Antibiotic Choice, Effectiveness, and Outcome Among Hospitalized Neonates with Gram-Negative Bloodstream Infection in India: A Prospective Cohort Study

Background: Neonatal sepsis is a leading cause of childhood mortality. Antimicrobial resistance complicates management in high burden countries, such as India. We sought to determine whether early use of microbiologically active antibiotics is associated with reduced mortality of neonatal Gram-negative (GN) bloodstream infections (BSI). Methods: Between May 2017 and July 2019, we recruited neonates with GN BSI admitted to three neonatal intensive care units in India. Antibiotic use, microbial data, and clinical outcomes were prospectively collected. We assessed the association between empiric therapy including an active agent, defined by in vitro susceptibility, and 30-day all-cause mortality using Cox proportional hazard models.   Findings: Of 9303 neonates admitted over a 27-month period, 3107 (33%) had at least one blood culture; 263 (3%) had a GN BSI identified at a median 6 days of life (IQR 3-11). Among isolates, 196 were Enterobacterales with 73 (37%) identified as carbapenem-resistant Enterobacterales (CRE), and 46 were Acinetobacter species with 28 (61%) being carbapenem-resistant Acinetobacter species (CRAb). Overall, 52 infants received initial empiric therapy including colistin, which was active in most (169 of 263, 64%) instances, but a minority of patients with CRE (33 of 73, 45%) and CRAb (11 of 28, 39%) received an active agent. Initial use of active antibiotics was not associated with decreased 30-day mortality for CRE or CRAb infections. Interpretation: Early initiation of currently available, active antibiotics was not associated with lower mortality among neonates with GN BSI in a setting with a high burden of carbapenem-resistant organisms. Funding: U.S. Centers for Disease Control and Prevention Declaration of Interests: All authors declare no competing interests. Ethics Approval Statement: The study was approved by the ethics committees of each participating hospital, the Johns Hopkins School of Medicine Institutional Review Board, and the Government of India Health Ministry Screening Committee.