Clinical features, risk factors and 28-day mortality in neonates with carbapenem-resistant sepsis or meningitis in a South African tertiary neonatal unit: a prospective cohort study.

Introduction: Carbapenem-resistant, Gram-negative bacteria (GNB) are a significant cause of neonatal sepsis, threatening survival. There is a scarcity of robust data on their burden and outcomes in low- and middle-income countries (LMICs). We aimed to describe clinical and microbiological characteristics, outcomes and mortality risk factors in neonates infected with GNB and assess the impact of carbapenem resistance. Methods: Prospective observational cohort study from 1 February 2021 to 30 June 2023 conducted in a tertiary neonatal unit in Johannesburg, South Africa, in infants <90 days with culture-confirmed blood or cerebrospinal fluid infection with GNB. The primary outcome was mortality by day-28 post-sepsis diagnosis. Results: Gram-negative sepsis incidence was 6.6/1000 patient-days. Among 353 infants enrolled (median birth weight 1465 g; gestational age 31 weeks), 173 (49%) had carbapenem-sensitive organisms (CSO), 152 (43%) had carbapenem-resistant organisms (CRO) and susceptibility was not reported in 28 (8%). There were 404 GNB isolated. Conclusions: There is a substantial burden of Gram-negative neonatal infections, particularly due to CRO, exceeding rates reported in other LMICs in Africa and globally. Although carbapenem resistance was not independently associated with mortality, infants with CRO had approximately two times higher crude mortality compared with those with CSO, emphasising the urgent need for antimicrobial stewardship and infection prevention interventions. Neonatal-specific trials are needed addressing prevention and optimal antibiotic treatment of CRO infections to improve outcomes.