In vitro effects of N-acetylcysteine in combination with antifungal agents against Malassezia pachydermatis isolated from canine otitis externa.

BACKGROUND: Many clinicians prescribe antifungal agents to treat canine otitis externa (OE). However, studies evaluating the antifungal effects of N-acetylcysteine (NAC) and its combinations are limited. HYPOTHESIS/OBJECTIVES: The aim of this study was to evaluate the antifungal effects of NAC alone and in combination with other antifungal agents against Malassezia pachydermatis isolated from canine OE. MATERIALS AND METHODS: M. pachydermatis samples were collected from 13 dogs with OE. The final concentration of the inoculum suspensions of M. pachydermatis was 1-5 × 106 colony forming units/mL. The concentrations of the test compounds ketoconazole (KTZ), terbinafine (TER), nystatin (NYS) and NAC were 0.02-300 µg/mL, 0.04-80 µg/mL, 0.16-40 µg/mL and 1.25-20 mg/mL, respectively. The minimum inhibitory concentration (MIC) was measured to evaluate the susceptibility of the M. pachydermatis to KTZ, TER, NYS and NAC. The checkerboard testing method and fractional inhibitory concentration index were used to evaluate the effect of NAC in combination with KTZ, TER and NYS against M. pachydermatis. RESULTS: The MIC90 values of M. pachydermatis were 4.6875-9.375 µg/mL, 1.25 µg/mL, 5-10 µg/mL and 10 mg/mL for KTZ, TER, NYS and NAC, respectively. The synergistic effects of KTZ, TER and NYS with NAC were identified in 0/13, 2/13 and 0/13 isolates, respectively. CONCLUSIONS AND CLINICAL RELEVANCE: NAC had an antifungal effect against M. pachydermatis but did not exert synergistic effects when used with KTZ, TER and NYS. Thus, the use of NAC alone as a topical solution could be considered an effective treatment option for canine OE involving M. pachydermatis.

Otology: Ear Infections.

Acute otitis media (AOM) is a common diagnosis in children who present with symptoms of otalgia, fever, or irritability and is confirmed by a bulging tympanic membrane or otorrhea on physical examination. It often is preceded by a viral infection, but the bacterial pathogens isolated most commonly are Streptococcus pneumonia, Haemophilus influenzae, and Moraxella catarrhalis. Watchful waiting may be appropriate in children 6 months or older with uncomplicated unilateral AOM. When antibiotics are indicated, amoxicillin is the first-line treatment in those without recent treatment with or allergy to this drug. Otitis media with effusion (OME) is fluid in the middle ear without symptoms of AOM and typically resolves within 3 months. Tympanostomy tube placement is the most common ambulatory surgery for children in the United States. It is used to ventilate the middle ear space and may be performed to treat recurrent AOM, persistent AOM, or chronic OME. Acute otitis externa is inflammation of the external ear canal, often due to infection. On examination, the ear canal is red and inflamed, with patients typically experiencing discomfort with manipulation of the affected ear. It is treated with a topical antibiotic with or without topical corticosteroid.

A rare cause of malignant otitis externa and skull base osteomyelitis.

An elderly male with type 2 diabetes presented with a 2-month history of otalgia and severe headaches. He was diagnosed with malignant otitis externa (MOE) and was commenced on empirical treatment with oral ciprofloxacin. Pseudomonas is the most common cause of MOE. A baseline CT scan was undertaken that demonstrated skull base osteomyelitis (SBO) due to findings of bone erosion at the mastoid tip and an infiltrating soft tissue mass eroding the clivus. Eight weeks later, he returned with worsening and bilateral symptoms of otitis externa, hearing loss, temporomandibular pain and dysfunction. Worsening and now bilateral malignant otitis externa were confirmed with an MRI scan that also demonstrated a small fluid collection in his left temporal region. The collection was aspirated and grew scedosporium apiospermum. He was diagnosed with fungal SBO and was commenced on treatment with the antifungal voriconazole, with significant improvement in symptoms and radiological findings. Fungal osteomyelitis is more likely in immunosuppressed patients, particularly those with type 2 diabetes. Fungal aetiology should be suspected in patients with progressive symptoms, despite treatment. A microbiology diagnosis of fungal SBO or MOE can be challenging to obtain and can lead to diagnostic delay. A sampling of the external auditory canal can aid in diagnosing MOE; however, scedosporium may also be isolated as a commensal organism. Aspirations from accessible fluid collections, infratemporal fossa needle sample and bone biopsy can provide material for diagnosis. Scedosporium is a rare cause of disease in humans, however, fungal infections are increasing in humans, due to an increase in susceptible populations. Scedosporium apiospermum is a rare cause of SBO and should be considered in patients not responding to standard treatment.

