Download Treatment of canine generalized demodicosis with a `spot

DOI: 10.1111/j.1365-3164.2009.00790.x
Treatment of canine generalized demodicosis with a
‘spot-on’ formulation containing 10% moxidectin and
2.5% imidacloprid (Advocate, Bayer Healthcare)
Ralf S. Mueller*, Daniela Meyer*, Emmanuel
Bensignor† and Carola Sauter-Louis‡
*
Medizinische Kleintierklinik, Ludwig Maximilian University, Munich,
Germany
†
Veterinary Referral Service, Paris, France
‡
Clinic for Ruminants, Ludwig Maximilian University, Munich,
Sonnenstr. 16, 85764 Oberschleißheim, Germany
Correspondence: Ralf S. Mueller, Medizinische Kleintierklinik, Ludwig Maximilian University, Munich, Germany. E-mail: ralf.mueller@
med.vetmed.uni-muenchen.de
Source of Funding
Bayer HealthCare.
Conflict of Interest
This study was designed by the authors and supported by Bayer
HealthCare. Participating veterinarians received reimbursement only
for costs of patient care; study dogs were treated at no cost to the
owner. The authors have no financial interest in Bayer HealthCare. In
the past 5 years, R. Mueller has been receiving support and ⁄ or funding for research studies and consulting activities from Bayer Animal
Health, Boehringer Ingelheim, Novartis Animal Health, Pfizer Animal
Health, Procter and Gamble Pet Care, Royal Canin and Virbac and
E. Bensignor has been receiving support and ⁄ or funding for research
studies and consulting activities from Bayer Animal Health, Janssen
Animal Health, LDCA, Sogeval, Pfizer Animal Health, Vetoquinol and
Virbac. D. Meyer served as Study Monitor and was supported by
Bayer during the study.
Abstract
In this multicentre study, the efficacy of a spot-on
formulation containing 10% imidacloprid and 2.5%
moxidectin (Advocate, Bayer HealthCare) was evaluated for the treatment of dogs with generalized demodicosis. The spot-on was applied every 2 weeks.
Secondary bacterial infections were diagnosed by
clinical examination, cytology and bacterial culture
as appropriate and treated with oral antibiotics.
Improvement or deterioration was determined
monthly by clinical scores and by assessing mite
numbers on microscopy of skin scrapings. Seventytwo dogs were included in the study. Fifty-two
dogs had juvenile-onset demodicosis (mean of
11 months, range 2–24 months) and 20 dogs were
adults at onset of disease (mean of 8.6 years, range
3.5–14 years). Twenty-six dogs went into remission,
three with adult-onset demodicosis, 23 with juvenile-onset. The latter group showed significantly
higher remission rates (P = 0.0252). Time until remission varied from 4 to 32 weeks (mean of
12.5 weeks). Dogs with a clinical score of <45 at the
beginning of the study showed a significantly better
response to the treatment (P = 0.0004), with a remission rate of 71%. In contrast, only 24% of those dogs
with a score >45 went into remission. Adverse
effects were not observed. One of the dogs responding to treatment showed recurrence of the disease
during a follow-up period of 12 months. This study
shows a better success rate of Advocate in dogs
with mild clinical signs, versus those with moderate
to severe clinical signs.
Accepted 19 May 2009
Introduction
Canine generalized demodicosis is a disease regularly
seen in small animal practice. The localized form of the
disease occurs most commonly in young dogs, is characterized by focal erythema and alopecia on face and distal
limbs and is self-resolving in most dogs.1 The lesions of
generalized canine demodicosis are variable and range
from generalized erythema and alopecia, comedones, follicular papules to pustules and scales. More severely
affected cases have deep folliculitis and furunculosis with
severe haemorrhagic exudation and thick crusting.1,2
Lymphadenopathy is common. Secondary bacterial infection is invariably present in these dogs. Staphylococci are
the most frequently involved bacteria, but Gram-negative
organisms such as Pseudomonas aeruginosa or Proteus
mirabilis also occur.3 Pain and pedal oedema may be present, particularly in large dogs. Successful treatment of
generalized demodicosis has been reported in a number
of publications and has been the topic of an extensive
review.3
Amitraz rinses are approved for the treatment of generalized canine demodicosis in many countries in various
concentrations. In general, higher concentrations are
associated with better success rates but also more pronounced adverse effects.4,5 Injectable formulations of
ivermectin and moxidectin approved for large animals
have been used daily as an oral treatment of canine generalized demodicosis with good success, but are not
licensed for the use in small animals at doses effective
against Demodex mites.3,6,7 In sensitive dogs, these
treatments will lead to neurological adverse effects such
as tremors, lethargy, ataxia, and coma with a possible fatal
outcome.8,9 Milbemycin oxime is licensed for use in
France and Sweden for the treatment of canine generalized demodicosis but the dosage needed (1–2 mg ⁄ kg ⁄ day
for up to 12 months) in large dogs is expensive. Recently
a spot-on formulation containing 10% imidacloprid and
2.5% moxidectin (Advocate, Bayer) has been approved
ª 2009 The Authors. Journal compilation ª 2009 ESVD and ACVD, Veterinary Dermatology, 20, 441–446.
