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Low Dosage and Long Treatment Duration of -Lactam

Risk Factors for Carriage of Penicillin-Resistant Streptococcus pneumoniae

Didier Guillemot, MD; Claude Carbon, MD; Beverley Balkau, PhD; Pierre Geslin, MD; Hervé Lecoeur, MD; Françoise Vauzelle-Kervroëdan, MD; Gilles Bouvenot, MD; Eveline Eschwége, MD

JAMA. 1998;279:365-370.

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 (PR Sp) pharyngeal carriage and characteristics of -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 PR Sp carriage. However, oral -lactam use was associated with an increased risk of PR Sp 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 -lactam (defined as lower than clinical recommendations) had an increased risk of PR Sp 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 -lactam was associated with an increased risk of PR Sp 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 -lactam contribute to the selective pressure in promoting pharyngeal carriage of PR Sp.

From the Institut National de la Santé et de la Recherche Médicale, Unité 21 and Faculté de Médecine Paris Sud, Villejuif, France (Drs Guillemot, Balkau, Vauzelle-Kervroëdan, and Eschwège); INSERM U13 and Service de Médecine Interne, Centre Hospitalo-Universitaire Bichat-Claude Bernard, Paris, France (Dr Carbon); Centre National de Référence du Pneumocoque, Créteil, France (Dr Geslin); MEDILOG, Senlis, France (Dr Lecoeur); and INSERM U21 and Service de Médecine Interne et de Thérapeutique, Centre Hospitalier Sud-Hôpital Ste Marguerite, Marseille, France (Dr Bouvenot).

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