus
by
days
5,10,
20,30,40:
Tx
gro
up
1:9,30,70,90,
100%
.
Tx
gro
up
2:4,50,75,94,
100%
.(N
.B.P
erc
enta
ges
are
estim
ate
das
data
were
only
pre
sente
d
gra
phic
ally
)
ª 2012 The Authors. Veterinary Dermatology
316 ª 2012 ESVD and ACVD, Veterinary Dermatology, 23, 305–e61.
Summers et al.
Tab
le4.
(Continued)
Refe
rences
Hors
poole
tal.
30
Chern
iet
al.
26
Fra
nk
and
Kunkle
33
Seena
et
al.
34
Llo
yd
et
al.
27
Laago
23
Carlott
iet
al.
31
Sta
tisticalc
om
parison
(test,
P-v
alu
e)
Auth
ors
report
no
sig
nifi
cant
diffe
rence
betw
een
treatm
ent
gro
ups
(test
uncle
ar,
P>
0.0
5)
No
sta
tisticalc
om
parisons
made
by
the
auth
ors
.
Insuffi
cie
nt
raw
data
report
ed
tom
ake
these
calc
ula
tions
independently
No
sta
tistical
com
parisons
were
made
by
the
auth
ors
,
and
insuffi
cie
nt
raw
data
were
report
ed
to
make
these
calc
ula
tions
independently
No
sta
tistical
com
parisons
were
made
by
the
auth
ors
,
and
the
very
sm
all
stu
dy
gro
up
siz
es
make
sta
tistical
analy
sis
inappro
priate
(See
Table
s1
and
2)
—A
uth
ors
report
no
sig
nifi
cant
diffe
rence
betw
een
treatm
ent
gro
ups
(v2,P
-valu
enot
report
ed)
Rela
pse
rate
(s)in
dogs
achie
vin
gre
solu
tion
(tim
epost-
treatm
ent
cessation)
Tx
gro
up
1:2
⁄76
(2.6
%)
of
resolv
ed
cases
(1m
onth
).
Tx
gro
up
2:10
⁄88
(11.4
%)of
resolv
ed
cases
(1m
onth
)
Not
assessed
Not
assessed
Not
assessed
See
Table
s1
and
2fo
r
this
outc
om
ein
separa
tedeep
and
superfi
cia
lpyoderm
a
gro
ups
Not
assessed
Tx
gro
up
1:1
⁄41
(2.4
%)of
resolv
ed
cases
(day
40).
Tx
gro
up
2:0
⁄31
resolv
ed
cases
(day
40)
Sta
tisticalc
om
parison
(test,
P-v
alu
e)
Sig
nifi
cantly
few
er
rela
pses
occurr
ed
in
dogs
treate
dw
ith
ibafloxacin
com
pare
d
with
those
giv
en
marb
ofloxacin
(Fis
her’
s
exact,
P=
0.0
376)
——
—S
ee
Table
s1
and
2—
Not
pre
sente
d
Advers
eeff
ects
Tx
gro
up
1:
dia
rrhoea
⁄gastr
oin
testinals
igns
(one
dog).
Tx
gro
up
2:
Alle
rgic
-type
reaction
(one
dog)
Tx
gro
up
1:le
tharg
y(t
wo
dogs),
reduced
appetite
(one
dog),
vom
itin
g(f
our
dogs),
dia
rrhoea
⁄soft
faeces
(four
dogs),
‘oth
er
unre
late
dabnorm
al
sig
ns’(e
ight
dogs).
Tx
gro
up
2:le
tharg
y(o
ne
dog),
reduced
appetite
(thre
edogs),
vom
itin
g
(one
dog),
‘oth
er
unre
late
dabnorm
al
sig
ns’(1
4dogs)
Tx
gro
up
1:vom
itin
g
(tw
odogs).
Tx
gro
up
2:unusual
aggre
ssio
n(o
ne
dog),
decre
ased
appetite
(one
dog).
Tx
gro
up
3:sta
tes
that
none
report
ed
Not
report
ed
Tx
gro
up
1:dia
rrhoea
(one
dog).
Tx
gro
up
2:vom
itin
g
(four
dogs)
Tx
gro
up
1:‘s
ignifi
cant
sid
eeff
ects
such
as
vom
itin
g’(o
ne
dog).
Tx
gro
up
2:‘s
ignifi
cant
sid
eeff
ects
such
as
vom
itin
g’(t
hre
edogs)
Overa
ll,‘v
arious
mild
sym
pto
ms
observ
ed
in
both
gro
ups
(vom
itin
g,
dia
rrhoea,decre
ased
appetite
or
thirst)
’.
Num
bers
not
report
ed
overa
llor
separa
tely
per
Tx
gro
up
Sta
tisticalc
om
parison
(test,
P-v
alu
e)
——
——
——
—
Abbre
via
tions:n.a
.,not
availa
ble
;TM
PS
,tr
imeth
oprim
–sulfadia
zine
;Tx,tr
eatm
ent;
‘Good
num
ber’
of
subje
cts
,>
50
subje
cts
per
gro
up;‘m
odera
te’num
ber
of
subje
cts
,20–50
subje
cts
per
gro
up;‘s
mall’
num
ber
of
subje
cts
,10–19
subje
cts
per
gro
up;‘v
ery
sm
all’
num
ber
of
subje
cts
,<
10
subje
cts
per
gro
up.
*P
erf
orm
ed/c
alc
ula
ted
by
the
syste
matic
revie
wauth
ors
.
ª 2012 The Authors. Veterinary Dermatology
ª 2012 ESVD and ACVD, Veterinary Dermatology, 23, 305–e61. 317
Systemic antimicrobials in canine pyoderma
derma cases) presented both a per-protocol analysis
(involving only animals completing the study) and a ‘last-
value-carried-forward’ approach designed to account for
losses to follow-up and attrition bias by replacing missing
outcome data.20 None of the remaining studies with
losses to follow-up presented any form of intention-to-
treat analysis (ITTA), either alone or alongside a per-proto-
col analysis.
Assessment of compliance
Although some studies did report a number of exclusions
due to deviations from the prescribed treatment protocol
(e.g. ‘overdosing’), formal assessments of owner compli-
ance and administration success over the treatment per-
iod was not presented by any of the studies reviewed. It
was therefore not possible to confirm that oral treatment
courses were administered to all dogs as prescribed or to
adjust for the potential effect of deviations from the treat-
ment protocol.
Efficacy of interventions
The studies reviewed were considered too hetero-
geneous in terms of study design and focus for a meta-
analytical approach to yield meaningful results, nor was it
possible to apply a common lesion scoring system across
the studies to assess case severity owing to wide varia-
tion in the nature and detail of clinical reporting between
trials. Details of individual study outcome measures
of clinical interest in this review (including ‘treatment
success’ rates, measures of time to treatment success,
and relapse rates) are presented where relevant in
Tables 2–4. Treatment recommendation statements
based on evidence from the 17 selected studies are
presented individually for superficial (Table 5) and deep
pyoderma (Table 6) as appropriate.
Superficial pyoderma
In superficial pyoderma, the high efficacy of one to three
consecutive subcutaneous (s.c.) injections of cefovecin at
8 mg ⁄ kg given 2 weeks apart22 was supported by a good
level of evidence. Fair evidence was available for the
moderate to high efficacy of the following six interven-
tions: oral amoxicillin–clavulanic acid (12.5 mg ⁄ kg, twice
daily) given for 21–28 days,21,22,24 oral cefadroxil (22–
35 mg ⁄ kg, twice daily) for 28–42 days,22 oral clindamycin
(5.5 mg ⁄ kg twice daily) for 21 days,24,29 oral trimetho-
prim–sulfadiazine (TMPS; 30 mg ⁄ kg either once or twice
daily) for 42 days and oral sulfadimethoxine–ormetoprim
(TMPO; 55 mg ⁄ kg on day 1, then 27.5 mg ⁄ kg once daily
thereafter) for 21–42 days.25
Within-study statistical comparison of success rates
demonstrated no evidence for a statistically significant
difference between the dogs receiving any of the inter-
ventions above and those receiving other interventions
tested in the study. Cefovecin demonstrated noninferiori-
ty (according to a 15% point threshold for the difference
between treatment success rates) when compared with
both oral amoxicillin–clavulanic acid at 12.5 mg ⁄ kg twice
daily21 and oral cefadroxil at 22–35 mg ⁄ kg, also twice
daily.22
Reporting of measures of treatment duration required
to achieve clinical remission was minimal. In one study,
approximately 80 and 70% of dogs treated were consid-
ered ‘cured’ 14 days after a single dose of cefovecin
at 8 mg ⁄ kg or after a 14 day course of oral cefadroxil at
22–35 mg ⁄ kg, twice daily.22 Relapse rates were not
assessed with respect to any of the treatment interven-
tions listed above.
Deep pyoderma
In deep pyoderma, the high efficacy of oral amoxicillin–
clavulanic acid (12.5 mg ⁄ kg, twice daily) for at least
28 days was supported by a good level of evidence,20,21
while fair evidence was available supporting the moder-
ate to high efficacy of the following interventions: two to
three consecutive s.c. injections of 8 mg ⁄ kg cefovecin
given 2 weeks apart,21 oral pradofloxacin (3 mg ⁄ kg, once
daily) for 7–63 days20 and oral cefadroxil (either 20 mg ⁄ kg
twice daily or 40 mg ⁄ kg once daily) for 21 days.23
Within-study statistical comparison of success rates
demonstrated no evidence for a statistically significant
difference between the dogs receiving the treatment
interventions listed above and those receiving other inter-
ventions tested in the study. Cefovecin demonstrated
noninferiority compared with amoxicillin–clavulanic
acid (12.5 mg ⁄ kg twice daily) according to a 15% point
threshold for the difference between treatment success
rates.21
Based on reported average treatment durations required
to achieve clinical resolution in studied dogs, resolution
could reasonably be hoped for after 4–8 weeks of the
amoxicillin–clavulanic acid intervention,20,21 5–7 weeks of
the pradofloxacin regime,20 and between 4 and 8 weeks
from initial cefovecin injection (two to four injections at
14 day intervals).21 Although significantly improved effi-
cacy has not been demonstrated, pradofloxacin treat-
ment may result in reduced occurrence of relapses in the
2 weeks after completion of therapy compared with
amoxicillin–clavulanic acid.20
Adverse reactions
Reporting of adverse effects in pyoderma cases spe-
cific to treatment group was evident in 11 stu-
dies.20,23,25–27,29,30,33,35,36 One of the remaining trials
made no mention of adverse effects34 and five only
reported adverse effects overall, regardless of treatment
group or across a group including nonpyoderma
cases.21,22,31,32
Reported adverse effects during the treatment period
were most commonly gastrointestinal disturbances (such
as vomiting, diarrhoea and soft stools) or general malaise
(reduced appetite and lethargy). Less frequently reported
problems included unusual aggression, allergic-type reac-
tion, polyuria ⁄ polydipsia, haematuria, hepatotoxicosis and
seizure (Table 7). The group of dogs treated with oral cef-
podoxime at 5 mg ⁄ kg once daily had the greatest reported
rate of adverse effects of all study treatment groups con-
sidered in this review. Nineteen instances of adverse
effects, including lethargy, inappetance and gastrointesti-
nal disturbance, were recorded (numerically 30.2% of trea-
ted dogs, although individual dogs could be affected by
more than one adverse effect).26 Termination of treatment
and removal from the study owing to severity of adverse
effects was reported in four dogs, from three treatment
ª 2012 The Authors. Veterinary Dermatology
318 ª 2012 ESVD and ACVD, Veterinary Dermatology, 23, 305–e61.
