Acute Otitis Media Treatment Failure Research Articles

Amoxicillin Versus Other Antibiotic Agents for the Treatment of Acute Otitis Media in Children

The objective of the study was to compare the antibiotic treatment failure and recurrence rates between antibiotic agents (amoxicillin, amoxicillin-clavulanate, cefdinir, and azithromycin) for children with uncomplicated acute otitis media (AOM). We completed a retrospective cohort study of children 6 months-12 years of age with uncomplicated AOM identified in a nationwide claims database. The primary exposure was the antibiotic agent, and the primary outcomes were treatment failure and recurrence. Logistic regression was used to estimate ORs, and analyses were stratified by primary exposure, patient age, and antibiotic duration. Among the 1 051 007 children included in the analysis, 56.6% were prescribed amoxicillin, 13.5% were prescribed amoxicillin-clavulanate, 20.6% were prescribed cefdinir, and 9.3% were prescribed azithromycin. Most prescriptions (93%) were for 10days, and 98% were filled within 1day of the medical encounter. Treatment failure and recurrence occurred in 2.2% (95% CI: 2.1, 2.2) and 3.3% (3.2, 3.3) of children, respectively. Combined failure and recurrence rates were low for all agents including amoxicillin (1.7%; 1.7, 1.8), amoxicillin-clavulanate (11.3%; 11.1, 11.5), cefdinir (10.0%; 9.8, 10.1), and azithromycin (9.8%; 9.6, 10.0). Despite microbiologic changes in AOM etiology, treatment failure and recurrence were uncommon for all antibiotic agents and were lower for amoxicillin than for other agents. These findings support the continued use of amoxicillin as a first-line agent for AOM when antibiotics are prescribed.

What are the risk factors for acute otitis media treatment failure?

ObjectiveTo identify risk factors associated with acute otitis media treatment failure (AOMTF) among 13-valent pneumococcal conjugate vaccine (PCV) immunized children. MethodsIn this retrospective study, we identified children <12 years who were admitted to our hospital November 2017–October 2020. Children were categorized either as acute otitis media treatment failure (AOMTF), if they received adequate pre-admission antibiotics, or as AOM without treatment failure (AOMwTF), if they did not receive any pre-admission antibiotics. We collected demographics, clinical behavior, laboratory results, length and hospitalization course. Hospitalization was justified if previously treated properly. ResultsThe AOMTF group included 84 children (43 boys, mean age: 1.30 ± 0.83 years), whereas the AOMwTF group included 251 children (132 boys, mean age: 1.20 ± 0.89 years). AOMTF accounted for 25% of all AOM admissions. Among the AOMTF group, 46 (54.8%) were treated with amoxicillin and 24 (28.6%) with amoxicillin/clavulanic acid. Risk factors for AOMTF included recurrent AOM episodes history (30.9% vs 5.5%, OR 7.6, 95%CI 3.5–15.4, p < 0.001), otorrhea (29.4% vs 9.5%, OR 4, 95%CI 2.1–7.5, p < 0.001), tympanic membrane perforation (14.2% vs 4.3%, OR 3.6, 95%CI 1.5–8.6, p < 0.0019). Children with AOMTF were treated more with 2nd- or 3rd-line antibiotics (90.2% vs 65.9%, OR 4, 95%CI 2.2–10.4, p < 0.001), and underwent more myringotomy/ventilation tube insertions (14.4% vs 6.9%, OR 2.3, 95%CI 1.0–5.0, p = 0.037). Mean admission durations were similar: 3.83 ± 1.6 days in the AOMTF group vs 3.37 ± 2.77 days in the AOMwTF group (p = 0.15). ConclusionRisk factors associated with AOMTF should be identified early during the AOM course to reduce complication rates and surgery referral.

COVID-19 and Acute Otitis Media in Children: A Case Series.

