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Background: The need for alternative antimicrobial therapy for recurrent and persistent acute otitis media (AOM) in children has raised interest in assessing the efficacy and safety of fluoroquinolones for treatment of these infections., Methods: In an evaluator-blinded, active-comparator, noninferiority, multicenter study, children (6 months to <5 years) were randomized 1:1 to receive levofloxacin (10 mg/kg twice daily) or amoxicillin/clavulanate (14:1; amoxicillin 45 mg/kg twice daily) for 10 days, with evaluations 4-6 days of therapy (visit 2), 2-5 days after completing therapy (visit 3), and 10-17 days after last dose (visit 4). Primary outcome was clinical cure at visit 3 based on resolution of clinical signs and symptoms of AOM., Results: A total of 1650 children were randomized and 1305 were clinically evaluable at visit 3 (630 levofloxacin, 675 comparator). Clinical cure rates were 72.4% (456 of 630) in levofloxacin-treated and 69.9% (472 of 675) in amoxicillin/clavulanate-treated children. Cure rates were also similar for levofloxacin and comparator for each age group (< or =24 months: 68.9% versus 66.2%; >24 months: 76.9% versus 75.1%; respectively). Cure rates at visit 4 were 74.9% and 73.8% in levofloxacin and amoxicillin/clavulanate groups, respectively. The upper limits of the confidence intervals were less than the noninferiority margin of 10% indicating that levofloxacin treatment is noninferior to comparator treatment overall and in both infants (6 months to 2 years) and children 2-5 years. No differences between treatment groups regarding the frequency or type of adverse events were apparent., Conclusions: Levofloxacin was not inferior to amoxicillin/clavulanate for the treatment of recurrent and/or persistent AOM in infants and children.

Background: The recommendation of the Drug-Resistant Streptococcus pneumoniae Therapeutic Working Group that high-dose amoxicillin, with or without clavulanate, be used to treat acute otitis media (AOM) addressed concerns about the efficacy of existing therapies against drug-resistant S. pneumoniae. This recommendation relied on pharmacodynamic predictions of concentrations of amoxicillin in middle-ear fluid remaining higher than minimum inhibitory concentrations against intermediately resistant S. pneumoniae for >40% of the dosing interval., Objective: This study compared the tolerability and efficacy of cefprozil and high-dose amoxicillin/clavulanate in patients with AOM., Methods: Patients were randomized to receive 10 days of investigator-blinded oral treatment with either cefprozil suspension (30 mg/kg/d in 2 divided doses) or amoxicillin/clavulanate (45/6.4 mg/kg/d) plus amoxicillin (45 mg/kg/d) in 2 divided doses. The primary efficacy end point was the clinical cure rate 4 to 7 days after the end of treatment. Clinical response by age (6 months-<2 years vs > or =2-7 years), disease severity, and unilateral versus bilateral ear infection was also examined. The primary measures of tolerability were the frequency and severity of adverse events and their relation to study drug. Adverse events were either spontaneously reported or elicited during examination and questioning of the patient. Identified adverse events were coded and recorded using the COSTART (Coding Symbols for Thesaurus of Adverse Reaction Terms) system., Results: Three hundred four children between the ages of 6 months and 7 years with > or =1 sign or symptom of AOM were enrolled in the study, and 303 (150 cefprozil, 153 amoxicillin/clavulanate) were treated. Twenty-three patients in each treatment group were not evaluable; thus, 257 children were included in the analysis of evaluable patients. Clinical cure rates were 87% (110/127) with cefprozil and 89% (116/130) with amoxicillin/clavulanate (95% CI for the difference in cure rate, -10.7% to 4.1%). No between-group differences in efficacy were noted by age, disease severity, or unilateral or bilateral involvement. The overall incidence of drug-related adverse events was significantly lower with cefprozil than with amoxicillin/clavulanate (19% vs 32%, respectively; P = 0.008), as was the incidence of diarrhea (9% vs 19%, respectively; P = 0.021). Adverse events prompted discontinuation of therapy in 4 (3%) cefprozil patients and 8 (5%) amoxicillin/clavulanate patients., Conclusions: Based on a search of MEDLINE, this study is the first direct comparison of cefprozil versus high-dose amoxicillin/clavulanate. Cefprozil was as effective as high-dose amoxicillin/clavulanate, with a lower incidence of adverse events.

Objective: To examine the microbiologic and clinical efficacy of a 5-day course of cefdinir in the treatment of tympanocentesis-documented acute otitis media (AOM)., Design: Open label noncomparative trial., Setting: Primary care, ambulatory., Patients: Children ages 6 months through 12 years with signs of AOM and middle ear effusion confirmed by tympanometry in at least one ear., Intervention: Patients underwent tympanocentesis at baseline and received cefdinir 7 mg/kg twice a day for 5 days., Main Outcome Measures: Presumptive eradication of middle ear pathogens determined by clinical cure of signs and symptoms of AOM at end of therapy (Study Days 7 to 9) and Visit 3 (Study Days 16 to 21)., Results: A total of 125 of 177 enrolled children had 134 pathogens isolated by tympanocentesis: Streptococcus pneumoniae, 69 (51.5%); Haemophilus influenzae 44 (32.8%; beta-lactamase-positive in 18 of 44 strains); beta-lactamase-positive Moraxella catarrhalis, 15 (11.2%); and Streptococcus pyogenes, 6 (4.5%). The clinical cure rates by patient in the microbiologically and overall clinically evaluable groups, respectively, were 73% (84 of 115) and 77.4% (130 of 168) at the end of therapy visit and 57.4% (66 of 115) and 61.9% (104 of 168) at Visit 3. Presumptive eradication rates at end of therapy were 8 of 11 (72.7%) and 4 of 8 (50%) for patients with penicillin-intermediate and -resistant S. pneumoniae isolates, respectively. Adverse reactions occurred in 16% of patients, with diarrhea (11%) occurring most frequently., Conclusions: A 5-day regimen of cefdinir was effective in the eradication of the common causative pathogens of nonrefractory AOM, including intermediate penicillin-resistant S. pneumoniae and beta-lactamase-producing organisms. Cefdinir should be considered a suitable second line antibiotic for AOM.

