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.

Bacteriology and resistance patterns of otitis media with effusion.

OBJECTIVES: Following the increased use of antibiotics, the emergence of antibiotic-resistant species in pediatric patients with otitis media has become a problem in recent years. The aim of this study was to investigate change in bacterial species, antibiotic resistance, and detection rate of highly pathogenic species, such as Methicillin-resistant Staphylococcus aureus (MRSA) and Pseudomonas aeruginosa according to the number of repeated ventilation tube insertion (VTI) procedures in pediatric patients diagnosed with otitis media with effusion (OME). MATERIALS & METHODS: From May 2010 to June 2018, 158 patients under 17 years of age who were admitted to the outpatient clinic of Kyung Hee Medical Center and diagnosed as OME and underwent unilateral or bilateral VTI were included in this study. Bacterial cultures were performed on aseptically collected middle ear effusion (MEF) at the time of VTI and antibiotic sensitivity tests were performed on the identified bacteria. RESULTS: Bacteria were not identified in 195 (70.1%) cultures and identified in 83 (29.9%) cultures. Coagulase-negative staphylococci (CNS) was the most frequently detected species in both the non-recurrent group and the recurrent group. MRSA detection rate was found to be significantly higher in the recurrent group than in the non-recurrent group (p = 0.029). The two groups showed no significant difference in antibiotic resistance against all antibiotics (p > 0.05). CONCLUSION: Staphylococcus species were detected most frequently in the MEF of pediatric OME patients, and the MRSA detection rate was higher in the recurrent group than in the non-recurrent group. There was no difference in antibiotic sensitivity between the two groups against all antibiotics, but resistance to penicillin G and cefoxitin was newly appeared in patients with repeated detection of same bacterial isolates.

Etiology of Acute Otitis Media and Characterization of Pneumococcal Isolates After Introduction of 13-Valent Pneumococcal Conjugate Vaccine in Japanese Children.

BACKGROUND: Acute otitis media is a leading cause of childhood morbidity and antibiotic prescriptions. We examined etiologic changes in acute otitis media after introduction of 13-valent pneumococcal conjugate vaccine as routine immunization for Japanese children in 2014. Serotypes, resistance genotypes, antibiotic susceptibilities and multilocus sequence typing of pneumococcal isolates were also characterized. METHODS: Otolaryngologists prospectively collected middle ear fluid from 582 children by tympanocentesis or sampling through a spontaneously ruptured tympanic membrane between June 2016 and January 2017. Causative pathogens were identified by bacterial culture and real-time polymerase chain reaction for bacteria. Serotypes, resistance genotypes, sequence types and susceptibilities to 14 antimicrobial agents were determined for pneumococcal isolates. RESULTS: At least 1 bacterial pathogen was identified in 473 of the samples (81.3%). Nontypeable Haemophilus influenzae (54.8%) was detected most frequently, followed by Streptococcus pneumoniae (25.4%), Streptococcus pyogenes (2.9%) and others. Pneumococci of current vaccine serotypes have decreased dramatically from 82.1% in 2006 to 18.5% (P < 0.001). Commonest serotypes were 15A (14.8%), 3 (13.9%) and 35B (11.1%). Serotype 3 was significantly less frequent among children receiving 13-valent pneumococcal conjugate vaccine compared with 7-valent pneumococcal conjugate vaccine (P = 0.002). Genotypic penicillin-resistant S. pneumoniae accounted for 28.7%, slightly less than in 2006 (34.2%; P = 0.393); the penicillin-resistant serotypes 15A and 35B had increased. Serotypes 15A, 3 and 35B most often belonged to sequence types 63, 180 and 558. CONCLUSIONS: Our findings are expected to assist in development of future vaccines, and they underscore the need for appropriate clinical choice of oral agents based on testing of causative pathogens.

Factors affecting sound energy absorbance in acute otitis media model of chinchilla.

