Abstract
Otodectes cynotis infestation is common in kittens housed in crowded environments like animal shelters. It is unknown how rapidly O cynotis is killed within the first 72 h of treatment with currently available products. Kittens ⩾4 weeks of age with live O cynotis in both ears (AU) were administered 0.5 ml of 0.01% ivermectin otic suspension (Acarexx; Idexx Pharmaceuticals) once, AU or selamectin (Revolution; Pfizer Animal Health) once, on the skin following the manufacturer's instructions. Repeat microscopic examination was performed on individual ears based on a randomization schedule during the 72 h after treatment. There was no evidence of toxicity with either drug and administration of 0.01% ivermectin significantly reduced the time to live mite-free status compared to selamectin. Both drugs have an effect against O cynotis as early as 10–12 h after administration with an increasing effect over time.
Otodectes cynotis infestations are a common problem in cats around the world with increased prevalence in kittens and dense populations. 1–3 Ear mites are rapidly contagious and live in the ear canal as well as other areas of the body and the environment. O cynotis can survive off the host from approximately 12 days. 4 A number of drugs with acaricidal activity as well as other substances have been shown to kill O cynotis. 5–11 However, rapid killing of the mites may be very important to crowded animal environments like animal shelters where infestations can spread rapidly. The objective of this study was to compare the speed to kill of two compounds with known efficacy against O cynotis.
All cats were examined by staff veterinarians (LN, RM, LR) who were employed as shelter interns at a busy urban shelter in central Colorado. Cats eligible for this clinical trial had to have clinical signs suggestive of an ear mite infestation (pruritic ears, dark characteristic otic debris, otic erythema, or self traumatization), be at least 4 weeks of age, be otherwise healthy, and have live O cynotis in both ears (AU) based on microscopic examination; full cytologically examinations were not performed. All concurrent medications were documented and cats previously administered any product with insecticide activity or topical otic drugs were excluded. Post-inclusion removal criteria included any cat that was adopted and was lost to follow-up.
Treatments were administered by one of two veterinary technicians to maintain consistency. During the study, the cats were housed individually to avoid cross-infestation from other cats. All cats were administered 0.5 ml of 0.01% ivermectin otic suspension (Acarexx; Boehringer-Ingelheim Vetmedica) once, AU or one container of selamectin (15 mg total dose for cats ≤5 lb; 45 mg total dose for cats >5 lb; Feline Revolution; Pfizer Animal Health) once, on the skin following the manufacturer's instructions on time 0. The recheck microscopic examinations (negative=live mite free; positive=live mites present) were based on a pre-determined computer generated randomization schedule and performed for each ear by one of the three attending veterinarians who were masked to the treatment groups (Table 1). The 12-h data collections were made between 10 and 12 h after treatment and the 36-h data collections were made between 34 and 36 h after treatment. Other collections were made on the appointed time. Live mites were defined as those actively moving during microscopic examination. The kittens were adopted as directed by the shelter and so all data points were not collected for all ears.
Distribution of 82 kittens by treatment group and recheck schedule showing the number of samples that were available for the first recheck examination.
Selamectin=Revolution; 0.01% Ivermectin=Acarexx.
For statistical analysis, the ears were assumed independent. Individual cat data was inspected by time, and the status of each ear was captured as an estimator of mite-free time. Five outcomes were possible for every cat: (1) Both ears were free of mites at their respective sampling times, in this instance both times were recorded as time-to-mite-free-status; (2) one ear was positive and the other ear was negative, in this instance the time that the negative finding occurred was recorded as the time-to-mite-free-status for that ear and the ear still harboring mites was assigned a time of 100; (3) both ears were positive, in this instance both ears were assigned a time of 100; (4) data was recorded for one ear with the other ear containing missing data, in this instance the outcome for the ear having data was used in the analysis, the ear having no observation was recorded as missing and had no effect on the outcome of the analysis; (5) both ears had missing data; in this instance the outcome for both ears were recorded as missing and had no effect on the outcome of the analysis.