441
Mueller et al.
for the control of canine demodicosis in all European
Union countries with a dose of 2.5–6 mg ⁄ kg moxidectin
monthly. The aim of this multicentre study was to evaluate the success rate of this spot-on in the treatment of
canine generalized demodicosis.
Materials and methods
Study participants
This study was an uncontrolled field study involving cases referred to
dermatology specialist practices in Belgium, France, Italy, Germany,
Switzerland and Canada.
Inclusion criteria
Owners with dogs of any breed, body weight and either sex demonstrating microscopic and clinical evidence of generalized demodicosis
(according to the judgement of the board certified dermatologists
examining the dogs) were invited to participate. Owners provided
written informed consent. The study compound was a registered
treatment for canine demodicosis at the time of this study. Diagnosis
was confirmed with three positive deep skin scrapings from the sites
worst affected by papules, pustules or crusts showing in total at least
three Demodex canis mites. If no papules, pustules or crusts were
present, the areas with the worst erythema or alopecia were
scraped. Generalized demodicosis was defined as affecting more
than four small areas (<100 cm2) on the body, affecting at least one
area of more than 100 cm2 or at least one paw.
Exclusion criteria
Puppies less than 7 weeks old, dogs weighing less than 1 kg, pregnant or lactating females and dogs with leishmaniosis were excluded
from the study. Glucocorticoids were discontinued immediately at
the beginning of the study, if the dog had received a short course of
prednisolone at anti-inflammatory doses (<0.5 mg ⁄ kg ⁄ day for less
than 4 weeks) in the month prior to the study. If higher doses or
longer courses had been administered, corticosteroids were discontinued 4 weeks prior to inclusion in the study. Immunosuppressive
drugs and additional ectoparasiticidal drugs were not permitted during the study. Antipruritic drugs such as fatty acid therapy and antihistamines were only permitted if they had been administered for at
least 2 weeks prior to the trial, and were continued at the same dose
and frequency for the duration of the trial. Topical glucocorticoids
were not permitted. Drugs with no known ectoparasitic or immunosuppressive activity (such as medications for cardiac diseases, neurologic disorders, i.e. epilepsy, or anti-diabetic medications) were
permitted.
Post-inclusion removal criteria
Dogs deteriorating on treatment were removed from the study.
These dogs were assessed as treatment failures. Similarly, dogs not
improving on treatment administered every 2 weeks for two subsequent visits were excluded from the study and considered treatment
failures. Further reasons for exclusion during the study were serious
deviations from the protocol, loss of follow-up or euthanasia. If these
occurred before the second evaluation and the dogs had thus
received only one treatment, their data were excluded from the statistical evaluation. Dogs were considered treatment failures if euthanasia or loss of follow-up occurred after two or more complete data
sets were obtained.
Study intervention
The dogs were treated with a spot-on preparation containing 10%
imidacloprid and 2.5% moxidectin (Advocate, Bayer HealthCare, Leverkusen, Germany) administered on the dorsal trunk onto the skin in
the shoulder region after parting of the hair. The dose of each individual treatment depended on body weight and is detailed in Table 1. In
dogs heavier then 25 kg it was recommended to apply the spot-on in
several locations along the dorsal midline of the dog.