Bilateral pyogranulomatous otitis externa with putative cartilage destruction in a dog: A severe case of auricular chondritis?

Auricular chondritis of unknown cause was suspected in a 10-year-old male Bolognese dog with a five-month history of painful bilateral nodular and ulcerative pyogranulomatous dermatitis of the pinnae with putative auricular cartilage destruction. Pain and lesions resolved with immunosuppressive doses of prednisolone, yet the condition resulted in deformity of both pinnae and external canals.

Une chondrite auriculaire d'étiologie inconnue est suspectée chez un bichon bolonais mâle de 10 ans qui présente depuis 5 mois une dermatite pyogranulomateuse nodulaire et ulcéreuse bilatérale douloureuse du pavillon de l'oreille avec une destruction présumée du cartilage auriculaire. La douleur et les lésions disparaissent avec des doses immunosuppressives de prednisolone, mais l'affection entraîne une déformation des deux pavillons et des conduits auriculaires externes.

Suspeitou­se de condrite auricular de causa desconhecida em um cão macho Bolonhês de 10 anos de idade com um histórico de cinco meses de dermatite piogranulomatosa ulcerativa e nodular bilateral no pavilhão auricular com suposta destruição de cartilagem auricular. A dor e as lesões resolveram com doses imunossupressoras de prednisolona apesar de a etiologia ter resultado na deformidade de ambas as orelhas e condutos auditivos.

Se sospechó la existencia de una condritis auricular de causa desconocida en un perro boloñés de 10 años con historia de 5 meses de duración de una dermatitis nodular ulcerativa piogramulomatosa y bilateral en las orejas con posible destrucción del cartílago auricular. El dolor y las lesiones se resolvieron con dosis inmunosupresoras de prednisolona pero la enfermedad produjo deformación de ambas orejas y de los canales auriculares externos.

Prevalence and clinical findings of feline otitis externa in Midwest Brazil.

This study was conducted to evaluate the prevalence of otitis externa (OE) in cats using cytology, direct otoscopic examination, and parasitological examination through swabs and curettage, and to compare the accuracy between collection methods for parasitological examination. Direct otoscopic evaluation of the external auditory canal (right and left), swabs for cytological examination of the external auditory canal, and collection of cerumen for parasitological examination through swabs and curettage of 137 cats from a veterinary hospital care were conducted between March 2021 and March 2022. The influences of age, sex, habitat, street access, and the presence of fleas on OE were evaluated. Cytological evidence of OE was observed in 25.5 % of cats and was statistically associated with flea and mite parasitism. Otodectes cynotis was found in 13.9 % of the cats. Cocci and Bacilli were the secondary factors in 34.3 % and 22.9 % of cats with OE, respectively. The Malassezia genus was a secundary factor in 57.1 % of the cats with OE. The frequency of OE was high in cats receiving hospital care. O. cynotis was a frequent primary cause of OE in cats. The curette sampling method is a great option for diagnosing O. cynotis infestation due to its ease of use.

Antibacterial effects of chitosan-based hydrogels containing Trachyspermum ammi essential oil on pathogens isolated from dogs with otitis externa.

