Auritidibacter ignavus: an underestimated pathogen?

Auritidibacter ignavus is an emerging diagnosed microorganism associated with fulminant otitis, mastoiditis and recurrent otitis. Here we describe a clinical case in a little girl in La Gomera Island together with images of the bacteriological culture and whole genome sequencing.

A new strategy for the treatment of middle ear infection using ciprofloxacin/amoxicillin-loaded ethyl cellulose/polyhydroxybutyrate nanofibers.

A middle ear infection occurs due to the presence of several microorganisms behind the eardrum (tympanic membrane) and is very challenging to treat due to its unique location and requires a well-designed treatment. If not treated properly, the infection can result in severe symptoms and unavoidable side effects. In this study, excellent biocompatible ethyl cellulose (EC) and biodegradable polyhydroxybutyrate (PHB) biopolymer were used to fabricate drug-loaded nanofiber scaffolds using an electrospinning technique to overcome antibiotic overdose and insufficient efficacy of drug release during treatment. PHB polymer was produced from Halomonas sp., and the purity of PHB was found to around be 90 %. Additionally, ciprofloxacin (CIP) and amoxicillin (AMX) are highly preferable since both drugs are highly effective against gram-negative and gram-positive bacteria to treat several infections. Obtained smooth nanofibers were between 116.24 and 171.82 nm in diameter and the addition of PHB polymer and antibiotics improved the morphology of the nanofiber scaffolds. Thermal properties of the nanofiber scaffolds were tested and the highest Tg temperature resulted at 229 °C. The mechanical properties of the scaffolds were tested, and the highest tensile strength resulted in 4.65 ± 6.33 MPa. Also, drug-loaded scaffolds were treated against the most common microorganisms that cause the infection, such as S.aureus, E.coli, and P.aeruginosa, and resulted in inhibition zones between 10 and 21 mm. MTT assay was performed by culturing human adipose-derived mesenchymal stem cells (hAD MSCs) on the scaffolds. The morphology of the hAD MSCs' attachment was tested with SEM analysis and hAD MSCs were able to attach, spread, and live on each scaffold even on the day of 7. The cumulative drug release kinetics of CIP and AMX from drug-loaded scaffolds were analysed in phosphate-buffered saline (pH: 7.4) within different time intervals of up to 14 days using a UV spectrophotometer. Furthermore, the drug release showed that the First-Order and Korsmeyer-Peppas models were the most suitable kinetic models. Animal testing was performed on SD rats, matrix and collagen deposition occurred on days 5 and 10, which were observed using Hematoxylin-eosin and Masson's trichrome staining. At the highest drug concentration, a better repair effect was observed. Results were promising and showed potential for novel treatment.

An infant mouse model of influenza-driven nontypeable Haemophilus influenzae colonization and acute otitis media suitable for preclinical testing of novel therapies.

Nontypeable Haemophilus influenzae (NTHi) is a major otitis media (OM) pathogen, with colonization a prerequisite for disease development. Most acute OM is in children <5 years old, with recurrent and chronic OM impacting hearing and learning. Therapies to prevent NTHi colonization and/or disease are needed, especially for young children. Respiratory viruses are implicated in driving the development of bacterial OM in children. We have developed an infant mouse model of influenza-driven NTHi OM, as a preclinical tool for the evaluation of safety and efficacy of clinical therapies to prevent NTHi colonization and the development of OM. In this model, 100% of infant BALB/cARC mice were colonized with NTHi, and all developed NTHi OM. Influenza A virus (IAV) facilitated the establishment of dense (1 × 105 CFU/mL) and long-lasting (6 days) NTHi colonization. IAV was essential for the development of NTHi OM, with 100% of mice in the IAV/NTHi group developing NTHi OM compared with 8% of mice in the NTHi only group. Histological analysis and cytokine measurements revealed that the inflammation observed in the middle ear of the infant mice with OM reflected inflammation observed in children with OM. We have developed the first infant mouse model of NTHi colonization and OM. This ascension model uses influenza-driven establishment of OM and reflects the clinical pathology of bacterial OM developing after a respiratory virus infection. This model provides a valuable tool for testing therapies to prevent or treat NTHi colonization and disease in young children.

"Give Me Five": The Case for 5 Days of Antibiotics as the Default Duration for Acute Respiratory Tract Infections.

