Abstract

BackgroundAntimicrobial prescription and administration-related errors occur frequently in very low birth weight (VLBW; <1,500 g) neonates treated for bloodstream infections (BSI).MethodsAntimicrobial prescriptions for the treatment of laboratory-confirmed BSI were retrospectively analyzed for VLBW neonates at Tygerberg Hospital, Cape Town, South Africa (1 July 2018 - 31 December 2019), describing antimicrobial type, indication, duration of therapy and BSI outcomes. The prevalence of, and risk factors for prescription (dose, interval) and administration errors (hang-time, delayed/missed doses) were determined.ResultsOne hundred and sixty-one BSI episodes [16 (9.9%)] early-onset, 145 [90.1%] healthcare-associated) affected 141 neonates (55% male, 25% born to mothers living with HIV, 46% <1,000 g birth weight) with 525 antimicrobial prescription episodes [median 3.0 (IQR 2–4) prescriptions/BSI episode]. The median duration of therapy for primary BSI, BSI-associated with meningitis and BSI-associated with surgical infections was 9, 22, and 28 days, respectively. The prevalence of dose and dosing interval errors was 15.6% (77/495) and 16.4% (81/495), respectively with prescription errors occurring most commonly for piperacillin-tazobactam and vancomycin given empirically. Administration errors were less frequent [3.8% (219/5,770) doses missed; 1.4% (78/5,770) delayed], however 64% had a hang-time (time from sepsis diagnosis to 1st dose of antimicrobial) exceeding 60 min. On multivariable analysis, postnatal age >7 days was associated with prescription errors (p = 0.028). The majority of neonates with BSI required escalation of respiratory support (52%) and 26% required intensive care admission. Despite fair concordance between empiric antimicrobial/s prescription and pathogen susceptibility (74.5%), BSI-attributable mortality in this cohort was 30.4%.ConclusionVLBW neonates with BSI's were critically ill and had high mortality rates. Hang-time to first antimicrobial administration was delayed in two-thirds of BSI episodes and prescription errors affected almost 1 in 6 prescriptions. Targets for intervention should include reducing hang-time, use of standardized antimicrobial dosing guidelines and implementation of antimicrobial stewardship recommendations.

Highlights

  • In Sub-Saharan Africa (SSA), ∼1 million deaths occur in the neonatal period annually [1], with prematurity, intrapartum related events and infection as the leading causes [2]

  • Given the limited data from SSA regarding this widespread problem we reviewed the prevalence of, and contributors to, antimicrobial prescription and administration errors in very low birth weight (VLBW:

  • Two-hundred and one laboratory confirmed BSI episodes were identified in 1,226 VLBW neonates admitted to Tygerberg Hospital during the study period

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Summary

Introduction

In Sub-Saharan Africa (SSA), ∼1 million deaths occur in the neonatal period annually [1], with prematurity, intrapartum related events and infection as the leading causes [2]. Physiology in the neonatal period is constantly changing and developing requiring frequent dose and interval changes to achieve adequate drug concentrations. These physiological changes may affect the pharmacokinetics and pharmacodynamics of drugs resulting in the need for dosing adjustments in accordance with age, weight and/or body surface area [13–15], increasing the potential for prescribing errors. Antimicrobial prescription and administration-related errors occur frequently in very low birth weight (VLBW;

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