Summers et al.
Tab
le5.
Sum
mary
of
treatm
ent
recom
mendation
sta
tem
ents
for
syste
mic
antim
icro
bia
ltre
atm
ent
inte
rventions
for
canin
esuperfi
cia
lpyoderm
abased
on
contr
olle
dtr
ials
identified
by
syste
matic
revie
wof
the
avail-
able
litera
ture
Antim
icro
bia
lcla
ss
Antim
icro
bia
l
agent
Dosin
gre
gim
e
Tre
atm
ent
recom
mendation
sta
tem
ent
with
respect
tocanin
esuperfi
cia
l
pyoderm
a(t
reatm
ent
success
rate
s
from
BR
CTS
)
Based
upon:(*
BR
CT
report
ing
outc
om
es
specifi
cto
superfi
cia
lpyoderm
a;
or
†stu
die
sre
port
ing
outc
om
es
for
mix
ed
dia
gnosis
gro
ups)
Stu
die
sre
port
ing
outc
om
es
with
no
diffe
rentiation
betw
een
superfi
cia
l⁄deep
pyoderm
a
Penic
illin
⁄b-lacta
mase
inhib
itor
Am
oxic
illin
+
cla
vula
nic
acid
20
mg
⁄kg
+5
mg
⁄kg,tw
ice
daily
,p.o
.
(maxim
um
90
days
treatm
ent)
Insuffi
cie
nt
evid
ence
for
⁄again
st
recom
mendin
gth
euse
of
the
dru
g
—Llo
yd
et
al.
27*†
10
mg
⁄kg
+2.5
mg
⁄kg,tw
ice
daily
,
p.o
.(2
1–28
days
treatm
ent
dura
tion)
Fair
evid
ence
for
recom
mendin
guse
of
the
dru
g
Success
rate
s:
29.6
%(1
5.7
–48.7
%),
21
days
of
Tx
90.3
%(7
4.3
–97.4
%),
28
days
of
Tx
Carlott
i(1995)3
1;G
uaguere
(1998)3
2;
Littlew
ood
(1999)2
4*;P
ere
go
(2006)3
5;S
tegem
ann
(2007)2
1*
Carlott
iet
al.
31†;
Llo
yd
et
al.
27*†
Cephalo
sporin
Cefa
dro
xil
22–35
mg
⁄kg,tw
ice
daily
,p.o
.
(14–42
days
treatm
ent
dura
tion)
Fair
evid
ence
for
recom
mendin
guse
of
the
dru
g.
Success
rate
s:
91.9
%(8
2.1
–96.9
%),
42
days
of
Tx
Six
(2008)2
2*
Fra
nk
and
Kunkle
(1993)3
3†
20
mg
⁄kg,tw
ice
daily
,p.o
.(2
1days
treatm
ent
dura
tion)
Insuffi
cie
nt
evid
ence
for
⁄again
st
recom
mendin
gth
euse
of
the
dru
g
—Laago
23*†
40
mg
⁄kg,once
daily
,p.o
.(2
1days
treatm
ent
dura
tion)
Insuffi
cie
nt
evid
ence
for
⁄again
st
recom
mendin
gth
euse
of
the
dru
g
—Laago
23*†
Cefa
lexin
30
(40
or
60)m
g⁄k
g(v
aries
inth
ete
xt)
,
once
daily
,p.o
.(2
8–56
days
treatm
ent
dura
tion)
Insuffi
cie
nt
evid
ence
for
⁄again
st
recom
mendin
gth
euse
of
the
dru
g
Tom
a(2
008)2
8—
15–35
mg
⁄kg,tw
ice
daily
,p.o
.
(18–60
days
treatm
ent
dura
tion)
Insuffi
cie
nt
evid
ence
for
⁄again
st
recom
mendin
gth
euse
of
the
dru
g
Guaguere
(1998)3
2;Tom
a(2
008)2
8Fra
nk
and
Kunkle
33†;
Seena
et
al.
34†;
Chern
iet
al.
26*†
Cefo
vecin
8m
g⁄k
g,every
14
days,s.c
.in
jection
(2–3
inje
ctions:28–42
days
treatm
ent
dura
tion)
Good
evid
ence
for
recom
mendin
g
use
of
the
dru
g.
Success
rate
s:
89.6
%(7
9.7
–95.1
%),
maxim
um
42
days
of
Tx
98.8
%(9
2.8
–>
99.9
%),
28
days
of
Tx
Ste
gem
ann
et
al.
21*;
Six
et
al.
22*
Cefp
odoxim
e5
mg
⁄kg,once
daily
,p.o
.(2
8–42
days
treatm
ent
dura
tion)
Insuffi
cie
nt
evid
ence
for
⁄again
st
recom
mendin
gth
euse
of
the
dru
g
—C
hern
iet
al.
26*†
Flu
oro
quin
olo
ne
Ibafloxacin
15
mg
⁄kg,once
daily
,p.o
.(2
1days
treatm
ent
dura
tion)
Insuffi
cie
nt
evid
ence
for
⁄again
st
recom
mendin
gth
euse
of
the
dru
g
—H
ors
poole
tal.
30†
Marb
ofloxacin
2m
g⁄k
g,once
daily
,p.o
.(5
–40
days
treatm
ent
dura
tion)
Insuffi
cie
nt
evid
ence
for
⁄again
st
recom
mendin
gth
euse
of
the
dru
g
Carlott
i(1995)3
1;P
ere
go
(2006)3
5C
arlott
iet
al.
31†;
Hors
poole
tal.
30†
Lin
cosam
ide
Clin
dam
ycin
5.5
mg
⁄kg,tw
ice
daily
,p.o
.
(21–42
days
treatm
ent
dura
tion)
Fair
evid
ence
for
recom
mendin
guse
of
the
dru
g.
Success
rate
:
58.6
%(4
0.7
–74.5
%),
21
days
of
Tx
Littlew
ood
(1999)2
4*
—
11
mg
⁄kg,once
daily
,p.o
.(2
1–42
days
treatm
ent
dura
tion)
Insuffi
cie
nt
evid
ence
for
⁄again
st
recom
mendin
gth
euse
of
the
dru
g
Harv
ey
(1993)2
9—
Lin
com
ycin
22
mg
⁄kg,tw
ice
daily
,p.o
.(2
1–42
days
treatm
ent
dura
tion)
Insuffi
cie
nt
evid
ence
for
⁄again
st
recom
mendin
gth
euse
of
the
dru
g
Harv
ey
(1993)2
9S
eena
et
al.
34†
ª 2012 The Authors. Veterinary Dermatology
ª 2012 ESVD and ACVD, Veterinary Dermatology, 23, 305–e61. 319
Systemic antimicrobials in canine pyoderma
groups in three trials, as follows (number of dogs
removed; clinical reason for removal): oral amoxicillin–cla-
vulanic acid, 12.5 mg ⁄ kg twice daily (one dog; vomiting20);
oral TMPS, 30 mg ⁄ kg twice daily (two dogs; haematuria,
hepatotoxicosis25); and oral cefadroxil at 40 mg ⁄ kg ⁄ day,
unspecified if given as a single or two halved daily doses
(one dog; vomiting23). In another study, three dogs show-
ing gastrointestinal disturbance when treated with oral ce-
falexin at 30–60 mg ⁄ kg once daily were switched to a
treatment group receiving oral cefalexin at 15–30 mg
twice daily, whereupon the effects disappeared.28 In the
remaining relevant studies where adverse effects were
reported, none was severe enough to result in exclusion of
participants from the trial. Across the 11 studies where
adverse effects were addressed (specific to pyoderma
cases and per treatment group), authors reported that
there were no adverse effects observed in any of the dogs
from eight individual treatment groups across five stud-
ies.24,25,29,33,35 Two of these groups had received therapy
with amoxicillin–clavulanic acid [12.5 mg ⁄ kg, twice daily,
per os (p.o.)],24,35 and a single group each had received the
following regimes: cefalexin (22–35 mg ⁄ kg, twice daily,
p.o.),33 clindamycin (5.5 mg ⁄ kg, twice daily or 11 mg ⁄ kg,
once daily, p.o.),24,29 lincomycin (22 mg ⁄ kg, twice daily,
p.o.),29 marbofloxacin (2 mg ⁄ kg, once daily, p.o.)35 and
TMPS (30 mg ⁄ kg, once daily, p.o.).25
Discussion
To the authors’ knowledge, this is the first systematic
review of systemic antimicrobial treatment interventions
for canine superficial and deep pyoderma. Seventeen
controlled trials published in four languages were identi-
fied, with nine reporting findings specific to superficial
and five to deep pyoderma. In total, 1463 dogs were eval-
uated; 577 and 341 dogs were evaluated in studies
reporting outcomes specific to superficial and deep
pyoderma, respectively. A good level of evidence was
found to support the high efficacy of subcutaneously
injected cefovecin in superficial pyoderma and for oral
amoxicillin–clavulanic acid in deep pyoderma. A fair level
of evidence was available for moderate to high efficacy of
oral amoxicillin–clavulanic acid, clindamycin, cefadroxil,
trimethoprim–sulphamethoxazole and sulfadimethoxine–
ormetoprim in superficial pyoderma and oral pradofloxa-
cin, oral cefadroxil and subcutaneously injected cefovecin
in deep pyoderma.
Review limitations
Several aspects of the systematic review protocol may
have adversely affected the selection and assessment of
reviewed trials, and thus influenced the overall review
findings.
