Role of Biofilms in Post-Tympanostomy Tube Otorrhea.

OBJECTIVE: Nearly half of children who undergo tympanostomy tube (TT) insertion may experience otorrhea following surgery. We sought to review the evidence for the role of bacterial biofilms in post-tympanostomy tube otorrhea (PTTO) and the accumulated experience regarding the preventive measures for biofilm formation/adhesion on TTs. METHODS: English literature search for relevant MeSH keywords was conducted in the following databases: MEDLINE (via PubMed), Ovid Medline, Google Scholar, and Clinical Evidence (BMJ Publishing) between January 1, 1995, and December 31, 2019. Subsequently, articles were reviewed and included if biofilm was evident in PTTO. RESULTS: There is an increased evidence supporting the role of biofilms in PTTO. Studies on TT design and material suggest that nitinol and/or silicone TTs had a lower risk for PTTO and that biofilms appeared in specific areas, such as the perpendicular junction of the T-tubes and the round rims of the Paparella-type tubes. Biofilm-component DNAB-II protein family was present in half of children with PTTO, and targeting this protein may lead to biofilm collapse and serve as a potential strategy for PTTO treatment. Novel approaches for the prevention of biofilm-associated PTTO include changing the inherent tube composition; tube coating with antibiotics, polymers, plant extracts, or other biofilm-resistant materials; impregnation with antimicrobial compounds; and surface alterations by ion-bombardment or surface ionization, which are still under laboratory investigation. CONCLUSIONS: Currently, there is no type of TT on which bacteria will not adhere. The challenges of treating PTTO indicate the need for further research in optimization of TT design, composition, and coating.

In vitro and in vivo efficacy of tea tree essential oil for bacterial and yeast ear infections in dogs / Uso in vitro e in vivo do óleo essencial de Melaleuca (Melaleuca alternifolia) em otites bacterianas e por leveduras

Otitis externa is a common complaint in dogs. Bacteria and yeasts are commonly involved and may perpetuate inflammatory reactions inside the ear canal. Otoscopy, cytological examination of secretion and microbiological culture embody forms of diagnosis. Cytology also has great use in accessing treatment evolution. Therapy usually consists of cleaning ear canals and subsequent use of antibiotics or antifungal products. As some of them may cause hypersensitivity and even ototoxicity, searching for new pharmacological bases is currently necessary and justifies this study, which aimed to evaluate in vitro and in vivo efficacy of tea tree essential oil for bacterial and yeast ear infections in dogs. Twenty-eight dogs from a particular shelter in Cuiabá (Mato Grosso, Brazil), presenting clinical signs of otitis externa, were enrolled in this clinical trial. In all of them, clinical and cytological evaluations, as well as culture and susceptibility testing of the affected ears were carried out. From each dog, one ear was treated with 5% tea tree essential oil lotion and the other with standard otic formulation, according to the type of infection (bacterial, yeast or both). In vitro susceptibility testings of all ear cultures, to the same drugs used in treatment, were also carried out. Culture results showed 62.5% bacterial and fungal infection, 33.9% bacterial infection and 3.6% fungal infection, from the 56 ear samples collected. The most common microorganisms isolated were Staphylococcus intermedius, Staphylococcus aureus, Proteus mirabilis and Malassezia pachydermatis. Gram-positive bacteria were susceptible to gentamycin in 60.5% and resistant in 16.3% of the samples. Five percent tea tree essential oil formulation produced a 5mm clear zone of inhibition around the disks in one of the 63 samples evaluated. Pure (100%) tea tree essential oil formulation produced a 10mm clear zone of inhibition around the disks in four of the 63 samples evaluated, a 9mm zone in three samples, an 8mm zone in 16 samples, a 7mm zone in seven samples, a 6mm zone in two samples and there was no clear zone in 31 samples. Inhibition zones were produced by strains of Staphylococcus intermedius, Staphylococcus hyicus, Corynebacterium sp., Proteus mirabilis and Enterobacter sp. tea tree essential oil ear solution significantly induced remission of clinical signs both in bacterial and yeast ear infections. It also reduced as much Malassezia pachydermatis ear infection as the nystatin solution used in this study, while gentamycin solution showed better antibacterial effect. More studies should be conducted to evaluate in vitro diffusion properties of tea tree essential oil. Good antimicrobial spectrum and the absence of adverse reactions confirm the importance of developing a tea tree formulation as an alternative therapy for ear infections in dogs.(AU)