BACKGROUND: Growing antibiotic resistance has made treating otitis externa (OE) increasingly challenging. On the other hand, local antimicrobial treatments, especially those that combine essential oils (EOs) with nanoparticles, tend to be preferred over systemic ones. It was investigated whether Ajwain (Trachyspermum ammi) EO, combined with chitosan nanoparticles modified by cholesterol, could inhibit the growth of bacterial pathogens isolated from OE cases in dogs. In total, 57 dogs with clinical signs of OE were examined and bacteriologically tested. Hydrogels of Chitosan were synthesized by self-assembly and investigated. EO was extracted (Clevenger machine), and its ingredients were checked (GC-MS analysis) and encapsulated in chitosan-cholesterol nanoparticles. Disc-diffusion and broth Micro-dilution (MIC and MBC) examined its antimicrobial and therapeutic properties. RESULTS: Staphylococcus pseudintermedius (49.3%) was the most common bacteria isolated from OE cases, followed by Pseudomonas aeruginosa (14.7%), Escherichia coli (13.3%), Streptococcus canis (9.3%), Corynebacterium auriscanis (6.7%), Klebsiella pneumoniae (2.7%), Proteus mirabilis (2.7%), and Bacillus cereus (1.3%). The investigation into the antimicrobial properties of Ajwain EO encapsulated in chitosan nanoparticles revealed that it exhibited a more pronounced antimicrobial effect against the pathogens responsible for OE. CONCLUSIONS: Using chitosan nanoparticles encapsulated with EO presents an effective treatment approach for dogs with OE that conventional antimicrobial treatments have not cured. This approach not only enhances antibacterial effects but also reduces the required dosage of antimicrobials, potentially preventing the emergence of antimicrobial resistance.

Epidemiology and risk factors for extension of necrotizing otitis externa.

PURPOSE: Necrotizing otitis externa (OEN) is an aggressive and morbid infection of the external acoustic meatus. What are the risk factors for OEN extension? METHODS: French monocentric retrospective study (2004-2021), including patients with OEN defined by the association of an inflamed EAM, a positive nuclear imaging, the presence of a bacteriological sample and the failure of a well-followed local and/or general antibiotic treatment. OEN was extensive if it was associated with vascular or neurological deficits, if nuclear imaging fixation and/or bone lysis extended beyond the tympanic bone. RESULTS: Our population (n = 39) was male (74%), type 2 diabetic (72%), aged 75.2 years and pseudomonas aeruginosa was found in 88% of cases. Complications for 43% of patients were extensive fixation on nuclear imaging, for 21% of them the presence of extensive bone lysis, for 13% the appearance of facial palsy, for 5.3% the presence hypoglossal nerve palsy and for 2.5% the presence of thrombophlebitis or other nerves palsies. 59% of our population had extensive OEN. The diagnosis of the extensive OEN was made 22 days later (p = 0.04). The clinical presentation was falsely reassuring due to easier identification of the tympanic membrane (70% vs 46%, p = 0.17) but associated with periauricular oedema (42% vs 0%), bone exposure (16% vs 0%) and a temporomandibular joint pain (41% vs 12%). CONCLUSION: Delayed treatment of OEN, identification of clinical bone lysis, especially when the tympanic membrane is easily visualized, and the presence of unbalanced diabetes are potential risk factors for extension of OEN.

Managing emergency department patients with otalgia.

Though the vast majority of conditions associated with otalgia are not life-threatening, there are nuances and controversies in the diagnosis and management of even the most common diseases, such as acute otitis media and otitis externa. For more severe disease processes, such as necrotizing otitis externa, acute mastoiditis, and perichondritis, early recognition and timely management are paramount in reducing morbidity and mortality. A systematic approach to the evaluation of these patients is key to establishing an accurate diagnosis, identifying patients who are at high risk for dangerous etiologies or complications, and providing optimal patient care. This issue summarizes the most recent guidelines and presents a systematic, evidence-based approach to the emergency department evaluation and management of patients with otalgia.

Clinical safety and efficacy of a single-dose gentamicin, posaconazole and mometasone furoate otic suspension for treatment of canine otitis externa.

