Update of the consensus document on the aetiology, diagnosis and treatment of acute otitis media and sinusitis.

Update of the consensus on acute otitis media (AOM) (2012) and sinusitis (2013) following the introduction of pneumococcal vaccines in the immunization schedule, and related changes, such as epidemiological variation, colonization by of nonvaccine serotypes and emerging antimicrobial resistances. A majority of studies show that the introduction of the pneumococcal 13-valent conjugate vaccine has been followed by a reduction in the nasopharyngeal carriage of pneumococcus, with an increase in the proportion of drug-resistant nonvaccine serotypes. The diagnosis of AOM is still clinical, although more stringent criteria are proposed, which are based on the visualization of abnormalities in the tympanic membrane and the findings of pneumatic otoscopy performed by trained clinicians. The routine diagnosis of sinusitis is also clinical, and the use of imaging is restricted to the assessment of complications. Analgesia with acetaminophen or ibuprofen is the cornerstone of AOM management; watchful waiting or delayed antibiotic prescription may be suitable strategies in select patients. The first-line antibiotic drug in children with AOM and sinusitis and moderate to severe disease is still high-dose amoxicillin, or amoxicillin-clavulanic acid in select cases. Short-course regimens lasting 5-7 days are recommended for patients with uncomplicated disease, no risk factors and a mild presentation. In allergic patients, the selection of the antibiotic agent must be individualized based on severity and whether or not the allergy is IgE-mediated. In recurrent AOM, the choice between watchful waiting, antibiotic prophylaxis or surgery must be individualized based on the clinical characteristics of the patient.

Improvement of Suspected Eosinophilic Otitis Media with Targeted Biologic Therapy.

OBJECTIVE: To compare the responses of suspected eosinophilic otitis media to treatment with or without a targeted biologic therapy against interleukin-4 (IL-4), IL-5, or IL-13 signaling. STUDY DESIGN: Retrospective review. SETTING: Tertiary referral center. PATIENTS: Subjects with type 2 chronic rhinosinusitis with nasal polyposis (CRSwNP), asthma, and otitis media who underwent treatment between 2005 and 2021. INTERVENTION: Treatment with targeted biologic therapy. MAIN OUTCOME MEASURES: Pre- and posttreatment nasal endoscopy, ear examination, and audiologic evaluation. RESULTS: Four hundred seventy-seven subjects with type 2 CRSwNP were treated between 2005 and 2021. Sixty-two had otitis media with pre- and posttreatment evaluation. Retrospective chart review assessed pre- and posttreatment exam findings, nasal endoscopy, audiometry, and tympanometry. Nineteen subjects received a biologic therapy, whereas 43 did not. Exam, endoscopy, and tympanometry were graded for severity and compared pre- and posttreatment. Subjective ear exam and tympanometry were significantly improved with biologic therapy (control = 0.05, biologic = 0.84, p = 9.3 × 10 -5 ; control = -0.1, biologic = 0.62, p = 0.0002). Conductive hearing loss as assessed by air-bone gaps did not change between groups (control = 1.2 dB better, biologic = 1.2 dB worse, p = 0.32). Nasal endoscopy findings improved with biologic therapy relative to the control group, although not statistically significant (control = 1.04, biologic = 1.36, p = 0.22). CONCLUSIONS: Biologic therapies targeting interleukin-4 (IL-4), IL-5, and IL-13 signaling are potential new treatments for eosinophilic otitis media. This is the largest study demonstrating improvement in subjects with suspected eosinophilic otitis media in response to biologic therapy, and immune modulation represents a novel treatment strategy for this challenging condition. PROFESSIONAL PRACTICE GAP AND EDUCATIONAL NEED: Current treatment strategies for otologic symptoms in eosinophilic disease are not tremendously effective or durable, resulting in a need for improved treatment options. LEARNING OBJECTIVE: To determine if targeted biologic therapy, often used for eosinophilic asthma and type 2 chronic rhinosinusitis with nasal polyposis, improves coexistent suspected eosinophilic otitis media. DESIRED RESULT: Treatment of suspected eosinophilic otitis media with targeted biologic therapy will result in improvement of otologic symptoms with a durable response compared with current treatment options. LEVEL OF EVIDENCE: Level IV. INDICATE IRB OR IACUC: Exempt. HUM00182703.