Background:The association of SARS-CoV-2 with acute otitis media (AOM) in children is poorly understood.Methods:Cases were identified as a subpopulation within the NO TEARS prospective AOM study in Denver, CO from March to December 2020. Children enrolled were 6 to 35 months of age with uncomplicated AOM; those with AOM and SARS-CoV-2 were included. Data was obtained from electronic medical records and research case report forms.Results:A total of 108 patients enrolled in the NO TEARS study from May 2019 through December 2020 (all subsequently tested for SARS CoV-2). During the COVID-19 pandemic study period (March-December 2020), 16 patients enrolled, and 7 (43.6%) were identified with AOM/COVID-19 co-infection. Fever was present in 3 of 7 children (29%). Four children (57%) attended daycare. Only 2 children (29%) had SARS CoV-2 testing as part of their clinical workup. Mean AOM-SOS© scores were similar among SARS CoV-2 positive and negative patients with no statistical significance with two-sided t-tests: 13.6 (±4.5) versus 14.2 (±4.9) at enrollment, 1.4 (±1.8) versus 4.2 (±4.9) on Day 5, and 0.6 (±0.9) versus 2.5 (±6.1) on Day 14. Among the 7 cases, no child had an AOM treatment failure or recurrence within 3 to 14 or 15 to 30 days respectively. Of the 6 patients with completed bacterial and viral testing, a bacterial pathogen was identified in all 6, and a viral pathogen in 3 (50%).Conclusions:COVID-19 and AOM can co-exist. Providers should maintain a high index of suspicion for COVID-19 even in patients with clinical AOM and should not use a diagnosis of AOM to exclude COVID-19.

347. SARS-CoV-2 and Acute Otitis Media in Children: A Case Series

BackgroundReports in adults with COVID-19 and acute otitis media (AOM) show that severe symptoms and hearing loss may be more common than with the clinical presentation of typical AOM. However, the association of SARS-CoV-2 with AOM in children is poorly understood. MethodsCases were identified as a subpopulation enrolled in the NOTEARS prospective AOM study in Denver, CO from March-December 2020. Children enrolled were 6-35 months of age with uncomplicated AOM and prescribed amoxicillin. Children diagnosed with AOM and SARS-CoV-2, detected by polymerase chain reaction assay, were included in the case series. Data was obtained from electronic medical records and research case report forms. Patients completed surveys at enrollment and 5, 14 and 30 days after enrollment that included the Acute Otitis Media Severity of Symptoms (AOM-SOS©) scale. All patients had nasopharyngeal otopathogen testing completed.ResultsA total of 108 patients had been enrolled through December 2020 (all of whom were subsequently tested for SARS CoV-2). During the study period for this case series, 16 patients were enrolled, and 7 (43.6%) were identified with AOM/SARS-CoV-2 co-infection. Among these 7 patients, fever was present in 3 children (29%). Four children (57%) attended daycare. Only 2 children (29%) had testing for SARS CoV-2 as part of their clinical workup. Mean AOM-SOS© scores were similar among the SARS CoV-2 positive and negative patients with no statistical significance noted with two-sided t-tests: 13.6 (± 4.5) vs 14.2 (± 4.9) at enrollment, 1.4 (± 1.8) vs 4.2 (±4.9) on Day 5, and 0.6 (± 0.9) vs. 2.5 (±6.1) on Day 14 (Table 1). Among the 7 patients, no child had an AOM treatment failure or recurrence. Of the 6 patients in whom bacterial and viral testing have been completed, a bacterial otopathogen was identified in 6 (100%), and a viral pathogen in 3 (50%) children (Table 2).Table 1. Clinical features of children with concurrent SARS-CoV-2 and AOM Table 2. Laboratory findings of children with concurrent SARS-CoV-2 and AOM. ConclusionSARS-CoV-2 can occur in children with AOM. It is important that providers maintain a high index of suspicion for COVID-19 even in patients with clinical evidence of AOM, particularly to ensure families are appropriately advised on isolation and quarantine requirements. AOM with SARS-CoV-2 does not appear to be more severe than AOM without SARS-CoV-2. Disclosures Samuel R. Dominguez, MD, PhD, BioFire Diagnostics (Consultant, Research Grant or Support)DiaSorin Molecular (Consultant)Pfizer (Grant/Research Support) Samuel R. Dominguez, MD, PhD, BioFire (Individual(s) Involved: Self): Consultant, Research Grant or Support; DiaSorin Molecular (Individual(s) Involved: Self): Consultant; Pfizer (Individual(s) Involved: Self): Grant/Research Support

Treatment failure in pediatric acute otitis media: How do you define?