BACKGROUND: A single-dose, in-clinic, veterinary professional-administered treatment for canine otitis externa was developed to improve compliance and canine welfare. METHODS: This multicentre, controlled, examiner-masked, randomised field trial was conducted in 316 dogs over 42 days. Dogs were treated once, on day 0, with the investigational product containing gentamicin, posaconazole and mometasone furoate (Mometamax Ultra [MU]) or twice (days 0 and 7) with a control product containing florfenicol, terbinafine and betamethasone acetate (CP). The primary endpoint was a composite otitis index score of 4 or less (of 12) on day 14 and 3 or less (of 12) on day 28. RESULTS: On day 28, treatment success was recorded in 128 of 143 MU-treated dogs (89.5%), significantly non-inferior to 116 of 133 (87.2%) CP-treated dogs (Farrington-Manning test, Z = 4.1351, p < 0.0001). For mixed cultures of Staphylococcus pseudintermedius and Malassezia pachydermatis, there was 100% treatment success in MU-treated dogs (n = 33), significantly non-inferior to 90.2% (37 of 41) in CP-treated dogs (Farrington-Manning test, Z = 3.1954, p = 0.0007). LIMITATIONS: Efficacy in chronic otitis externa cases was not investigated. Cytology was not used to aid in diagnosis or for identification of secondary pathogens. CONCLUSION: This unique combination, single-dose product is safe and effective in dogs with otitis externa. It offers enhanced compliance, canine welfare and quality of life by eliminating the owner burden of treating this painful condition.

Otitis externa.

External otitis (EO) is a common and often painful infection in the ear canal. This review provides an overview of the typical presentation, causes, complications, and treatment of EO. The condition is influenced by factors like pH levels, inflammation, and bacterial or fungal invasion. Most common bacteria involved are Pseudomonas aeruginosa and Staphylococcus aureus, and most common fungi are Aspergillus and Candida species. EO can lead to serious complications, such as necrotising EO, which requires prompt medical attention. Treatment involves local care, ear drops, and, in severe cases, systemic antibiotics.

Evaluation of plasma canine C-reactive protein concentrations in dogs with otitis media, healthy dogs and dogs with chronic otitis externa.

BACKGROUND: Otitis is characterised by inflammation of one or more of the structures of the ear. At present, to confirm or exclude otitis media (OM), it is most often necessary to perform a computed tomography (CT) scan or magnetic resonance imaging. Inflammation is an immune defence response found in many conditions that can be detected and tracked by measuring biological markers of inflammation as the Canine C-reactive protein (CRP). OBJECTIVES: The objective of this study was to determine whether CRP measurement is useful as an adjunctive diagnostic tool in dogs with otitis and whether elevated concentrations correlated with disease severity/presence of OM. ANIMALS: Twenty-four client-owned dogs were recruited over 1 year. MATERIALS AND METHODS: The dogs were divided into three groups: chronic or recurrent otitis externa (CO), otitis media (OM) and H (healthy). The dogs with otitis underwent a CT scan of the head, measurement of the plasma CRP concentration and evaluation of a 0-3 Otitis Index Score 3 (OTIS3 score). RESULTS: No dog (0%) in group H had an increased CRP value, compared to 20% in the CO group (one of five dogs) and 23% in the OM group (3 of 13 dogs). Plasma CRP concentrations show a statistically significant positive relationship with the OTIS3 score (p = 0.04). CONCLUSION AND CLINICAL RELEVANCE: Plasma CRP concentration is not reliable as a discriminatory tool in cases of otitis, although there is a trend for elevation in cases with more severe disease. However, a larger study may provide a statistically more reliable correlation between the severity of OM and CRP concentrations.

Chronic otorrhea and osteomyelitis of the external auditory canal by Achromobacter xylosoxidans: an uncommon diagnosis.

PURPOSE: Achromobacter xylosoxidans is an emerging pathogen mainly associated with resistant nosocomial infections. This bacteria had been isolated in the ear together with other pathogens in cultures from patients with chronic otitis media, but it had never been reported as a cause of osteomyelitis of the external auditory canal. CASE PRESENTATION: We present a unique case of a healthy 81-year-old woman who presented with left chronic otorrhea refractory to topical and oral antibiotic treatment. Otomicroscopy revealed an erythematous and exudative external auditory canal (EAC) with scant otorrhea. The tympanic membrane was intact, but an area of bone remodeling with a small cavity anterior and inferior to the bony tympanic frame was observed. Otic culture isolated multi-drug-resistant A. xylosoxidans, only sensitive to meropenem and cotrimoxazole. Temporal bone computed tomography showed an excavation of the floor of the EAC compatible with osteomyelitis. Targeted antibiotherapy for 12 weeks was conducted, with subsequent resolution of symptoms and no progression of the bone erosion. CONCLUSIONS: Atypical pathogens such as A. xylosoxidans can be the cause of chronic otitis externa. Early diagnosis and specific antibiotherapy can prevent the development of further complications, such as osteomyelitis. In these cases, otic cultures play an essential role to identify the causal germ. This is the first case of EAC osteomyelitis due to A. xylosoxidans reported to date.

