Evaluation of in vitro activity of herbal formula Di Er You and herb Coptis against bacteria isolated from dogs with otitis externa.

OBJECTIVE: To determine the in vitro activity of the herbal formula Di Er You (DEY) and the single-herb Coptis against bacteria cultured from dogs with otitis externa. ANIMALS: 32 client-owned dogs diagnosed with otitis externa. METHODS: A sample of otic debris from each patient was collected and plated onto a fresh Sheep's Blood Agar plate in the hospital. After bacterial growth was confirmed, 4 wells were created, numbered randomly, and treated with saline (placebo), DEY, Coptis, and Zymox Otic Enzymatic Solution with 1% Hydrocortisone (Zymox). After 24 hours of incubation, the diameter of the zone of inhibition (dZOI) of each treatment was measured and recorded, and compared among treatments. A sample of the bacterial colonies grown was submitted to an outside lab for bacterial identification. RESULTS: The mean ± SD dZOI values for saline, DEY, Coptis, and Zymox treated wells were 0.25 ± 1.41, 12.47 ± 3.92, 14.25 ± 7.12, and 3.22 ± 5.12, respectively. Post hoc multiple comparisons test revealed that (1) saline-treated wells had significantly smaller dZOI values than the other 3 groups (all P < .001), (2) Zymox treated wells had significantly smaller dZOI values than either herbal treated groups (both P < .001), and (3) DEY treated wells had significantly smaller dZOI values than those treated with Coptis (P = .0042). CLINICAL RELEVANCE: The results from this in vitro study suggested that both DEY and Coptis could be effective treatments in inhibiting the growth of bacteria in dogs with otitis externa. Prospective randomized controlled clinical trials are warranted to confirm these findings.

Management and Clinical Outcomes of 37 Patients with Necrotizing Otitis Externa: Retrospective Review of a Standardized 6-Week Treatment Pathway.

BACKGROUND: Necrotizing otitis externa is an invasive infection, affecting older patients, with significant associated morbidity. Despite this, there are no randomized controlled trials that address management, and therefore, treatment approaches may vary considerably. We describe the management and outcomes of 37 patients managed using a multidisciplinary treatment pathway for necrotizing otitis externa over a 5-year period. The pathway is based on a standardized antibiotic regime of 3 weeks of intravenous ceftazidime plus oral ciprofloxacin, followed by a further 3 weeks of ciprofloxacin. METHODS: This is a retrospective review of all patients diagnosed with necrotizing otitis externa since the introduction of our pathway in 2016. We include data on patient demographics, comorbidities, microbiology, length of stay, and length of antimicrobial treatment. Outcome data, including mortality, relapse and treatment failure, and adverse effects of treatment, are presented. RESULTS: The median age of our patients was 82 years. About 54% of patients had diabetes mellitus or another cause of immunocompromise. Pseudomonas aeruginosa was isolated in 68%. The median duration of inpatient stay was 9 days, and median treatment duration was 6 weeks. Of 37 patients, 32 were cured (86%), and of the remaining 5 patients, there were 2 mortalities unrelated to necrotizing otitis externa and 3 patients with recurrent infections due to anatomical abnormalities. CONCLUSION: We note favorable treatment outcomes when using a standardized multidisciplinary pathway and a 6-week course of antibiotic therapy.

In vitro and in vivo evaluation of a new phytotherapic blend to treat acute externa otitis in dogs.

