Abstract
The efficacy of Oridermyl® (acaricidal/antibiotic/antifungal/anti-inflammatory ointment) and Revolution® (selamectin spot-on) was compared in a blinded randomized study on 24 adult cats with otoacariasis. Twelve cats were treated once daily for 10 d with Oridermyl® and 12 cats were treated on Day 0 with Revolution®. Otitis was assessed with cytological counts of mean number of bacteria and yeast on Days 0 and 10, and scored clinically every other day. All auricular secretions were removed for mite count on Day 10. On Day 0, cytological examination confirmed the presence of secondary bacterial (24/24) and fungal (21/24) infections. No live mites were observed otoscopically after Day 4 and in auricular secretions at Day 10 in both groups. On Day 10, secondary infections were resolved for all cats treated with Oridermyl® but were present in all cats treated with Revolution®. Improvement in clinical signs of otitis over time was superior in the Oridermyl® group (P < 0.001).
Résumé
Efficacité comparative à court terme de l’onguent auriculaire Oridermyl® et de la solution topique de selamectin Revolution® contre Otodectes cynotis et ses otites externes secondaires associées chez le chat. L’efficacité d’Oridermyl® (onguent acaricide/antibiotique/antifongique/anti-inflammatoire) et de Revolution® (solution topique de selamectin) a été comparée dans un essai aléatoire à l’insu chez 24 chats adultes avec de l’otoacariose. Douze chats ont été traités une fois par jour pendant 10 jours avec Oridermyl® et 12 chats ont été traités avec Revolution® au Jour 0. L’otite était évaluée par des numérations cytologiques du nombre moyen de bactéries et de levures aux Jours 0 et 10, et un score clinique était attribué un jour sur deux. Toutes les sécrétions auriculaires ont été retirées au Jour 10 pour une numération d’acariens. Au Jour 0, les examens cytologiques ont confirmé la présence d’infections secondaires bactériennes (24/24) et fongiques (21/24). Aucun acarien vivant n’a été observé à l’otoscope après le Jour 4, ainsi que dans les sécrétions auriculaires au Jour 10, dans les deux groupes. Au Jour 10, les infections secondaires étaient résolues chez tous les chats traités avec Oridermyl®, mais étaient encore présentes chez tous les chats traités avec Revolution®. L’amélioration des signes cliniques d’otite dans le temps était supérieure pour le groupe Oridermyl® (P < 0,001).
(Traduit par les auteurs)
Introduction
Otodectes cynotis is considered to be the primary factor in more than half of the cases of otitis externa in feline patients (1). This mite, which feeds on epidermal debris and tissue fluids from superficial epidermis, can cause a hypersensitivity reaction in some individuals (2,3). Secondary bacterial and fungal infections are also very common in cats affected by otoacariasis, with staphylococci and Malassezia spp. being the most frequently isolated microorganisms in such cases (4). A possible explanation for this observation could be that the parasite stimulates local inflammation, leading to modification of environmental conditions in the external ear canal. Disequilibrium in the normal bacterial and fungal flora could then occur, resulting in proliferation of some microorganisms and consequently development of secondary bacterial and fungal otitis externa.
Feline otoacariasis is frequently treated with a single application of an acaricidal spot-on preparation. Secondary bacterial and fungal infections are not always addressed by veterinarians prescribing these products who may be thinking that micro-organism populations will re-establish their normal equilibrium with time after elimination of the primary factor (mites). Blot et al (5) studied the efficacy over 30 d of a selamectin spot-on in 30 cats with natural otoacariasis. They demonstrated its efficacy and quick action against O. cynotis even if clinical signs such as erythema and scratch reflex persisted for 2 wk after the cats tested negative for mites. They also concluded that it had no effect against bacteria and yeasts and that otitis externa caused by these agents required other products such as antibiotics and antifungal preparations.
The aim of this study on feline otoacariasis was to compare (over 10 d) the efficacy of Oridermyl®, an acaricidal/antibiotic/antifungal/anti-inflammatory auricular ointment and Revolution®, a selamectin spot-on, with regards to elimination of O. cynotis, resolution of local clinical signs, and quantity of bacteria and yeasts seen at cytology. The hypothesis was that Oridermyl® would be superior in relieving local clinical signs and secondary bacterial/fungal infections/overgrowth in cats, but would have an equivalent acaricidal effect when compared to Revolution®.