Haemophilus influenzae drug resistance in France from 2017 to 2021: consideration for treatment of otitis media.

OBJECTIVES: Haemophilus influenzae is a prevalent agent of respiratory infections, including acute otitis media (AOM), that lead to high antibiotic prescription and may contribute to the development of bacterial resistance to antibiotics. The objective of this work was to describe and analyse antibiotic resistance of H. influenzae from 2017 to 2021 in France. METHODS: We characterized H. influenzae isolates transmitted to the French national reference centre for H. influenzae between 2017 and 2021. We included all the 608 non-invasive respiratory isolates. Resistance rates to the main antibiotics were described. The relationship between resistance rate, age, and sex of patients and germ serotype was investigated. RESULTS: Isolates were mainly from alveolar lavage (29.3%), expectoration (22.9%), or sputum (15%). Resistance to amoxicillin (61.4%), amoxicillin/clavulanic acid (47.4%), and cefotaxime (39.3%) was high and correlated with the presence of ß-lactamase and/or modifications of the ftsI gene encoding penicillin-binding protein 3. Resistance to sulfamethoxazole/trimethoprim (33.2%) was more moderate. There were no significant differences according to serotype, age, or gender. CONCLUSIONS: The benefit/risk balance of first choice use of amoxicillin and even of amoxicillin/clavulanic acid in AOM is questionable in view of the significant resistance to H. influenzae. The use of sulfamethoxazole/trimethoprim could be an alternative but may still need further evaluation.

Complementary/Integrative Medicine for Pediatric Otitis Media.

Complementary/integrative medicine can be used in treating otitis media, especially during the watchful waiting phase. Elimination of risk factors can be important. Products such as echinacea, xylitol, and probiotics may help in prevention. Herbal eardrop formulations can relieve symptoms in some patients. Other modalities such as homeopathy can lead to faster relief of symptoms in combination with conventional therapy. Chinese, Japanese, and other forms of traditional medicine have varying formulations with unclear safety, but initial results are promising. Most studies are limited by methodological failures and small sample sizes, emphasizing the need for continued research in this area.

Antibiogram guided optimized medical treatment in chronic otitis media: A useful interventional strategy before surgery?

BACKGROUND: Chronic otitis media is a middle ear cleft disease presenting with tympanic membrane perforation and discharge. Wet ear after tympanoplasty and discharging mastoid cavity are problematic in clinical practice. MATERIAL AND METHODS: 1050 patients of age 10 to 50 years presenting with active ear discharge and clinically diagnosed with unilateral chronic suppurative otitis media were included in the study. The patients were equally divided into two equal groups, Group ET, and AT. All patients were prescribed topical ciprofloxacin, oral levocetirizine 5 mg and n-acetyl cysteine 600 mg BD for one week. Swabs of ear discharge were collected in ET groups for antibiogram. Both groups were evaluated on next visit and treatment changed in AT groups and result observed in next visit. Surgical outcome was evaluated at end of 2 yrs. RESULT: A total of 1158 organisms were isolated in culture out of which, 69.94 % were aerobes, 13.47 % anaerobes and 16.58 % were fungi. On the second visit in group AT, treatment of 85.14 % patients was changed in accordance with culture sensitivity report. In patients with mucosal disease, only 46.87 % patients of group ET had a favorable outcome in comparison to 90.28 % patients of group AT while in patients with squamosal disease, 17.56 % patients of group ET and 28.99 % patients in group AT had a dry ear. Surgeries in AT group were found to have statistically significant higher success rate as compared to ET group.