Acute respiratory tract infections (ARTIs) account for most antibiotic prescriptions in pediatrics. Although US guidelines continue to recommend ≥10 days antibiotics for common ARTIs, evidence suggests that 5-day courses can be safe and effective. Academic imprinting seems to play a major role in the continued use of prolonged antibiotic durations. In this report, we discuss the evidence supporting short antibiotic courses for group A streptococcal pharyngitis, acute otitis media, and acute bacterial rhinosinusitis. We discuss the basis for prolonged antibiotic course recommendations and recent literature investigating shorter courses. Prescribers in the United States should overcome academic imprinting and follow international trends to reduce antibiotic durations for common ARTIs, where 5 days is a safe and efficacious course when antibiotics are prescribed.

Bilateral Nontuberculous Mycobacterial Otitis Media: A Case Report.

Established treatment strategies for nontuberculous mycobacterial (NTM) infections are currently lacking, and whether surgical treatment should be applied in combination with antibiotic therapy remains debatable. Here, we report a case of bilateral otitis media caused by Mycobacterium abscessusa, a highly antibiotic-resistant bacterium. Many reported cases of NTM otitis media are unilateral, in which hearing of the contralateral ear is preserved. In the present case, strategies to improve hearing outcomes were considered, as both ears were affected. A 27-year-old woman presented with bilateral otorrhea that had lasted for the past 9 months. Bacterial culture showed M. abscessus in both ears. Based on drug sensitivity tests, clarithromycin, amikacin, and imipenem were administered. Three days after treatment initiation, diseased tissues were removed from the right middle ear, which had impaired hearing. On day 38, otorrhea stopped in both ears, and the hearing improved. Computed tomography revealed air in both middle ears. No apparent recurrence was detected. Under the same antibiotic therapy, resolution of diseased tissues and improvement in hearing were similar between the ears with and without surgery, suggesting that surgery is not always necessary. This finding may be incorporated into the treatment guidelines for NTM infections in the future.

Gram-negative Bacteria are Associated With Sensorineural Hearing Loss in Chronic Otitis Media.

OBJECT: Chronic otitis media (COM) is an inflammatory disease that commonly presents with otorrhea and hearing loss. Bacteria-induced inflammation can cause inner ear damage, leading to sensorineural hearing loss (SNHL). This study aimed to compare the prevalence and severity of SNHL in patients with gram-negative versus gram-positive cultures and examine associations between the concentrations of circulating monocytes and neutrophils with bacteria species and SNHL. METHODS: This was a retrospective study. Cholesteatoma or chronic suppurative otitis media patients with otorrhea were enrolled. Middle ear secretions were collected using sterile swabs under an otoscope, and sent for bacterial detection within 30 min. Pure tone audiometry and circulating leukocyte counts were recorded and analyzed in patients infected with different pathogens. Logistic regression analysis was used to identify the risk factors associated with SNHL. RESULTS: A total of 137 patients were enrolled, including 45 patients infected with gram-negative bacteria, 41 with gram-positive bacteria, 20 with polymicrobial infection, and 31 with no bacterial growth. Logistic regression analysis showed that bacterial culture positive infections (OR = 7.265, 95% CI 2.219-23.786, p = 0.001) were an independent risk factor for SNHL. Patients with gram-negative bacteria had higher risks of SNHL (p < 0.0001) and more severe hearing loss (p = 0.005) than those with gram-positive bacteria. COM patients infected with gram-negative bacteria showed an increase in circulating monocytes, which correlated with the occurrence of SNHL (p = 0.0343). CONCLUSION: Gram-negative bacteria are associated with elevated circulating monocyte counts and have a higher risk of severe SNHL. LEVEL OF EVIDENCE: 4 Laryngoscope, 134:3335-3341, 2024.

Clinical Outcomes Associated with Amoxicillin Treatment for Acute Otitis Media in Children.