IntroductionReaching the point of treatment failure in the management of pediatric acute otitis media (AOM) is decision-changing, and is often associated with switching to a broader coverage antibiotic with/without middle ear surgical drainage. Yet, still there is no consensus on the definition of what is treatment failure, which may lead to confusion for clinical decision-making purposes. We sought to review the heterogeneity of treatment failure definitions in AOM. MethodsWe searched for relevant English language manuscripts using the following key-words: ['otitis media' (OM) or (AOM)] AND ['treatment failure' or 'failure' or 'response failure' or 'response'] AND 'human' in various electronic databases from 1/1/2005 through 10/31/2020. ResultsIn the 60 retrieved papers, treatment failure was considered only when antibiotics had been prescribed beforehand, but not when watchful waiting had been adopted. We categorized the manuscripts into 5 major treatment failure definition subgroups, which occasionally overlapped: unimprovement or worsening of symptoms or signs of failure in otoscopy (n = 36), specialist(s) referral or hospital admission (n = 12), changing or adding antibiotic treatment (n = 22), failure to eradicate causative bacteria (n = 7) and failure as perceived by parents (n = 4). ConclusionsWe suggest a broader definition of AOM treatment failure including physical examination findings and degree of initial treatment response, which will enable an unbiased, uniform comparison of treatments for pediatric AOM.

Reduced-Concentration Clavulanate for Young Children with Acute Otitis Media

Amoxicillin-clavulanate (A/C) is currently the most effective oral antimicrobial in treating children with acute otitis media (AOM), but the standard dosage of 90 mg amoxicillin/6.4 mg clavulanate/kg of body weight/day commonly causes diarrhea. We examined whether an A/C formulation containing lower concentrations of clavulanate would result in less diarrhea while maintaining plasma levels of amoxicillin and clavulanate adequate to eradicate middle-ear pathogens and to achieve clinical success. We conducted an open-label study in children with AOM who were 6 to 23 months of age. In phase 1, we treated 40 children with a reduced-clavulanate A/C formulation providing 90 mg amoxicillin/3.2 mg clavulanate/kg/day for 10 days. In phase 2, we treated 72 children with the same formulation at a dosage of 80 mg amoxicillin/2.85 mg clavulanate/kg/day for 10 days. We compared the rates of protocol-defined diarrhea (PDD), diaper dermatitis, and AOM clinical response in these children with rates we had reported in children who received the standard A/C regimen, and we obtained plasma levels of amoxicillin and clavulanate at various time points. Outcomes in phase 1 children and in children who had received the standard regimen did not differ significantly. Rates of PDD in children receiving phase 2 and standard regimens were 17% and 26%, respectively (P = 0.10). The corresponding rates of diaper dermatitis were 21% and 33% (P = 0.04) and of AOM treatment failure were 12% and 16% (P = 0.44). Symptomatic responses did not differ significantly between regimens; both gave clavulanate levels sufficient to inhibit β-lactamase activity. In young children with AOM, clavulanate dosages lower than those currently used may be associated with fewer side effects without reducing clinical efficacy. (This study has been registered at ClinicalTrials.gov under registration no. NCT02630992.).

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

ObjectivesThe 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. MethodsThis 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. ResultsPositive 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. ConclusionsWe 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.

Non typable-Haemophilus influenzae biofilm formation and acute otitis media.

