An evolutionary model to predict the frequency of antibiotic resistance under seasonal antibiotic use, and an application to Streptococcus pneumoniae
CONTEXT The spread of drug-resistant Streptococcus pneumoniae in the community is a public health problem in developed and developing nations, but whether antibiotic use is responsible for the increase in drug resistance is not known. OBJECTIVE To analyze the relationship between penicillin-resistant S pneumoniae (PRSp) pharyngeal carriage and characteristics of beta-lactam use. DESIGN Observational study of children attending 20 randomly sampled schools. SETTING The Loiret, in the center of France. PARTICIPANTS A total of 941 children, 3 to 6 years old. MAIN OUTCOME MEASURE(S) Pharyngeal carriage of S pneumoniae, antibiotic use, and medical events during the preceding 30 days. Pneumococcal penicillin G sodium minimal inhibitory concentrations and serotyping were performed. RESULTS Medical illnesses and the use of antibiotics were not associated with PRSp carriage. However, oral beta-lactam use was associated with an increased risk of PRSp carriage (odds ratio [OR], 3.0; 95% confidence interval [CI], 1.1-8.3; P=.03). Children treated by low daily doses of an oral beta-lactam (defined as lower than clinical recommendations) had an increased risk of PRSp carriage, as compared with children who did not (OR, 5.9; 95% CI, 2.1-16.7; P=.002). A treatment of long duration (>5 days) with a beta-lactam was associated with an increased risk of PRSp carriage (OR, 3.5; 95% CI, 1.3-9.8; P=.02). CONCLUSIONS Our results suggest that a low daily dose and a long duration of treatment with an oral beta-lactam contribute to the selective pressure in promoting pharyngeal carriage of PRSp.