Objective: To compare the safety and efficacy, in treating acute otitis media (AOM) in children, of a new formulation of amoxicillin/clavulanate potassium (Augmentin) oral suspension providing 45/6.4 mg/kg/day and administered twice daily (bid) for 5 and 10 days, respectively, with the safety and efficacy of the original formulation providing 40/10 mg/kg/day and administered three times daily (tid) for 10 days., Study Design: Eight hundred sixty-eight children ages 2 months to 12 years with AOM were randomly assigned to one of the three treatment groups. Stringent criteria were used for the diagnosis of AOM and for determinations of "cure" and "improvement." Subjects were reexamined on Days 12 to 14 and 32 to 38., Results: Among subjects whose treatment and follow-up conformed fully to protocol, the proportion of treatment successes (clinically cured or improved) on Days 12 to 14 was 78.8% (149 of 189) in the tid 10-day group, 86.5% (154 of 178) in the bid 10-day group and 71.1% (140 of 197) in the bid 5-day group. Corresponding values on Days 32 to 38 were 64.2% (95 of 148) in the tid 10-day group, 63.1% (94 of 149) in the bid 10-day group and 57.8% (93 of 161) in the bid 5-day group. None of the differences between the tid 10-day regimen and either of the 2 bid regimens were statistically significant, but the bid 10-day regimen was significantly more effective than the bid 5-day regimen in younger subjects. In the study population as a whole, results were similar to those in per protocol subjects. Overall the incidence of protocol-defined diarrhea was 26.7% (74 of 277) in the tid 10-day group, compared with 9.6% (27 of 280) in the bid 10-day group (P < 0.0001) and 8.7% (25 of 286) in the bid 5-day group (P < 0.0001)., Conclusions: In comparison with the original formulation of Augmentin administered tid for 10 days in the treatment of AOM in children, the new formulation administered bid for 10 days provides at least equivalent efficacy and causes substantially less diarrhea. Administration for 5 days appears not to provide equivalent efficacy, but the difference appears limited to younger children and the margin of difference is small.

From January, 1992, to January, 1994, penicillin-resistant (minimal inhibition concentration (MIC) > 0.06 microgram/ml) Streptococcus pneumoniae (PRSP) isolates accounted for 48 (17%) of 283 isolates from acute otitis media (AOM) or recurrent AOM in 246 ambulatory patients in rural Kentucky. By broth microdilution, relatively penicillin-resistant (MIC > 0.06 to 1.0 microgram/ml) and highly penicillin-resistant (MIC > or = 2.0 micrograms/ml) strains were detected in 25 (16%) and 23 (15%), respectively, of 157 pneumococcal middle ear isolates. Using 1994 National Committee for Clinical Laboratory Standards breakpoints for pneumococci (unavailable for oral cephalosporins except cefuroxime), highly PRSP strains were almost uniformly susceptible to clindamycin and vancomycin. In contrast highly PRSP strains were resistant to most oral antimicrobials customarily used for AOM with one-third of strains highly resistant (MIC > or = 2.0 micrograms/ml) to ceftriaxone. Serotypes 6B, 19F and 23F accounted for 95% of highly PRSP strains and serotype 9V for 48% of relatively PRSP strains. By multivariate analysis, otitis-prone condition (P = 0.0008) and number of antibiotic courses before day of culture (P < 0.0001) were independently predictive of PRSP. Highly PRSP isolates were more commonly isolated from patients recently treated within 3 days (30%) vs. those who completed therapy more than 3 days earlier (2%) (P < 0.0001).(ABSTRACT TRUNCATED AT 250 WORDS)

The epidemiology, microbiology and clinical outcome of the conjunctivitis-otitis syndrome (CJ-AOM) was investigated in a rural private practice concurrent to a double blind placebo-controlled study of orally administered amoxicillin for prevention of acute otitis media (AOM) secondary to conjunctivitis. Bacterial pathogens were isolated when greater than 15 polymorphonuclear leukocytes/high power field were observed on Gram-stained smear of conjunctival secretions. Nontypable Haemophilus influenzae biotype 2 predominated in CJ-AOM; however, Streptococcus pneumoniae was isolated nearly as frequently as H. influenzae in conjunctivitis without AOM. Younger age (P = 0.001) and more episodes of AOM in the previous year (P = 0.006) were risk factors for CJ-AOM. Persistence of AOM was frequently observed in CJ-AOM. The frequency of AOM secondary to conjunctivitis was reduced (P = .01) in amoxicillin recipients (2 of 41) compared with placebo (11 of 42), but amoxicillin failed to eradicate nasopharyngeal carriage of H. influenzae. More episodes of AOM per year (P less than 0.001) and day care (P less than 0.001) were found to be risk factors for AOM secondary to conjunctivitis.