Participants
Pyoderma in the dog can present as a wide spectrum of
clinical manifestations, and at present there are no
formally recognized guidelines to use as a gold-standard
approach to correct diagnosis of the condition. Specificity
of diagnostic criteria for pyoderma varied across the
17 studies, from clinical impression of one of various exam-
ining veterinarians supported by unspecified cytologicalTab
le5.
(Continued)
Antim
icro
bia
lcla
ss
Antim
icro
bia
l
agent
Dosin
gre
gim
e
Tre
atm
ent
recom
mendation
sta
tem
ent
with
respect
tocanin
esuperfi
cia
l
pyoderm
a(t
reatm
ent
success
rate
s
from
BR
CTS
)
Based
upon:(*
BR
CT
report
ing
outc
om
es
specifi
cto
superfi
cia
lpyoderm
a;
or
†stu
die
sre
port
ing
outc
om
es
for
mix
ed
dia
gnosis
gro
ups)
Stu
die
sre
port
ing
outc
om
es
with
no
diffe
rentiation
betw
een
superfi
cia
l⁄deep
pyoderm
a
Pote
ntiate
d
sulp
honam
ide
Sulfadim
eth
oxi-
neorm
eto
prim
55
mg
⁄kg
on
day
1,th
en
27.5
mg
⁄kg
there
aft
er,
once
daily
,p.o
.(2
1–42
days
treatm
ent
dura
tion)
Fair
evid
ence
for
recom
mendin
guse
of
the
dru
g.
Success
rate
s:
75.0
%(5
0.0
–90.3
%)aft
er
21
days,
100%
(77.3
–100.0
%)aft
er
42
days
Tx
Messin
ger
(1993)2
5*
—
Trim
eth
oprim
sulp
ha-
meth
oxazo
le
30
mg
⁄kg,once
daily
,p.o
.(2
1–42
days
treatm
ent
dura
tion)
Fair
evid
ence
for
recom
mendin
guse
of
the
dru
g(4
2days).
Success
rate
s:
38.5
%(1
7.6
–64.6
%)at
21
days,76.9
%
(49.1
–92.5
%)aft
er
42
days
Tx
Messin
ger
(1993)2
5*
—
30
mg
⁄kg,tw
ice
daily
,p.o
.(2
1–42
days
treatm
ent
dura
tion)
Fair
evid
ence
for
recom
mendin
guse
of
the
dru
g.
Success
rate
s:
57.1
%(3
2.6
–78.7
%)aft
er
21
days,
78.6
%(5
1.7
–93.2
%)aft
er
42
days
Tx
Messin
ger
(1993)2
5*
Seena
et
al.
34
†
Abbre
via
tions:B
RC
T,blin
ded
random
ized
contr
olle
dtr
ial;
Tx,tr
eatm
ent.
ª 2012 The Authors. Veterinary Dermatology
320 ª 2012 ESVD and ACVD, Veterinary Dermatology, 23, 305–e61.
Summers et al.
Tab
le6.
Sum
mary
of
treatm
ent
recom
mendation
sta
tem
ents
for
syste
mic
antim
icro
bia
ltr
eatm
ent
inte
rventions
for
canin
edeep
pyoderm
abased
on
contr
olle
dtr
ials
identified
by
syste
matic
revie
wof
the
availa
ble
litera
ture
Antim
icro
bia
lcla
ss
Antim
icro
bia
lagent
Dosin
gre
gim
e
Tre
atm
ent
recom
mendation
sta
tem
ent
with
respect
todeep
canin
epyoderm
a
(Tre
atm
ent
success
rate
sfr
om
BR
CTS
)
Based
upon:(*
BR
CT
report
ing
outc
om
es
specifi
cto
deep
pyoderm
a;or
†stu
die
sre
port
ing
outc
om
es
for
mix
ed
dia
gnosis
gro
ups)
Additio
nals
tudie
sre
port
ing
outc
om
es
with
no
diffe
rentiation
betw
een
superfi
cia
l⁄deep
pyoderm
a
Penic
illin
⁄b-lacta
mase
inhib
itor
Am
oxic
illin
+
cla
vula
nic
acid
20
mg
⁄kg
+5
mg
⁄kg,tw
ice
daily
,p.o
.
(maxim
um
90
days
treatm
ent)
Insuffi
cie
nt
evid
ence
for
⁄again
st
recom
mendin
gth
euse
of
the
dru
g
Guaguere
(1998)3
2Llo
yd
et
al.
27*†
10
mg
⁄kg
+2.5
mg
⁄kg,tw
ice
daily
,
p.o
.(2
8–60
days
treatm
ent
dura
tion)
Good
evid
ence
for
recom
mendin
guse
of
the
dru
g.
Success
rate
s:
72.6
%(5
9.0
–83.0
%),
maxim
um
60
days
of
Tx;
85.7
%(6
4.5
–95.9
%),
28
days
of
Tx
Carlott
i(1995)3
1;M
uelle
r
(2007)2
0*;S
tegem
ann
(2007)2
1*
Carlott
iet
al.
31†;Llo
yd
et
al.
27*†
Cephalo
sporin
Cefa
dro
xil
22–35
mg
⁄kg,tw
ice
daily
,p.o
.
(21–42
days
treatm
ent
dura
tion)
Insuffi
cie
nt
evid
ence
for
⁄again
st
recom
mendin
gth
euse
of
the
dru
g
—Fra
nk
and
Kunkle
33†
20
mg
⁄kg,tw
ice
daily
,p.o
.(2
1days
treatm
ent
dura
tion)
Fair
evid
ence
for
recom
mendin
guse
of
the
dru
g.
Success
rate
s:
72.2
%(4
8.8
–87.8
%*),
21
days
of
Tx
Laago
(2008)2
3*
Laago
23*†
40
mg
⁄kg,once
daily
,p.o
.(2
1days
treatm
ent
dura
tion)
Fair
evid
ence
for
recom
mendin
guse
of
the
dru
g.
Success
rate
s:
48.0
%(3
0.0
–66.5
%*),
21
days
of
Tx
Laago
(2008)2
3*
Laago
23*†
Cefa
lexin
25–26
mg
⁄kg,tw
ice
daily
,p.o
.
(7–42
days
treatm
ent
dura
tion)
Insuffi
cie
nt
evid
ence
for
⁄again
st
recom
mendin
gth
euse
of
the
dru
g
—S
eena
et
al.
34†;C
hern
i
et
al.
26*†
15
mg
⁄kg,tw
ice
daily
,p.o
.(2
8–90
days
treatm
ent
dura
tion)
Insuffi
cie
nt
evid
ence
for
⁄again
st
recom
mendin
gth
euse
of
the
dru
g
Guaguere
(1998)3
2—
30
mg
⁄kg,tw
ice
daily
,p.o
.(2
8–90
days
treatm
ent
dura
tion)
Insuffi
cie
nt
evid
ence
for
⁄again
st
recom
mendin
gth
euse
of
the
dru
g
Guaguere
(1998)3
2—
Cefa
lexin
22–35
mg
⁄kg,tw
ice
daily
,p.o
.
(21–42
days
treatm
ent
dura
tion)
Insuffi
cie
nt
evid
ence
for
⁄again
st
recom
mendin
gth
euse
of
the
dru
g
—Fra
nk
and
Kunkle
33†
Cefo
vecin
8m
g⁄k
g,every
14
days,s.c
.in
jection
(tw
oin
jections;28
days
treatm
ent
dura
tion)
Fair
evid
ence
for
recom
mendin
guse
of
the
dru
g.
Success
rate
s:
94.0
%(8
3.2
–98.6
%*),
28
days
of
Tx
Ste
gem
ann
(2007)2
1*
—
Cefp
odoxim
e5
mg
⁄kg,once
daily
,p.o
.(2
8–42
days
treatm
ent
dura
tion)
Insuffi
cie
nt
evid
ence
for
⁄again
st
recom
mendin
gth
euse
of
the
dru
g
—C
hern
iet
al.
26
*†
Flu
oro
quin
olo
ne
Ibafloxacin
15
mg
⁄kg,once
daily
,p.o
.(2
1days
treatm
ent
dura
tion)
Insuffi
cie
nt
evid
ence
for
⁄again
st
recom
mendin
gth
euse
of
the
dru
g
—H
ors
poole
tal.
30†
ª 2012 The Authors. Veterinary Dermatology
ª 2012 ESVD and ACVD, Veterinary Dermatology, 23, 305–e61. 321
Systemic antimicrobials in canine pyoderma
findings to fulfilment of strict requirements based on
clinical evaluation of particular lesion types, standard cyto-
logical examination and ⁄ or bacterial culture and sensitivity
testing. Significant variability in the diagnostic process
between studies may have led to heterogeneity of true
clinical status within the total dogs enrolled, potentially
influencing the response of individual animals to particular
treatment interventions. Overall, based on the criteria set
out in the review protocol, all but one study enrolled what
were considered to be well-characterized cases.
Acceptable diagnostic criteria for diagnosis of canine
pyoderma did not alter significantly between publication
dates of the earliest and most recent study. Despite the
reclassification of the S. intermedius group in 2007, it is
generally accepted that coagulase-positive staphylococci
reportedly found on pyoderma-affected canine skin (and
reported as S. intermedius or S. aureus) pre-2007 can be
considered S. pseudintermedius.37 Thus, the range of
study publication dates is unlikely to have much effect on
reliability of diagnosis. However, the possible develop-
ment of drug resistance amongst causal bacterial species
over time may have introduced an unquantifiable element
of bias related to study publication date.
Other potential sources of variability in treatment
responses (alongside or independent of the effect of
the treatment intervention received) include physical or
physiological factors associated with breed, and the com-
plicating effect of different underlying conditions and any
concurrent therapies. Various breeds are represented in
all the studies reporting baseline characteristics of study
groups, but none reports outcomes specific to breed.
Several of the studies reviewed clearly stated underlying
disease conditions (where identified) in all study dogs,
and some specified that these must be successfully man-
aged at the beginning of the antimicrobial trial.24,28,33,34
Reporting of outcomes grouped by underlying cause of
pyoderma lesions was rare, and such subgroups are likely
to be too small for meaningful statistical analysis when
also divided into deep and superficial pyoderma catego-
ries. In addition, the source of cases differed between
trials. Three studies enrolled exclusively from referral-
level dermatology clinics,24,27,33 three exclusively from
first-opinion clinics,22,23,30 and two from a combination of
first-opinion and referral settings.20,28 In nine studies, the
clinical scenario from which subjects were enrolled
was unclear or not specified.21,25,26,29,31,32,34,35 Studies
recruiting subjects only from a referral level clinical setting
are at risk of enrolling dogs from a population of particu-
larly complex, unusual or intractable pyoderma cases,
thus limiting generalizability of findings to the majority of
cases encountered in first-opinion practice.