Otite externa é queixa frequente em cães. Bactérias e leveduras estão comumente envolvidas e podem perpetuar as reações inflamatórias dentro do canal auditivo. Dentre as formas de diagnóstico, encontram-se a otoscopia, o exame citológico da secreção e a cultura microbiológica. Citologia também tem grande utilidade no acesso à evolução do tratamento. A terapia consiste de limpeza dos canais auditivos e posterior utilização de antibióticos ou produtos antifúngicos. Como alguns antimicrobianos utilizados no tratamento podem causar hipersensibilidade e até mesmo ototoxicidade, a busca por novas bases farmacológicas justifica a existência deste estudo, que teve como objetivo avaliar in vitro e in vivo a eficiência do óleo de Melaleuca alternifolia em otites bacterianas e fúngicas de cães. Vinte e oito cães, de um abrigo particular, apresentando sinais clínicos de otite externa, foram incluídos neste estudo clínico. Todos passaram por avaliação clínica, citologia e cultura de material das orelhas afetadas. De cada animal, uma orelha foi tratada com óleo de Melaleuca 5% e a outra com formulação ótica padrão, de acordo com a afecção (bacteriana, fúngica ou mista). As culturas também foram submetidas a testes de susceptibilidade in vitro aos mesmos agentes utilizados no tratamento in vivo. Os resultados da cultura mostraram 62,5% de infecção mista (bacteriana e fúngica), 33,9% de infecção bacteriana e 3,6%, de infecção fúngica a partir das 56 orelhas. Os micro-organismos mais isolados foram Staphylococcus intermedius, Staphylococcus aureus, Proteus mirabilis e Malassezia pachydermatis. As bactérias GRAM-positivas foram sensíveis à gentamicina em 60,5% e resistentes em 16,3% das amostras. A formulação com 5% de óleo essencial de Melaleuca produziu uma zona de inibição de 5mm em torno dos discos em uma das 63 amostras avaliadas. A formulação pura (100%) do mesmo produto produziu uma zona de 10mm de inibição em quatro das 63 amostras analisadas, uma zona de 9 mm em três amostras, uma zona de 8mm em 16 amostras, uma zona de 7mm em sete amostras, uma zona de 6mm em duas amostras e não havia nenhuma zona clara em 31 amostras. Zonas de inibição foram produzidas por estirpes de Staphylococcus intermedius, Staphylococcus hyicus, Corynebacterium sp., Proteus mirabilis e Enterobacter sp. Clinicamente, a formulação com o óleo essencial de melaleuca induziu significativamente uma melhora nas manifestações, tanto nas otites bacterianas quanto nas causadas por leveduras, sendo estatisticamente semelhante ao tratamento com nistatina (nas otites por levedura), mas menos eficaz que a solução de gentamicina nas otites bacterianas. Mais estudos devem ser realizados para avaliar as propriedades de difusão in vitro do óleo essencial de melaleuca. O bom espectro antimicrobiano, a boa resposta clínica e a ausência de reações adversas confirmam a possibilidade de desenvolvimento de formulação ótica com o óleo essencial de melaleuca, como uma alternativa para a terapia de infecções do ouvido em cães.(AU)

In Vitro Susceptibility of Ciprofloxacin-Resistant Methicillin-Resistant Staphylococcus aureus to Ototopical Therapy.