Acute otitis media (AOM) is a rapid-onset infection of the middle ear which results in middle ear pressure (MEP), middle ear effusion (MEE), and structural changes in middle ear tissues. Previous studies from our laboratory have identified that MEP, MEE, and middle ear structural changes are three factors affecting tympanic membrane (TM) mobility and hearing levels (Guan et al., 2014, 2013). Sound energy reflectance or absorbance (EA) is a diagnostic tool increasingly used in clinical settings for the identification of middle ear diseases. However, it is unclear whether EA can differentiate these three factors in an AOM ear. Here we report wideband EA measurements in the AOM model of chinchilla at three experimental stages: unopened, pressure released, and effusion removed. These correspond to the combined and individual effects of the three factors on sound energy transmission. AOM was produced by transbullar injection of Haemophilus influenzae in two treatment groups: 4 days (4D) and 8 days (8D) post inoculation. These time points represent the relatively early and later phase of AOM. In each group of chinchillas, EA at 250-8000 Hz was measured using a wideband tympanometer at three experimental stages. Results show that the effects of MEP, MEE, and tissue structural changes over the frequency range varied with the disease time course. MEP was the primary contributor to reduction of EA in 4D AOM ears and had a smaller effect in 8D ears. MEE reduced the EA at 6-8 kHz in 4D ears and 2-8 kHz in 8D ears and was responsible for the EA peak in both 4D and 8D ears. The residual EA loss due to structural changes was observed over the frequency range in 8D ears and only at high frequencies in 4D ears. The EA measurements were also compared with the published TM mobility loss in chinchilla AOM ears.

Using Pneumococcal Carriage Data to Monitor Postvaccination Changes in the Incidence of Pneumococcal Otitis Media.

Pneumococcal conjugate vaccines (PCVs) have substantially reduced the burden of pneumococcal disease, including the incidence of otitis media (OM). However, in most countries, no surveillance exists to monitor the change in pneumococcal OM incidence after the introduction of PCVs. We explored whether measuring pneumococcal carriage was a useful surrogate for monitoring postvaccination changes in the incidence of pneumococcal OM. The 7-valent PCV was introduced to Israel's national immunization program in July 2009 and gradually replaced by the 13-valent PCV starting in November 2010. Each day since 2009, nasopharyngeal swabs have been obtained from the first 4 Bedouin children and the first 4 Jewish children who were younger than 5 years old and attended a pediatric emergency room in southern Israel. During the same time, OM surveillance in southern Israel included all children younger than 2 years of age who were diagnosed with OM and had undergone a middle-ear fluid culture. The relative change in the prevalence of vaccine-serotype (VT) pneumococcal carriage was predictive of the relative change in incidence of OM due to VT pneumococcus. However, the serotype replacement observed in non-VT carriage is not paralleled in the incidence of OM due to non-VT pneumococcus. This could indicate that there are more complex mechanisms of the immune response involved in preventing initial and consecutive episodes of OM, which has been changed through declining prevalence of the most virulent serotypes as a result of vaccination.

Evaluation of nasopharyngeal microbial flora and antibiogram and its relation to otitis media with effusion.

Acute otitis media and otitis media with effusion (OME) are the main causes of hearing impairment in children which require proper treatment, mainly antibiotic therapy. Patients whom were appropriate candidates for adenoidectomy were divided into two groups regarding the presence of middle ear effusion. Adenoid tissue specimens were cultured in both groups and the bacterial flora and anti-microbial resistance pattern were determined. 72 patients were studied, 42 % had OME while 58 % did not. The following bacteria were isolated and cultured from both groups with no meaningful difference in prevalence: Streptococcus viridans (p = 0.265), Staphylococcus aureus (p = 0.72), H. influenza (p = 0.806), Entrococcus. spp (0.391), Streptococcus pneumonia (p = 0.391), nonhemolytic Streptococcus (p = 0.230). Bacterial sensitivity was similar for Amoxicillin-clavulanate (p = 0.935), Amoxicillin (p = 0.935), Cephalexin (p = 0.806), Cefixime (p = 0.391) and Azithromycin in both groups. The two groups showed no meaningful difference considering the bacterial flora of nasopharynx and their sensitivity. Bacteria in both groups were sensitive to Amoxicillin and Amoxicillin-clavulanate and resistant to Azithromycin, Cefixime and Cephalexin.

Antibiotic resistance of Streptococcus pneumoniae in children with acute otitis media treatment failure.