Performance bias may have been introduced at varying
levels across the reviewed studies, based on the cotreat-
ments permitted during (or closely preceding) the anti-
microbial treatment period. Most studies stated at least
one permitted or prohibited concurrent treatment, and
some therapies were disallowed during a specified period
before entering the trial. Most studies permitted continua-
tion of regular ectoparasite prophylaxis, and a few studies
permitted regular bathing with medicated shampoos
throughout the study treatment period.33 In most cases,
treatment with other drugs of particular relevance to theTab
le6.
(Continued)
Antim
icro
bia
lcla
ss
Antim
icro
bia
lagent
Dosin
gre
gim
e
Tre
atm
ent
recom
mendation
sta
tem
ent
with
respect
todeep
canin
epyoderm
a
(Tre
atm
ent
success
rate
sfr
om
BR
CTS
)
Based
upon:(*
BR
CT
report
ing
outc
om
es
specifi
cto
deep
pyoderm
a;or
†stu
die
sre
port
ing
outc
om
es
for
mix
ed
dia
gnosis
gro
ups)
Additio
nalstu
die
sre
port
ing
outc
om
es
with
no
diffe
rentiation
betw
een
superfi
cia
l⁄deep
pyoderm
a
Marb
ofloxacin
2m
g⁄k
g,once
daily
,p.o
.(5
–40
day
treatm
ent
period)
Insuffi
cie
nt
evid
ence
for
⁄again
st
recom
mendin
gth
euse
of
the
dru
g
Carlott
i(1995)3
1C
arlott
iet
al.
31
†;H
ors
pool
et
al.
30†
Pra
dofloxacin
3m
g⁄k
g,once
daily
,(r
oute
not
sta
ted)
(7–63
day
treatm
ent
period)
Fair
evid
ence
for
recom
mendin
guse
of
the
dru
g.
Success
rate
s:85.7
%(7
4.0
–92.8
%),
7–63
days
Muelle
r(2
007)2
0*
—
Lin
cosam
ide
Lin
com
ycin
22
mg
⁄kg,tw
ice
daily
,p.o
.(7
days
to
unspecifi
ed
maxim
um
Tx
dura
tion)
Insuffi
cie
nt
evid
ence
for
⁄again
st
recom
mendin
gth
euse
of
the
dru
g
—S
eena
et
al.
34†
Pote
ntiate
d
sulp
honam
ide
Trim
eth
oprim
–
sulp
ham
eth
oxazo
le
30
mg
⁄kg,tw
ice
daily
,p.o
.(7
days
to
unspecifi
ed
maxim
um
Tx
dura
tion)
Insuffi
cie
nt
evid
ence
for
⁄again
st
recom
mendin
gth
euse
of
the
dru
g
—S
eena
et
al.
34†
Abbre
via
tions:B
RC
T,blin
ded
random
ized
contr
olle
dtr
ial;
Tx,tr
eatm
ent.
ª 2012 The Authors. Veterinary Dermatology
322 ª 2012 ESVD and ACVD, Veterinary Dermatology, 23, 305–e61.
Summers et al.
Table 7. Summary of adverse effects reporting in the 17 studies evaluated in the systematic review
Antimicrobial class Antimicrobial agent Dosing regime
Adverse effects reported
(no. of dogs affected, % of
total treatment group affected) Reference
Penicillin ⁄ b-lactamase
inhibitor
Amoxicillin + clavulanic
acid
10 mg ⁄ kg + 2.5 mg ⁄ kg, twice
daily (route not stated)
Diarrhoea and vomiting (1 ⁄ 56
dogs, 1.8%), vomiting only
(1 ⁄ 56 dogs, 1.8%)
Mueller and
Stephan20
10 mg ⁄ kg + 2.5 mg ⁄ kg, twice
daily, p.o.
Not reported* Stegemann (2007)21
10 mg ⁄ kg + 2.5 mg ⁄ kg, twice
daily, p.o.
Observed in 0 ⁄ 27 dogs Littlewood et al.24
10 mg ⁄ kg + 2.5 mg ⁄ kg, twice
daily, p.o.
Diarrhoea (1 ⁄ 31 dogs, 3.2%) Lloyd et al.27
20 mg ⁄ kg + 5 mg ⁄ kg, twice
daily, p.o.
Vomiting (4 ⁄ 37 dogs, 10.8%) Lloyd et al.27
10 mg ⁄ kg + 2.5 mg ⁄ kg, twice
daily, p.o.
Not reported† Carlotti et al.31
10 mg ⁄ kg + 2.5 mg ⁄ kg, twice
daily, p.o.
Not reported‡ Guaguere et al.32
20 mg ⁄ kg + 5 mg ⁄ kg, twice
daily, p.o.
Not reported‡ Guaguere et al.32
10 mg ⁄ kg + 2.5 mg ⁄ kg, twice
daily, p.o.
Observed in 0 ⁄ 10 dogs Perego et al.35
Cephalosporin Cefadroxil 22 mg ⁄ kg, twice daily,
p.o. + (1· placebo injection)
Not reported* Six et al.22
22–35 mg ⁄ kg, twice daily, p.o. Vomiting on administration
(2 ⁄ 15 dogs, 13.3%)
Frank and Kunkle33
20 mg ⁄ kg, twice daily, p.o. ‘Significant side effects such as
vomiting’ (1 ⁄ 49 dogs, 2.0%)
Laago23
40 mg ⁄ kg, once daily, p.o. ‘Significant side effects such as
vomiting’ (3 ⁄ 52 dogs, 5.8%)
Laago23
Cefalexin 30 (40 or 60) mg ⁄ kg (varies in
the text), once daily, p.o.
Vomiting or diarrhoea (5 ⁄ 20
dogs, 25.0%)
Toma et al.28
15–30 mg ⁄ kg, twice daily, p.o. Diarrhoea (1 ⁄ 20 dogs, 5.0%) Toma et al.28
26 mg ⁄ kg, twice daily, p.o. Lethargy (1 ⁄ 66 dogs, 1.5%),
reduced appetite (3 ⁄ 66 dogs,
4.5%), vomiting (1 ⁄ 66 dogs,
1.5%), ‘other abnormal signs’
(14 ⁄ 66 dogs, 21.2%)
Cherni et al.26
25 mg ⁄ kg, twice daily (route not
stated)
Not reported Seena et al.34
15 mg ⁄ kg, twice daily, p.o. Not reported‡ Guaguere et al.32
15 mg ⁄ kg, twice daily, p.o. Not reported‡ Guaguere et al.32
30 mg ⁄ kg, twice daily, p.o. Not reported‡ Guaguere et al.32
Cefalexin (‘generic’) 22–35 mg ⁄ kg, twice daily, p.o. Unusual aggression (1 ⁄ 15 dogs,
6.7%), decreased appetite
(1 ⁄ 15 dogs, 6.7%)
Frank and Kunkle33
Cefalexin (‘proprietary’) 22–35 mg ⁄ kg, twice daily, p.o. Observed in 0 ⁄ 15 dogs Frank and Kunkle33
Cefovecin 8 mg ⁄ kg, every 14 days, s.c.
injection
Not reported* Stegemann (2007)21
8 mg ⁄ kg, every 14 days, s.c.
injection (+ oral daily placebo)
Not reported* Six et al.22
Cefpodoxime 5 mg ⁄ kg, once daily, p.o. Lethargy (2 ⁄ 63 dogs, 3.2%),
reduced appetite (1 ⁄ 63 dogs,
1.6%), vomiting (4 ⁄ 63 dogs,
6.3%), diarrhoea ⁄ soft faeces
(4 ⁄ 63 dogs, 6.3%), ‘other
abnormal signs’ (8 ⁄ 63 dogs,
12.7%)
Cherni et al.26
Fluoroquinolone Ibafloxacin 15 mg ⁄ kg, once daily, p.o. Diarrhoea ⁄ gastrointestinal signs
(1 ⁄ 113 dogs, 0.88%)
Horspool et al.30
Marbofloxacin 2 mg ⁄ kg, once daily, p.o. Allergic-type reaction (1 ⁄ 115
dogs, 0.87%)
Horspool et al.30
2 mg ⁄ kg, once daily, p.o. Observed in 0 ⁄ 10 dogs Perego et al.35
2 mg ⁄ kg, once daily, p.o. Not reported† Carlotti et al.31
Pradofloxacin 3 mg ⁄ kg, once daily, (route not
stated)
Polyuria ⁄ polydipsia (1 ⁄ 56 dogs,
1.8%), diarrhoea (1 ⁄ 56 dogs,
1.8%)
Mueller and
Stephan20
ª 2012 The Authors. Veterinary Dermatology
ª 2012 ESVD and ACVD, Veterinary Dermatology, 23, 305–e61. 323
Systemic antimicrobials in canine pyoderma
improvement of the clinical appearance of pyoderma (such
as topical antimicrobials, topical and systemic glucocortic-
oids) were prohibited during the study period and for a
specified, clinically appropriate period before commencing
the study treatment. A few studies stated the permitted
use of nonsteroidal anti-inflammatory drugs and limited
prednisone ⁄ methylprednisolone administration, and these
are likely to be most affected by performance bias.21,22,26
In seven studies enrolling both deep and superficial
pyoderma cases, there was limited, inadequate or no dis-
tinction made between these clinically distinct conditions
with respect to treatment groups at baseline and when
reporting certain outcomes.23,26,27,30,31,33,34 This pre-
cluded the findings of these studies from contributing to
the formulation of treatment recommendation state-
ments specific to either deep or superficial pyoderma,
limiting the amount of useful evidence available to inform
antimicrobial choice in either clinical situation.
Study design
Overall risk of introduction of bias (based on aspects of
study design and implementation) ranged from low to
moderate ⁄ high. The 17 studies were categorized as
follows: low risk (two studies),24,25 low ⁄ moderate (three
studies),20–22 moderate (eight studies)23,26,27,30–33 and
moderate ⁄ high (four studies).28,29,34,35 Publication dates
for studies with various levels of overall bias risk were dis-
tributed unevenly throughout the 15 year range (1993–
2008), showing no trend towards reduced likelihood of
bias in newer trials.