Objective Despite the rising incidence of methicillin-resistant Staphylococcus aureus (MRSA) otologic infections, choice of treatment remains controversial. Only fluoroquinolone-containing ototopical preparations are approved by the US Food and Drug Administration for middle ear application. Furthermore, American Academy of Otolaryngology-Head and Neck Surgery Foundation guidelines advocate ototopical monotherapy for both tympanostomy tube otorrhea and acute otitis externa. Unfortunately, MRSA may be ciprofloxacin resistant. This causes confusion regarding antibiotic selection, because susceptibility profiles reflect a minimum inhibitory concentration (MIC), referenced against systemic, not ototopical, drug delivery dosing. The goal of this study is to determine the ciprofloxacin MIC for ciprofloxacin-resistant MRSA isolates from otologic infections and compare that value to the expected drug concentration achieved by fluoroquinolone ear drops and determine MRSA genotype for each isolate. Study Design In vitro assay with retrospective medical record review. Setting Tertiary care university hospital. Subjects and Methods Thirty otologically sourced ciprofloxacin-resistant MRSA isolates collected from adult and pediatric patients. MICs were calculated by broth dilution method. Isolates underwent multilocus sequence typing and polymerase chain reaction for arcA and Panton-Valentine leukocidin to establish the genotype. Results MICs ranged from 16 to 1025 µg/mL. There was a relationship between MIC and genotype; of the 7 isolates with an MIC value greater than 512 µg/mL, 6 were sequence type (ST)8. Conclusion These findings support the practice of ototopical monotherapy for patients with uncomplicated ciprofloxacin-resistant MRSA otitis externa. However, they raise concern that ototopical therapy may not be adequate to treat highly resistant strains of MRSA infecting the middle ear space.

Ethnopharmacological uses of Sempervivum tectorum L. in southern Serbia: Scientific confirmation for the use against otitis linked bacteria.

ETHNOPHARMACOLOGICAL RELEVANCE: Sempervivum tectorum L. (Crassulaceae), known as houseleek, is used in traditional medicine in the treatment of ear inflammation. It can be spread as a pack on wounds, sores, burns, and abscesses and also on painful areas attacked by gout as a refrigerant and astringent. Drinking tea prepared from leaves of S. tectorum is recommended for ulcer treatment. The present study was designed to investigate ethopharmacological use of S. tectorum in the southern Serbia and to further scientifically justify and confirm effectiveness of the leaf juice used in ethnomedicine for ear inflammation, against otitis linked bacteria. MATERIAL AND METHODS: Ethnopharmacological survey on the use of S. tectorum in southern Serbia was performed using semi structured questionnaires via a face-to-face interview. Chemical composition of the leaf juice regarding phenolic compounds and organic acids was analyzed. Antimicrobial activity was tested on bacteria isolated from ear swabs of the patients suffering from the ear pain (otitis). Anti-quorum-sensing activities of the juice were further investigated on Pseudomonas aeruginosa. RESULTS: Ethnopharmacological survey revealed the use of S. tectorum in southern Serbia for the treatment of ear pain, warts, cancer, stomachache, ulcer and high blood sugar level with the highest fidelity level (FL) for the ear pain. The phenolic composition of the S. tectorum leaf juice consisted of flavonol glycosides, with kaempferol-3-O-rhamnosyl-glucoside-7-O-rhamnoside as the majority compound. Organic acids composition revealed malic acid as the most dominant one. Antimicrobial and anti-quorum-sensing activities of the juice showed to be promising. CONCLUSION: Ethnopharmacological use of S. tectorum juice for treating ear pain is justified, since the juice possessed antimicrobial activity towards clinical isolates of bacteria linked to otitis.

In vitro and in vivo activity of a killer peptide against Malassezia pachydermatis causing otitis in dogs.

In order to overcome the limitations inherent in current pharmacological treatments for Malassezia pachydermatis, the cause of otitis externa in dogs, the efficacy of a killer decapeptide (KP) was evaluated in vitro and in vivo. Sixteen dogs with naturally occurring M. pachydermatis otitis externa were enrolled, and the in vitro fungicidal activity of KP was evaluated using yeasts recovered from these animals. The therapeutic activity was evaluated in four groups of four animals each. The dogs were topically treated with KP (150 µl, 2 mg/ml) three times per week (group A) or every day (group B), treated with a scramble peptide every day (group C), or left untreated (group D). Assessment of clinical signs (pruritus, erythema, and lichenification and/or hyperpigmentation), expressed as mean of the total clinical index score (mTCIS), the population size of M. pachydermatis at the cytological examination (mean number of yeast cells at 40× magnification [mYC]), and culture testing (mean number of log10 CFU/swab [mCFU]), were conducted daily from the first day of treatment (T0) until two consecutive negative cultures (mCFU ≤ 2). KP showed an in vitro fungicidal effect against M. pachydermatis isolates, with an MFC90 value of 1 µg/ml. The mTCIS, mYC and mCFU were negative only in animals in group B after T8. Daily administration of KP for 8 days was safe and effective in controlling both clinical signs and the population size of M. pachydermatis causing otitis externa, thus offering an alternative to the currently available therapeutic or prophylactic protocols for recurrent cases of Malassezia otitis in dogs.