BackgroundNon-typable Haemophilus influenzae (NT-Hi) infection is frequently associated with acute otitis media (AOM) treatment failure, recurrence or chronic otitis media. Persistence of otopathogens in a biofilm-structured community was implicated in these situations. Here, we compared biofilm production by H. influenzae strains obtained by culture of middle ear fluid (MEF) from children with AOM treatment failure and by strains isolated from nasopharyngeal (NP) samples from healthy children or those with AOM (first episode or recurrence). We aimed to evaluate an association of clinical signs and in vitro biofilm formation and establish risk factors of carrying a biofilm-producing strain.MethodsWe used a modification of the microtiter plate assay with crystal violet staining to compare biofilm production by 216 H. influenzae strains: 41 in MEF from children with AOM treatment failure (group MEF), 43 in NP samples from healthy children (NP group 1), 88 in NP samples from children with a first AOM episode (NP group 2, n = 43) or recurrent (NP group 3, n = 45) and 44 in NP samples from children with AOM associated with conjunctivitis (NP group 4).ResultsAt all, 106/216 (49%) H. influenzae strains produced biofilm as did 26/43 (60.5%) in NP samples from healthy children. Biofilm production in MEF samples and NP samples did not significantly differ (40.5% vs 60.5%, 55.8%, 56.8% and 31.1% for NP groups 1, 2, 3 and 4, respectively). On multivariate analysis, only presence of conjunctivitis was significantly associated with low biofilm production (OR = 0.3, CI [0.16-0.60], p = 0.001). The ampicillin resistance of H. influenzae produced by penicillin-binding protein modification was significantly associated with low biofilm production (p = 0.029).ConclusionWe found no association of biofilm production and AOM treatment failure or recurrence. Biofilm production was low from H. influenzae strains associated with conjunctivitis-otitis syndrome and from strains with modified penicillin-binding protein.

Payment analysis of two diagnosis and management approaches of acute otitis media.

We determined the cost of care for 2 diagnosis and management approaches for acute otitis media (AOM) among children 6 to 30 months old. A case-control design was used. Cases included 208 children diagnosed with AOM based on a bulging tympanic membrane (TM) and treated with amoxicillin/clavulanate. Controls (5:1 ratio) included 1020 children with AOM diagnosed not requiring bulging of the TM and treated with amoxicillin. Fewer cases (49%) than controls (69%) were diagnosed with AOM (P < .001), fewer were diagnosed with recurrent AOM or AOM treatment failure (0.34 vs 1.6/child; P < .0001), and fewer had insertion of tympanostomy tubes (6.3% vs 14.8%) due to recurrent AOM (P < .0001). The combined direct payments and indirect costs for management of AOM were $539/case versus $1,023/control. Using Rochester NY payments generalized to the US birth cohort, this case diagnosis and treatment strategy could save $1.008 billion per year.

Microbiology of bacteria causing recurrent acute otitis media (AOM) and AOM treatment failure in young children in Spain: Shifting pathogens in the post-pneumococcal conjugate vaccination era

ObjectiveTo prospectively identify the bacterial aetiology and antimicrobial susceptibility of problematic (recurrent and treatment failure) acute otitis media in Spanish children several years after the introduction of 7-valent pneumococcal conjugate vaccine. MethodsTympanocentesis or careful sampling of spontaneous otorrhoea was performed on children aged 3 to <36 months with recurrent acute otitis media, acute otitis media treatment failure or unresolved acute otitis media. Results105 acute otitis media episodes (77 sampled by tympanocentesis, 28 otorrhoea samples) were evaluated: 46 recurrent, 35 treatment failures, 24 unresolved acute otitis media. 74 episodes (70.4%) had at least one bacterium identified on culture: Streptococcus pneumoniae was identified in 21 episodes, Haemophilus influenzae (all non-typeable) in 44, Streptococcus pyogenes in 2, Moraxella catarrhalis in 2. No statistically significant difference in bacterial aetiology by episode type was detected. Non-typeable H. influenzae was the most commonly isolated pathogen in all acute otitis media types and in all age sub-groups. Forty percent of S. pneumoniae isolates were multi-drug resistant. Pneumococcal serotype 19A was the most frequently identified serotype (7/21 episodes). Multi-drug resistance was found in 56% of 19A isolates. Of non-typeable H. influenzae isolates, 15% were ampicillin resistant and 13% were amoxicillin/clavulanate resistant. S. pneumoniae and non-typeable H. influenzae DNA were each detected in 57% of samples culture negative for these pathogens, including 12 co-infections. ConclusionCombining culture and polymerase chain reaction results, H. influenzae and S. pneumoniae may be implicated in 70% and 43% of clinically problematic bacterial acute otitis media episodes, respectively. The impact of new vaccines to prevent both S. pneumoniae and non-typeable H. influenzae acute otitis media may be substantial in this population and is worth investigating.