Constraints on report length inherent in writing for
scientific publication may have contributed to the frequency
of incomplete methodology description. While direct
communication with trial authors could have clarified
these details, the remit of this review was assessment
of existing evidence as available to the clinician or
researcher without recourse to contacting individual
study investigators. Aspects of good study design com-
monly judged inadequate or unclear in the selected stud-
ies were randomization method, blinding of outcome
assessment, and inclusion of all dogs assigned to treat-
ment groups in the analysis regardless of completion of
the trial. Randomization was adequately described in four
of the five studies reporting outcomes specific to deep
pyoderma (Table 3). Only four22,28,31,32 of nine studies rel-
evant to superficial pyoderma reported adequate random-
ization, with randomization either unconfirmed21,24,25,29
or not used35 in the remaining five studies (Table 2).
Blinding of the outcome assessor was considered
adequate in three of the studies reporting outcomes spe-
cific to deep pyoderma20,21,23 but was unclear in the
remaining two31,32 (Table 3). Blinding was confirmed in
four21,22,24,25 studies relevant to superficial pyoderma
and unclear in three others,31,32,35 while the remaining
two studies self-identified as open RCTs28,29 (Table 2).
Thus, the potential levels of selection and detection bias
within the overall available evidence specific to superficial
and deep pyoderma are difficult to estimate.38
All five studies reporting outcomes specific to deep
pyoderma had confirmed or possible losses to follow-up,
but only one of these studies attempted to address this
by presenting both a per-protocol and a ‘last-value-car-
ried-forward’ approach to analysis.20 Of the studies rele-
vant to superficial pyoderma, none of the six trials with
confirmed or possible losses to follow-up21,22,24,25,29,31
presented any form of ITTA, either alone or alongside a
per-protocol analysis. Evaluation of the findings of such
trials may benefit from applying the ‘last-value-carried-
forward’ approach to produce results based on an
ITTA.39 However, based on the analyses presented, a
degree of attrition bias was likely to affect the evidence
related to both deep and superficial pyoderma.
Table 7. (Continued)
Antimicrobial class Antimicrobial agent Dosing regime
Adverse effects reported
(no. of dogs affected, % of
total treatment group affected) Reference
Lincosamide Clindamycin 5.5 mg ⁄ kg, twice daily, p.o. Observed in 0 ⁄ 29 dogs Littlewood et al.24
11 mg ⁄ kg, once daily, p.o. Observed in 0 ⁄ 16 dogs Harvey et al.29
Lincomycin 22 mg ⁄ kg, twice daily (route not
stated)
Not reported Seena et al.34
22 mg ⁄ kg, twice daily, p.o. Observed in 0 ⁄ 14 dogs Harvey et al.29
Potentiated
sulphonamide
Sulfadimethoxine–
ormetoprim
55 mg ⁄ kg on day 1, then
27.5 mg ⁄ kg thereafter, once
daily, p.o.
Seizure (1 ⁄ 16 dogs, 6.3%) Messinger and
Beale25
Trimethoprim–
sulphamethoxazole
30 mg ⁄ kg, once daily, p.o. Observed in 0 ⁄ 13 dogs Messinger and
Beale25
30 mg ⁄ kg, twice daily, p.o. Haematuria (1 ⁄ 14 dogs, 7.1%),
hepatotoxicosis (1 ⁄ 14 dogs,
7.1%)
Messinger and
Beale25
30 mg ⁄ kg, twice daily (route not
stated)
Not reported Seena et al.34
*Details and figures are not reported for pyoderma cases separately from other skin infections in the study group.
†Carlotti (1995)31 stated only that ‘No side effects requiring a change in treatment were observed in either group. Various mild symptoms were
observed in both groups (vomiting, diarrhoea, decreased appetite or thirst).’ Details and numbers affected per treatment group were not reported.
‡Guaguere (1998)32: Adverse effects only reported overall (i.e. combined for all treatment groups across all pyoderma types in both studies repor-
ted in this paper). Stated that ‘general adverse effects (loss of appetite, apathy)’ were seen in 5% of all dogs given cephalexin and 8% of those
given amoxicillin ⁄ clavulanic acid, and that ‘no adverse events required discontinuation of the antibiotic treatment in progress’. Details and num-
bers affected per treatment group were not reported.
ª 2012 The Authors. Veterinary Dermatology
324 ª 2012 ESVD and ACVD, Veterinary Dermatology, 23, 305–e61.
Summers et al.
Outcome measures
The 17 studies identified did not report outcomes based
on a common, standardized set of outcome measures.
Marked heterogeneity was evident between trials with
respect to the outcome measures of interest in this
review (rates of ‘treatment success’ within intervention
groups, treatment duration required to achieve clinical
remission and rates of relapse after clinical remission was
achieved). As such, it was very difficult to make any legiti-
mate comparison of measures of treatment efficacy
across multiple studies where similar interventions were
under investigation.
‘All studies reported some form of ‘treatment success’
rate for different intervention groups, but the definitions
used for this classification varied substantially. ‘Treat-
ment success’ was most frequently described as clinical
remission, resolution, absence of specific signs or similar
equivalents, though in some studies significant improve-
ment of previous lesions was sufficient for classification
of a case as a ‘treatment success’. Measures used to
assess treatment success varied from overall clinical
impression of drug efficacy by the veterinary assessor to
detailed scoring systems for specific lesions, or composite
scores for skin lesions and other clinical signs. Lesion
scores allow comparison of improvement and success
rates, both within and between treatment groups, over
time in a reproducible way, and were more likely to be
used in more recent studies.
The time point at which treatment success was
assessed also varied widely, from standard assessment
of all study subjects after the same treatment period to
the use of each subject’s last outcome assessment, the
timing of which is unspecified or could lie anywhere
within a wide time period. The latter approach is more
difficult to translate into recommendations for effective
treatment length for a particular agent. Duration of treat-
ment required for resolution was a recorded outcome in
eight studies. Where reported, this measure was gener-
ally presented in terms of the average (mean or median)
period of treatment after which clinical resolution was
declared in a treatment group. However, wide variation in
the frequency and timing of re-examinations makes these
measures difficult to compare meaningfully between
studies. The nature of some treatments (such as cefove-
cin, a long-acting injectable cephalosporin) dictates that
required treatment duration for resolution is quantified as
the number of complete, consecutive courses after
which clinical remission is achieved.21,22 This can be prob-
lematic when comparing required treatment periods with
drugs administered on a daily basis, resulting in overesti-
mation of the required treatment length in agents with
long-acting formulation.
Evaluation of the occurrence and timing of relapse in
successfully treated dogs was a recorded outcome in
only two studies. Follow-up periods ranged from 2 to
4 weeks after treatment was completed at the point of
clinical resolution,20,30 but neither study recorded time
from completion of treatment to reappearance of clinical
signs according to daily examinations. In both studies, the
number of dogs available for follow-up decreased with
increasing time from completion of treatment. This
increasing loss of evaluable study subjects increases the
risk of attrition bias associated with this particular out-
come measure in comparison to outcomes assessed dur-
ing the initial treatment period.
Validity of reviewed interventions
The collection of treatment interventions investigated by
the selected trials does not reflect the full range of anti-
microbial agents recommended as suitable for treatment
of canine pyoderma.15 However, the antimicrobial drugs
tested in these studies were considered therapeutically
relevant to pyoderma in the dog and accessible to all
levels of veterinary practice. None of the selected trials
reported clinical outcomes for an untreated or entirely
placebo-treated group of pyoderma cases. This may be
due to ethical constraints; in the absence of reliable evi-
dence for the natural course of untreated canine pyo-
derma, it is generally assumed that antimicrobials are
necessary to achieve resolution.
Exclusion of unpublished studies and those unavailable
as a full-length report (e.g. conference abstracts or short
communications) could have introduced publication bias
related to the increased likelihood of publication of
studies reporting positive outcomes. Overall, the authors
of eight studies declared some degree of study funding,
support or personal affiliation to a manufacturer of one of
the drugs investigated, and all manufacturer-funded stud-
ies reported favourable efficacy of the drug concerned.
Overall, the heterogeneity of the reviewed studies (in
terms of study design, subject inclusion criteria and out-
come assessment measures reported) precluded any
pooling of results from studies investigating similar treat-
ment interventions.
Implications for practice
It is outside the remit of this review of available evidence
to issue definitive best-practice guidelines for the empiri-
cal choice of systemic antimicrobial therapy in superficial
and deep canine pyoderma. Variation in the antimicrobial
susceptibility pattern of local populations of pyoderma-
causing pathogens and regional differences in drug
availability, legal status and cost can all impact substan-
tially on the effectiveness of particular antimicrobial drugs
within different clinical populations and geographical
locations. As repeated courses of empirically prescribed
antimicrobial therapy have been identified as one of the
most important risk factors for meticillin-resistant Staphylo-
coccus aureus (MRSA) infections in dogs and cats, treat-
ment failure should always be followed by re-evaluation,
including bacterial culture and susceptibility testing, rather
than change to another empirically chosen antimicrobial
agent.40 The reader is also referred to the BVA ‘eight-point
plan’ on the responsible use of antimicrobials in veterinary
practice, which summarizes the principles of prudent
antimicrobial use [www.bva.co.uk/public/documents/BVA_
Antimicrobial_Guidance.pdf (accessed 12 September 2011)].
Findings from the present systematic review do, how-
ever, provide some useful guidance for clinicians with
respect to potential efficacy of treatment interventions
represented in the current literature of highest design
quality.
No treatment intervention with fair or good evidence
to support moderate to high efficacy in either deep or
ª 2012 The Authors. Veterinary Dermatology
ª 2012 ESVD and ACVD, Veterinary Dermatology, 23, 305–e61. 325
Systemic antimicrobials in canine pyoderma
superficial pyoderma was shown to result in statistically
superior success rates when compared with other inter-
ventions tested in the same study. Confidence intervals
for treatment success rates were generally wide across
all studies and particularly in smaller-scale studies or
when evaluating outcomes in study subgroups of a larger
total study group. Thus, the accuracy of these rates
should be interpreted with caution.
Superficial pyoderma
According to the described criteria, the high efficacy of
only one systemic antimicrobial treatment strategy (s.c.
injection of cefovecin at 8 mg ⁄ kg once every 14 days)
is supported by a good level of evidence specific to
superficial pyoderma.21,22 It must be noted, however,
that this higher level of supporting evidence (compared
with the fair level assigned to other regimes) was
based largely on the availability of more than one
blinded RCT investigating this dose of cefovecin, rather
than dramatically superior treatment outcomes or
design quality. Fair levels of evidence were available to
support the moderate to high efficacies of the following
antimicrobial treatment interventions in dogs with
superficial pyoderma: oral amoxicillin–clavulanic acid at
12.5 mg ⁄ kg twice daily given for 21–28 days;21,24 oral
clindamycin at either 5.5 mg ⁄ kg twice daily or
11 mg ⁄ kg once daily for 21 days;24,29 oral cefadroxil at
22–35 mg ⁄ kg, twice daily for 28–42 days;22 oral TMPS
at 30 mg ⁄ kg either once or twice daily for 42 days; and
oral TMPO (55 mg ⁄ kg on day 1, then 27.5 mg ⁄ kg once
daily thereafter for 21–42 days.25 Reported adverse
effects associated with these treatment regimes
include low to moderate levels of mild gastrointestinal
disturbances and lethargy, and a small number of more
serious problems; only two of all dogs evaluated in the
relevant reviewed studies were withdrawn owing to
severity of these episodes.