Canine otitis externa is frequently encountered in veterinary practice, caused by primary factors with bacteria and yeast overgrowth acting as secondary and perpetuating factors. The pharmacological support includes anti-inflammatory, antimicrobials, and antimycotic drugs, but therapeutic failure and antimicrobial resistance are leading to alternative strategies based on phytotherapic products. This study aimed to evaluate an essential oil blend (Otogen® ) to treat otitis externa in dogs. The experimental design was divided in: (a) an in vitro approach, based on the European Normative UNI EN 1275:2006, to assess the efficacy of the product against the most frequently isolated microorganisms during otitis externa. (b) an in vivo part, 12 owned dogs presenting with acute otitis externa were enrolled. A significant growth reduction (>99.9%) of Malassezia pachydermatis and Candida albicans after 15 min of contact and Pseudomonas aeruginosa after 1 h of incubation was recorded. For Staphylococcus pseudintermedius, 50% of growth reduction were appreciated after 15 min. Results obtained in vivo after 7 days of blend administration, noted a significant improvement of all the considered parameters (most important were head shaking, erythema, and scraping). The results obtained may support the usefulness of the tested phytotherapic blend to manage acute otitis externa in dogs.

[Modern aspects of inflammatory external ear diseases treatment]. / Sovremennye aspekty lecheniya vospalitel'nykh zabolevanii naruzhnogo ukha.

The article deals with the problem of inflammatory diseases of the external ear. A review of pruritic dermatoses of the external auditory canal was carried out. It has been shown that in chronic dermatoses, the contamination of the skin with bacterial and fungal pathogens significantly increases, which leads to a high risk of developing secondary infectious pathological processes. Treatment of dermatological inflammatory ear diseases includes careful daily hygiene of the external auditory canal and pharmacotherapy, a key aspect of which is the use of topical etiotropic, anti-inflammatory, and symptomatic drugs. The advantage of the combined drug candiderm is described, which, thanks to the unique combination of beclomethasone, gentamicin and clotrimazole in the composition, effectively relieves the symptoms of external ear dermatoses.

Standardised treatment protocol for necrotizing otitis externa: retrospective case series and systematic literature review.

OBJECTIVES: There is currently no consensus on the most effective treatment protocol for necrotizing otitis externa (NOE). This article aims to produce a NOE treatment protocol from the literature and clinical experience. METHODS: A total of 26 case series from the literature were reviewed in combination with a retrospective case series of inpatients from Hull University Teaching Hospitals NHS Trust from 2013-2018. Over 5 years, 40 patients were identified, with only 29 being analysed due to unavailable or incomplete case notes. RESULTS: In the literature review, the most common bacterial species causing NOE was Pseudomonas aeruginosa. Resistance to ciprofloxacin was prevalent, however multidrug resistance was rare. Ciprofloxacin and ceftazidime were the most widely used antibiotics. No ceftazidime resistance was reported in the literature or in our cohort. The average age of the patients in our cohort was 80 years. Moreover, 62% had either diabetes mellitus or were immunosuppressed. One patient died directly due to NOE-related sepsis. Intravenous ceftazidime monotherapy was mostly used. The duration of treatment was 6-7 weeks, with no relapses documented. CONCLUSION: Ceftazidime monotherapy was an effective empirical treatment in our cohort, and a total duration of 6-7 weeks of antibiotics was sufficient. We have created a standardised treatment protocol based on our findings that will need to be validated in a larger cohort of patients.

Effect of an anti-inflammatory pomegranate otic treatment on the clinical evolution and microbiota profile of dogs with otitis externa.

BACKGROUND: Canine otitis externa (OE) is a common disease characterised by inflammation of the epithelial tissue of the external ear canal. Secondary infections are frequent, and Malassezia pachydermatis and Staphylococcus pseudintermedius are routinely isolated and treated with antifungal and antibiotic compounds. HYPOTHESIS/OBJECTIVES: To analyse the otitis ear microbiome before and after a treatment with prednisolone plus pomegranate or antimicrobial drugs ANIMALS: 15 dogs with nonpurulent OE. METHODS AND MATERIALS: A 30 day, double-blinded, multicentre, randomized and controlled parallel-group (1:1) trial was conducted in 15 dogs with nonpurulent OE, following two different topical treatments (prednisolone plus pomegranate versus prednisolone plus antibiotic and antifungal drugs). On days (D)0, D15 and D30, serum and skin otic samples were collected, and clinical examination and microbiome analysis (bacteria and fungi) were performed. Results were compared with validated otitis clinical scores to assess the effectiveness of both treatments. RESULTS: Nine bacterial and four fungal families were detected during the three time-points tested. An increase in fungal diversity (Shannon index) and composition was the most significant change observed after both treatments. At treatment D15 and D30, the reduction in clinical signs was statistically significant in both treatment groups (P ≤ 0.05). Prednisolone plus pomegranate cleanser treatment was able to control the clinical signs of otitis as well as the bacterial and fungal overgrowth. CONCLUSIONS AND CLINICAL IMPORTANCE: Mild otitis cases associated with microbial overgrowth may be managed with topical antiseptic and anti-inflammatory agents without the need for antibiotic and/or antifungal compounds.