BACKGROUND: Acute otitis media (AOM) is the most common reason children are prescribed antibiotics. Bacteria that produce beta-lactamase are an increasingly frequent cause of AOM and may be resistant to amoxicillin, the currently recommended treatment for AOM. We aimed to evaluate the clinical outcomes of children treated with amoxicillin for AOM and assessed whether outcomes vary by infecting pathogen or beta-lactamase production. METHODS: 205 children 6-35 months old diagnosed with AOM and prescribed amoxicillin were included. Bacterial culture and qualitative multiplex real-time polymerase chain reaction were performed on nasopharyngeal swabs collected at enrollment. Parents completed surveys assessing symptoms, antibiotic adherence, and potential adverse events. The primary outcome was treatment failure with amoxicillin. Secondary outcomes included recurrence, symptom improvement, resolution, and adverse drug events (ADE). RESULTS: 8 children (5.4%) experienced treatment failure and 14 (6.8%) had recurrence. By day 5, 152 (74.1%) children had symptom improvement and 97 (47.3%) had resolution. Parents reported ADE for 56 (27.3%) children. Among 149 children who did not take any amoxicillin before enrollment, 98 (65.8%) had one or more beta-lactamase-producing bacteria. Common bacterial otopathogens were Moraxella catarrhalis (79, 53.0%), Streptococcus pneumoniae (51, 34.2%), Haemophilus influenzae (30, 20.1%), and Staphylococcus aureus (21, 14.1%). Treatment failure did not differ between children that did (5, 5.1%) and did not (3, 5.9%) have beta-lactamase-producing otopathogens (p = .05). CONCLUSIONS: Among children diagnosed with AOM treated with amoxicillin, treatment failure was uncommon and did not differ by pathogen or beta-lactamase production. These data support guidance recommending amoxicillin despite an increasing prevalence of beta-lactamase-producing bacteria.

Bacterial pathogens and antimicrobial resistance in acute otitis media.

INTRODUCTION: Recent studies show an increase in the prevalence of Haemophilus influenzae and a decrease in Streptococcus pneumoniae among the bacteria that cause acute otitis media (AOM). The objective of our study was to analyse the distribution of pathogens identified in children aged less than 14 years presenting to the emergency department with AOM and their patterns of antimicrobial resistance. PATIENTS AND METHODS: Single centre retrospective, analytical study in patients aged less than 14 years with a diagnosis of AOM in whom an ear drainage sample was collected for culture in the paediatric emergency department of a tertiary care hospital between 2013 and 2021. RESULTS: During the study period, there were 14 684 documented care episodes corresponding to children with a diagnosis of AOM. An ear drainage culture was performed in 768 of those episodes. The median age of the patients was 2 years, 57% were male and 70% had a previous history of AOM. The most frequently isolated pathogens were: Haemophilus influenzae (n = 188 [24.5%]; 15.5% of them resistant to ampicillin), Streptococcus pyogenes (n = 86 [11.2%]), Staphylococcus aureus (n = 82 [10.7%]), Streptococcus pneumoniae (n = 54 [6.9%]; 9.4% with intermediate resistance to penicillin), Pseudomonas aeruginosa (n = 42 [5.5%]) and Moraxella catarrhalis (n = 11 [1.4%]). No pathogen was isolated in 34.9% of cases. CONCLUSIONS: Haemophilus influenzae is the leading cause of AOM in children aged less than 14 years. This, combined with the low frequency of isolation and penicillin resistance of Streptococcus pneumoniae, calls into question the appropriateness of high-dose amoxicillin for empiric treatment of AOM.

Microbiological study of the auditory canal in dairy calves with otitis media.

Otitis media (OM) in calves, is caused by different bacteria. OM treatment requires identification of etiological agents and antibiotic sensitivity testing. The gold standard method of bacteriological study of OM is tympanocentesis, but using this technique in farm condition would be difficult. As a hypothesis, it is possible that bacteriologic examining the auditory canal can help to accelerate the bacteriological investigation of OM. This study was conducted with the aim of comparing the microbiota of the auditory canal in healthy calves and calves with OM. The present research which was a case-control study, mainly compared control group (18 swab samples from healthy and non-infected ear) with two case groups (20 swab samples from the non-affected ear and 32 swab samples from the affected ear in unilateral OM, 11 swab samples from both affected ears in bilateral OM). The results of bacteriological investigations showed three categories of bacteria including: pathogens (Staphylococcus chromogenes, Corynebacterium pilosum, Corynebacterium ovis, Pseudomonas aeruginosa, Pasteurella multocida, Proteus vulgaris, Trueperella pyogenes, Klebsiella, Escherichia coli, Mycoplasma bovis), opportunists (Staphylococcus intermedius, Bacillus licheniformis) and commensals (Staphylococcus epidermidis, Corynebacterium bovis, Corynebacterium renale, Bacillus subtilis, Bacillus cereus). Based on the antibiotic sensitivity test of the isolates, enrofloxacin, florfenicol, and gentamicin were the chosen antibiotics for treatment. All affected animals were treated based on bacteriological results and antibiotic sensitivity tests. All treated animals were fully cured. Based on the results, it seems that in calves with OM, examining the microbiota of the auditory canal can be further studied as an alternative to tympanocentesis in farm conditions.