Materials and methods
This blinded randomized experimental study involved 24 adult cats (14 males and 10 females) from a shelter for rescued cats. To be included, cats had to be in good general health, based on complete blood (cell) count (CBC), serum chemistry, urinalysis, and physical examination, but affected by a unilateral or bilateral parasitic otitis externa. Moving Otodectes cynotis had to be visualized during otoscopic examination or found in auricular secretions examined under the microscope. Animals were kept in individual cages at the Complexe de Bioévaluation of the Faculté de médecine vétérinaire, Université de Montréal.
An otoscopic examination was done on Day −1 to determine the severity of the otitis in each ear based on the amount of secretions and presence of mites in the ear canal. Random group assignment was performed to ensure homogeneous infestation levels and disease severity between the 2 treatment groups.
The experiment was from Day 0 to Day 10. The 12 cats from the Revolution® group were treated only once on Day 0 with a selamectin spot-on (Revolution®; Pfizer Animal Health, Kirkland, Quebec). In the Oridermyl® group, the auricular ointment (Oridermyl®; Vétoquinol N.-A., Lavaltrie, Quebec) was applied once daily in both ears of the 12 cats from Day 0 to Day 9. Animals were observed once daily to detect any sign of adverse reaction to the test products.
This study was approved by the Institutional Animal Care and Use Committee in accordance with the guidelines of the Canadian Council on Animal Care.
Test substances
Each gram of Oridermyl® auricular ointment contained 3500 units of neomycin sulphate, 100 000 units of nystatin, 1 mg of triamcinolone acetonide, and 10 mg of permethrin in an oily base. After application of 0.3 mL in each external ear canal, the ears were massaged for approximately 60 s to ensure adequate penetration of the ointment.
The 45-mg tube of Revolution® was administered as recommended by the manufacturer. Briefly, the hairs on the back of the animal were parted at the base of the neck in front of the shoulder blades until the skin was visible. The tip of the tube was placed on the skin and squeezed 3 or 4 times to empty its entire content directly onto the skin in one spot. The content of each tube of Revolution® was formulated to provide a minimum of 6 mg/kg of body weight (BW) of selamectin.
Parasitology
On Day −1, a small amount of auricular secretions was collected from each ear of all the cats and examined under the microscope to confirm infestation.
Removal of all the auricular secretion under sedation was the last procedure performed to determine a total mite count on Day 10. Using a cotton swab impregnated with mineral oil, the maximum possible quantity of auricular secretions was collected from each ear. The auricular material was placed in a small bottle containing a small quantity of mineral oil. The cotton swab was also inserted in the bottle at the end of the procedure. To ensure retrieval of the maximum number of mites, tweezers were used to pull the cotton swab to pieces in the mineral oil. Samples were analyzed microscopically (40× or 100× magnification) within hours of collection and the total number of live and dead adult mites per ear was recorded, as well as the number of juvenile forms and presence of eggs. Physical integrity and movement of mites were used to establish if they were alive or not.
Cytology
A sample was collected with a swab from the vertical portion of the external ear canal of both ears on Days 0 and 10. Secretions were spread by gently rolling the swab onto a glass microscope slide. Samples were air-dried, fixed, and stained with a modified Wright’s stain using a cytology slide stainer (Aerospray; Wescor, Logan, Utah, USA). Yeasts and bacteria were counted, and a semi-quantitative evaluation similar to that described by Ginel et al (6) was performed under 500× magnification. Numbers of bacteria and yeasts were counted in 10 microscope fields and the average number of bacteria and yeasts per field was calculated for each slide. For fields with more than 100 microorganisms, data were reported as > 100/high power field (hpf).
Clinical efficacy
Otoscopic examinations were done by the same investigator on Days 0, 2, 4, 6, 8, and 10. A score was attributed for the approximate number of visible mites. The appearance of the external ear canal and of the inner pinnae was noted (erythema, pruritus, quantity of secretions, and pain at palpation). Each criterion was attributed a score on a scale from 0 to 3, the lowest score corresponding to a condition typically observed in a cat with clinically normal ears. The scoring chart is presented in Table 1. The total otoscopic score was calculated for each cat by totaling the individual scores for number of visible mites, erythema, pruritus, pain, and quantity of secretions from both ears.
