Safety and effectiveness of meropenem in infants with suspected or complicated intra-abdominal infections.

(See the Editorial Commentary by Jacqz-Aigrain, on pages 1503–4.) Intra-abdominal infections in young infants (<91 days of age) lead to substantial morbidity and mortality; approximately 20% of infants with necrotizing enterocolitis die, and survivors suffer from severe neurodevelopmental impairment [1–3]. Consequently, most infants with suspected or confirmed intra-abdominal infections are treated with empirical antimicrobial therapy. Broad-spectrum or combination antimicrobial agents are often prescribed for these infections given their polymicrobial nature [4, 5]. Meropenem possesses one of the broadest spectra of antimicrobial activity available [6], due to its stability against most extended-spectrum and AmpC chromosomal β-lactamases. This property increases the drug's activity against many antibiotic-resistant bacteria commonly responsible for life-threatening infections among young infants [6]. Meropenem is currently approved by the Food and Drug Administration (FDA) for use in children ≥3 months of age with bacterial meningitis and/or complicated intra-abdominal infections; however, there is substantial off-label use of meropenem in infants <3 months of age [7] despite the lack of adequate dosing, safety, and efficacy data in this vulnerable group. Owing to this lack of data and under the Best Pharmaceuticals for Children Act, the FDA made a formal written request to obtain needed pediatric information on meropenem. Therefore, a study was conducted to determine the pharmacokinetics (PK), safety, and effectiveness of meropenem in young infants with suspected or confirmed intra-abdominal infections. The PK results of the meropenem study have been published previously [8]. Here the safety and effectiveness data are described.