Atividade antimicrobiana do oleorresina de copaíba (Copaifera reticulata) frente a Staphylococcus coagulase positiva isolados de casos de otite em cães / Antimicrobial activity of copaiba oil (Copaifera reticulata) against coagulase positive Staphylococcus of canine otitis

The aim of this study was to investigate the antimicrobial activity of the oleoresin Copaifera reticulata Ducke against Staphylococcus coagulase positive (SCP) isolated from otitis externa in dogs. The minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) of the oleoresin were determined by broth microdilution method. In addition, we verified the antimicrobial susceptibility profile of the isolates of SCP by agar diffusion method. Eight classes of antimicrobial were used to calculate the multidrug resistance. The chemical composition of the oleoresin was performed by gas chromatography coupled to the mass spectrometry (GC/MS), and β-caryophyllene, β-bisabolene, and (E)-α-bergamotene were the main compounds found. The copaiba oleoresin showed a MIC90 of 0.164mg/mL and a CBM90 of 1.3mg/mL. The multidrug resistance was found in 27% of the strains tested. The results suggest that copaiba oleoresin has bacteriostatic and bactericidal activity even in multidrug-resistant coagulase-positive strains.

O objetivo do presente trabalho foi investigar o potencial antimicrobiano do oleorresina de Copaifera reticulata Ducke em isolados de Staphylococcus coagulase positiva (SCP) provenientes de casos de otite externa em cães. O método de microdiluição em caldo foi utilizado para determinação da concentração inibitória mínima (CIM) e concentração bactericida mínima (CBM) de oleorresina de copaíba. Em adição, foi determinado o perfil de suscetibilidade aos antimicrobianos dos isolados de SCP pelo método de difusão em ágar. Oito classes de antimicrobianos foram usadas para o cálculo de multirresistência antimicrobiana. A determinação da composição química do oleorresina de copaíba foi realizada por cromatografia em fase gasosa acoplada à espectrometria de massas (GC/MS), sendo que β-cariofileno, β-bisaboleno e (E)-α-bergamoteno foram os compostos majoritários. O oleorresina de copaíba demonstrou CIM90 de 0,164mg/mL e CBM90 de 1,31mg/mL. A multirresistência foi verificada em 27% das cepas testadas. Os resultados sugerem que o oleorresina de copaíba exerceu atividade bacteriostática e bactericida mesmo em cepas multirresistentes de Staphylococcus coagulase-positiva.

Antimicrobial activity of Terminalia arjuna Wight & Arn.: an ethnomedicinal plant against pathogens causing ear infection.

UNLABELLED: Ear infection is one of the common diseases occurring throughout the world. Different etiological agents are responsible for ear infections. AIM: To assess the antimicrobial potential of Terminalia arjuna leaves and bark extracts against Staphylococcus aureus, Acinetobacter sp., Proteus mirabilis, Escherchia coli, Pseudomonas aeruginosa and Candida albicans, pathogens causing ear infections and their comparison with locally available ear drops. MATERIALS AND METHODS: Methanol, ethanol, acetone, aqueous (hot and cold) extracts from the leaves and bark of T. arjuna were tested for their antimicrobial activity. RESULTS: Of the three organic solvents evaluated, acetonic leaf extract was found to be best against S. aureus. Organic bark extract showed almost equal inhibition of all tested Gram negative bacteria except P. aeruginosa. However, aqueous extract of T. arjuna bark exhibited good activity against S. aureus. All the extracts were unable to exhibit any antifungal activity. CONCLUSION: Organic extract obtained from the T. arjuna bark and leaves may be used to treat the bacterial ear pathogens especially S. aureus, which has shown greater inhibition zones than the herbal drops, however, we still need more detailed studies as in vivo testing and pharmacokinetics properties for their therapeutic utility in treating ear infections.