Deep pyoderma
In deep pyoderma, the high efficacy of oral amoxicillin–
clavulanic acid (12.5 mg ⁄ kg, twice daily) for at least
28 days was supported by a good level of evidence,20,21
while fair evidence was available supporting the moder-
ate to high efficacy of the following interventions: two
to three consecutive s.c. injections of 8 mg ⁄ kg cefovecin
given 2 weeks apart;21 oral pradofloxacin (3 mg ⁄ kg,
once daily) for 7–63 days;20 and oral cefadroxil (either
20 mg ⁄ kg twice daily or 40 mg ⁄ kg once daily) for
21 days.23 Adverse effects associated with these treat-
ment interventions appeared to be minimal.
Implications for research
Based on the findings of this systematic review, several
general recommendations can be made for authors of
future treatment studies. At present, the scale, homoge-
neity and number of RCTs primarily evaluating treatment
efficacy in veterinary species are rarely sufficient to per-
mit stringent meta-analysis as defined by the Cochrane
systematic review group and the CONSORT state-
ment.19,41 However, application of these freely available
study design principles could still improve the comparabil-
ity, transparency and consistency of reporting in future
veterinary research, even if pooling of results is not appro-
priate.42
To allow more effective generalization of findings to
cases in the field, the authors recommend that future tri-
als of antimicrobial therapy in canine pyoderma report
treatment outcomes for recruited study dogs with deep
and superficial pyoderma separately, reflecting the clinical
distinction between the two conditions. Inextricably
pooled response data from deep and superficial pyo-
derma cases are unlikely to represent either condition
accurately. A set of accepted diagnostic guidelines for
deep and superficial pyoderma would aid consistency and
form a valuable basis upon which researchers could confi-
dently and consistently base enrolment criteria for future
treatment studies. Such guidelines could also form the
basis for a standardized, lesion-based grading system of
pyoderma severity.
Few statistically significant differences were demon-
strated between treatment groups despite apparent
numerical trends. Many of the treatment outcomes also
had very wide 95% confidence intervals, indicating that
accuracy of these findings was poor. To maximize the
chance of accurately quantifying outcomes and identify-
ing any genuine differences between treatment groups,
the authors recommend sample size calculations at the
planning stage of future treatment studies. To reduce the
impact of attrition bias, authors of studies with losses to
follow-up are also advised to present an ITTA alongside
the usual per-protocol analysis of results.
Conclusions
There are currently an insufficient number of studies at
the blinded RCT level investigating the efficacy of sys-
temic antimicrobials in the treatment of either superficial
or deep canine pyoderma upon which to base reliable
treatment recommendations. Confirmation of blinding
in RCTs where this design aspect was unclear could
have increased the volume of evidence contributing to
treatment recommendation statements; design of future
studies should include both effective randomization and
adequate blinding of outcome assessment. In studies
enrolling both deep and superficial pyoderma cases,
reporting baseline characteristics and outcome measures
by intervention group and separately for dogs with super-
ficial and deep pyoderma would also expand the evidence
available for treatment of these distinct clinical condi-
tions.
The existing evidence is also limited with respect to
the range of treatment interventions (antimicrobial
agents and dosing regimes) represented and the heter-
ogeneity of existing studies. A lack of standardized
guidelines for diagnosis of canine pyoderma, the wide
range of outcome measures described and the inability
to apply a common lesion scoring system to assess
changes to case severity over time made pooling of
data impossible and direct comparison of available stud-
ies challenging. The statistical power of existing studies
could be greatly improved by basing numbers of
enrolled study subjects on sample size calculations
using data from appropriate pilot studies or similar exist-
ing trials.
ª 2012 The Authors. Veterinary Dermatology
326 ª 2012 ESVD and ACVD, Veterinary Dermatology, 23, 305–e61.
Summers et al.
Acknowledgements
The authors would like to thank Ross Bond, David Lloyd,
Hilary Jackson (The Dermatology Referral Service, Glas-
gow) and Keith Thoday (Royal (Dick) School of Veterinary
Studies, Easter Bush Veterinary Centre) for assistance
with location of conference proceedings.
Supporting Information
Additional Supporting Information may be found in the
online version of this article:
Data S1. All 1103 unique research items identified by the
electronic database section of the systematic review
search strategy (listed by ascending year of publication,
then alphabetically by first author).
Table S1. Numerical scoring system used to allocate a
score-based grade for the overall risk of bias in each of
the 17 reviewed studies.
Please note: Wiley-Blackwell are not responsible for the
content or functionality of any supporting materials sup-
plied by the authors. Any queries (other than missing
material) should be directed to the corresponding author
for the article.
References
1. Noli C. Staphylococcal pyoderma. In: Foster A, Foil C, eds. BSA-
VA Manual of Small Animal Dermatology. Gloucester: BSAVA
Publications, 2003: 159–168.
2. Bannoehr J, Ben Zakour NL, Waller AS et al. Population genetic
structure of the Staphylococcus intermedius group: insights into
agr diversification and the emergence of methicillin-resistant
strains. J Bacteriol 2007; 189: 8685–8692.
3. Fitzgerald JR. The Staphylococcus intermedius group of bacterial
pathogens: species re-classification, pathogenesis and the emer-
gence of meticillin resistance. Vet Dermatol 2009; 20: 490–495.
4. Hauschild T, Wojcik A. Species distribution and properties of
staphylococci from canine dermatitis. Res Vet Sci 2007; 82: 1–6.
5. Krogh HV, Kristensen S. A study of skin diseases in dogs and
cats. VI. Microflora of the major canine pyodermas. Nord Vet
Med 1981; 33: 17–22.
6. Hillier A, Alcorn JR, Cole LK et al. Pyoderma caused by Pseudo-
monas aeruginosa infection in dogs: 20 cases. Vet Dermatol
2006; 17: 432–439.
7. Fazakerley J, Williams N, Carter S et al. Heterogeneity of Staphy-
lococcus pseudintermedius isolates from atopic and healthy
dogs. Vet Dermatol 2010; 21: 578–585.
8. Muller G. Bacterial skin diseases. In: Scott DMW, Griffin C, eds.
Muller and Kirk’s Small Animal Dermatology. 6th edn. Philadel-
phia, PA: W.B. Saunders Co., 2000; 274–335.
9. Ihrke PJ. An overview of bacterial skin disease in the dog. Br Vet
J 1987; 143: 112–118.
10. Loeffler A, Cobb MA, Bond R. Comparison of a chlorhexidine
and a benzoyl peroxide shampoo as sole treatment in canine
superficial pyoderma. Vet Rec 2011; 169: 249.
11. Ihrke PJ, Harvey RG. Antibacterial Therapy in Canine Pyoderma.
Oxford: Butterworth-Heinemann Ltd, 1998; 394–397.
12. Anderson RK, Stewart LJ. Therapy options for canine pyoderma.
Adv Vet Dermatol 2002; 4: 337–340.
13. Loeffler A, Cobb M, Bond R. Topical antimicrobial therapy as the
sole treatment of canine superficial pyoderma. BSAVA 53rd
Annual Congress 2010, Scientific Proceedings, Veterinary Pro-
gramme, 8–11 April 2010; 462–463.
14. May ER. Bacterial skin diseases: current thoughts on pathogene-
sis and management. Vet Clin North Am Small Anim Pract 2006;
36: 185–202.
15. Horvath C, Neuber A. Management of canine pyoderma. Com-
panion Animal 2007; 12: 55–64.
16. Carlotti DN, Jasmin P, Gardey L et al. Evaluation of cephalexin
intermittent therapy (weekend therapy) in the control of recur-
rent idiopathic pyoderma in dogs: a randomized, double-blinded,
placebo-controlled study. Vet Dermatol 2004; 15 (Supplement):
8–9 (Abstract).
17. Rantala M, Holso K, Lillas A et al. Survey of condition-based pre-
scribing of antimicrobial drugs for dogs at a veterinary teaching
hospital. Vet Rec 2004; 155: 259–262.
18. Olivry T, Mueller RS. Evidence-based veterinary dermatology: a
systematic review of the pharmacotherapy of canine atopic der-
matitis. Vet Dermatol 2003; 14: 121–146.
19. Higgins JPT, Altman DG, Sterne JAC et al. In: Higgins JPT,
Green S, eds. Cochrane Handbook for Systematic Reviews of
Interventions Version 5.1.0. Part 2: General methods for Cochra-
ne reviews, Chapter 8: Assessing risk of bias in included studies,
Table 8.5.d: Criteria for judging risk of bias in the ‘Risk of bias’
assessment tool. The Cochrane Collaboration, 2011. Available at
www.cochrane-handbook.org
20. Mueller RS, Stephan B. Pradofloxacin in the treatment of canine
deep pyoderma: a multicentred, blinded, randomized parallel
trial. Vet Dermatol 2007; 18: 144–151.
21. Stegemann MR, Coati N, Passmore CA et al. Clinical efficacy
and safety of cefovecin in the treatment of canine pyoderma and
wound infections. J Small Anim Pract 2007; 48: 378–386.
22. Six R, Cherni J, Chesebrough R et al. Efficacy and safety of cefo-
vecin in treating bacterial folliculitis, abscesses, or infected
wounds in dogs. J Am Vet Med Assoc 2008; 233: 433–439.
23. Laago M. Treatment of pyoderma with cefadroxil in different
intervals in the dog. Svensk Veterinartidning 2008; 60: 11–15.
24. Littlewood JD, Lakhani KH, Paterson S et al. Clindamycin hydro-
chloride and clavulanate-amoxycillin in the treatment of canine
superficial pyoderma. Vet Rec 1999; 144: 662–665.
25. Messinger LM, Beale KM. A blinded comparison of the efficacy
of daily and twice daily trimethoprim-sulfadiazine and daily sulfa-
dimethoxine-ormethoprim therapy in the treatment of canine
pyoderma. Vet Dermatol 1993; 4: 13–18.
