Characterization of antimicrobial-resistant Gram-negative bacteria that cause neonatal sepsis in seven low- and middle-income countries

TLDR

Antimicrobial resistance in neonatal sepsis is rising and its mobile genetic element–mediated mechanisms are poorly understood, limiting treatment options in LMICs. The BARNARDS network was launched to characterize the causes and burden of antimicrobial resistance in neonatal sepsis across seven LMICs in Africa and South Asia. The study enrolled 36,285 neonates, identified 2,483 culture‑confirmed sepsis cases, and performed whole‑genome sequencing, antimicrobial susceptibility testing, and clinical data analysis on 916 of 1,038 isolates. Klebsiella pneumoniae dominated neonatal sepsis, with other Enterobacterales also detected; all isolates carried multiple cephalosporin and carbapenem resistance genes, were multidrug‑resistant, and intraspecies diversity revealed several resistant lineages, highlighting the urgency for better treatments in LMICs.

Abstract

Antimicrobial resistance in neonatal sepsis is rising, yet mechanisms of resistance that often spread between species via mobile genetic elements, ultimately limiting treatments in low- and middle-income countries (LMICs), are poorly characterized. The Burden of Antibiotic Resistance in Neonates from Developing Societies (BARNARDS) network was initiated to characterize the cause and burden of antimicrobial resistance in neonatal sepsis for seven LMICs in Africa and South Asia. A total of 36,285 neonates were enrolled in the BARNARDS study between November 2015 and December 2017, of whom 2,483 were diagnosed with culture-confirmed sepsis. Klebsiella pneumoniae (n = 258) was the main cause of neonatal sepsis, with Serratia marcescens (n = 151), Klebsiella michiganensis (n = 117), Escherichia coli (n = 75) and Enterobacter cloacae complex (n = 57) also detected. We present whole-genome sequencing, antimicrobial susceptibility and clinical data for 916 out of 1,038 neonatal sepsis isolates (97 isolates were not recovered from initial isolation at local sites). Enterobacterales (K. pneumoniae, E. coli and E. cloacae) harboured multiple cephalosporin and carbapenem resistance genes. All isolated pathogens were resistant to multiple antibiotic classes, including those used to treat neonatal sepsis. Intraspecies diversity of K. pneumoniae and E. coli indicated that multiple antibiotic-resistant lineages cause neonatal sepsis. Our results will underpin research towards better treatments for neonatal sepsis in LMICs.