Sonodynamic therapy exciting the herbal nanocomposite with spider-web-like effect to combat otitis media.

Otitis media, mainly caused by bacteria, is prevalent in young children and can cause hearing loss and growth retardation. Antibiotics are the most widely utilized treatment for otitis media, however, they can cause drug resistance and harmful side effects. In this study, we reported an antibacterial nanocomposite in combination with sonodynamic therapy that consists of herbal antibacterial agents such as Curcumin (CUR) and Tanshinone IIA (TSIIA), as well as Chitosan (CS), for the treatment of acute otitis media. CUR/TSIIA/CS nanocomposite (NC) with ultrasonic irradiation demonstrated that it could eliminate Staphylococcus aureus. In vivo experiments revealed that NC-mediated sonodynamic therapy had excellent antibacterial and anti-inflammatory activity, displaying a consistent performance comparable to ofloxacin. The therapeutic efficiency was attributed to capturing bacteria through spider-web-like effect and destroying bacteria through the reactive oxygen species generated under ultrasonic irradiation. Significantly, NC did not induce bacterial resistance and showed good biocompatibility. This study provides a novel strategy to develop an ultrasound-assisted nanocomposite with an enhanced antibacterial effect. Further, it unlocks new doors for the substitute of antibiotics to combat otitis media by establishing efficient therapeutic systems.

Sequential Biotherapy Targeting IL-5 and IL-4/13 in Patients with Eosinophilic Asthma with Sinusitis and Otitis Media.

Type 2 (T2) inflammation plays an important role in the pathogenesis of allergic diseases such as asthma, eosinophilic chronic rhinosinusitis (ECRS), or eosinophilic otitis media (EOM). Currently, in severe asthma with the T2 phenotype, biologics targeting mediators of T2 inflammation dramatically improve the management of severe asthma. While treatment with a single biologic is common, little is known about cases of the sequential use of two biologics. Here, we report a case of severe asthma with refractory ECRS and EOM in which total control of these allergic diseases could not be achieved with a single biologic but could be achieved via the sequential use of the anti-IL-5 receptor antibody and human anti-IL-4/13 receptor monoclonal antibody. It is suggested that it is necessary to control multiple T2 inflammatory pathways to achieve total control of severe allergic diseases. Sequential biotherapy may help solve the clinical challenges associated with single-agent molecular-targeted therapies.

Non-prescription treatments for childhood infections: an Austrian, monocentric, cross-sectional questionnaire study.

BACKGROUND: Infectious diseases like the common cold, otitis media, or gastroenteritis frequently occur in childhood. In addition to prescription drugs, parents often use supplementary over-the-counter (OTC) products recommended by pharmacists and other non-medical professionals to relieve their children's symptoms. However, the efficacy of such alternative treatments lacks conclusive evidence. The objective of this study was to investigate the use of OTC products and related active ingredients in children, and the motivations behind this choice. METHODS: The present study included 215 children aged between 1 and 14 years with an acute respiratory tract infection, e.g., common cold, bronchitis, otitis media, tonsillitis, or gastroenteritis. During their visit to the pediatric practice, parents filled in a self-administered questionnaire about their child's diagnosis, additional treatment options, and motivations to integrate supplementary medicinal products after their first visit for acute infection or follow-up examination. Children with chronic illnesses and patients visiting for a routine maternal and child health program check-up were excluded. RESULTS: The study included 111 (51.6%) males and 104 (48.4%) females. Median age was 3.00 (IQR 2.0 - 5.0) years. The most common reason for a visit was a respiratory tract infection (78.6%). Out of 215 parents, 182 (84.7%) resorted to non-prescription remedies to alleviate their child's symptoms. Teas (45.1%), and home remedies (43.3%) were the most popular. At total 133 (74.3%) followed recommendations from friends and family regarding additional medications usage. Parents with previous experience with complementary medicine tended to prefer this approach to treat their children (p.adjust = 0.08). CONCLUSION: The use of non-prescription medicine is increasing as well as the range of related information sources. Evidence-based recommendations in this field might improve pediatric care.