Table 1.
Scoring system for otoscopic examinations
| Score | Paina | Erythema | Pruritusb | Visible mitesc | Secretion |
|---|---|---|---|---|---|
| 0 | Absent | Absent | Absent | None | Normal |
| 1 | Mild | Mild | Mild | Low (≤5) | Slight increase |
| 2 | Moderate | Moderate | Moderate | Moderate (>5 to ≤ 10) | Moderate increase |
| 3 | Severe | Severe | Severe | High (> 10) | Severe increase |
Local auricular pain could have been manifested by the cat trying to pull away, rubbing its ear with its ipsilateral front paw, meowing, and/or responding with aggressiveness (growls, hisses, tries to bite or scratch).
Pruritus could have been manifested by the cat trying to shake its head and/or scratch the ear with its ipsilateral hindpaw (auriculo-pedal reflex). If excoriation on the dorsal face of the pinnae was observed, it automatically led to attribution of a moderate or severe score (depending on the extent of the lesions and presence of 1 or both of the 2 manifestations of pruritus).
Number of mites.
Statistical analysis
To evaluate the effect of Time, Treatment, and Time * Treatment interaction, a generalized linear model was used to analyze total otoscopic score and cytological findings (bacterial and yeast counts) under Poisson distribution function. The scale factor was estimated by Pearson’s chi-square/Degree of freedom. The best working matrix was determined to be autoregressive after having ensured good quality of adjustment. When appropriate, ears (left or right) and fields (n = 10) were random effects nested in treatment groups. At each time point, group’s least square means were compared with appropriate Bonferroni adjustments. Alpha threshold for significance was set at 5%. Data are presented as mean ± standard deviation (SD). Statistical analyses were done using SPSS Statistics software v17.0 (SPSS, Chicago, Illinois, USA).
Results
Parasitology
No live adult mites, juvenile mites, or eggs were observed at Day 10 in cats from both treatment groups.
Cytology
Based on cytological examination of ear secretions on Day 0, all 24 cats had a bacterial infection or overgrowth in at least 1 ear. When considering the most affected ear of each cat, 19 patients showed a mean count > 100 bacteria/hpf and among the remaining cats, the lowest mean count seen on cytology was 34.3 bacteria/hpf. A fungal infection or overgrowth was also present in 21 patients: 10 cats with a mean count > 100 yeasts/hpf in at least 1 ear and 11 others with at least 1 ear showing a mean count > 25.0 yeasts/hpf.
During treatment, bacterial and yeast counts decreased significantly over time (Time effect, P < 0.001). This overall decrease was mostly attributed to the auricular ointment treatment as counts of bacteria and yeasts were significantly lower in cats in the Oridermyl® group compared with those in the Revolution® group (Treatment effect, P < 0.001). As a result, significant interactions between Time and Treatment were found for bacterial and yeast counts (Time * Treatment interaction, P < 0.001).
Comparative results are presented in Table 2. According to post hoc analyses, initial bacterial and yeast counts were not significantly different between the 2 treatment groups. In the Revolution® group, mean bacterial and yeast counts at Day 10 were not significantly different compared with those on Day 0. At the end of the study, all 12 cats in this group had a bacterial infection or overgrowth in at least 1 ear (and both ears for most patients). Seven of these cats also had a fungal infection or overgrowth in at least 1 ear; the lowest mean count seen in the most affected ear was 38 yeasts/hpf.
Table 2.
Results of the cytological examinations
| Microorganism count | |||
|---|---|---|---|
| Time | Group | Bacteria | Yeast |
| Day 0 | Oridermyl | 68 ± 25 | 47 ± 24 |
| Revolution | 82 ± 22 | 45 ± 34 | |
| Day 10 | Oridermyl | 1 ±1*§ | 1 ± 1*§ |
| Revolution | 94 ± 12 | 38 ± 32 | |
Data are expressed as mean ± standard deviation.
Data are the mean of 20 high power fields obtained from both ears.
Significant difference (P < 0.05) when compared to Day 0 (least square means, Bonferroni correction).
Significant difference (P < 0.05) when compared to Revolution (least square means, Bonferroni correction).