26. Cherni JA, Boucher JF, Skogerboe TL et al. Comparison of the
efficacy of cefpodoxime proxetil and cephalexin in treating bacte-
rial pyoderma in dogs. Int J Appl Res Vet Med 2006; 4: 85–93.
27. Lloyd DH, Carlotti DN, Koch HJ et al. Treatment of canine pyo-
derma with co-amoxyclav: a comparison of two dose rates. Vet
Rec 1997; 141: 439–441.
28. Toma S, Colombo S, Cornegliani L et al. Efficacy and tolerability
of once-daily cephalexin in canine superficial pyoderma: an open
controlled study. J Small Anim Pract 2008; 49: 384–391.
29. Harvey RG, Noble WC, Ferguson EA. A comparison of lincomy-
cin hydrochloride and clindamycin hydrochloride in the treatment
of superficial pyoderma in dogs. Vet Rec 1993; 132: 351–353.
30. Horspool LJI, van Laar P, van den Bos R et al. Treatment of
canine pyoderma with ibafloxacin and marbofloxacin – fluoroqui-
nolones with different pharmacokinetic profiles. J Vet Pharmacol
Ther 2004; 27: 147–153.
31. Carlotti DN, Jasmin P, Guaguere E et al. Use of marbofloxacin in
the treatment of canine pyoderma. Pratique Medicale & Chirurgi-
cale de l’Animal de Compagnie 1995; 30: 281–293.
32. Guaguere E, Salomon C, Maynard L. Using cephalexin in the
treatment of canine pyoderma. Comparing the efficacy of differ-
ent dosages. Pratique Medicale & Chirurgicale de l’Animal de
Compagnie 1998; 33: 237–246.
33. Frank LA, Kunkle GA. Comparison of the efficacy of cefadroxil
and generic and proprietary cephalexin in the treatment of pyo-
derma in dogs. J Am Vet Med Assoc 1993; 203: 530–533.
34. Seena VB, Kumari KN, Singari NA et al. Clinico-diagnostic and
therapeutic studies of canine pyoderma. Indian J Vet Med 2005;
25: 121–122.
35. Perego R, Proverbio D, Spada E et al. Comparison of the efficacy
of two antibiotics for systemic use in the treatment of superficial
pyoderma in the dog. Obiettivi e Documenti Veterinari 2006; 27:
31–38.
ª 2012 The Authors. Veterinary Dermatology
ª 2012 ESVD and ACVD, Veterinary Dermatology, 23, 305–e61. 327
Systemic antimicrobials in canine pyoderma
36. Chapman S, Thompson C, Wilcox A et al. What is your diagno-
sis? Rectal scraping from a dog with diarrhea. Vet Clin Pathol
2009; 38: 59–62.
37. Devriese LA, Hermans K, Baele M et al. Staphylococcus pseud-
intermedius versus Staphylococcus intermedius. Vet Microbiol
2009; 133: 206–207.
38. Dohoo I, Martin M, Stryhn H. Validity in observational studies. In:
Veterinary Epidemiological Research. 2nd ed. Charlottetown:
VER Inc., 2010; 243–248.
39. Dohoo I, Martin M, Stryhn H. Controlled studies – analysis. In:
Veterinary Epidemiological Research. 2nd edn. Charlottetown:
VER Inc., 2010; 227–229.
40. Soares Magalhaes RJ, Loeffler A, Lindsay J et al. Risk factors
for methicillin-resistant Staphylococcus aureus (MRSA) infec-
tion in dogs and cats: a case–control study. Vet Res 2010;
41: 55.
41. Moher D, Hopewell S, Schulz KF et al. CONSORT 2010
Explanation and Elaboration: Updated guidelines for reporting
parallel group randomised trials. J Clin Epidemiol 2010; 63: e1–
e37.
42. Kane RL, Wang J, Garrard J. Reporting in randomized clinical
trials improved after adoption of the CONSORT statement.
J Clin Epidemiol 2007; 60: 241–249.
43. Bywater RJ, Hewett GR, Marshall AB et al. Efficacy of clavula-
nate-potentiated amoxycillin in experimental and clinical skin
infections. Vet Rec 1985; 116: 177–179.
44. Carlotti D, Ovaert P. Use of an amoxicillin-clavulanic acid
combination in the treatment of pyodermas in dogs. Pratique
Medicale & Chirurgicale de l’Animal de Compagnie 1988; 23:
519–522.
45. Angarano DW, MacDonald JM. Efficacy of cefadroxil in the treat-
ment of bacterial dermatitis in dogs. J Am Vet Med Assoc 1989;
194: 57–59.
46. DeBoer DJ. Strategies for management of recurrent pyoderma
in dogs. Vet Clin North Am Small Anim Pract 1990; 20: 1509–
1524.
47. Gravino AE, Cerundolo R, Agresti A. Use of cephalexin in the oral
therapy of deep pyoderma in dogs. Obiettivi e Documenti Veteri-
nari 1990; 11: 13–15.
48. Paradis M, Lemay S, Scott DW et al. Efficacy of enrofloxacin in
the treatment of canine bacterial pyoderma. Vet Dermatol 1990;
1: 123–124, 126–127.
49. Wustenberg T, Rodenbeck H. Canine pyoderma: symptomatol-
ogy and therapy with special regard to a new cephalosporin
preparation (Cephalexin-monohydrate). Kleintierpraxis 1990; 35:
483–492.
50. Hove Wv, Lettow E, Opitz M. Experience with the anti-infective
agent enrofloxacin for pyoderma in dogs and cats. Kleintier-
praxis 1992; 37: 817–818, 820-822.
51. Koch HJ, Peters S. Enrofloxacin therapy for bacterial skin dis-
eases (pyoderma) of dogs. Praktische Tierarzt 1992; 73: 1126–
1138.
52. Trailovic D, Nikolic V, Markovic B et al. Ceftriaxone and its use in
veterinary medicine. Veterinarski Glasnik 1992; 46: 7–12.
53. Prost C, Arfi L. Treatment of pyoderma in dogs using lincomycin.
Pratique Medicale & Chirurgicale de l’Animal de Compagnie
1993; 28: 495–498.
54. Scott DW, Miller WH, Wellington JR. The combination of orme-
toprim and sulfadimethoxine in the treatment of pyoderma due
to Staphylococcus intermedius infection in dogs. Canine Prac
1993; 18: 29–33.
55. Scott DW, Miller WH Jr, Cayatte SM et al. Efficacy of tylosin
tablets for the treatment of pyoderma due to Staphylococcus
intermedius infection in dogs. Can Vet J 1994; 35: 617–
621.
56. Bell A. Prophylaxis of German Shepherd recurrent furunculosis
(German Shepherd dog pyoderma) using cephalexin pulse ther-
apy. Aust Vet Pract 1995; 25: 30–36.
57. Guaguere E, Maynard L, Salomon C. Cephalexin in the treatment
of canine pyoderma: comparison of two dose rates. In: Kwochka
KW, Willemse T, von Tscharner C, eds. Advances in Veterinary
Dermatology. volume 3. Edinburgh, Scotland: Butterworth-Hei-
nemann Ltd, 1996; 547–548.
58. Harvey RG. Tylosin in the treatment of canine superficial pyo-
derma. Vet Rec 1996; 139: 185–187.
59. Koch HJ, Peters S. Antimicrobial therapy in German Shepherd
dog pyoderma (GSP). An open clinical study. Vet Dermatol
1996; 7: 177–181.
60. Scott DW, Miller WH Jr, Rothstein SE et al. Further studies on
the efficacy of tylosin tablets for the treatment of pyoderma due
to Staphylococcus intermedius infection in dogs. Can Vet J
1996; 37: 617–618.
61. Rosser EJ Jr. German shepherd dog pyoderma: a prospective
study of 12 dogs. J Am Anim Hosp Assoc 1997; 33: 355–363.
62. Bettenay SV, Mueller RS, Dell’Osa D. Doxycycline hydrochloride
in the treatment of canine pyoderma. Aust Vet Pract 1998; 28:
14–19.
63. Bourdeau P, Kwochka KW, Willemse T et al. (1998). Treatment
of canine pyodermas with an oral long-acting association: baqui-
loprim + sulphadimethoxine (Zaquilan�). In: Kwochka KW,
Willemse T, von Tscharner C, eds. Advances in Veterinary Der-
matology. volume 3. Edinburgh, Scotland: Butterworth-Heine-
mann Ltd., 1998; 541–542.
64. Hummel PH, Kohne K, Weiskopf S. Use of clindamycin for the
treatment of chronic wound infections, interdigital pyoderma
and anal sac infections in dogs and cats. Praktische Tierarzt
1998; 79: 718–726.
65. Carlotti DN, Guaguere E, Pin D et al. Therapy of difficult cases of
canine pyoderma with marbofloxacin: a report of 39 dogs.
J Small Anim Pract 1999; 40: 265–270.
66. Bloom PB, Rosser EJ. Efficacy of once-daily clindamycin hydro-
chloride in the treatment of superficial bacterial pyoderma in
dogs. J Am Anim Hosp Assoc 2001; 37: 537–542.
67. Paradis M, Abbey L, Baker B et al. Evaluation of the clinical effi-
cacy of marbofloxacin (Zeniquin) tablets for the treatment of
canine pyoderma: an open clinical trial. Vet Dermatol 2001; 12:
163–169.
68. Jaham CD. Effects of an ethyl lactate shampoo in conjunction
with a systemic antibiotic in the treatment of canine superficial
bacterial pyoderma in an open-label, nonplacebo-controlled
study. Vet Ther 2003; 4: 94–100.
69. Bassett RJ, Burton GG, Robson DC. Antibiotic responsive ulcera-
tive dermatoses in German Shepherd Dogs with mucocuta-
neous pyoderma. Aust Vet J 2004; 82: 485–489.
70. Blanco AL, Wolberg A. Double-blinded comparative study of the
efficacy of azithromycin and cephalexin in canine pyoderma. Vet
Dermatol 2004; 15 (Supplement): 42 (Abstract).
71. Chakrabarti A, Baksi S, Mukherjee A. Canine pyoderma and its
clinical management by green antibiotic – an alternative
approach. J Interacademicia 2004; 8: 433–435.
72. Bensignor E, Guaguere E. Treatment of canine acne with doxy-
cycline: an open trial. Pratique Medicale & Chirurgicale de l’Ani-
mal de Compagnie 2005; 40: 77–80.
73. Senturk S, Ozel E, Sen A. Clinical efficacy of rifampicin for the
treatment of canine pyoderma. Acta Vet Brno 2005; 74: 117–
122.