442
Table 1. Dosing of Advocate (10% imidacloprid and 2.5% moxidectin) administered during the study
Weight of
the dog (kg)
Advocate
(mL)
Imidacloprid
(mg)
Moxidectin
(mg)
1–4
4 – 10
10 – 25
25 – 40
40 – 65
0.4
1.0
2.5
4.0
6.5
40
100
250
400
650
10
25
62.5
100
162.5
Study protocol
Clinicians evaluated the cases every 4 weeks. On each visit, cytology
and at least three deep skin scrapings were performed. A small area
of approximately one square centimetre was scraped until capillary
bleeding was present; where possible the skin was squeezed during
the scraping. The skin scraping sites were noted and were taken
from the same location on revisits. The average mite number of the
three skin scrapings was recorded at each visit. Erythema, comedones ⁄ papules ⁄ pustules, and scales ⁄ crusts were evaluated on 36 different body sites and graded between 0 (normal) and 6 (severe). A
clinical score for that day was achieved by adding the individual
scores.
In animals with adult-onset generalized demodicosis, diagnostic
evaluation for underlying diseases was recommended. A panel consisting of a general blood screen, urinalysis, radiographs of the thorax
and abdominal ultrasonography at the initial visit and a urine cortisol–
creatinine ratio and T4 ⁄ TSH assay at the first or second revisit as
appropriate was recommended as part of the protocol.
The initial stage of the protocol called for monthly treatments. If
there was a clinical or microscopic deterioration at the next visit or no
improvement (either clinical or microscopic) on two consecutive visits, the frequency of administration was increased to every 2 weeks.
If again there was deterioration (or lack of improvement in clinical
scores and ⁄ or the number of mites on skin scrapings at two subsequent visits), the dog was classified as a treatment failure. Because
of insufficient success rates with monthly administration, for ethical
reasons the protocol was adjusted after inclusion of the first 19 dogs
and application of Advocate every 2 weeks was permitted at the
first visit.
When negative skin scrapings and clinical remission on two consecutive monthly visits were obtained, the therapy was regarded as
successful and treatment was discontinued. If, after a follow-up period of 12 months, a dog was still in remission, it was considered
cured.
Appropriate antibacterial therapy was based on cytologic examination. If rod-shaped organisms were identified, a bacterial culture was
obtained and antibiotic therapy was then chosen based on that susceptibility testing. If cocci were observed, therapy with cefalexin at
20–30 mg ⁄ kg twice daily was begun. Failure to respond to this antibiotic therapy resulted in a bacterial culture and a subsequent change
of antibiotic therapy based on susceptibility testing. If an anti-bacterial shampoo was used, shampooing was not permitted during the
first 48 h after application of the spot-on.
Statistics
The proportion of cured cases was determined for juvenile and adultonset demodicosis and compared by using Fisher’s exact test. Dogs
were divided into two groups depending on their clinical score and
the best cut-point was chosen using receiver operating characteristic
(ROC) curve analysis. The proportions of cured cases in the group of
dogs with milder disease and of cured cases in the more severely
affected group were compared by using Fisher’s exact test. The
mean number of mites per skin scraping and the clinical score were
determined for dogs responding to therapy and for treatment failures
and the two groups were compared by use of a Mann–Whitney
U-test. The dose of moxidectin per month in dogs responding to therapy was compared to that of the dogs failing to respond, also using a
Mann–Whitney test. P < 0.05 was considered significant. A logistic
ª 2009 The Authors. Journal compilation ª 2009 ESVD and ACVD, Veterinary Dermatology, 20, 441–446.
Moxidectin spot-on for canine demodicosis
regression analysis was used to evaluate the correlation between
the number of mites and the outcome being a failure.
Results
Study participants
Seventy-two dogs were enrolled in the study. Fifty-two
dogs had juvenile-onset demodicosis with a mean age of
onset of 11 months (range 2–24 months) and 20 dogs
were adults at onset of disease (mean of 8.6 years, range
3.5–14 years). Twelve dogs were pugs, seven were
English bulldogs, five were West Highland white terriers,
three were French bulldogs, doberman pinschers, dogues
de Bourdeaux, Jack Russell terriers and Yorkshire
terriers, respectively, and two were shi tzus, German
shepherd dogs, Chihuahuas and shar peis. Of the remaining 25 dogs, the disease was diagnosed in 10 mixed
breeds and only once in dogs of 15 further breeds. Of the
dogs with adult-onset demodicosis, five were West Highland white terriers, all other breeds occurred only once.
Thirty-nine dogs were females of which 6 were spayed;
there were 33 males and 2 of those were castrated. The
mean clinical score of the included cases was 99 (range
9–518) and the mean number of mites per skin scraping
was 27 (range 1–149).