Analysis of pathogens and antimicrobial treatment in different groups of patients with chronic otitis media.

OBJECTIVE: Microbial infection plays an important role in exacerbation of chronic otitis media. The aim of this study was to analyse the microbiota in chronic otitis media in the context of local treatment. METHOD: In this prospective study, samples for microbiological examination were taken from 119 patients who underwent operation because of chronic otitis media. RESULTS: The results were compared between groups depending on the type of operation (none, tympanoplasty or radical), the presence of cholesteatoma or granulomatous tissue or discharge from the ear as a symptom of exacerbation. Antibiotic susceptibility of germs was analysed to define the strategy of treatment. A total of 209 samples were collected from 119 patients with chronic otitis media. CONCLUSION: Pseudomonas aeruginosa and Staphylococcus aureus were pathogens most frequently identified from the ear in the course of chronic otitis media. Pseudomonas aeruginosa was concerned with major pathology of the middle ear (radical surgery, cholesteatoma or granulomatous tissue, persisting discharge after treatment), whereas Staphylococcus aureus was obtained in dry perforations without other pathology in the middle-ear cavity. Ciprofloxacin was effective against Staphylococcus aureus, but Pseudomonas aeruginosa strains were ciprofloxacin resistant.

Structural elucidation, mechanism of action, antibacterial proficiency and synergistic forte of purified Euphorbia hirta whole plant extract against multi-drug resistant otitis media infection / Elucidación estructural, mecanismo de acción, competencia antibacteriana y fuerza sinérgica del extracto de planta entera de Euphorbia hirta purificado contra la infección por otitis media resistente a múltiples fármacos

This study investigated the antibacterial potential of Euphorbia hirtawhole plant extracts, honey and conventional antibiotics and their synergistic effects against selected multidrug resistant and typed bacterial strains associated with otitis media. E. hirtawhole plant extract was purified using column chromatography technique. The antibacterial assays of extracts were done using standard microbiological procedures. Protein, sodium and potassium ion leakage of the synergistic mixtures was determined using flame-photometry. At 100 mg/ml, acetone extracts presented highest inhibition against S. aureus (NCTC 6571) with 32 ± 0.83 mm zone of inhibition. The fractional inhibitory concentration indices displayed higher synergism in combination of plant extract, honey and ciprofloxacin against P. mirabilisat 0.02 compared to drug combination synergy standard (≤ 0.5). This work revealed augmentation of ciprofloxacin potency when combined with purified E. hirta acetone extract and honey and implies their high potential in the treatment of multidrug resistant infectionof otitis media.

Este estudio investigó el potencial antibacteriano de extractos de plantas enteras de Euphorbia hirta, miel y antibióticos convencionales y sus efectos sinérgicos contra cepas bacterianas seleccionadas multirresistentes y tipificadas asociadas con la otitis media. El extracto de la planta entera de E. hirtase purificó usando la técnica de cromatografía en columna. Los ensayos antibacterianos de extractos se realizaron utilizando procedimientos microbiológicos estándar. La fuga de iones de proteínas, sodio y potasio de las mezclas sinérgicas se determinó mediante fotometría de llama. A 100 mg/ml, los extractos de acetona presentaron la mayor inhibición contra S. aureus (NCTC 6571) con una zona de inhibición de 32 ± 0,83 mm. Los índices de concentración inhibitoria fraccional mostraron un mayor sinergismo en combinación de extracto de planta, miel y ciprofloxacina contra P. mirabilisa 0,02 en comparación con el estándar de sinergia de combinación de fármacos (≤ 0,5). Este trabajo reveló un aumento de la potencia de la ciprofloxacina cuando se combina con extracto de acetona purificado de E. hirtay miel e implica sualto potencial en el tratamiento de infecciones de otitis media resistentes a múltiples fármacos.

