New Antibiotic Dosing in Infants

Abstract

Infection is common in premature infants and can cause significant morbidity and mortality. To prevent these devastating consequences, most infants admitted to the neonatal intensive care unit (NICU) are exposed to antibiotics. However, dosing regimens are often extrapolated from data in adults and older children, increasing the risk for drug toxicity and lack of clinical efficacy because they fail to account for developmental changes in infant physiology. Despite legislation promoting and, in some cases, requiring pediatric drug studies, infants remain therapeutic orphans who often receive drugs "off-label" without data from clinical trials. Pharmacokinetic (PK) studies in premature infants have been scarce due to low study consent rates; limited blood volume available to conduct PK studies; difficulty in obtaining blood from infants; limited use of sensitive, low-volume drug concentration assays; and a lack of expertise in pediatric modeling and simulation. However, newer technologies are emerging with minimal-risk study designs, including ultra-low-volume assays, PK modeling and simulation, and opportunistic drug protocols. With minimal-risk study designs, PK data and dosing regimens for infants are now available for antibiotics commonly used in the NICU, including ampicillin, clindamycin, meropenem, metronidazole, and piperacillin/tazobactam. The discrepancy between previous dosing recommendations extrapolated from adult data and newer dosing regimens based on infant PK studies highlights the need to conduct PK studies in premature infants.

Dosing Antibiotics in Neonates: Review of the Pharmacokinetic Data

“…Like clindamycin, metronidazole has excellent oral bioavailability, with more than 90% absorbed. Metronidazole is commonly used in preterm infants for anaerobic infections, including NEC, menin gitis and bacteremia [82][83][84][85][86]. The metabolism of metronidazole is primarily hepatic [87].…”

Infections nosocomiales en néonatologie

“…La colonisation, le plus souvent digestive, par un germe résistant aux céphalosporines de troisième génération, chez un nouveau-né suspect d'infection, implique de remplacer la céphalosporine par le méropénème [44], de préférence à l'imipénème qui a un risque neuro-toxique. Cette antibiothérapie probabiliste est ensuite adaptée en fonction de la sensibilité du germe isolé.…”

Simplified Dosing Regimens for Gentamicin in Neonatal Sepsis

“…In fact, a few historical antibiotic efficacy trials were performed in neonates >20 years ago and these have been conducted without careful evaluation of the implications that differences in drug disposition represent for the dose rationale ( Evans et al, 1986 ; Buring et al, 1988 ; Wiese, 1988 ; Fisk, 1993 ). By contrast, a vast body of evidence is currently available that allows one to assess the role of age and disease-related changes in drug disposition and overall differences in the pharmacokinetic properties of antibiotics ( Manolis and Pons, 2009 ; Pandolfini et al, 2013 ; Roberts et al, 2014 ; Stockmann et al, 2014 ; Pineda and Watt, 2015 ). Here we assess the feasibility of a simplified regimen of gentamicin taking into account the effect of body size and organ maturation on pharmacokinetics.…”