Fungal Otitis Externa (Otomycosis) Associated with Aspergillus Flavus: A Case Image.

A 48-year-old man presented with a chief complaint of intermittent right ear otorrhea of several-month duration, occasional otalgia and progressive unilateral hearing impairment. He also reported frequent episodes of headache and pressure in the sinuses and maxilla. Previous systemic treatment with antibiotics failed to alleviate the symptoms. A head/neck CT showed completely normal mastoid, middle ear and external auditory canal regions without any evidence of opacification or bone erosion. Otoscopic examination of the right ear disclosed aggregates of dried, brown, fibrillar material and debris occluding the external auditory canal and obstructing the otherwise intact tympanic membrane. Dilation of the external auditory canal or thickening of the tympanic membrane were not appreciated. The canal was debrided and the fibrillar material was placed in formalin. Histopathologic examination revealed numerous branching, septated fungal hyphae organized in densely-packed clusters. In other areas, the fungal hyphae abutted or were attached to lamellated collections of orthokeratin. As highlighted by GMS staining, the fungi were morphologically compatible with Aspergillus species. The clinicopathologic findings supported a diagnosis of fungal otitis externa, while the numerous anucleate squamous cells were compatible with colonization of an underlying, probably developing, cholesteatoma. Culture of material isolated from the external auditory canal confirmed the presence of Aspergillus flavus. In this illustrative case, we present the main clinical and microscopic characteristics of Aspergillus-related otomycosis developing in the setting of a tautochronous cholesteatoma.

Diagnostic accuracy of eosinophil-to-lymphocyte ratio and eosinophil-to-neutrophil ratio as biomarkers for differentiating between fungal and bacterial infection in necrotising otitis externa.

INTRODUCTION: Necrotizing otitis externa (NOE) is a serious, progressive, and potentially life-threatening infection of the external auditory canal, affecting soft tissue and bone. The most common organism causing NOE is Pseudomonas Aeruginosa and less common are Fungal infections. When managing a patient with NOE, a culture is taken from the EAC in order to tailor the appropriate antimicrobial treatment, however commonly, the culture is sterile. Inflammation biomarkers may be used as adjuncts to inform on the differential diagnosis and as prognostic markers. AIM: To characterize and compare values and ratios of components of the complete blood count (CBC) at admission, at patients with positive swab culture. METHODS: A retrospective study of NOE patients was conducted. We included all patients admitted between the years 2001-2023, for whom a culture swab tested positive. We compared CBC findings at hospitalization between bacteria and fungi-positive culture patients. RESULTS: Eosinophils-to-Neutrophils Ratio (ENR) was significantly lower in the fungal group compared to the bacterial group 0.023 ± 0.02 and 0.04 ± 0.03, respectively (p-value = 0.025). Eosinophils-to-Leukocyte Ratio (ELR) was significantly lower in the fungal group compared to the bacterial group 0.058 ± 0.04 and 0.12 ± 0.1 respectively (p-value = 0.009). For definition of ELR ≤ 0.1 we found that, sensitivity was 88% (95%CI = 0.679-0.979) and NPV 90% (95%CI = 0.709-0.982). For definition of ENR ≤ 0.03 sensitivity was 88% (95%CI = 0.679-0.979) and NPV 88% (95%CI = 0.679-0.979). CONCLUSION: Lower values of ELR and ENR in patients with NOE are associated with fungal infection and can serve as a tool in adjusting an appropriate antimicrobial therapy in cases of sterile or when no culture is available.

A pilot study of antimicrobial effects and ototoxicity of a Norway spruce (Picea abies) resin-based canine otic rinse product.

