Clinical pharmacology of carbapenems in neonates.

Carbapenems are an effective tool to treat complicated bacterial infections. This review aims to summarize the available information on carbapenems in neonates to guide clinicians on drug choice and indications in neonates. Moreover, identification of knowledge gaps may stimulate researchers to design studies to further improve pharmacotherapy in neonates. To do so, a bibliographic search [infant/newborn and meropenem, imipenem, panipenem, ertapenem, doripenem or imipenem] was performed (PubMed, EMBASE) and public clinical trial registries (clinicaltrials.gov, EU registry) were searched to summarize the available information. Carbapenem clearance in neonates is low. Variability relates to maturation (weight, age) and renal function (creatinine clearance), while observations in neonates with renal failure are absent. Pharmacodynamics are almost exclusively limited to meropenem, and the available information will further increase (NeoMero-1-2, necrotizing enterocolitis, meningitis). Finally, there are also some ongoing doripenem pharmacokinetics (PK) studies in neonates. It was concluded that observations on carbapenems in neonates are limited, but studies (NeoMero, doripenem) are ongoing. Until this information becomes available, off label prescription of meropenem seems to be the most reasonable choice when a carbapenem is appropriate. Knowledge gaps relate to PK in neonates with renal failure and to the potential benefit of prolonged compared to short duration of infusion.