In contrast, microorganism counts decreased significantly over time in the Oridermyl® group when comparing Day 0 and Day 10 values (post hoc analyses P < 0.001). In this group, 19/24 ears showed a mean bacterial count compatible with a normal ear (<1.8 bacteria/hpf) and 18/24 ears showed a mean yeast count as expected in a healthy ear (< 0.5 yeast/hpf) at the end of the treatment [cut-off values reported by Ginel et al (6)]. At Day 10, cats treated with Oridermyl® ointment had significantly lower counts than cats treated with Revolution® (post hoc analyses P < 0.001).
Clinical efficacy
Results for each criterion at the various examination days are presented in Table 3. Prior to treatment, mild to severe pruritus (mild: 5/24 cats, moderate: 10/24, severe: 8/24), mild (11/24) or moderate (1/24) erythema, and increased quantity of secretions (24/24) were observed in at least 1 ear. Only 3 cats manifested signs of pain during the initial otoscopic examination. The total otoscopic scores at Day 0 were not significantly different between cats from the 2 groups. Both treatments seemed to have a rapid acaricidal effect as shown by a mean score of virtually zero for visible mites at Day 4.
Table 3.
Clinical scores determined by otoscopic examination
| Otoscopic Score | |||||||
|---|---|---|---|---|---|---|---|
| Time | Group | Pain | Erythema | Pruritus | Visible mites | Secretion | Total otoscopic score |
| Day 0 | Oridermyl | 0.1 ± 0.3 | 0.4 ± 0.7 | 3.7 ± 1.7 | 3.5 ± 1.7 | 4.0 ± 1.7 | 11.7 ± 4.0 |
| Revolution | 0.4 ± 1.2 | 0.8 ± 0.7 | 3.3 ± 1.6 | 2.8 ± 1.6 | 5.0 ± 1.2 | 12.3 ± 3.2 | |
| Day 2 | Oridermyl | 0.0 ± 0.0 | 0.3 ± 0.7 | 1.7 ± 1.8 | 0.5 ± 0.5 | 3.3 ± 1.4 | 5.8 ± 2.4*§ |
| Revolution | 0.3 ± 0.7 | 1.0 ± 0.7 | 2.6 ± 1.5 | 1.7 ± 0.7 | 5.6 ± 0.9 | 11.2 ± 2.2 | |
| Day 4 | Oridermyl | 0.1 ± 0.3 | 0.3 ± 0.5 | 0.8 ± 1.2 | 0.1 ± 0.3 | 2.6 ± 1.0 | 3.8 ± 2.1*§ |
| Revolution | 0.0 ± 0.0 | 1.0 ± 0.7 | 1.6 ± 1.1 | 0.0 ± 0.0 | 5.4 ± 0.7 | 8.0 ± 1.2* | |
| Day 6 | Oridermyl | 0.0 ± 0.0 | 0.4 ± 0.9 | 0.4 ± 0.8 | 0.0 ± 0.0 | 1.4 ± 0.8 | 2.3 ± 2.1*§ |
| Revolution | 0.0 ± 0.0 | 0.4 ± 0.8 | 0.5 ± 0.7 | 0.0 ± 0.0 | 5.0 ± 1.0 | 5.9 ± 1.6* | |
| Day 8 | Oridermyl | 0.0 ± 0.0 | 0.6 ± 0.8 | 0.5 ± 0.8 | 0.0 ± 0.0 | 1.6 ± 1.2 | 2.7 ± 2.3*§ |
| Revolution | 0.3 ± 0.8 | 0.9 ± 1.0 | 0.6 ± 0.9 | 0.0 ± 0.0 | 4.9 ± 0.8 | 6.8 ± 2.0* | |
| Day 10 | Oridermyl | 0.1 ± 0.3 | 0.4 ± 0.5 | 0.0 ± 0.0 | 0.0 ± 0.0 | 1.3 ± 1.1 | 1.8 ± 1.1*§ |
| Revolution | 0.2 ± 0.4 | 0.8 ± 0.8 | 0.7 ± 0.9 | 0.0 ± 0.0 | 4.3 ± 1.0 | 5.9 ± 1.5* | |
Data are expressed as mean ± standard deviation. Data are the mean of the sum of both ears.
Significant difference (P < 0.05) when compared to Day 0 (least square means, Bonferroni correction).
Significant difference (P < 0.05) when compared to Revolution (least square means, Bonferroni correction).