Pathogens Implicated in Acute Otitis Media Failures After 7-valent Pneumococcal Conjugate Vaccine Implementation in France

Before 7-valent pneumococcal conjugate vaccine (PCV7) implementation in France, several studies had described the microbiology of acute otitis media (AOM) treatment failures. The causative pathogens were Streptococcus pneumoniae (Sp) followed by nontypable Haemophilus influenzae (NTHi). The aim of this study was to describe the epidemiology of pathogens involved in AOM treatment failures or recurrences. This French multicentric prospective study enrolled 143 children with AOM treatment failure between 2007 and 2009 observed by 8 ear, nose, and throat specialists. Failure was defined as the persistence of AOM symptoms after at least 48 hours of antibiotic therapy or their recurrence within 4 days after the end of treatment. Standardized history and physical examination findings were recorded, and culture of middle ear fluid (MEF) was obtained. Mean age was 16.9 ± 9.9 months (median, 13.7). Eighty-eight percent of children had received more than 1 dose of PCV7, and 70.6% attended day care. The most common antibiotic used at the time of treatment failure or recurrence was a combination of amoxicillin and clavulanate (51.1%). Bacteriologic sampling demonstrated that in 35% of cases (n=50), no otopathogen was cultured at the time of treatment failure or recurrence. Similar proportions of Sp and NTHi were observed in the 86 patients (60.1%) from whom only a single species was recovered from MEF (46.5% for Sp, n=40 and 45.3% for NTHi, n=39). Among Sp strains, 4.4% were penicillin susceptible, 77.8% were penicillin intermediate, and 17.8% were fully penicillin resistant, and serotype 19A represented 84.5% of all serotypes detected. Among NTHi isolates, 15.5% (n=7) were β-lactamase-producing strains (including 2 strains with only this mechanism of resistance), and strains with reduced susceptibility by changes in protein binding to penicillin (β-lactamase-negative ampicillin resistant strains) represented 35.5% of cases. Among the 50 sterile MEF samples, polymerase chain reaction was performed in 32, of which 4 were positive for HI, 3 for Sp, and 3 for both. Among children with AOM treatment failures in France, Sp and NTHi were equally distributed; 19A was the main Sp serotype, and the main resistance mechanism for NTHi was β-lactamase-negative ampicillin resistance.

Treatment, Failure, Recurrence, and Antibiotic Prescription Rates for Different Acute Otitis Media Treatment Methods

This retrospective analysis from Woodcreek Healthcare Inc., in Puyallup, Washington, evaluated acute otitis media (AOM) episodes managed with either immediate antibiotics (ABX), typmanocentesis + observation (Tap+OBS), or tympanocentesis + immediate antibiotics (Tap +ABX) and the rates of acute otitis media treatment failure (AOMTF), recurrent acute otitis media (RAOM), and antibiotic prescription rates for each treatment group. Diagnostic criteria for AOM were a bulging or full tympanic membrane accompanied by otalgia, fever, or parent-reported irritability or sleeplessness. Any instance of a patient returning to clinic and receiving a subsequent diagnosis of AOM within 10 days of initial diagnosis was defined as AOMTF. RAOM was defined as any instance of a patient returning to clinic and receiving a subsequent diagnosis of AOM 11–30 days after an initial diagnosis. Two cohorts of patients were included in the study. The first cohort included all patients younger than 37 months who received tympanocentesis for AOM from July 1, 2005 to July 30, 2009. This cohort was either immediately treated with antibiotics or observed based on the decision of the treating physician. The second cohort of patients included in the study received immediate antibiotic therapy for AOM during the same period. AOMTF, RAOM, and antibiotic prescription data were analyzed for the first, second, and third AOM episodes experienced by each patient in the second cohort (ABX-1, 2, or 3). The data collected were then assessed using the Fisher exact test (two-tailed). There were 212 patients identified to have AOM and treated with tympanocentesis. Of these patients, 12 episodes of AOM were excluded due to insufficient post-treatment data. The second cohort produced 128 patients that were treated with antibiotics. Twenty-one of these patients were excluded from the study due to insufficient post-treatment data. The 30-day antibiotic prescription rate was 27% (one prescription per 3.8 episodes) in the Tap+OBS group vs. ∼ 120% (1.2 prescriptions per episode) in each of the immediate antibiotic groups (p<0.001). There were no significant differences in AOMTF or RAOM between any of the treatment groups. The authors concluded that antibiotics provide marginal benefit for most AOM episodes. Alternatives to AOM therapies can help reduce reliance on antibiotics without inviting significant increases in rates of clinical failure.