Exclusions
Sixty-three dogs completed the study. Six dogs were lost
to follow-up and three died or were euthanized. Of these
nine dogs, six only received one treatment and thus were
excluded from the statistical evaluation, including the
three dead dogs. Thus, 66 dogs were evaluated.
Of the three diseased dogs, a young pug was euthanized by the referring veterinarian after 1 month of
treatment due to prominent lymphadenopathy and suspected lymphoma, although a prior lymph node aspirate at the referral centre had revealed reactive lymph
nodes and no further tests were conducted. An adult
pug was euthanized 2 weeks after the second monthly
treatment due to lethargy and lack of improvement. A
Boston terrier died after a few days of lethargy
4 weeks after the first and only treatment; the owner
refused a necropsy.
Treatment outcome
Twenty-six dogs (39.4%) went into remission, three with
adult-onset demodicosis, 23 with juvenile-onset. The
latter showed significantly higher remission rates (Fisher’s exact test, P = 0.0252). Time until remission varied
from 4 to 32 weeks (mean of 12.5 weeks). In a Labrador
retriever with lymphoma, Demodex canis mites could
always be found on microscopy of skin scrapings, but
clinical signs could be controlled with treatment.
The mean score of dogs included in the study was
123. The cut-point for dividing clinically more and less
severe disease was a clinical score of 45. Dogs with a
clinical score of <45 at the beginning of the study
showed a significantly better response to the treatment (Fisher’s exact test, P = 0.0004), with a remission rate of 71% (15 ⁄ 21). In contrast, only 24% of
those dogs (11 ⁄ 45) with a score >45 went into remission. The mean score of dogs responding to therapy
was 74 [95% confidence interval (CI) 44–105], that of
dogs failing to improve was 153 (95% CI 114–192);
this difference was significant (Mann–Whitney test,
P = 0.0004).
The mean numbers of mites found per skin scraping on
the first visit in dogs achieving remission with treatment
was 20 (95% CI 14–26). The mean number of mites in
dogs considered as treatment failures was 30 (95% CI
22–38). This difference was also significant (Mann–Whitney test, P = 0.0082). The number of mites was significantly correlated with the outcome being a failure (logistic
regression analysis, P = 0.0094). The odds ratio for the
factor mites was 1.056.
A number of different logistic regression methods were
performed to check the interaction between age and
score (categorical as well as numerical). There was no
interaction between the two variables.
The average dose of moxidectin in dogs responding to
therapy was 6.1 mg ⁄ kg ⁄ month and almost identical to
the 6.7 mg ⁄ kg ⁄ month of the dogs failing to respond
(Mann–Whitney test, P = 0.325).
Adverse effects were not seen. One of the dogs
responding to treatment showed recurrence of the disease during a follow-up period of 12 months.
In seven of the dogs with adult-onset demodicosis, a
diagnostic evaluation for underlying disease was refused.
Of the remaining 13 dogs, one dog had cardiac and renal
insufficiency, another dog had only cardiac insufficiency,
one was hypothyroid, one had hyperadrenocorticism, one
dog had lymphoma and one had testicular tumour. In
seven dogs, an underlying disease could not be identified.
Of the five West Highland white terriers with adult-onset
demodicosis, one was hypothyroid, in two dogs evaluation failed to detect an underlying disease, in a further
dog more diagnostic tests were refused by the owner
and the last of these dogs was lost to follow-up. All dogs
with an identified underlying disease failed to achieve
remission, and only the hypothyroid dog was treated adequately for the underlying disease and later on responded
to alternative treatment.
Discussion
In this study, the efficacy of a spot-on formulation containing 10% imidacloprid and 2.5% moxidectin (Advocate, Bayer HealthCare) for the treatment of generalized
canine demodicosis had a better success rate in dogs
with less severe disease (as assessed by clinical scores).
However, in dogs with more severe disease, the spot-on
did not achieve the success rates reported in the literature for other therapies.3 In dogs with adult-onset demodicosis, the remission rate was lower than in juvenile
demodectic dogs.
In the literature, it is occasionally stated that some dogs
with generalized onset of juvenile demodicosis recover
spontaneously.1 To the authors’ knowledge, there is no
scientific data available confirming such statements. As
most dogs presented in referral practice have quite extensive disease, it would be unethical to include a control
group treated with placebo. Furthermore, it would be difficult to convince owners to participate in such a study.