The individual evolution of the total otoscopic score by treatment group is presented in Figure 1 and summarized in Table 3. Over time, the score decreased significantly (Time effect, P < 0.001) following the administration of both treatments. A significant interaction between Time and Treatment was found (Time * Treatment interaction, P < 0.001). This result indicates that the change in clinical score over time was affected by the treatment administered. Cats treated with Oridermyl® ointment showed a significantly higher level of improvement over time (Treatment effect, P < 0.001).
Figure 1.
Changes in total otoscopic score over time in the 2 treatment groups.
From Day 2 to Day 10, Oridermyl® ointment provided a significant decrease in total otoscopic score compared with the initial score obtained at Day 0 (P < 0.001). A significant decrease was observed from Day 4 to Day 10 (P < 0.001) for cats which received Revolution®. From Day 2 to Day 10, the Total otoscopic scores in cats treated with Oridermyl® were significantly lower than in cats treated with Revolution® (P < 0.001).
No drug-related adverse reaction was observed during this study. All cats tolerated both test products well.
Discussion
The rapid acaricidal effect of Revolution® is in accordance with results from Blot et al (5) who did not see live adult mites in auricular secretions 3 d after treatment. In a previous study, the efficacy of Oridermyl® ointment in eliminating O. cynotis was demonstrated but its speed of action was not evaluated (4). The present study seems to indicate that mites are killed by the acaricidal ointment within the first days of application.
Secondary bacterial and fungal infections or overgrowth were also seen in most cats infested with ear mites, and this is in agreement with previously reported observations (4). The antibacterial and antifungal effect of Oridermyl® ointment observed here is also in accordance with previous results (4).
The selamectin spot-on was not expected to have any bactericidal nor fungicidal effect, but one could have anticipated that rapid elimination of the mites may have enabled microorganism populations to re-establish their normal equilibrium within a reasonable time period. Based on cytology, this was not the case within the 10 d of the trial.
Clinical signs of otitis externa decreased over time for both treatment groups although it was more pronounced and rapid for cats which received Oridermyl® ointment. The elimination of the parasites can partly explain this observation over time for both treatment groups. For cats treated with the ointment, the steroidal anti-inflammatory agent it contains was also probably involved in this positive effect, and could explain in part the difference observed between treatment groups. Secondary bacterial and fungal infections can cause significant inflammation of the external ear canal and inner pinnae. It is also likely that resolution of these infections for cats in the Oridermyl® group would partly explain its superior effect on improvement of local clinical signs.
It is unclear what role the oily vehicle and massaging of the ear canals played in the effects observed in the Oridermyl® group. The efficacy of auricular preparations without acaricidal agent for the treatment of otoacariasis has been reported in the past (4,7,8). The success rate for elimination of O. cynotis seemed to depend on the volume of preparation applied, the frequency of applications, and the duration of treatment. It was hypothesized that the oily base of these preparations killed mites. The oily vehicle in the ointment along with the massage did soften the ear secretions and could have helped secretions being dispersed toward the pinnae and the skin at the base of the ear, where cats could have removed them when grooming.
Limitations of the present study include the relatively low number of animals from a single source and the relatively short duration of the observation period.
Treatment of otoacariasis with an acaricidal only spot-on does not resolve the secondary bacterial and fungal infections nor does it directly resolve the local signs of inflammation. Using a treatment that combines acaricidal, antibiotic, antifungal, and anti-inflammatory agents results in faster relief of symptoms. It would be advisable when using an acaricidal spot-on against Otodectes cynotis to combine it with an auricular antimicrobial and anti-inflammatory preparation in order to address secondary infections and patient comfort.
In conclusion, the study herein confirms the presence of bacterial and fungal infections or overgrowth associated with feline otoacariasis and demonstrates the superiority of Oridermyl® auricular ointment over Revolution® spot-on to rapidly control secondary infections and clinical signs of otitis externa.
Acknowledgments
The authors thank Dr. Alain Villeneuve, Mrs. Sabrina Giroux, and Mrs. Evelyne Nadeau for their contributions to the conduct of this study. CVJ
Footnotes
This study was supported financially by Vétoquinol Canada Inc.
Use of this article is limited to a single copy for personal study. Anyone interested in obtaining reprints should contact the CVMA office (hbroughton@cvma-acmv.org) for additional copies or permission to use this material elsewhere.
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