Evolving microbiology of complicated acute otitis media before and after introduction of the pneumococcal conjugate vaccine in France

We compare the microbiology of otopathogens causing recurrent acute otitis media (AOM) or AOM treatment failure in 600 children during 2000 to 2008 before and after the introduction of 7-valent pneumococcal conjugate vaccine (PCV-7). Streptococcus pneumoniae predominated before PCV-7 introduction and during 2007 to 2008, whereas Haemophilus influenzae predominated during 2005 to 2006. S. pneumoniae 19A became the most frequent serotype after PCV-7 introduction.

Treatment Failure, Recurrence, and Antibiotic Prescription Rates for Different Acute Otitis Media Treatment Methods

In an era of increasing antibiotic resistance, reliance on empirical antibiotic therapy for management of acute otitis media (AOM) will eventually become an untenable strategy. New research efforts are needed to identify effective treatment alternatives. In this retrospective analysis, we assessed AOM treatment failure (AOMTF), recurrent AOM (RAOM), and antibiotic prescription rates for groups of AOM episodes managed with either immediate antibiotics (ABX), tympanocentesis + observation (Tap + OBS), or tympanocentesis + immediate antibiotics (Tap + ABX). No significant differences in rates of AOMTF or RAOM were observed between any of the treatment groups. The 30-day rate of antibiotic prescriptions written for AOM was significantly lower in the TAP + OBS group (1 prescription per 3.8 episodes) than in the immediate antibiotic therapy groups (1.2 prescriptions per episode), P < .001. The comparative risk of AOMTF was slightly higher among AOM episodes caused by Streptococcus pneumoniae (OR 2.523; CI 1.070-5.944; P = 0.056). Neither the presence of other particular otopathogens, nor the presence of drug-resistant otopathogens, nor the choice of any particular AOM antibiotic therapy correlated with increased risk of either AOMTF or RAOM. The observed absence of significant differences in clinical outcomes between the various treatment groups in this study is consistent with findings published by other authors: alternative AOM therapies can help reduce reliance on antibiotics without inviting significant increases in rates of clinical failure.

Systemic Cytokine Response Profiles Associated With Respiratory Virus-Induced Acute Otitis Media

Acute otitis media (AOM) results from a complex interplay between the infectious agents and host immune responses. Cytokines play a major role in the pathogenesis of AOM, but there are few studies on the systemic cytokine response during AOM. Sera were collected from 145 children (median age = 13.5 months) at the time of diagnosis of AOM. Concentrations of 17 cytokines (IL-1beta, -2, -4, -5, -6, -7, -8, -10, -12, -13, -17, granulocyte-colony stimulating factor (G-CSF), granulocyte-monocyte-colony stimulating factor, interferon-gamma, MCP-1, MIP-1beta, TNF-alpha) were determined and correlated with viral etiology and clinical outcome. The statistical analysis was conducted using bioinformatics software. Cluster patterns of concentrations of cytokines were examined by unsupervised hierarchical clustering algorithms. Four major cluster groups were identified, one of the groups was significantly enriched for cases of respiratory syncytial virus (RSV)-induced AOM as compared with other viruses. Specifically, RSV-induced AOM had significantly higher concentrations of G-CSF, MCP-1, IL-10, IL-6, interferon-gamma, and IL-8 (P < 0.05). Using a decision tree classifier, higher G-CSF concentrations produced 87.6% accuracy to predict RSV-induced AOM. Overall, higher IL-13 concentrations produced 84.2% accuracy to predict early clinical failure of antibiotic treatment. Children with AOM have a unique pattern of systemic cytokine response that relates to virus etiology and clinical outcome. Based on G-CSF and IL-13 measurements, it is possible to accurately classify RSV-induced AOM and early treatment failure, respectively; these observations will need to be validated in an independent population.