BACKGROUND: Norway spruce (Picea abies) resin-based products are used in human medicine. A resin-based otic rinse also could be useful in supportive care of canine otitis externa (COE), yet information on its antimicrobial effect against canine pathogens or ototoxicity is lacking. OBJECTIVES: To investigate the antimicrobial properties and ototoxicity of a commercial resin-based otic product. MATERIALS AND METHODS: Antimicrobial effect was evaluated using a standardised challenge test on Staphylococcus pseudintermedius, Corynebacterium auriscanis, Pseudomonas aeruginosa, Escherichia coli, Malassezia pachydermatis, and Streptococcus halichoeri strains to measure reduction in growth after 24 h exposure to the product. Effect on cell morphology was investigated by exposing S. pseudintermedius, C. auriscanis, P. aeruginosa and M. pachydermatis to the product in 20% and 100% (v/v) concentrations for 6, 24 and 48 h, and evaluating cells by transmission (TEM) and scanning (SEM) electron microscopy. An in vitro microbial kill-rate assay also was performed. Auditory brain stem response test, clinical evaluation and postmortem histological evaluation of ear canals were undertaken on experimental guinea pigs treated with the test product or saline controls. RESULTS: The product showed >log 5 growth reduction for all strains in the challenge test. TEM and SEM images showed clear changes in the cells' inner structures and deterioration of cells, and 100% (v/v) test product exposure induced microbial killing in 1-2 h. Ototoxicity was not detected in guinea pigs. CONCLUSIONS AND CLINICAL RELEVANCE: The product may be an option in supportive care of COE because of antimicrobial effects and lack of ototoxic properties in a guinea pig model.

Aspergillus infections of lateral skull base: a case series.

PURPOSE: While extensive research with accurate classification has been done in mycoses of the paranasal sinuses and anterior skull base, a similar understanding of lateral skull base fungal pathologies is lacking due to relative rarity and diagnostic difficulties. We introduce a series of eleven cases and two different invasive entities of Aspergillus temporal bone diseases-fungal skull base osteomyelitis (SBO)/malignant otitis externa (MOE) and chronic invasive granulomatous fungal disease (CIGFD). METHODOLOGY: A retrospective observational study was conducted at the neuro-otology unit of a tertiary care referral center between July 2017 and November 2022. Diagnosed cases of lateral skull base osteomyelitis with atypical symptoms and lack of response to culture-directed antibiotics were evaluated for fungal origin. Patient data, including history, laboratory findings, serum galactomannan assay, CT and MRI imaging findings, clinical examination findings, and co-morbidities, were analyzed. The treatment course and response were assessed. RESULTS: A total of 11 cases were included in the study. Of these, 9 were cases of Aspergillus-induced skull base osteomyelitis (SBO) and 2 of Aspergillus-induced chronic invasive granulomatous fungal disease (CIGFD). CIGFD presented with persistent ear discharge and slowly progressive post-aural swelling, while all patients of fungal SBO had lower cranial nerve palsies. CIGFD responded to excision and antifungals, while SBO responded well to conservative anti-fungal treatment. CONCLUSION: In cases of lateral SBO not responding to antibiotic therapy, the possibility of fungal etiology should be considered. Aspergillus spp. seems to be the major fungal pathogen.

Predictive role of facial nerve palsy improvement in malignant external otitis.

PURPOSE: To evaluate the effects of different factors on facial nerve palsy improvement in patients with malignant external otitis (MEO) and the predictive role of improvement on MEO. METHODS: Data were collected from all MEO patients with facial paralysis who were hospitalized between 2012 and 2017 at a tertiary referral center. We contacted patients at least 6 months after their admission to evaluate their facial nerve function and survival rate. RESULTS: In a study of 19 samples with a mean age of 69.1 years, 9 patients (47.7%) had some or complete improvement, while 10 (52.6%) had no or very minimal improvement. In this study, there was no statistically significant difference between patients with and without facial nerve palsy improvement in terms of age, sex, usage of antifungal treatment alongside antibiotics, duration of hospital stays, HbA1c level, presentation of hearing loss and vertigo, the severity of facial palsy, comorbidity score, mean of fasting blood sugar, leukocytosis, first ESR and ESR drop, CRP and physiotherapy. We found a positive correlation between improving facial palsy and patients' survival rates. CONCLUSION: Considering the possible influence of facial paralysis improvement prognosis on MEO patients' survival, it could affect our approach to the disease.