Antimicrobial Peptide Recognition Motif of the Substrate Binding Protein SapA from Nontypeable Haemophilus influenzae.

Nontypeable Haemophilus influenzae (NTHi) is an opportunistic pathogen associated with respiratory diseases, including otitis media and exacerbations of chronic obstructive pulmonary disease. NTHi exhibits resistance to killing by host antimicrobial peptides (AMPs) mediated by SapA, the substrate binding protein of the sensitivity to antimicrobial peptides (Sap) transporter. However, the specific mechanisms by which SapA selectively binds various AMPs such as defensins and cathelicidin are unknown. In this study, we report mutational analyses of both defensin AMPs and the SapA binding pocket to define the specificity of AMP recognition. Bactericidal assays revealed that NTHi lacking SapA are more susceptible to human beta defensins and LL-37, while remaining highly resistant to a human alpha defensin. In contrast to homologues, our research underscores the distinct specificity of NTHi SapA, which selectively recognizes and binds to peptides containing the charged-hydrophobic motif PKE and RRY. These findings provide valuable insight into the divergence of SapA among bacterial species and NTHi SapA's ability to selectively interact with specific AMPs to mediate resistance.

The Unneglectable Disease Burden of Otitis Media Among Children in China: A Systematic Review and Meta-analysis.

BACKGROUND: Otitis media (OM) is one of the most commonly diagnosed infections among children yet with obscure disease burden. METHODS: The literature published from 1980 to 2022 was retrieved in PubMed, Ovid-EMBASE, Web of Science, CNKI, Wanfang and VIP. Literature screening, quality assessment and data extraction were conducted by 2 independent reviewers. Heterogeneity and publication bias were detected by I2 , Egger's and Begg's tests. The data were pooled using the random-effects model. The number of OM cases was estimated by the multiplied model based on pooled results and the 2020 China census data. RESULTS: A total of 28,378 literatures were identified with 67 finally included for data analysis. The OM incidence among children was 7.89% [95% confidence interval (CI): 5.43%-11.33%] and the prevalence of OM was 5.13% (95% CI: 3.49%-7.49%). The most common pathogen of the OM cases was Streptococcus pneumoniae ( S. pneumoniae ), with a positive rate of 33.52% (95% CI: 26.55%-41.29%). The most common serotypes of S. pneumoniae isolated from OM cases were serotypes 19F, 19A, 6B, 23F and 3, with 85.8% covered by the PCV13. We estimated that there were 8,950,797 (95% CI: 6,080,533-12,928,051) OM cases among under-fives in China in 2020, of which 3,374,451 (95% CI: 1,698,901-6,277,862) cases of OM were caused by S. pneumoniae . CONCLUSIONS: The burden of OM in China was considerable yet neglected. To date, S. pneumoniae was the most frequently detected bacterial pathogen of OM. Vaccination may be effective to protect young children from OM.

The Prevalence and Association of Biofilms With Otitis Media With Effusion: A Systematic Review and Meta-Analysis.

PURPOSE: We aimed to identify the role of bacterial biofilms in the chronicity of otitis media with effusion and its resistance to antibiotics. We illustrated this role by reviewing, analyzing, and correlating the findings with the results of the included studies to reach clear evidence. METHODS: A comprehensive search of electronic databases (Scopus, PubMed, Web of Science, Cochrane, and GHL databases) was performed for all studies using the following strategy till April 2021 with the search terms: Biofilm and Middle ear effusion. We found 935 references, 421 were duplicates, and 514 were needed for further screening, and it was as follows: PubMed 215, Scopus 18, Cochrane 130, Web of Science 136, and GHL 15. RESULTS: The pooled prevalence of culture-positive effusions was estimated to be 40% (95% CI [28%, 53%]) of the total OME population. Overall, the prevalence of PCR-positive effusions was estimated to be 97% (95% CI [95%, 99%]) of the total OME population. The pooled prevalence of EM-positive effusions was estimated to be 82% (95% CI [69%, 95%]) of the total OME population. CONCLUSION: The data presented in this study coincide with the significant role of bacterial biofilms in the pathogenesis of chronic otitis media with effusion. The involvement of bacterial biofilm as a component of the OME pathogenic process can help us to explain why antimicrobial therapy is not always effective in the eradication of the disease process and, also explain the recurrence of middle ear effusion after treatment with tympanostomy tubes either with or without adenoidectomy.