Is Multidrug Resistance in Acute Otitis Media with Streptococcus pneumoniae Associated with a More Severe Disease?

OBJECTIVES: Streptococcus pneumoniae is the leading bacterial etiologic agent in acute otitis media (AOM), and it produces a more severe inflammatory response than other otopathogens. Additionally, the presence of multidrug-resistant (MDR) S. pneumoniae is an important issue in the management of AOM. The present pilot study aimed to ascertain whether MDR S. pneumoniae is associated with a higher inflammatory response and/or a more severe disease. METHODS: This was a prospective, single-center study on nonpneumococcal conjugate vaccine-immunized pediatric patients with severe AOM. Demographic and clinical characteristics were recorded. Middle ear fluid was obtained and cultured for each patient; antibiotic-resistance profiling was tested for S. pneumoniae isolates. The C-reactive protein (CRP) level and complete blood count were determined. Patients with positive middle ear fluid culture for S. pneumoniae were divided into 2 groups according to antibiotic resistance profile: MDR and non-MDR. RESULTS: MDR S. pneumoniae was identified in 15 (35.7%) of the 42 eligible patients. Children in this group had significantly higher CRP levels (72.23 ± 62.92 vs. 14.96 ± 15.57 mg/L, p < 0.001), higher absolute neutrophil count (8.46 ± 3.97 vs. 5.22 ± 4.5 × 103/mm3, p = 0.004), higher percentage of neutrophils (52.85 ± 13.49% vs. 38.34 ± 16.16%, p = 0.004), and were more prone to develop acute mastoiditis (p = 0.01). Receiver operating characteristic analysis identified CRP as the best biomarker to discriminate between the 2 groups of patients (AUC = 0.891). CONCLUSION: MDR S. pneumoniae was associated with a more severe inflammatory response and a higher incidence of mastoiditis.

Inactivation and sensitization of Pseudomonas aeruginosa by microplasma jet array for treating otitis media.

Otitis media (OM), known as a middle ear infection, is the leading cause of antibiotic prescriptions for children. With wide-spread use of antibiotics in OM, resistance to antibiotics continues to decrease the efficacy of the treatment. Furthermore, as the presence of a middle ear biofilm has contributed to this reduced susceptibility to antimicrobials, effective interventions are necessary. A miniaturized 3D-printed microplasma jet array has been developed to inactivate Pseudomonas aeruginosa, a common bacterial strain associated with OM. The experiments demonstrate the disruption of planktonic and biofilm P. aeruginosa by long-lived molecular species generated by microplasma, as well as the synergy of combining microplasma treatment with antibiotic therapy. In addition, a middle ear phantom model was developed with an excised rat eardrum to investigate the antimicrobial effects of microplasma on bacteria located behind the eardrum, as in a patient-relevant setup. These results suggest the potential for microplasma as a new treatment paradigm for OM.

A kinase inhibitor screen identifies signaling pathways regulating mucosal growth during otitis media.

Otitis media, the most common disease of childhood, is characterized by extensive changes in the morphology of the middle ear cavity. This includes hyperplasia of the mucosa that lines the tympanic cavity, from a simple monolayer of squamous epithelium into a greatly thickened, respiratory-type mucosa. The processes that control this response, which is critical to otitis media pathogenesis and recovery, are incompletely understood. Given the central role of protein phosphorylation in most intracellular processes, including cell proliferation and differentiation, we screened a library of kinase inhibitors targeting members of all the major families in the kinome for their ability to influence the growth of middle ear mucosal explants in vitro. Of the 160 inhibitors, 30 were found to inhibit mucosal growth, while two inhibitors enhanced tissue proliferation. The results suggest that the regulation of infection-mediated tissue growth in the ME mucosa involves multiple cellular processes that span the kinome. While some of the pathways and processes identified have been previously implicated in mucosa hyperplasia others are novel. The results were used to generate a global model of growth regulation by kinase pathways. The potential for therapeutic applications of the results are discussed.

