Abstract: In low- and middle-income countries, where antimicrobial access may be erratic and
neonatal sepsis pathogens are frequently multidrug-resistant, empiric antibiotic prescribing prac-
tices may diverge from the World Health Organization (WHO) guidelines. This study examined
antibiotic prescribing for neonatal sepsis at a tertiary referral hospital neonatal unit in Gaborone,
Botswana, using data from a prospective cohort of 467 neonates. We reviewed antibiotic prescriptions
for the first episode of suspected sepsis, categorized as early-onset (EOS, days 0–3) or late-onset
(LOS, >3 days). The WHO prescribing guidelines were used to determine whether antibiotics were
“guideline-synchronous” or “guideline-divergent”. Logistic regression models examined indepen-
dent associations between the time of neonatal sepsis onset and estimated gestational age (EGA)
with guideline-divergent antibiotic use. The majority (325/470, 69%) were prescribed one or more
antibiotics, and 31 (10%) received guideline-divergent antibiotics. Risk factors for guideline-divergent
prescribing included neonates with LOS, compared to EOS (aOR [95% CI]: 4.89 (1.81, 12.57)). Prema-
turity was a risk factor for guideline-divergent prescribing. Every 1-week decrease in EGA resulted
in 11% increased odds of guideline-divergent antibiotics (OR [95% CI]: 0.89 (0.81, 0.97)). Premature
infants with LOS had higher odds of guideline-divergent prescribing. Studies are needed to define
the causes of this differential rate of guideline-divergent prescribing to guide future interventions.
Keywords: neonatal sepsis; antibiotic utilization; antibiotic guidelines; antimicrobial resistance;
middle-income country; global health; neonatology; infectious diseases

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