Atividade antimicrobiana da Terminalia arjuna Wight & Arn.: uma planta etnomedicinal contra patógenos causadores de infecções no ouvido / Antimicrobial activity of Terminalia arjuna Wight & Arn.: an ethnomedicinal plant against pathogens causing ear infection

Infecções de ouvido representam uma das doenças mais comuns do mundo. Diferentes agentes etiológicos são responsáveis por tais infecções. OBJETIVO: Avaliar o potencial antimicrobiano de extratos de folhas e da casca de Terminalia arjuna contra Staphylococcus aureus, Acinetobacter sp., Proteus mirabilis, Escherchia coli, Pseudomonas aeruginosa e Candida albicans - patógenos que causam infecções de ouvido e como esses extratos se comparam às medicações tópicas atualmente disponíveis. MATERIAIS E MÉTODOS: Metanol, etanol, acetona, extratos aquosos (quentes e frios) de folhas e casca da T. arjuna foram testados para avaliação de suas atividades antimicrobianas. RESULTADOS: Dos três solventes orgânicos avaliados, o extrato acetônico das folhas foi o que teve o melhor resultado contra S. aureus. O extrato orgânico da casca exibiu quase o mesmo grau de ação antimicrobiana entre todas as bactérias gram-negativas, exceto contra P. aeruginosa. Entretanto, o extrato aquoso da casca de T. arjuna exibiu boa atividade contra S. aureus. Nenhum dos extratos exibiu atividade antifúngica. CONCLUSÃO: O extrato orgânico obtido a partir da casca e folhas de T. arjuna pode ser usado para tratar infecções bacterianas de ouvido, especialmente aquelas causadas por S. aureus, que exibiu maiores zonas de inibição do que gotas herbáceas; entretanto, ainda necessitamos de estudos mais detalhados - como ensaios in vivo e avaliações de propriedades farmacocinéticas para avaliarmos sua utilidade terapêutica no tratamento de infecções de ouvido.

Ear infection is one of the common diseases occurring throughout the world. Different etiological agents are responsible for ear infections. AIM: To assess the antimicrobial potential of Terminalia arjuna leaves and bark extracts against Staphylococcus aureus, Acinetobacter sp., Proteus mirabilis, Escherchia coli, Pseudomonas aeruginosa and Candida albicans, pathogens causing ear infections and their comparison with locally available ear drops. MATERIALS AND METHODS: Methanol, ethanol, acetone, aqueous (hot and cold) extracts from the leaves and bark of T. arjuna were tested for their antimicrobial activity. RESULTS: Of the three organic solvents evaluated, acetonic leaf extract was found to be best against S. aureus. Organic bark extract showed almost equal inhibition of all tested Gram negative bacteria except P. aeruginosa. However, aqueous extract of T. arjuna bark exhibited good activity against S. aureus. All the extracts were unable to exhibit any antifungal activity. CONCLUSION: Organic extract obtained from the T. arjuna bark and leaves may be used to treat the bacterial ear pathogens especially S. aureus, which has shown greater inhibition zones than the herbal drops, however, we still need more detailed studies as in vivo testing and pharmacokinetics properties for their therapeutic utility in treating ear infections.

[Treatment of fungal infections of upper respiratory tract and ear]. / Leczenie grzybic górnych dróg oddechowych i ucha.