Otitis media: Interactions between host and environment, immune and inflammatory responses.

OBJECTIVE: To review and highlight progress in otitis media (OM) research in the areas of immunology, inflammation, environmental influences and host-pathogen responses from 2019 to 2023. Opportunities for innovative future research were also identified. DATA SOURCES: PubMed database of the National Library of Medicine. REVIEW METHODS: Key topics were assigned to each panel member for detailed review. Search of the literature was from June 2019 until February 2023. Draft reviews were collated, circulated, and discussed among panel members at the 22nd International Symposium on Recent Advances in Otitis Media in June 2023. The final manuscript was prepared and approved by all the panel members. CONCLUSIONS: Important advances were identified in: environmental influences that enhance OM susceptibility; polymicrobial middle ear (ME) infections; the role of adaptive immunity defects in otitis-proneness; additional genes linked to OM; leukocyte contributions to OM pathogenesis and recovery; and novel interventions in OM based on host responses to infection. Innovative areas of research included: identification of novel bacterial genes and pathways important for OM persistence, bacterial adaptations and evolution that enhance chronicity; animal and human ME gene expression, including at the single-cell level; and Sars-CoV-2 infection of the ME and Eustachian tube.

[ACUTE OTITIS MEDIA BACTERIOLOGY IN CHILDREN YOUNGER THAN THREE MONTHS IN THE LAST 16 YEARS].

BACKGROUND: Only scant information is available regarding the bacteriology of acute otitis media (AOM) in neonates. OBJECTIVES: To investigate the bacteriology of AOM post the introduction of Pneumococcal Conjugate Vaccine (PCV13) in children younger than 3 months and its relation to the mode of delivery. METHODS: Retrospective bacteriological analysis of middle ear fluids taken from children younger than 60 months suffering from AOM. The effect of PCV13 and mode of delivery, caesarian section vs vaginal delivery, on AOM bacteriology was evaluated and compared between children younger than 3 months (group 1) and children aged 3-60 months (group 2). RESULTS: The prevalence of Streptococcus pneumoniae (S.pneumoniae) and Enterobacteriaceae (E.bact) was higher in group 1 compared to group 2, 47.1% vs 35.8% and 12.3% vs 4.3%, respectively (p<0.001), while that of Haemophilus influenza (H. influenzae) and Group A streptococcus (GAS) was higher in group 2 compared to group 1, 40.3% vs 30.1% and 17.5% vs 8.3% respectively (p<0.001). The mode of delivery did not affect AOM bacteriology. The introduction of PCV13 yielded in an increase in the prevalence of GAS (7% to 15%, P<0.001) in group 1. CONCLUSIONS: S. pneumoniae and E. bact are more common AOM pathogens in neonates. Also, the prevalence of GAS was increased in this age group following the introduction of PCV13. DISCUSSION: Our results are applicable towards the formulation AOM treatment guidelines in neonates. This study contributed additional information on a topic that has not been adequately researched so far - neonatal AOM.

Molecular epidemiology and antimicrobial resistance of Haemophilus influenzae isolates from otitis media in Bulgaria.

Haemophilus influenzae is one of the main bacteria responsible for otitis media (OM) among children worldwide. We aimed to estimate the distribution of encapsulated and non-capsulated variants (NTHi), biotypes, antibiotic susceptibility, and molecular epidemiology of H. influenzae isolates recovered from pediatric OM cases in Bulgaria.Capsule detection was done by PCR for bexB gene, absent in NTHi. All encapsulated strains were subjected to PCR serotyping. MIC susceptibility testing was performed according to the criteria of EUCAST. MLST was conducted for all 71 OM isolates.The capsule detection and PCR - serotyping disclosed a predominance of NTHi (90.1%) and a few "a", "f", and "c" types. Biotype I was the most widespread (42.3%). ß-lactam resistance was found in 35.2% of the isolates. MLST represented heterogenic population structure, whereas the most represented clonal complexes belonged to ST-3, ST-57, ST-105, and ST-1426. 42.3% of the STs showed relatedness to globally represented clones, and 11.3% displayed affiliation to international type 2.Most of the H. influenzae isolates recovered from children with otitis media were non-typable strains from biotype I. The examined population structure was genetically diverse, with a predominance of international type 2 isolates.