OBJECTIVES: The emergence of antibiotic-resistant bacteria is a major cause of treatment failure in children with acute otitis media (AOM). This study aimed to analyze the types of bacterial strains in fluid isolated from the middle ear of children with AOM who did not respond to oral antibiotic treatment. We also determined the antibiotic resistance of the most frequently isolated bacterial strain (Streptococcus pneumoniae) found in these children. METHODS: This was a prospective study of 157 children with AOM aged from 6 months to 7 years admitted due to unsuccessful oral antibiotic treatment. All children underwent a myringotomy, and samples of the middle ear fluid were collected for bacteriological examination. RESULTS: Positive bacterial cultures were obtained in 104 patients (66.2%), with Streptococcus pneumoniae (39.69%), Haemophilus influenzae (16.03%) Staphylococcus aureus (16.03%), Staphylococcus haemolyticus (6.9%) and Streptococcus pyogenes (5.34%) found most frequently. The majority (65.4%) of S. pneumoniae strains were penicillin-intermediate-resistant or penicillin-resistant, and 67.2% strains of S. pneumoniae were multidrug-resistant. CONCLUSIONS: We identified S. pneumoniae as the most frequently isolated pathogen from the middle ear in children with AOM treatment failure and determined that the majority of strains were antibiotic-resistant. We propose that the microbiological identification of bacterial strains and their degree of antibiotic resistance should be performed prior to therapy in order to choose the most appropriate antibiotic therapy for children with AOM treatment failure.

Strategies to prevent biofilm-based tympanostomy tube infections.

OBJECTIVE: To review the potential contributory role of biofilms to post-tympanstomy tube otorrhea and plugging as well as the available interventions currently utilized to prevent biofilm formation on tympanostomy tubes. DATA SOURCES: A literature review was performed utilizing the MEDLINE/Pubmed database from 1980 to 2013. REVIEW METHODS: Electronic database was searched with combinations of keywords "biofilm", "tympanostomy tube", "ventilation tube", and "post-tympanostomy tube otorrhea". RESULTS: Two of the most common sequelae that occur after tympanostomy tube insertion are otorrhea and tube occlusion. There is an increased evidence supporting a role for biofilms in the pathogenesis of otitis media. In this review, we have shown a multitude of novel approaches for prevention of biofilm associated sequelae of otitis media with effusion. These interventions include (i) changing the inherent composition of the tube itself, (ii) coating the tubes with antibiotics, polymers, plant extracts, or other biofilm-resistant materials, (iii) tubal impregnation with antimicrobial compounds, and (iv) surface alterations of the tube by ion-bombardment or surface ionization. CONCLUSION: Currently, there is not one type of tympanostomy tube in which bacteria will not adhere. The challenges of treating chronic post-tympanostomy tube otorrhea and tube occlusion indicate the need for further research in optimization of tympanostomy tube design in addition to development of novel therapies.

[The treatment of MRSA colonized middle ear; case report and literature review]. / Die Behandlung des MRSA besiedelten Mittelohres; eine Fallbeschreibung und Literaturübersicht.

BACKGROUND: The treatment of MRSA (methocillin resistant staphylococcus aureus) colonized middle ear is difficult. According to the guidelines, a MRSA colonized Patient is not to be treated with systemic antibiotics. The topical treatment shows the problem of the ototoxicity of most of the used antiseptic as well as antibiotic substances. METHOD: Selective literature review and consideration of the author's own clinical experience. RESULTS AND CONCLUSIONS: Antibiotic treatment options include aequeous Tetracyclin drops, aequeous chloramphenicol drops and quinolon ear drops (unfortunately the MRSA is resistent mostly). Antiseptics without ototoxic effects are the Burow's solution, Povidone-iode, acetic acid solutions and aequeous dequalinium solutions.

Bactericidal activity of different types of honey against clinical and environmental isolates of Pseudomonas aeruginosa.

OBJECTIVES: Honey has had a valued place in traditional medicine for centuries. Renewed interest in honey for various therapeutic purposes, including treatment of infected wounds, has led to the search for different types of honey with antibacterial activity. In this study, we have assessed the antibacterial activity of different types of honey (manuka honey from Australia, heather honey from the United Kingdom, and locally marketed Indian honey). METHODS: The agar dilution method was used to assess the antibacterial activity of honey against 152 isolates of Pseudomonas aeruginosa by determining minimum inhibitory concentrations. RESULTS AND CONCLUSIONS: The locally available (khadikraft) honey produced the best activity against Pseudomonas aeruginosa and was found to be better than all of the imported varieties of therapeutic honey.