Pathogens Causing Recurrent and Difficult-to-Treat Acute Otitis Media, 2003-2006

This study sought to determine the microbiology of recurrent acute otitis media (AOM) and AOM treatment failure (AOMTF) in the context of widespread use of heptavalent pneumococcal conjugate vaccine (PCV7). In this retrospective cohort study, 244 AOM isolates obtained by tympanocentesis during 3 respiratory seasons--2003-2004 (n = 126), 2004-2005 (n = 52), 2005-2006 (n = 66)--from three geographically diverse pediatric populations were compared. Most isolates were from children less than 2 years old, who had received PCV7. For the 3 seasons the proportion of Streptococcus pneumoniae isolates was 35%, 35%, and 46% and for Haemophilus influenzae was 55%, 58%, and 39%, respectively (change in trend, P = .09). A total of 37%, 39%, and 50% of S. pneumoniae were penicillin nonsusceptible (PNSP) and 48%, 67%, and 50% of H. influenzae produced beta-lactamase, respectively. Although H. influenzae remains the most frequently isolated pathogen in children with AOMTF or recurrent AOM, S. pneumoniae that are PNSP are reemerging as important organisms.

Safety and Efficacy of Gatifloxacin Therapy for Children with Recurrent Acute Otitis Media (AOM) and/or AOM Treatment Failure

Because of concerns about arthrotoxicity, fluoroquinolones are restricted for use in children. This study describes the safety and efficacy of gatifloxacin when used for treatment of children with recurrent acute otitis media (ROM) or acute otitis media (AOM) treatment failure (AOMTF). We performed an analysis of 867 children included in 4 clinical trials who had ROM and/or AOMTF and were treated with gatifloxacin (10 mg/kg once daily for 10 days). Gatifloxacin had adverse event rates that were similar overall to those of a comparator antibiotic (amoxicillin-clavulanate), except for increased diarrhea in children <2 years old receiving amoxicillin-clavulanate. There was no evidence of arthrotoxicity, hepatotoxicity, alteration of glucose homeostasis, or central nervous system toxicity acutely or during 1 year follow-up in any child. Regarding efficacy, in 2 noncomparative trials, the gatifloxacin cure rate of AOM was 89% (95% confidence interval [CI], 83%-95%) at the test of cure (TOC) visit, 3-10 days after completion of therapy. In 2 comparative trials of gatifloxacin versus amoxicillin-clavulanate, the efficacy of gatifloxacin was 88% (95% CI, 82%-94%). Gatifloxacin led to better clinical outcomes than amoxicillin-clavulanate for AOMTF (91% vs. 81%; P=.029), for AOMTF and age <2 years old (89% vs. 69%; P=.009), and for severe AOM in children <2 years old (90% vs. 75%; P=.012). Among children with AOMTF previously treated with amoxicillin-clavulanate or ceftriaxone injections, gatifloxacin cure rates were high (88% and 75%, respectively). Gatifloxacin appears to be safe for children, with no evidence of producing arthrotoxicity in 867 children exposed to the antibiotic when used as treatment for ROM and AOMTF.

