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Common community-acquired infections include those of the upper respiratory tract. In the 1990s, the antimicrobial treatment of upper respiratory tract infections focused on penicillin-resistant Streptococcus pneumoniae. However, following the introduction of a pneumococcal conjugate vaccine, a decrease in invasive pneumococcal disease occurred, and in the case of otitis media a shift towards Haemophilus influenzae as the predominant causative pathogen was observed. Future antimicrobial therapy for outpatient upper respiratory tract infections may need to focus on pathogens such as penicillin-susceptible S. pneumoniae, beta-lactamase-producing H. influenzae, beta-lactamase-negative amoxicillin-resistant H. influenzae and Moraxella catarrhalis. In these circumstances, third-generation oral cephalosporins, such as cefixime and cefdinir, could be increasingly used as an optional first-line therapy in community practice for upper respiratory tract infections suspected to be caused by these key pathogens, as an alternative to amoxicillin-clavulanate.

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.

Clarithromycin, an advanced-generation macrolide antibiotic, has demonstrated excellent in vitro activity against group A beta-hemolytic streptococcus (GABHS). Potent activity against Streptococcus pyogenes and a favorable pharmacokinetic profile have made it a reasonable alternative for treatment of patients with streptococcal pharyngitis. The safety and efficacy of clarithromycin and penicillin V were compared in a randomized, investigator-blind study. Children 6 months to 12 years of age received 5 days of clarithromycin suspension 7.5 mg/kg twice daily (n = 268) or 10 days of penicillin V suspension 13.3 mg/kg three times daily (n = 260). Patients were evaluated for signs and symptoms of pharyngitis, and throat swabs for culture were obtained prior to therapy, at the end of therapy, and at follow-up. Clarithromycin and penicillin V produced comparable rates of clinical success (cure + improvement) at the posttreatment (97% and 94%) and follow-up (81% and 82%) evaluations. The GABHS eradication rate, however, was significantly higher with clarithromycin (94% vs 78%, P < .001). Both drugs were well tolerated; gastrointestinal complaints were similar and mild. Resistance did not occur with the short course of clarithromycin or the standard regimen of penicillin V. Five days' treatment with clarithromycin was superior to 10 days of penicillin in eradicating S. pyogenes.