Penicillin resistance is not extrapolable to amoxicillin resistance in Streptococcus pneumoniae isolated from middle ear fluid in children with acute otitis media.

OBJECTIVES: We evaluated the in vitro antibacterial activity of amoxicillin against penicillin-susceptible and -nonsusceptible Streptococcus pneumoniae strains isolated from children with acute otitis media (AOM). METHODS: Children more than 3 months of age with AOM who were seen in the Dr Sótero del Rio and Luis Calvo Mackenna Hospitals in Santiago, Chile, between July 1998 and December 2002 were subjected to tympanic puncture for middle ear fluid culture. The penicillin and amoxicillin susceptibilities of the S pneumoniae isolates were determined by epsilometer test (E test). RESULTS: A bacterial pathogen was isolated in 432 of 543 children (80%) as follows: S pneumoniae, 40%; Haemophilus influenzae, 29%; Moraxella catarrhalis, 7%; and Streptococcus pyogenes, 4%. Penicillin-susceptible S pneumoniae strains were less common than amoxicillin-susceptible strains (60% versus 95%; odds ratio [OR], 0.08; 95% confidence interval [CI], 0.04 to 0.18). Both intermediate- and high-resistance strains were more common for penicillin (22% versus 4.5%; OR, 5.6; 95% CI, 2.5 to 12.7) than for amoxicillin (18% versus 0.5%; OR, 41.3; 95% CI, 6.0 to 821). CONCLUSIONS: Penicillin resistance is not extrapolable to amoxicillin among S pneumoniae strains isolated from middle ear fluid of children with AOM. Our results support the recommendation to evaluate the minimal inhibitory concentrations of penicillin-nonsusceptible S pneumoniae for amoxicillin and to continue use of this antimicrobial as a first-line antimicrobial choice for children with AOM.

In vitro activities of levofloxacin and comparable agents against middle ear fluid, nasopharyngeal, and oropharyngeal pathogens obtained from Costa Rican children with recurrent otitis media or failing other antibiotic therapy.

This study analyzes the in vitro activities of levofloxacin and other commonly used antimicrobials against middle ear fluid, nasopharyngeal, and oropharyngeal pathogens obtained from children with otitis media at risk of having a resistant pathogen. Levofloxacin proved to be very active against these pathogens and had intermediate activity against Streptococcus pyogenes.

Community prescribing and resistant Streptococcus pneumoniae.

We investigated the association between prescribing antimicrobial agents and antimicrobial resistance of Streptococcus pneumoniae among children with acute otitis media in southern Israel. During a 6-year period, all prescriptions of a sample of approximately 20% of Jewish and Bedouin children <5 years of age were recorded and all pneumococcal isolates from middle ear fluid were collected. Although antimicrobial drug use was significantly higher in Bedouin children, the proportion of S. pneumoniae isolates with penicillin MIC = or > 1.0 microg/mL was significantly higher in Jewish children. In both populations, antimicrobial prescriptions were markedly reduced over time, especially for penicillins and erythromycin. In contrast, azithromycin prescriptions increased from 1998 to 2001 with a parallel increase in macrolide and multidrug resistance. Penicillin resistance was associated with macrolide resistance. These findings strongly suggest that azithromycin affects increased antimicrobial resistance, including multidrug resistance, in S. pneumoniae.

Comparison of microbial isolates and susceptibility patterns from the external ear canal of dogs with otitis externa.

Otic exudate was obtained from 33 dogs with otitis externa for cytopathology and culture. Two samples were taken from the same location in the external ear canal, for a total of 100 samples. Thirty-six (36%) samples isolated only a single organism, of which 21 (21%) were Malassezia spp. Two organisms were present in 23 (23%) of the samples. Cultures of the two samples agreed in 40 (80%) of the 50 pairs. Cytopathology agreed with culture results only 68% of the time. Cytopathology and culture may not be as definitive as previously assumed because of apparent variability of the microbial population within the external canal.

