Tamara van Donge

Chapter 4 62 Identification of dosing recommendations Intravenous amoxicillin dosing regimens for the indication of neonatal infection (< 1 month after birth) were collected from nine Swiss level III neonatal intensive care units (NICUs) in 2015. Dosing recommendations were identified from six international guidelines, namely the Swiss Agency for Therapeutic Products 2015 (Swissmedic), the British National Formulary for Children 2015 (BNFc), the Neonatal Formulary 7 th edition (NNF7), Frank Shann’s Drug Doses 2014 (Shann), The Harriet Lane 2014 and Lexicomp 2016. Dose per administration, dosing interval, total daily dose, and demographics used for dynamic dosing regimens were extracted from each recommendation. Population of interest Our model population (Table 1) was derived from the clinical data for neonates in the Antibiotic Resistance and Prescribing in European Children (ARPEC) study, an international antibiotic prescribing point prevalence study. 12 To reflect the population managed in neonatal care, neonates and young infants with a postmenstrual age (PMA; sum of gestational age (GA) and postnatal age (PNA)) of ≤44 weeks, were considered. We consider this cohort to represent neonates likely to be exposed to amoxicillin, and therefore to reflect our population of interest (no microbiological data were available). Individual amoxicillin exposure was simulated by attributing each dosing regimen to each cohort patient, i.e. for each regimen each patient was simulated once taking demographic characteristics such as age or weight into account as recommended for the regimen of interest. Table 1: Demographic characteristics of European neonates and infants in the ARPEC database. Patient group and demographics N (%) Total 1063 (100%) Preterm (< 37 weeks gestation) 713 (67%) Male, N (%) 597 (56%) Gestational age, median (IQR) / [min - max] (weeks) 34 (29 - 39) / [22 - 42] Birth weight, median (IQR) / [min - max] (kg) 2.1 (1.1 – 3.2) / [0.4 – 4.8] Age a , median (IQR) / [min - max] (days) 6 (3 – 16) / [0 - 60] ≤ 7 days, N (%) 580 (55 %) > 7 and ≤ 14 days, N (%) 177 (17 %) > 14 and ≤ 28 days, N (%) 186 (28 %) > 28 and ≤ 60 days, N (%) 120 (11 %) Weight, median (IQR) / [min - max], (kg) 2.2 (1.2 – 3.2) / [0.5 – 4.8] Postmenstrual age, median (IQR) / [min - max] (weeks) 35.6 (31 – 35.2) / [23.7 - 44] a Postnatal age at the time of assessment