Preliminary evaluation of two commercial ear solutions in the treatment of canine otitis externa.

OBJECTIVES: Preliminary evaluation of the efficacy of two commercial ear solutions composed of (1) chlorhexidine-Tris-ethylenediaminetetraacetic acid (EDTA) or (2) medical grade honey, for the treatment of otitis externa in dogs. MATERIALS AND METHODS: Dogs affected with otitis externa housed in an animal shelter were eligible for inclusion. Treatment was applied daily for 10 days and effect was measured by otitis clinical scores and microbiological counts. One of the treatments was applied to affected left ears, while the other was applied to affected right ears. RESULTS: A total of 24 ears from 13 dogs were included in the study. During the treatment period, with both treatments it was observed an improvement in clinical scores and a decrease in microbiological counts. At the end of the study 22 of 24 ears were deemed to have mild (4 ears), or no (18 ears) pain, with only two ears still showing pruritus. CLINICAL SIGNIFICANCE: The application of ear solutions composed of chlorhexidine-Tris-EDTA or medical grade honey, in the absence of antimicrobial treatment, might be effective for the control of clinical signs and microbial colonisation in dogs with otitis externa. Additional randomised studies on clinical patients are required to validate these findings.

Carriage of Staphylococcus schleiferi from canine otitis externa: antimicrobial resistance profiles and virulence factors associated with skin infection.

The recent emergence of Staphylococcus schleiferi in dogs with otitis externa or skin and soft tissue infections has become a significant zoonotic issues. In the current study, we investigated 1) the carriage rates of S. schleiferi among major staphylococci in healthy dogs and dogs with otitis externa, 2) antibiotic susceptibility profiles of S. schleiferi, particularly methicillin resistance (MR), and 3) virulence factors associated with skin and soft tissue infections such as ability to form biofilm, resistance to cationic antimicrobial peptides (CAMPs), and carriage of staphylococcal enterotoxin genes. Among the 21 S. schleiferi isolates, 5 isolates (24%) were determined to be methicillin-resistant (MRSS). Staphylococcal cassette chromosome mec (SCCmec) typing revealed the presence of SCCmec type V in 4 MRSS isolates and type VII in one MRSS. Higher levels of antibiotic resistance, especially multidrug resistance, were observed in MRSS isolates compared to the methicillin-susceptible S. schleiferi (MSSS) isolates. In addition, MRSS isolates exhibited enhanced ability to form biofilm under static condition and all the 5 MRSS isolates carried three or more enterotoxin genes. However, there were no significant differences in resistance to CAMPs between MRSS and MSSS isolates. These findings suggest that coagulase-negative S. schleiferi is becoming more prevalent in canine otitis externa cases. Our results also highlight the presence of multidrug-resistant MRSS isolates with enhanced biofilm production and carriage of multiple enterotoxins.

OTO-201 for the Treatment of Acute Otitis Externa: Results from a Phase 3 Randomized Clinical Study.