Topical ciprofloxacin/dexamethasone otic suspension is superior to ofloxacin otic solution in the treatment of children with acute otitis media with otorrhea through tympanostomy tubes.

OBJECTIVE: To determine the efficacy and safety of topical ciprofloxacin/dexamethasone otic suspension compared with ofloxacin otic solution in the treatment of acute otitis media with otorrhea through tympanostomy tubes (AOMT) in pediatric patients. METHODS: This multicenter, prospective, randomized, observer-masked, parallel-group study was conducted at 39 sites in 599 children aged >or=6 months to 12 years with an AOMT episode of

Antibiotics and the development of resistant microorganisms. Can homeopathy be an alternative?

Antibiotic resistance is a global public health problem. Once confined primarily to hospitals it is now increasingly common in primary care. The prevalence of resistant bacteria is rising, and organisms resistant to almost all antibiotics have been identified. The main causes are indiscriminate prescribing and the use of antibiotics in animal feeds and other agricultural applications. Policies to restrict use of antibiotics have had limited success. Homeopathy may have a role to play in combating the development of antibiotic resistance. Clinical research suggests that homeopathy is effective in the treatment of upper respiratory tract infections in children, a frequent cause of inappropriate antibiotic prescribing. The EU recommends the use of homeopathy in organic animal husbandry, and it is used by significant numbers of farmers. At present there is little data on the effectiveness of homeopathy in this setting. Further research should be done.

Recurrent acute otitis media occurring within one month from completion of antibiotic therapy: relationship to the original pathogen.

OBJECTIVES: (1) To determine the relationship between acute otitis media (AOM) pathogens isolated in cases of early clinical recurrence of AOM (occurring within 1 month from completion of therapy) to the original pathogens causing the initial AOM episode; and (2) To determine whether shorter time intervals between completion of antibiotic therapy and clinical recurrences of AOM are associated with higher rates of true bacteriologic relapse. PATIENTS AND METHODS: From 1995 through 2000, 1077 infants and young children ages 3 to 36 months with AOM were enrolled in double tympanocentesis (performed on Day 1 in all patients and Days 4 to 6 in those initially culture-positive) studies. Of these, 834 (77%) completed successfully the antibiotic treatment [pathogen eradication on Days 4 to 6 of therapy or no pathogen on middle ear fluid (MEF) culture on Day 1 and clinical improvement at end of therapy]. Patients were followed for 3 to 4 weeks after completion of therapy, and additional MEF cultures were obtained if clinical recurrence occurred. True bacteriologic relapse was defined as the presence of a pathogen identical with that isolated before therapy by serotype and pulsed field gel electrophoresis for and by pulsed field gel electrophoresis for Streptococcus pneumoniae and beta-lactamase production for Haemophilus influenzae. RESULTS: MEF cultures were performed in 108 consecutive patients with early recurrent AOM. One hundred pathogens were isolated at recurrence in 88 of 108 (81%) patients: 54 H. influenzae; 45 S. pneumoniae; and 1 Moraxella catarrhalis. Most recurrent AOM episodes developed during the first 2 weeks of follow-up; 39 (36%), 38 (35%), 21 (19%) and 10 (9%) recurrent AOM episodes occurred on Days 1 to 7, 8 to 14, 15 to 21 and 22 to 28 after completion of therapy, respectively. In most patients these episodes were caused by a new pathogen. True bacteriologic relapses were found in 30 (28%) of 108 patients whose MEF cultures were positive for 35 pathogens: 13 of 108 (12%) S. pneumoniae; 12 of 108 (11%) H. influenzae; and 5 of 108 (5%) both. When timing of recurrent AOM after completion of therapy was analyzed, true bacteriologic relapses were found in 16 of 39 (41%), 10 of 38 (26%), 3 of 21 (14%) and 1 of 10 (10%) of all episodes on Days 1 to 7, 8 to 14, 15 to 21 and 22 to 28 after completion of therapy, respectively (P = 0.01). The respective rates for were 11 of 17 (65%), 3 of 10 (30%), 3 of 13 (23%) and 1 of 5 (20%) (P = 0.02). For H. influenzae the respective rates were 8 of 19 (42%), 9 of 23 (39%), 0 of 8 (0%) and 0 of 4 (0%) (P = 0.02). CONCLUSIONS: Most recurrent AOM episodes occurring within 1 month from completion of antibiotic therapy are in fact new infections. Most of the true bacteriologic AOM relapses occur within 14 days after completion of therapy, but even during this time interval most of the recurrences are caused by new pathogens. H. influenzae is very unlikely to cause true bacteriologic AOM relapses 14 days or later after completion of therapy.