74. Hillier A, Alcorn JR, Cole LK et al. Pyoderma caused by Pseudo-
monas aeruginosa infection in dogs: 20 cases. Vet Dermatol
2006; 17: 432–439.
75. Hillier A, Pinchbeck LR, Cole LK. Efficacy of cefpodoxime proxe-
til in the treatment of canine superficial pyoderma. Vet Dermatol
2006; 17: 209 (Abstract).
76. Horspool LJI, van Laar P, van den Bos R et al. Clinical efficacy of
two ibafloxacin formulations in the treatment of canine pyo-
derma. Vet Rec 2006; 158: 236–237.
77. Pin D, Carlotti DN, Jasmin P et al. Prospective study of bacterial
overgrowth syndrome in eight dogs. Vet Rec 2006; 158: 437–
441.
78. Scott DW, Peters J, Miller WH Jr. Efficacy of orbifloxacin tablets
for the treatment of superficial and deep pyoderma due to Sta-
phylococcus intermedius infection in dogs. Can Vet J 2006; 47:
999–1002.
ª 2012 The Authors. Veterinary Dermatology
328 ª 2012 ESVD and ACVD, Veterinary Dermatology, 23, 305–e61.
Summers et al.
79. Udayasree VJ, Pillai UN, Baby PG. Canine pyoderma and its man-
agement with Cynodon dactylon. Indian Vet J 2006; 83: 1274–
1276.
80. Grommelt P. Therapy of pyoderma in dogs with cefovecin. Klein-
tierpraxis 2007; 52: 487–494.
81. Sprucek F, Svoboda M, Toman M et al. Therapy of canine deep
pyoderma with cephalexin and immunomodulators. Acta Vet
Brno 2007; 76: 469–474.
82. Centeno Eizaguirre MI. Use of cefovecin in dermatology therapy.
Argos - Informativo Veterinario 2009; 106: 68–69.
83. Bhat UR, Bhagwat VG. Study to assess the beneficial effects of
immunol liquid in the management of canine pyoderma. Vet
World 2010; 3: 78–81.
84. Restrepo C, Ihrke PJ, White SD et al. Evaluation of the clinical
efficacy of pradofloxacin tablets for the treatment of canine pyo-
derma. J Am Anim Hosp Assoc 2010; 46: 301–311.
ResumeObjectif – Identifier et evaluer les preuves existantes de l’efficacite des traitements antimicrobiens sys-
temiques sur les pyodermites canines spontanees superficielles et profondes.
Methode – Les recherches sur Pub Med, MEDLINE et CAB Direct ont ete realisees (25.05.11) sans
restriction de date ou de langue. Les proceedings des congres annuels de l’ESVD ⁄ ECVD, AAVD ⁄ ACVD,
NAVDF et WCVD ont ete etudies. Les etudes non publiees ont ete cherchees via la liste de discussion Vet-
erinary Dermatology et Veterinary Information Network.
Resultats – Dix-sept essais complets, controles et revus portant sur les resultats cliniques de traitements
antimicrobiens systemiques des pyodermites canines ont ete identifies. Les resultats specifiques des
pyodermites superficielles ou profondes ont ete rapportes respectivement dans neuf et cinq etudes.
Seulement cinq etudes ont rapporte les resultats sans distinguer la profondeur des pyodermites. L’hetero-
geneite des structures des etudes et des evaluations des resultats n’ont pas permis de meta-analyse. Un
bon niveau de preuve a ete identifie pour soutenir la haute efficacite d’injections sous-cutanees de cefove-
cine dans les pyodermites superficielles et pour l’amoxicilline ⁄ acide clavulanique dans les pyodermites
profondes. Un niveau de preuve moyen a ete identifie pour une efficacite moderee a elevee de l’amoxicil-
line ⁄ acide clavulanique oral, la clindamycine, le cefadroxile, le trimethoprim-sulfamethoxazole et l’ormeto-
prime sulfadimethoxine dans les pyodermites superficielles et la prodofloxacine orale, le cefadroxile oral et
la cefovecine sous-cutanee dans les pyodermites profondes. Onze essais ont mentionne l’observation
d’effets secondaires de cas de pyodermites traites par groupe d’intervention; quatre chiens ont ete retires
en raison de la gravite des effets indesirables.
Conclusions – Un plus grand nombre d’etudes en aveugle, de taille adaptee portant sur les traitements
systemiques antimicrobiens des pyodermites canines sont necessaires. Une meilleure differenciation
entre les pyodermites superficielles et profondes dans les rapports des resultats, une standardisation des
mesures des resultats et l’association des resultats et des especes bacteriennes en cause et de leur
patron de resistance sont necessaires.
ResumenProposito – Identificar y evaluar la evidencia existente demostrando la eficacia de los tratamientos
antimicrobianos sistemicos frente a la pioderma canina superficial y profunda espontaneas.
Metodo – Se realizaron busquedas electronicas en PubMed, MEDLINE y CAB Direct (25.05.11) sin restric-
ciones de fecha o de lenguaje. Tambien se busco en los resumenes de presentaciones a congresos anu-
ales de ESVD ⁄ ECVD, de AAVD ⁄ ACVD, de NAVDF y de WCVD. Estudios ineditos fueron buscados a traves
de la lista de discusiones de Veterinary Dermatology y de la Red de Informacion Veterinaria (VIN).
Resultados – Se identificaron diecisiete estudios completos, revisados cientıficamente y controlados
que publicaban resultados clınicos del tratamiento antimicrobiano sistemico frente a la pioderma canina.
Resultados especıficos frente a pioderma superficial o profunda fueron publicados en nueve y cinco estu-
dios, respectivamente. Cinco estudios presentaron resultados solamente frente a pioderma sin especifi-
car si era superficial o profunda. La heterogeneidad de los disenos de los estudios y de las medidas de
los resultados hizo el meta-analisis inadecuado. Hay buena evidencia con respecto a la eficacia de cefo-
vecina por vıa subcutanea en el tratamiento de pioderma superficial y de la combinacion amoxicili-
na ⁄ acido clavulanico por vıa oral en el tratamiento de pioderma profunda. Hubo menos evidencia en
cuanto a una eficacia media a alta de la mezcla amoxicilina ⁄ clavulanico, clindamicina, cefadroxil, trimetho-
prim-sulfametoxazol y sulfadimetoxine-ormetoprima en el tratamiento de la pioderma superficial por vıa
oral y de pradofloxacina oral, cefadroxil oral y de cefovecina por vıa subcutanea en el tratamiento de pio-
derma profunda. Once estudios indicaron efectos adversos en casos tratados frente a pioderma por
grupo de intervencion; cuatro perros fueron retirados del tratamiento debido a la severidad de efectos
nocivos.
Conclusiones – Hay necesidad de realizar mayor numero de estudios ciegos RCTs con un numero alto de
individuos evaluando los resultados de tratamientos antimicrobianas frente a la pioderma canina. Asimismo
se necesita una mayor uniformidad en la diferenciacion de pioderma superficial y profunda cuando se publi-
quen resultados, en los metodos de evaluacion de parametros y en la asociacion de los resultados de
tratamientos con el agente causante y los patrones de resistencia frente a antimicrobianos.
ª 2012 The Authors. Veterinary Dermatology
ª 2012 ESVD and ACVD, Veterinary Dermatology, 23, 305–e61. 329
Systemic antimicrobials in canine pyoderma
ZusammenfassungZiel – Erkennung und Evaluierung der existierenden Evidenz fur die Wirksamkeit systemischer antimikrobi-
eller Behandlungen bei naturlich auftretender oberflachlicher und tiefer Pyodermie.
Methode – Die elektronischen Datenbanken von PubMed, MEDLINE und CAB Direct wurden ohne
Datums- oder Spracheinschrankung durchsucht (25.05.11). Proceedings der jahrlichen Kongresse von
ESVD ⁄ ECVD, AAVD ⁄ ACVD, NAVDF and WCVD wurden durchgesehen. Unpublizierte Studien wurden mit-
tels einer Veterinardermatologischen Diskussionsliste und einem Veterinarmedizinischen Informations-
Netzwerk gesucht.
Ergebnisse – Es wurden siebzehn kontrollierte Studien gefunden, die in ihrer Gesamtlange existierten,
Peer-reviewed waren und die klinischen Ergebnisse einer systemischen antimikrobiellen Behandlung von
caniner Pyodermie beschrieben. Neun beziehungsweise (bzw.) funf Studien beschrieben die Ergebnisse
speziell im Bezug auf eine oberflachliche bzw. tiefe Pyodermie. Funf Studien beschrieben die Ergebnisse
ausschließlich fur eine Pyodermie mit nicht-differenzierter Tiefe. Aufgrund der Heterogenitat der Studien-
designs und der unterschiedlichen Bewertungen der Ergebnisse war eine Metaanalyse unangebracht. Es
wurde ein gutes Ausmaß an Evidenz gefunden, welche die hohe Wirksamkeit von subkutan injiziertem
Cefovecin bei oberflachlicher Pyodermie und die Verabreichung von Amoxicillin ⁄ Clavulansaure per os
bei tiefer Pyodermie unterstutzte. Ausreichende Evidenz wurde gefunden fur die moderate bis hohe
Wirksamkeit von Amoxicillin ⁄ Clavulansaure, Clindamycin, Cefadroxil, Trimethoprim-Sulphamethoxazol und
Sulfadimethoxin-Ormetoprim per os bei oberflachlicher Pyodermie sowie Pradofloxacin, Cefadroxil per os
und subkutan injiziertem Cefovacin bei tiefer Pyodermie. Elf Studien beschrieben die Beobachtung von
Nebenwirkungen bei behandelten Fallen von Pyodermie; vier Hunde wurden aufgrund der Schwere der
Nebenwirkungen aus der Studie genommen.
Schlussfolgerung – Es besteht der Bedarf an zahlreichen weiteren Studien, die ausreichend groß ange-
legt, randomisiert, kontrolliert und geblindet sind und den systemischen Einfluss antimikrobieller Interven-
tionen bei der caninen Pyodermie evaluieren. Eine verbesserte Differenzierung zwischen oberflachlicher
und tiefer Pyodermie bei der Publikation der Ergebnisse, eine Standardisierung der Messgroßen der
Ergebnisse und ein Zusammenhang zwischen den Ergebnissen der verursachenden Bakterien und ihres
Resistenzverhaltens sind angebracht.
Summers et al.
ª 2012 The Authors. Veterinary Dermatology
e61 ª 2012 ESVD and ACVD, Veterinary Dermatology, 23, 305–e61.