OBJECTIVES: OTO-201 is a ciprofloxacin otic suspension previously approved by the US Food and Drug Administration to treat children with bilateral otitis media with effusion requiring tympanostomy tube placement. In this phase 3, double-blind, randomized, prospective, sham-controlled, multicenter study, a single dose of OTO-201 was administered to the external auditory canal in subjects with unilateral or bilateral acute otitis externa. METHODS: Two hundred sixty-two subjects, 3 to 83 years of age, were randomized, and 260 subjects were included in the intent-to-treat analysis population: OTO-201 (0.2 mL, 12 mg, n = 130) or sham (air injection, n = 130). The primary efficacy measure was clinical cure (CC) on day 8, judged by blinded assessor for erythema, edema, otorrhea, and tenderness. Subjects were monitored over 28 days for efficacy and safety. RESULTS: OTO-201 demonstrated a significant increase in CC compared with sham at day 8 (69.2% vs 46.1%, P < .001). Higher CC was also noted on day 4 ( P = .028), day 15 ( P < .001), and day 29 ( P < .001). A similar effect was observed in the pathogen-positive population. Single OTO-201 administration in the office setting was well tolerated by subjects. CONCLUSIONS: In this study in subjects with acute otitis externa, a single administration of 12 mg OTO-201 to the external auditory canal demonstrated a significantly higher proportion of subjects with CC and bacterial eradication compared with sham starting on day 4 and on all other observation days through day 29, with no safety or tolerability concerns identified. OTO-201 is the first agent in a randomized phase 3 study to demonstrate the efficacy and safety of a single-dose, health care professional-administered topical antibiotic for the treatment of acute otitis externa.

Oxythiamine improves antifungal activity of ketoconazole evaluated in canine Malassezia pachydermatis strains.

BACKGROUND: Malassezia pachydermatis is an opportunistic yeast involved in skin and ear canal infections of dogs and cats. Reports suggest that strains of M. pachydermatis resistant to commonly used antifungal agents may be emerging. Therefore, new therapeutic strategies should be explored. OBJECTIVES: The synergistic effect of oxythiamine (OT) and ketoconazole (KTC) was analysed using a reference strain and field isolates (n = 66) of M. pachydermatis. Hydrogel formulations containing these components also were evaluated. METHODS AND MATERIALS: The minimum inhibitory concentrations (MICs) and minimum fungicidal concentrations (MFCs) of OT, KTC and their mixtures were determined by a broth macrodilution method. The antifungal effects of hydrogel formulations were determined by a plate diffusion method. RESULTS: The MIC and MFC values of OT were in the range 0.08 × 103 to 10 × 103  mg/L. All M. pachydermatis strains showed higher susceptibility to KTC (MICs and MFCs in the range 0.04-0.32 mg/L). Formulations that combined OT and KTC showed a synergistic effect for all tested isolates (n = 66). Hydrogels that contained OT at a concentration of 10 × 103 or 20 × 103  mg/L and KTC at the concentration of 0.1 × 103  mg/L showed a stronger effect than a commercially available product with KTC alone (20 × 103  mg/L). CONCLUSIONS AND CLINICAL IMPORTANCE: Synergy of these drugs may allow for successful topical treatment which utilizes lower doses of KTC without changing its therapeutic effectiveness. Hydrogel formulations proved to be attractive drug carriers for potential topical use.

Malignant external otitis: The shifting treatment paradigm.

IMPORTANCE: Malignant external otitis (MEO) is an aggressive infection occurring in immunocompromised hosts. Increasing antimicrobial resistance is making the disease more difficult to treat. OBJECTIVE: Determine if there has been a shift in the microbiology and outcomes of MEO. DESIGN: A retrospective case series at a tertiary care institution. SETTING: Inpatient and outpatient tertiary care hospital. PARTICIPANTS: 12 cases of recent MEO were reviewed. MAIN OUTCOMES AND MEASURES: The primary outcome was progression of disease. Secondary outcomes were drug resistance and complications of MEO. RESULTS: Only 4 patients were cured of MEO. Four patients expired during the study period and at least one of these deaths was a direct result of the MEO. 7 patients developed Cranial nerve palsies, and 3 patients developed abscesses. CONCLUSIONS: Select cases of MEO now require multi-drug and long-term parenteral antibiotic therapy with extended hospital stays.