Preventing recurrent acute otitis media with Streptococcus salivarius 24SMB and Streptococcus oralis 89a five months intermittent treatment: An observational prospective cohort study.

INTRODUCTION: Acute otitis media (AOM) is the most common childhood disease leading to antibiotic use. More than 80% of children under three years of age experience at least one episode, and about one-third of these report significant recurrence of episodes. In recent years, several studies reported that normal nasopharyngeal flora inhibits growth of common otopathogens, suggesting that maintenance of an "adequate" nasopharyngeal flora might prevent occurrence of upper respiratory tract infections, including AOM. This study aims to determine whether five-month treatment with Streptococcus salivarius 24SMB and Streptococcus oralis 89a nasal spray prevents recurrence of AOM and prescription of antibiotics in children with diagnosis of recurrent AOM. METHODS: Observational prospective cohort study including children aged 1-6 years with diagnosis of recurrent AOM registered with 31 Italian family pediatricians. 81 children were enrolled in the study from September 2016 to the end of the five therapeutic cycles of the Streptococcus salivarius 24SMB and Streptococcus oralis 89a supplied 7 days each month for 5 consecutive months. For each treated child, one untreated control was randomly selected, 1:1 matched for gender, age, and follow-up. RESULTS: 158 children (79 treated and 70 untreated) were included into the analysis (mean age, 3.9 years; 47% female). Univariate analysis showed a statistically significant 34% (95% CI 1%-56%) reduction in number of AOM episodes in treated children compared with those not treated. Significantly fewer antibiotics were dispensed among treated children (24%, 95% CI 1%-41%). CONCLUSIONS: Our findings suggest that intermittent treatment of children with diagnosis of recurrent AOM with nasal spray containing Streptococcus salivarius 24SMB and Streptococcus oralis 89a for a period of five months might be effective in preventing antibiotic use associated with recurrent episodes of AOM. Additional larger studies to address this important clinical problem are recommended.

Updated Guidelines for the Management of Acute Otitis Media in Children by the Italian Society of Pediatrics: prevention

In recent years, new information has been acquired regarding the diagnosis, treatment and prevention of acute otitis media (AOM). The Italian Pediatric Society, therefore, decided to issue an update to the Italian Pediatric Society guidelines published in 2010. The search was conducted on Pubmed, and only those studies regarding the pediatric age alone, in English or Italian, published between January 1, 2010 and December 31, 2018, were included. Each study included in the review was assessed using the Grading of Recommendations, Assessment, Development and Evaluations (GRADE) methodology. The quality of the systematic reviews was evaluated using the A MeaSurement Tool to Assess systematic Reviews (AMSTAR) 2 appraisal tool. The guidelines were formulated using the GRADE methodology by a multidisciplinary panel of experts. The importance of eliminating risk factors (passive smoking, environmental pollution, use of pacifier, obesity, limitation of day-care center attendance) and the promotion of breastfeeding and hygiene practices (nasal lavages) was confirmed. The importance of pneumococcal vaccination in the prevention of AOM was reiterated with regard to the prevention of both the first episode of AOM and recurrences. Grommets can be inserted in selected cases of recurrent AOM that did not respond to all other prevention strategies. Antibiotic prophylaxis is not recommended for the prevention of recurrent AOM, except in certain carefully selected cases. The use of complementary therapies, probiotics, xylitol and vitamin D is not recommended. The prevention of episodes of AOM requires the elimination of risk factors and pneumococcal and influenza vaccination. The use of other products such as probiotics and vitamin D is not supported by adequate evidence.

Pneumococcal susceptibility to antibiotics in carriage: a 17 year time series analysis of the adaptive evolution of non-vaccine emerging serotypes to a new selective pressure environment.