Presumably for these two reasons, a placebo control had
ª 2009 The Authors. Journal compilation ª 2009 ESVD and ACVD, Veterinary Dermatology, 20, 441–446.
443
Mueller et al.
not be included in previous studies on this disease.3 It is
possible that similar to previous studies some juvenile
dogs included would have recovered without miticidal
therapy.
Most previous reports regarding the treatment of generalized demodicosis evaluate amitraz rinses4,10,11 and
daily oral administration of macrocyclic lactones such as
ivermectin,6,12–14 milbemycin oxime15–17 and moxidectin.7,18 Amitraz rinses are laborious, require total body
clipping in dogs with medium or longer coat, and have
been associated with a number of adverse effects in the
treated case. It is recommended to perform the rinses in
well-ventilated areas to prevent inhalation of active ingredients by the personal and subsequent adverse effects
such as headaches.3 Injectable formulations of ivermectin
and moxidectin approved for large animals given orally
daily have been reported as successful treatments for
canine generalized demodicosis.7,18 However, such a use
of these drugs is not covered by registration and dogs
sensitive to macrocyclic lactones may develop neurological adverse effects such as lethargy, ataxia, tremors and
potentially fatal coma.8,9 Milbemycin oxime is registered
in some countries as an oral daily treatment for canine demodicosis,19 but is costly and difficult to obtain in many
others. Thus, an effective and safe spot-on treatment for
canine demodicosis is of great benefit to the small animal
practitioner. Monthly administration of a spot-on containing 10% imidacloprid and 2.5% moxidectin (Advocate,
Bayer HealthCare) was recently reported to be as efficacious as milbemycin oxime in the treatment of canine
generalized demodicosis20 and is registered for the control of this disease in Europe. The success rate in that
study was over 80%, which compares favourably with
most studies published previously.3 After registration,
this current study was initiated by Bayer to confirm this
efficacy in a larger, multicentre study involving veterinary
dermatologists in five European countries. However,
administration every 2 weeks is an off-label use for this
product. The percentage of dogs achieving remission in
our study was much smaller. There are a number of possible reasons for this discrepancy. The population of this
current study consisted of dogs referred to veterinary dermatologists, and thus more dogs with severe skin disease may have been included. Unfortunately, a different
body score was used in the two studies, making comparison of disease severity difficult. However, the better success rate of dogs with a lower clinical score compared to
dogs with more severe clinical disease supports this. The
number of mites per skin scraping was not specifically
evaluated in the former study. Higher mite numbers were
seen in our study in the dogs not responding to treatment. Furthermore, with amitraz and milbemycin oxime it
is known that the success rate in dogs with adult-onset
demodicosis is lower than that in juvenile dogs affected
with demodicosis.3,19 In our study, the dogs with adultonset demodicosis did not respond as well as juvenile
dogs, providing further evidence for the difficulty to cure
adult dogs developing generalized demodicosis. Although
the age range of included dogs was given in another
study evaluating topical imidacloprid ⁄ moxidectin and indicates participants with adult-onset demodicosis, it is not
known, how many of the participants were adult dogs.20
444
Although there was a significant difference between
the mean clinical scores of responders and treatment failures, some of the dogs cured by the moxidectin ⁄ imidacloprid spot-on had clinical scores above 200, indicating that
other factors besides disease severity influence treatment outcome. Similarly, a number of dogs responding to
treatment had very high mite numbers despite the difference in mean mite numbers on skin scrapings between
successfully treated dogs and treatment failures.
For the evaluation of treatments for canine generalized
demodicosis, a follow-up period of 12 months is typically
recommended to identify the recurrence rate. In studies
evaluating amitraz therapy for generalized demodicosis
and providing data on follow-up, the overall recurrence
of dogs responding to treatment was 11%.3 With
milbemycin oxime, the recurrence rate was over 20%,
and the recurrence rate seen with ivermectin was
between those of the latter two drugs.3 Only one of the
dogs in our study showed recurrence of demodicosis
within 12 months after cessation of therapy, indicating
that a high rate of recurrence is not likely with this
therapy.