A survival analysis was employed to test the hypothesis of no differences in speed of kill between the two treatments using live-mite-free status as a surrogate for mortality in a standard survival analysis. A time of 100 was assigned to time points that were positive for ear mites and later this value was designated as ‘censored’ in the analysis. In this analysis, hour 100 was treated as the end of the study and animals that were still positive at the last observation point (hour 72) were assigned a censored value of 100. Evaluations of heterogeneity of survival data were performed using life table analysis (SAS Proc Lifetest and SAS Proc TPHREG). The data were also evaluated using rank tests for homogeneity (log rank and Wilcoxon). Significance was defined as P<0.05.
A total of 82 kittens with live O cynotis detected microscopically (41 kittens in the selamectin group and 41 kittens in the 0.01% ivermectin group) were initially entered into the study. Of these, 68 kittens were still available at the first recheck time point (36 kittens in the selamectin group and 32 kittens in the 0.01% ivermectin). For both drugs, the percentages of ears with live mites, by ear, detected on recheck examination decreased over time (Fig 1). The product-limit survival estimates for the two treatment groups are shown in Fig 2. The rank tests for homogeneity indicate a significant difference between the treatment groups (P=0.0338 for the log-rank test; P=0.0371 for the Wilcoxon test) with cats treated with 0.01% ivermectin achieving live mite-free status faster than those treated with selamectin.
Percentage of ears with live O cynotis mites after administration of one dose of topical ivermectin or systemic selamectin. Selamectin=Revolution; 0.01% Ivermectin=Acarexx.
The product-limit survival estimates for the two treatment groups were calculated and compared. The rank tests for homogeneity indicate a significant difference between the treatment groups (P=0.0338 for the log-rank test; P=0.0371 for the Wilcoxon test) with cats treated with 0.01% ivermectin achieving live mite-free status faster than those treated with selamectin. Selamectin=Revolution; 0.01% Ivermectin=Acarexx.
In this study, adverse effects were not noted for either drug and both drugs appeared to kill O cynotis as soon as 10–12 h after a single administration. Treatment of O cynotis with 0.01% ivermectin significantly reduced the time to live mite-free status compared to selamectin in this study group. This result may relate to the fact that this product is applied directly to the ear canal allowing for the drug to reach the organisms more quickly than selamectin that must be absorbed systemically prior to reaching the ear canal.
The results of this study differed from a previous study performed in France where a single application of 6% selamectin given to 29 O cynotis-infested cats resulted in dead mites in 100% of the cats on day 3. 7 It is possible that the European formulation of the product differs in some way compared to the United States formulation. It is also possible that there is a difference in susceptibility between O cynotis between the countries. Lastly, the cats in the study described here may have a higher degree of inflammation and debris or a higher incidence of co-infections with bacteria or yeast that may have affected the results. Limitations of this study include the failure to perform cultures or complete cytological evaluations and to design and apply a standardized clinical score sheet to factor into treatment failures.
Use of the product with the most rapid O cynotis speed to kill has the potential benefit of lessening spread to other cats by limiting environmental contamination. Based on the results of this study, use of 0.01% ivermectin topically as a primary therapy appears to be indicated for use in crowded cat environments. However, our study design precludes the assessment of the long-term effects on repeat infestation rates after administration of this drug. In addition, other drugs like selamectin or drug combinations like imidacloprid and moxidectin that are used for cats with O cynotis infestation, also have other potential benefits including effects against O cynotis that may be residing on the cat outside the ear canal and effects against Ctenocephalides felis, Dirofilaria immitis, Ancylostoma tubaeforme, and Toxocara cati.
Conflict of interest
Dr Kordick was previously with Idexx Pharmaceuticals which provided the funding for this project.
Footnotes
Acknowledgements
This study was funded by a grant from