[In vivo-efficacy of an ear medication using gelatin powder as a vehicle for the therapy of canine otitis externa]. / In-vivo-Wirksamkeit eines Ohrmedikaments mit Gelatinepulver als Wirkstoffträger bei der Therapie kaniner Otitis externa.

OBJECTIVE: Otitis externa is normally treated with daily topical medication. Longer application intervals may be useful to facilitate therapy. In this study, the in vivo efficacy of a gel preparation containing marbofloxacin, dexamethasone and enilconazole was compared to that of a commercial otologic agent containing marbofloxacin, dexamethasone and clotrimazole based on clinical signs, ear cytology and bacterial/fungal cultures. MATERIAL AND METHODS: A gel preparation (group A) or a registered otologic agent (group B), respectively, was applied to 41 dogs. A total of 50 ears (25 per group) were analysed. The gel preparation was administered on days 0 and 5; the combination preparation was administered daily according to the manufacturer's recommendations. Dogs were reevaluated clinically and cytologically after 5 and 10 days. Initially and after 10 days, ear swabs were taken for bacterial and fungal cultures. RESULTS: No significant clinical or cytological differences were found between the groups. Significantly more isolates resistant to marbofloxacin were identified in group A after 10 days, although >98% of marbofloxacin was still detectable in vitro after 15 days. CONCLUSION: The clinical and cytological efficacy of a gel containing defined active agents applied twice 5 days apart was comparable to that of an authorised otologic agent applied once daily. There appears to be an increased risk with the gel in that a resistance to fluoroquinolones develops. Local adverse effects are also possible. CLINICAL RELEVANCE: A gelatine preparation containing active agents may be an alternative to daily topical therapy of canine otitis externa. The development of resistances is possible.

Traditional Mediterranean plants: characterization and use of an essential oils mixture to treat Malassezia otitis externa in atopic dogs.

Several plants extracts from Mediterranean countries are traditionally employed in skin troubles both in humans and in animals. Malassezia pachydermatis is a lipophylic yeast responsible for otitis externa and dermatitis in dogs and for cutaneous and systemic disease in humans. Five mixtures of essential oils obtained from Mediterranean plants (Citrus paradisi, Salvia sclarea, Ocimum basilicum, Rosmarinus officinalis, Citrus limon, Anthemis nobilis, Lavandula hybrida and Thymus vulgaris) provided with antifungal and/or anti-inflammatory action assayed in vitro, were tested in vivo versus M. pachydermatis to treat once daily for 2 weeks 25 atopic dogs with Malassezia otitis externa. Mixture composed by C. limon 1%, S. sclarea 0,5%, R. officinalis 1%, A. nobilis 0,5% yielded excellent results in all treated dogs. Despite of clinical resolution after all treatments the number of blastospores did not decrease. This study confirms recent findings suggesting a multifactorial alternative approach for the management of canine Malassezia otitis.

[The current views of the treatment of diffuse external otitis].

The objective of the present study was to evaluate the clinical effectiveness and safety of the local application of triderm for the treatment of diffuse external otitis. The study included 68 patients presenting with bacterial and fungal diffuse external otitis. The treatment in the form of local empiric therapy was continued till the results of microbiological treatment became apparent. The beneficial outcome achieved in 91.2% of the patients was clinically manifest as the regression of the inflammatory process in the external auditory meatus. No complications, such as ototoxic events, either local or systemic allergic reactions, were documented. The authors substantiate the possibility of the application of the medication under consideration for the treatment of diffuse external otitis based on the knowledge of the mechanism of the actin of its constituent components, viz. betamethasone, dipropionate, gentamicin sulfate, and clotrimazole, taking into account the occurrence of the most common causative agents of diffuse external otitis. It is concluded that triderm is a safe medication for the local application and, probably, for the initial empiric therapy of diffuse external otitis to be continued till the results of the microbiological treatment become apparent.

National Utilization and Forecasting of Ototopical Antibiotics: Medicaid Data Versus "Dr. Google".