In previous studies evaluating daily moxidectin orally,
the success rate has been comparable to that seen with
ivermectin or amitraz.3 The oral bioavailability of moxidectin in the dog compared with other species has been
reported as very high.21 It has a half life of approximately
2 days in the dog.22,23 Thus, daily administration will
increase serum concentrations for quite some time and
those high serum concentrations may be responsible for
its excellent therapeutic effects observed in canine generalized demodicosis.7,18 However, oral moxidectin is not
approved for the treatment of demodicosis and adverse
effects such as lethargy and ataxia have been reported.7
The therapeutic acaricidal effects of moxidectin in the
spot-on combination with imidacloprid used in this study
resulted in lower treatment success than that reported
for oral administration. This may be due to less frequent
administration and lower systemic absorption and subsequent serum concentration compared to oral administration. Moxidectin serum and skin concentrations have
been shown to increase proportional to frequency of
application of the imidacloprid ⁄ moxidectin spot-on (Bayer
HealthCare, data on file). Possibly, more frequent application of the spot-on results in increased success rates.
Supporting this, the initial protocol of monthly administration, that was only to be changed to administration every
2 weeks in dogs not responding to treatment, had to be
abandoned in favour of treatments every other week
from the start due to ethical concerns following the low
response rate of the first dogs included in the study.
Further study is under progress to determine, if weekly
administration would further increase the success rate
for canine generalized demodicosis.
Although breed predispositions could not be evaluated
statistically due to the involvement of a number of centres, the frequent occurrence of demodicosis in bulldogs,
terriers and doberman pinschers confirms previous
reports in the literature.1 Pugs were the most common
breed in this study and may be predisposed in Europe. All
five West Highland white terriers included in the study
developed demodicosis as adult dogs. All other breeds in
ª 2009 The Authors. Journal compilation ª 2009 ESVD and ACVD, Veterinary Dermatology, 20, 441–446.
Moxidectin spot-on for canine demodicosis
the group of adult dogs were represented only once.
Thus, West Highland white terriers may be predisposed
to adult onset demodicosis.
In summary, a satisfactory outcome was achieved in
the majority of dogs with mild to moderate generalized
demodicosis when treated with a spot-on containing
10% imidacloprid and 2.5% moxidectin (Advocate,
Bayer). Dogs with severe clinical disease did not respond
as well and may require additional therapy or a change of
treatment.
Acknowledgements
The authors would like to thank participating investigators
for their contribution of cases to this study: Luc Beco
(Spa, Belgium); Emmanuel Bensignor (Cesson Sevigne,
France); Patrick Bourdeau (Nantes, France); Eric Guaguere (Lomme, France); Monika Linek (Hamburg, Germany);
Christine Löwenstein (Hofheim, Germany); Ralf Mueller
(Munich, Germany); Daniela Meyer (Munich, Germany,
Study Coordinator); Chiara Noli (Peveragno, Italy); Manon
Paradis (Montréal, Canada); Pascal Prélaud (Maisons
Alfort, France); Petra Roosje (Bern, Switzerland).
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Résumé Dans cette étude multicentrique, l’efficacité d’un spot-on contenant 10% d’imidaclopride et
2.5% de moxidectine (Advocate, Bayer HealthCare) a été évaluée dans le traitement de démodécie
canine généralisée. Le spot-on était appliqué toutes les deux semaines. Les infections bactériennes secondaires ont été diagnostiquées par des examens clinique, cytologique et bactériologique adaptés et traitées
par une antibiothérapie orale. L’évolution était déterminée chaque mois en fonction des scores cliniques et
du nombre d’acariens identifiés à l’examen microscopique de produits de raclages cutanés. Soixantedouze chiens ont été inclus dans l’étude. Cinquante deux chiens étaient atteints de démodécie juvénile
(moyenne de 11 mois, amplitude de 2 à 24 mois). Vingt chiens étaient adultes au commencement de la
maladie (moyenne de 8.6 ans, amplitude de 3.5 à 14 ans). Vingt-six chiens sont entrés en rémission, 3 présentant une démodécie de l’adulte et 23, une démodécie juvénile. Ce dernier groupe a montré des taux de
rémission significativement plus élevés (P=0.0252). La rémission intervenait à partir de 4 à 12 semaines
(moyenne de 12.5 semaines). Les chiens avec un score clinique <45 au début de l’étude ont montré une
réponse au traitement significativement plus élevée (P=0.0004), avec un taux de rémission de 71%. En
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revanche, seuls 24% des chiens ayant un score clinique > 45 se sont améliorés. Aucun effet secondaire
n’a été observé. Un des chiens répondant au traitement a montré une récidive au cours de la période de
suivi de 12 mois. Cette étude montre qu’ Advocate a un taux de succès plus élevé chez les chiens présentant des signes cliniques faibles contrairement à ceux présentant des signes cliniques modérés à sévères.