Microbiology of acute otitis media recently treated with aminopenicillins.

INTRODUCTION: Sparse recent data are available in the United States regarding the pathogens of acute otitis media (AOM) most likely to be recovered from children recently treated with the two most frequently prescribed antibiotics, amoxicillin or amoxicillin/clavulanate (AMC). METHODS: Of the 704 rural Kentucky children with culture-positive AOM who underwent a single tympanocentesis or culture of otorrhea between 1992 and 1998, 96 pathogens were recovered from 90 children during therapy or within 7 days posttherapy with an aminopenicillin. Identification and susceptibility testing of AOM pathogens were performed by routine National Committee for Clinical Laboratory Standards methods. RESULTS: Pathogens recovered from children with AOM recently treated (0 to 7 days) with amoxicillin (n = 38) and AMC (n = 58), respectively, were as follows: Haemophilus influenzae (beta-lactamase-negative), 16 and 29%; H. influenzae (beta-lactamase-positive), 11 and 22%; penicillin-susceptible Streptococcus pneumoniae, 26 and 12%; intermediately penicillin-nonsusceptible S. pneumoniae (PNSP), 20 and 10%; resistant PNSP 13 and 17%; Moraxella catarrhalis (beta-lactamase-positive), 13 and 7%; and Streptococcus pyogenes, 3 and 2%. H. influenzae was also isolated from 8 (75%) of 12 children treated with high dose AMC ( approximately 80 mg/kg/day amoxicillin component). Significantly fewer children recently treated with amoxicillin were otitis-prone than those given AMC (24% vs. 74%, P < 0.0001). CONCLUSIONS: The predominant pathogen recovered from children with AOM recently treated with amoxicillin was S. pneumoniae (59%) rather than beta-lactamase-producing organisms (24%). H. influenzae was the predominant (51%) pathogen, rather than PNSP (27%), recovered from children recently treated with AMC.

Bacteriologic and clinical efficacy of amoxicillin/clavulanate vs. azithromycin in acute otitis media.

OBJECTIVES: To compare the bacteriologic and clinical efficacy of amoxicillin/clavulanate and azithromycin in patients with acute otitis media (AOM), particularly the ability to eradicate the predominant AOM pathogens from middle ear fluid as assessed by mandatory second tympanocentesis. METHODS: In this single blind study 238 infants and children with AOM were randomized to receive amoxicillin/clavulanate (45/6.4 mg/kg/day in two divided doses for 10 days) or azithromycin (10 mg/kg on Day 1, then 5 mg/kg daily on Days 2 through 5). Tympanocentesis was performed before the first dose and repeated on Day 4, 5 or 6. Clinical response was assessed at end of therapy between Days 12 and 14 and at follow-up between Days 22 and 28. RESULTS: Amoxicillin/clavulanate was significantly more likely to eradicate all bacterial pathogens [83% (54 of 65) vs. 49% (35 of 71), P = 0.001] and Haemophilus influenzae [87% (26 of 30) vs. 39% (13 of 33), P = 0.0001] from middle ear fluid than was azithromycin. Amoxicillin/clavulanate was also more likely to eradicate Streptococcus pneumoniae, but the difference was not statistically significant [90% (18 of 20) vs. 68% (13 of 19) [corrected], P = 0.095]. On Days 12 to 14, signs and symptoms were more likely to resolve completely or improve in all culture-positive patients [86% (60 of 70) vs. 70% (51 of 73), P = 0.023] and in those with H. influenzae infections [91% (30 of 33) vs. 65% (22 of 34), P = 0.010] who received amoxicillin/clavulanate compared with those who received azithromycin. Otherwise there were no significant differences between groups in clinical outcomes on Days 12 to 14 or at follow-up. CONCLUSIONS: Our findings indicate that amoxicillin/clavulanate has superior bacteriologic and clinical efficacy compared with azithromycin in children with AOM.