Fungi, in comparison with other pathogenic factors, have high pathogenicity. The number of fungal species which are able to infect people is over 500. The upper respiratory tract and ear have permanent contact with external environment which makes their ontocenoses open to continuous exchange of microorganisms of which they consist. In etiology of inflammatory processes 21 species which belonging to 3 genera (Zygomycota, Ascomycota, Basidiomycota) of fungi play important role. Administration of antifungal drugs can be: prophylactic, empiric preemptive and therapeutic. Physicians may prescribe antibiotics (mainly pollens: amphotericin B, natamycin and nystatin) and chemiotherapeutics (mainly azoles and fluorpirymidins, pigments, chlorhexidine and chlorquinaldol). In ENT practice topical and systemic drugs can be administrated. Topical lozenges include amphotericin B, clotrimazole, chlorhexidine or chlorquinaldol and oral gels: nystatin and miconazole. Some of drugs are in the form of suspension/solution, which can be used for inhalation, into the sinus, for swabbing or for lavage: amphotericin B, natamycin, nystatin, clotrimazol, flucytosine, miconazole, fluconazole, vorykonazole, caspofungin. It should be underlined that only a few of dugs can be absorbed from the digestive tract: flucytosine, fluconazole, itraconazole, ketoconazole, miconazole, vorykonazole.

Isolation of Staphylococcus schleiferi from healthy dogs and dogs with otitis, pyoderma, or both.

OBJECTIVE: To determine the frequency of isolation and susceptibility patterns of Staphylococcus schleiferi from healthy dogs and dogs with otitis, pyoderma, or both that had or had not received antimicrobial treatment. DESIGN: Prospective study. ANIMALS: 50 dogs. PROCEDURE: Dogs were allocated to 1 of 4 groups: healthy dogs (n=13), dogs without otitis but with pyoderma (10), dogs with otitis but without pyoderma (11), and dogs with otitis and pyoderma (16). Bacteriologic culture of ear swab specimens was performed in all dogs. Bacteriologic culture of skin swab specimens was also performed in dogs with concurrent pyoderma. Isolates were identified as S schleiferi subsp schleiferi or S schleiferi subsp coagulans on the basis of growth and biochemical characteristics. RESULTS: S schleiferi was not isolated from any dogs with pyoderma only. Staphylococcus schleiferi subsp schleiferi was isolated from the ears of 2 healthy dogs, and the skin and ears of 2 dogs and the skin of 1 dog with otitis and pyoderma. Staphylococcus schleiferi subsp coagulans was isolated from the ears of 3 dogs with otitis only, and the ears of 6 dogs and the skin of 2 dogs with otitis and pyoderma. One of the S schleiferi subsp schleiferi isolates from ears, 2 of the S schleiferi subsp coagulans isolates from ears, and 1 of the S schleiferi subsp coagulans isolates from the skin were resistant to methicillin. One methicillin-resistant isolate from the ears and 1 from the skin were also resistant to fluoroquinolones. CONCLUSIONS AND CLINICAL RELEVANCE: S schleiferi subsp schleiferi was detected in healthy dogs and dogs with otitis and pyoderma. Methicillin-resistant and -susceptible S schleiferi subsp schleiferi and S schleiferi subsp coagulans were detected as the predominant organisms in dogs with otitis.

Potentiating effect of EDTA-Tris on the activity of antibiotics against resistant bacteria associated with otitis, dermatitis and cystitis.

Possible synergistic effects of the combination of EDTA-tromethamine (EDTA-Tris) and three antimicrobial agents (cephaloridine, kanendomycin and enrofloxacin) against resistant Gram-positive and Gram-negative bacteria are reported. Bacteria were isolated from eight cases of chronic otitis externa, five cases of chronic dermatitis and four cases of recurrent cystitis in dogs which had previously been treated with one of the three antibiotics without success. Animals exposed to EDTA-tromethamine plus the antibiotic recovered completely within 10 days, and were controlled clinically and bacteriologically for 180 days. Local irrigation with EDTA-tromethamine solution was well tolerated and no side effects were recorded.

[Bacterial infections of the ear: case contribution on clinical and microbiological aspects]. / Le infezioni batteriche dell'orecchio: contributo casistico sugli aspetti microbiologici e clinici.

Ciprofloxacin was given in oral doses of 250 mg. each 8 hours to 21 patients with otitis. The efficacy of treatment was assessed by clinical and bacteriological parameters. The 61.9% of isolated bacteria are opportunistic. A case of chronic otitis by Achromobacter xylosoxidans is described.