Impact of IL-17-producing γδ T cells on chronic otitis media induced by nontypeable Haemophilus influenzae in a mouse model.

Nontypeable Haemophilus influenzae (NTHi) is considered a major pathogen underlying middle ear infection. This study aimed to investigate the impact of IL-17 on chronic otitis media (COM) induced by NTHi in mice. NTHi was inoculated into the tympanic bulla with eustachian tubal obstruction. Middle ear effusions (MEEs) and tissues were collected on days 3, 14, and at 1, 2, and 6 months after injection. The expression of interleukin-17A (IL-17A) in MEEs was significantly elevated compared to that in the control group at the translational and transcriptional levels during the experiments. The quantities of IL-17-producing γδ T cells were significantly increased compared to that in the control group during COM, but that of Th17 cells did not. Depletion of γδ T cells by anti-γδ T-cell receptor (TCR) monoclonal antibody (mAb) administration significantly decreased the bacteria counts and the concentrations of IL-1ß, IL-6, IL-17A, TNF-α, and IL-10 in MEEs. Our results suggest that IL-17 may play an important role in prolonging the inflammation in the middle ear in COM and that IL-17-producing γδ T cells may contribute to the exacerbated inflammatory response in the middle ear. In this study, anti-γδ TCR mAb administration was found to improve chronic middle ear inflammatory conditions.

Reliability of nasopharyngeal PCR for the detection of otopathogens in children with uncomplicated acute otitis media compared to culture.

Otopathogens in acute otitis media (AOM) have implications for care because the likelihood of resolution without antibiotics and optimal antibiotic agent varies by microorganism. We aimed to determine the sensitivity, specificity, positive predictive value, and negative predictive value of nasopharyngeal (NP) qualitative polymerase chain reaction (PCR) for common bacterial otopathogens in children with AOM compared to NP culture. NP flocked swabs collected from enrolled children aged 6 to 35 months with uncomplicated AOM in Denver, CO were tested by culture and multiplex PCR. The sensitivity and negative predictive value of PCR using culture as a reference were high (H. influenzae 93.3%, 98.0%; S. pneumoniae 94.2%, 95.1%; M. catarrhalis 92.3%, 86.4%); whereas the specificity and positive predictive value were lower and varied by organism (54.2%-84.1%, 55.1%-69.2%, respectively). PCR detected 1.5 times more organisms than culture. NP PCR has a high predictive value for excluding otopathogens compared to culture and warrants exploration as a diagnostic tool.

Efficacy of antimicrobials or placebo compared to amoxicillin-clavulanate in children with acute otitis media: a systematic review.

BACKGROUND: Acute otitis media (AOM) is the inflammation of the middle ear. It constitutes one of the most frequent infections which affects children and usually occurs between 6 to 24 months of age. AOM can emerge due to viruses and/or bacteria. The aim of the current systematic review is to assess in children between 6 months and 12 years of age with AOM, the efficacy of any antimicrobial agent or placebo compared with amoxicillinclavulanate, to measure the resolution of AOM or symptoms. METHODS: The medical databases PubMed (MEDLINE) and Web of Science were used. Data extraction and analysis were performed by two independent reviewers. Eligibility criteria were set, and only randomised control trials (RCTs) were included. Critical appraisal of the eligible studies was performed. Pooled analysis was conducted using the Review Manager v. 5.4.1 software (RevMan). RESULTS: Twelve RCTs were totally included. Three (25.0%) RCTs studied the impact of azithromycin, two (16.7%) investigated the impact of cefdinir, two (16.7%) investigated placebo, three (25.0%) studied quinolones, one (8.3%) investigated cefaclor and one (8.3%) studied penicillin V, compared to amoxicillin-clavulanate. In five (41.7%) RCTs, amoxicillin-clavulanate proved to be superior to azithromycin, cefdinir, placebo, cefaclor and penicillin V, while in seven (58.3%) RCTs its efficacy was comparable with other antimicrobials or placebo. The rates of AOM relapse after treatment with amoxicillin-clavulanate were comparable to those of other antimicrobials or placebo. However, amoxicillin-clavulanate was more effective in eradicating Streptococcus pneumoniae from the culture, when compared to cefdinir. The results of the meta-analysis were not evaluated due to substantial heterogeneity between studies. CONCLUSIONS: Amoxicillin-clavulanate should be the treatment of choice for children between 6 months and 12 years of age with AOM.