Effect of Short-Course, High-Dose Amoxicillin Therapy on Resistant Pneumococcal Carriage

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Abstract
Context Emerging drug resistance threatens the effectiveness of existing therapies for pneumococcal infections. Modifying the dose and duration of antibiotic therapy may limit the spread of resistant pneumococci. Objective To determine whether short-course, high-dose amoxicillin therapy reduces risk of posttreatment resistant pneumococcal carriage among children with respiratory tract infections. Design and Setting Randomized trial conducted in an outpatient clinic in Santo Domingo, Dominican Republic, October 1999 through July 2000. Participants Children aged 6 to 59 months who were receiving antibiotic prescriptions for respiratory tract illness (n = 795). Interventions Children were randomly assigned to receive 1 of 2 twice-daily regimens of amoxicillin: 90 mg/kg per day for 5 days (n = 398) or 40 mg/kg per day for 10 days (n = 397). Main Outcome Measures Penicillin-nonsusceptible Streptococcus pneumoniae carriage, assessed in nasopharyngeal specimens collected at days 0, 5, 10, and 28; baseline risk factors for nonsusceptible pneumococcal carriage; and adherence to regimen, compared between the 2 groups. Results At the day 28 visit, risk of penicillin-nonsusceptible pneumococcal carriage was significantly lower in the short-course, high-dose group (24%) compared with the standard-course group (32%); relative risk (RR), 0.77; 95% confidence interval (CI), 0.60-0.97; P = .03; risk of trimethoprim-sulfamethoxazole nonsusceptibility was also lower in the short-course, high-dose group (RR, 0.77; 95% CI, 0.58-1.03; P = .08). The protective effect of short-course, high-dose therapy was stronger in households with 3 or more children (RR, 0.72; 95% CI, 0.52-0.98). Adherence to treatment was higher in the short-course, high-dose group (82% vs 74%; P = .02). Conclusion Short-course, high-dose outpatient antibiotic therapy appears promising as an intervention to minimize the impact of antibiotic use on the spread of drug-resistant pneumococci.