BACKGROUND: Pneumococcal conjugate vaccine (PCV) implementations led to major changes in serotype distribution and antibiotic resistance in carriage, accompanied by changes in antibiotic consumption. OBJECTIVES: To assess the dynamic patterns of antimicrobial non-susceptibility across non-PCV13 serotypes following PCV implementations. METHODS: We conducted a quasi-experimental interrupted time series analysis based on a 17 year French nationwide prospective cohort. From 2001 to 2018, 121 paediatricians obtained nasopharyngeal swabs from children with acute otitis media who were aged 6 months to 2 years. The main outcome was the rate of penicillin-non-susceptible pneumococci (PNSP), analysed by segmented regression. RESULTS: We enrolled 10 204 children. After PCV13 implementation, the PNSP rate decreased (-0.5% per month; 95% CI -0.9 to -0.1), then, after 2014, the rate slightly increased (+0.7% per month; 95% CI +0.2 to +1.2). Global antibiotic use within the previous 3 months decreased over the study period (-22.2%; 95% CI -33.0 to -11.3), but aminopenicillin use remained high. Among the main non-PCV13 serotypes, four dynamic patterns of penicillin susceptibility evolution were observed, including unexpected patterns of serotypes emerging while remaining or even becoming penicillin susceptible. In contrast to PNSP strains, for these latter patterns, the rate of co-colonization with Haemophilus influenzae increased concomitant with their emergence. CONCLUSIONS: In a context of continuing high antibiotic selective pressure, a progressive increase in PNSP rate was observed after 2014. However, we highlighted an unexpected variability in dynamic patterns of penicillin susceptibility among emerging non-PCV13 serotypes. Antibiotic resistance may not be the only adaptive mechanism to antimicrobial selective pressure, and co-colonization with H. influenzae may be involved.

ELOM-080 as Add-On Treatment for Respiratory Tract Diseases - A Review of Clinical Studies Conducted in China.

ELOM-080, also known as Myrtol, represents a distillate of a mixture of 4 rectified essential oils: eucalyptus oil, sweet orange oil, myrtle oil, and lemon oil. ELOM-080 is an approved herbal medicinal product for the secretolytic therapy and facilitation of expectoration in acute and chronic bronchitis and for the secretolytic therapy of sinusitis. Its clinical efficacy has been reported by several randomized control trials. Interestingly, in the recent past, a considerable number of clinical studies on the use of ELOM-080 as add-on treatment of different respiratory tract diseases has been conducted and published in China. As these publications were only available in Chinese, the international attention in the literature was limited. Based on the translation of these studies into English, this review aims to provide a brief overview of the studies' major results, which contribute to the knowledge on the efficacy of ELOM-080 in the treatment of respiratory tract diseases: ELOM-080 was shown to be of great value as add-on treatment not only for the well-established indications bronchitis and sinusitis, but also for pharyngitis, asthma, chronic obstructive pulmonary disease, and, most importantly, otitis media. Besides this clinical evidence, this review also summarizes the great progress in deciphering the mode of action of ELOM-080 that has been made by Chinese publications.

Genetic characteristics and antibiotic resistance of Haemophilus influenzae isolates from pediatric patients with acute otitis media after introduction of 13-valent pneumococcal conjugate vaccine in Japan.

Acute otitis media (AOM) occurs commonly in pediatric populations. We examined resistance genotype, antibiotic susceptibility, quinolone (QL) resistance, and multilocus sequence type (MLST) among Haemophilus influenzae isolates causing AOM following introduction of pneumococcal conjugate vaccines in Japan. The AOM surveillance group included 69 participating otolaryngologists. Causative pathogens isolated from middle ear fluid (MEF) samples collected from 582 children with AOM were identified using both bacterial culture and real-time PCR. H. influenzae isolates among these pathogens were characterized by capsular type, resistance genotype, antibiotic susceptibility, QL resistance, and MLST. In 2016, H. influenzae was identified in 319 samples (54.8%), among which 72.4% (n = 231) tested positive by both culture and PCR; remaining H. influenzae cases were only PCR-positive. This proportion of H. influenzae positivity has increased significantly from 41.2% in 2006 (p < 0.001). Among culture-positive strains, genotypic ß-lactamase-nonproducing ampicillin (AMP)-resistant (gBLNAR) strains were frequent (63.2%), with ß-lactamase-nonproducing AMP-susceptible (gBLNAS) strains accounting for only 24.2%. Susceptibilities of gBLNAR to oral antimicrobials were best for tosufloxacin, followed by cefditoren and tebipenem; MIC90s were 0.031 µg/mL, 0.5 µg/mL, and 1 µg/mL, respectively. In 7 gBLNAR isolates (3.0%), QL susceptibility was low, owing to amino acid substitutions in GyrA and/or ParC. Sequence types identified numbered 107, including 28 that were new. Prevention of further increases in resistance to antimicrobial agents will require antibiotic selection based on characterization of causative pathogens in clinical practice.