Resumen En este estudio multicéntrico se evaluó la eficacia de una formulación tópica conteniendo 10%
de imidacloprid y 2,5% de moxidectina (Advocate, Bayer Healthcare) en el tratamiento de perros con
demodicosis generalizada. El producto de aplicación única fue administrado cada dos semanas. Se diagnosticaron las infecciones bacterianas mediante examen clı́nico, citologı́a y cultivo bacteriano, según fue
necesario, y se trataron con antibióticos por vı́a oral. Se determinó mensualmente la mejora o el deterioro
mediante valoración clı́nica y evaluando el numero de ácaros mediante microscopı́a de raspados de piel.
Setenta y dos perros se incluyeron en el estudio. Cincuenta y dos perros tenı́an demodicosis juvenil (media
de 11 meses, rango de 2-24 meses) y veinte perros eran adultos en el momento de aparición de la enfermedad (media 8,6 años, rango 3,5-14 años). Veintiséis perros entraron en remisión, tres con demodicosis
de aparición en adultos, 23 con demodicosis juvenil. Este último grupo mostró grados de remisión significativamente mayores (P=0,0252). El tiempo pasado hasta la remisión varió de 4 a 32 semanas (media 12,5
semanas). Los perros con una valoración clı́nica > 45 al principio del estudio mostraron una respuesta significativamente mayor al tratamiento (P=0,0004), con un ı́ndice de remisión del 71%. Por el contrario, sólo
24% de los perros con una valoración clı́nica inicial >45 entraron en remisión. No se observaron efectos
adversos. Uno de los perros que respondió al tratamiento presentó recidiva de la enfermedad durante el
periodo de seguimiento de 12 meses. Este estudio muestra una mayor eficacia de Advocate en perros
con signos clı́nicos ligeros, en contraste con los animales con signos clı́nicos moderados o severos.
Zusammenfassung In dieser Multi-Center-Studie wurde die Wirksamkeit einer Spot-on Formulierung,
welche 10%iges Imidacloprid und 2,5%iges Moxidectin enthielt (Advocate, Bayer HealthCare) für die
Behandlung der generalisierten Demodikose des Hundes beurteilt. Das Spot-on wurde alle zwei Wochen
aufgetragen. Sekundäre bakterielle Infektionen wurden mittels klinischer Untersuchung, Zytologie und falls
nötig mittels Bakterienkultur diagnostiziert und mit oralen Antibiotika behandelt. Eine Verbesserung oder
Verschlechterung wurde mittels klinischer Werteskala und durch Schätzung der Milbenzahlen in den mikroskopischen Präparaten der Hautgeschabsel monatlich erhoben. Zweiundsiebzig Hunde wurden in die
Studie aufgenommen. Zweiundfünfzig Hunde hatten eine juvenile Demodikose (Durchschnittsalter von 11
Monaten, bei einer Breite von 2-24 Monaten) und 20 Hunde waren erwachsen, als die Krankheit auftrat
(Durchschnittsalter von 8,6 Jahren, bei einer Breite von 3,5-14 Jahren). Sechsundzwanzig Hunde wurden
gesund, 3 davon mit Adulter Demodikose, 23 mit Juveniler Demodikose. Die letztere Gruppe zeigte signifikant höhere Remissionsraten (P=0,0252). Die Zeit bis zur Remission variierte von 4 bis 32 Wochen
(durchschnittlich 12,5 Wochen). Hunde mit einer klinischen Bewertung von <45 am Anfang der Studie zeigten eine signifikant bessere Reaktion auf die Behandlung (P=0,0004) mit einer Remissionsrate von 71%.
Im Gegensatz dazu gingen nur 24% der Hunde mit einer Bewertung von > 45 in Remission. Nebenwirkungen wurden nicht beobachtet. Einer der Hunde, der auf die Behandlung ansprach, zeigte während einer
Folgeperiode von 12 Monaten ein Wiederaufflammen der Krankheit. Diese Studie zeigte eine bessere
Erfolgsrate für Advocate bei Hunden mit milden klinischen Symptomen im Gegensatz zu denen mit moderat bis schwerer klinischer Symptomatik.
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ª 2009 The Authors. Journal compilation ª 2009 ESVD and ACVD, Veterinary Dermatology, 20, 441–446.