Randomized, Investigator-Blinded, Multicenter, Comparative Study of Gatifloxacin Versus Amoxicillin/Clavulanate in Recurrent Otitis Media and Acute Otitis Media Treatment Failure in Children

Recurrent otitis media and acute otitis media treatment failure are commonly encountered in the pediatric population. To compare the clinical efficacy of gatifloxacin with amoxicillin/clavulanate for the treatment of acute otitis media treatment failure and recurrent otitis media. Three hundred fifty-four children 6 months-7 years with recurrent otitis media and/or acute otitis media failure were stratified according to age (younger than 2 years versus 2 years or older) and then randomly assigned to 10 days of treatment with gatifloxacin 10 mg/kg once daily or amoxicillin/clavulanate 90 mg/6.4 mg in 2 divided doses. Tympanocentesis was performed in 116 children with acute otitis media treatment failure and 52 with recurrent otitis media at study entry to validate the clinical diagnosis and provide microbiologic data. The primary outcome measure was clinical resolution of infection at the test-of-cure visit 3-10 days after completing treatment. Clinical resolution of acute otitis media was observed in 79.0% (49 of 62) of clinically evaluable children younger than 2 years and 90.3% (56 of 62) of those 2 years or older who were treated with gatifloxacin as compared with 77.6% (45 of 58) of children younger than 2 years and 79.7% (47 of 59) of children 2 years or older treated with amoxicillin/clavulanate. In patients with acute otitis media treatment failure, clinical response rates for children younger than 2 years and those 2 years or older were 87.5% (21 of 24) and 97.0% (32 of 33) with gatifloxacin versus 63.6% (14 of 22) and 83.9% (26 of 31) with amoxicillin/clavulanate. The corresponding clinical response rates in patients with recurrent otitis media were 79.2% (19 of 24) and 85.7% (18 of 21) with gatifloxacin and 90.5% (19 of 21) and 76.0% (19 of 25) with amoxicillin/clavulanate. Clinical success in those subjects having pretreatment middle ear fluid pathogens was similar for the 2 regimens [80.0% (24 of 30) gatifloxacin, 77.1% (27 of 35) amoxicillin/clavulanate]. Emergence of fluoroquinolone-resistant strains was not observed. Both drugs were generally well-tolerated. Diarrhea was the most common drug-related adverse event (10% gatifloxacin, 18% amoxicillin/clavulanate). No evidence of abnormal joint or gait findings was found during a 12-month follow-up. Gatifloxacin once daily is at least as effective and well-tolerated as amoxicillin/clavulanate twice daily in children with acute otitis media treatment failure or recurrent otitis media. There was no evidence of arthrotoxicity or emergence of fluoroquinolone-resistant bacteria in gatifloxacin-treated children.

Open label, multicenter study of gatifloxacin treatment of recurrent otitis media and acute otitis media treatment failure

Recurrent otitis media and treatment failures of acute infections are refractory to therapy. Newer fluoroquinolones have excellent activity against respiratory pathogens, but their use in children has been limited because of concerns about adverse effects. This was an open label, multicenter trial in which patients with recurrent otitis media or acute otitis media (AOM) treatment failure were treated with 10 mg/kg gatifloxacin oral suspension once daily for 10 days. Before treatment a tympanocentesis or a swab of middle ear fluid was obtained. Nasopharyngeal swabs were obtained at baseline and at the end of therapy. Efficacy was evaluated 3 to 10 days after cessation of treatment and at 3 to 4 weeks. Safety monitoring included special attention to any sign or symptom suggestive of joint or bone abnormality. The study enrolled 254 patients 6 months to 7 years of age, with one-half (52%) of the patients having recurrent otitis media, 17% having AOM treatment failure and 28% having both. Cure was achieved posttreatment in 88% of 198 clinically evaluable patients, with similar outcomes for patients younger or older than 2 years of age. Of the 45 evaluable patients with Streptococcus pneumoniae, 38 (84%) were cured, including 25 of 28 with penicillin-nonsusceptible strains. Also cured were 89% of those with Haemophilus influenzae and those with Moraxella catarrhalis. No selection of resistance to gatifloxacin was detected among nasopharyngeal pathogens. Eighty-three percent of the children had sustained cure at the 4 weeks follow-up visit. Adverse events were primarily mild gastrointestinal, with no occurrences of arthropathy. Gatifloxacin is safe and effective for treatment of recurrent otitis media and AOM treatment failure in children.