OBJECTIVES: To forecast national Medicaid prescription volumes for common ototopical antibiotics, and correlate prescription volumes with internet user search interest using Google Trends (GT). STUDY DESIGN: National United States Medicaid prescription and GT user search database analysis. METHODS: Quarterly national Medicaid summary drug utilization data and weekly GT search engine data for ciprofloxacin-dexamethasone (CD), ofloxacin (OF), and Cortisporin (CS) ototopicals were obtained from January 2008 to July 2014. Time series analysis was used to assess prescription seasonality, Holt-Winter's method for forecasting quarterly prescription volumes, and Pearson correlations to compare GT and Medicaid data. RESULTS: Medicaid prescription volumes demonstrated sinusoidal seasonality for OF (r = 0.91), CS (r = 0.71), and CD (r = 0.62) with annual peaks in July, August, and September. In 2017, OF was forecasted to be the most widely prescribed ototopical, followed by CD. CS was the least prescribed, and volumes were forecasted to decrease 9.0% by 2017 from 2014. GT user search interest demonstrated analogous sinusoidal seasonality and significant correlations with Medicaid data prescriptions for CD (r = 0.38, p = 0.046), OF (r = 0.74, p < 0.001), CS (r = 0.49, p = 0.008). CONCLUSION: We found that OF, CD, and CS ototopicals have sinusoidal seasonal variation with Medicaid prescription volume peaks occurring in the summer. After 2012, OF was the most commonly prescribed ototopical, and this trend was forecasted to continue. CS use was forecasted to decrease. Google user search interest in these ototopical agents demonstrated analogous seasonal variation. Analyses of GT for interest in ototopical antibiotics may be useful for health care providers and administrators as a complementary method for assessing healthcare utilization trends.

Assessment of the Antimicrobial Activity of Algae Extracts on Bacteria Responsible of External Otitis.

External otitis is a diffuse inflammation around the external auditory canal and auricle, which is often occurred by microbial infection. This disease is generally treated using antibiotics, but the frequent occurrence of antibiotic resistance requires the development of new antibiotic agents. In this context, unexplored bioactive natural candidates could be a chance for the production of targeted drugs provided with antimicrobial activity. In this paper, microbial pathogens were isolated from patients with external otitis using ear swabs for over one year, and the antimicrobial activity of the two methanol extracts from selected marine (Dunaliella salina) and freshwater (Pseudokirchneriella subcapitata) microalgae was tested on the isolated pathogens. Totally, 114 bacterial and 11 fungal strains were isolated, of which Staphylococcus spp. (28.8%) and Pseudomonas aeruginosa (P. aeruginosa) (24.8%) were the major pathogens. Only three Staphylococcus aureus (S. aureus) strains and 11 coagulase-negative Staphylococci showed resistance to methicillin. The two algal extracts showed interesting antimicrobial properties, which mostly inhibited the growth of isolated S. aureus, P. aeruginosa, Escherichia coli, and Klebsiella spp. with MICs range of 1.4 × 108 to 2.2 × 10(10) cells/mL. These results suggest that the two algae have potential as resources for the development of antimicrobial agents.

Finafloxacin: first global approval.

Finafloxacin is a fluoroquinolone antimicrobial agent that exhibits optimum efficacy in slightly acidic environments. It is being developed by MerLion Pharmaceuticals to treat serious bacterial infections associated with an acidic environment, including urinary tract infections and Helicobacter pylori infections. An otic suspension of finafloxacin (Xtoro™), developed by Alcon (a division of Novartis), was recently approved in the USA for the treatment of acute otitis externa, and a Common Technical Document for this indication was also filed in Canada. Oral and/or intravenous formulations are in phase I and II evaluation in uncomplicated urinary tract infections (Germany and Singapore), complicated urinary tract infections and pyelonephritis (Germany and Poland) and H. pylori infection (Germany). This article summarizes the milestones in the development of finafloxacin leading to this first approval for otitis externa.