Application of pharmacokinetic/pharmacodynamic analysis to evaluate the adequacy of antimicrobial therapy for pediatric acute otitis media in Spain before and after the introduction of the PCV7 vaccine.

OBJECTIVE: To evaluate, by applying pharmacokinetic/pharmacodynamic (PK/PD) analysis, if the change in antibiotic susceptibility after the introduction of the 7-valent pneumococcal conjugate vaccine (PCV7) in Spain had any influence on the usefulness of the antimicrobials more frequently used as empirical treatment of pediatric acute otitis media (AOM). METHODS: PK parameters and susceptibility of Streptococcus pneumoniae and Haemophilus influenzae were obtained from bibliography. Monte Carlo simulation was used to estimate the cumulative fraction of response (CFR), understood as the expected probability of therapy success. For amoxicillin and amoxicillin/clavulanate, the target was free antibiotic concentration remaining above the minimum inhibitory concentration (MIC) for ≥50% of the dosing interval (fT>MIC≥50%), whereas for cefuroxime axetil and cefotaxime, the target was fT>MIC≥60%. CFR values ≥90% were considered successful. RESULTS: When all serotypes of S. pneumoniae are considered, amoxicillin and cefotaxime turned out to reach a high probability of success, and difference before and after vaccination was scarce. For H. influenzae, CFR values were higher with amoxicillin/clavulanate than with amoxicillin. For both microorganisms, cefuroxime axetil resulted in low probability of success in the two periods of study. CONCLUSIONS: We have shown that the introduction of the PCV7 vaccination did not lead to changes in the probability of success of the current empiric treatments of the AOM. Integrated PK/PD analysis has demonstrated to be a useful tool to identify changes in antimicrobial activity after the implantation of a vaccination program, providing complementary information to the simple assessment of MIC values.

Treatment of Streptococcus pneumoniae otitis media in a chinchilla model by transtympanic delivery of antibiotics.

Otits media (OM) is the most frequent indication for antimicrobial prescription to US children. Streptococcus pneumoniae (S. pneumoniae) remains one of the most common pathogens causing OM. Successful eradication of S. pneumoniae in the middle ear can be achieved by adhering to a 7-10 day regimen of oral antibiotics. However, oral drug administration is challenging for parents. Lack of adherence has been associated with treatment failure or early relapse. To overcome this challenge, we used a noninvasive formulation to achieve high transtympanic antibiotic flux and cured S. pneumoniae OM in chinchillas. The formulation consists of a thermosensitive in situ gelling hydrogel, chemical permeation enhancers, and an antibiotic. The direct transport of drugs into the middle ear produced high concentrations of ciprofloxacin (in the range of hundreds of micrograms per milliliter) within the first 24 hours of administration. Drug concentrations above the minimum inhibitory concentration (MIC) for S. pneumoniae were sustained throughout the 7-day treatment. S. pneumoniae OM in a chinchilla model was successfully eradicated, without causing tissue toxicity. Transtympanic delivery minimized systemic drug exposure, as evidenced by undetectable levels in blood, measured by high-performance liquid chromatography.