Alarming Rise in Untreatable Neonatal Sepsis: A Prospective Study of Multidrug-Resistant (MDR) and Extensively Drug-Resistant (XDR) Pathogens in an Indian Tertiary NICU

Background: Culture-positive neonatal sepsis is a leading cause of mortality. The emergence of multidrug-resistant (MDR) and extensively drug-resistant (XDR) bacteria exacerbates the clinical outcomes. This study aimed to determine the bacteriological profile and antibiotic resistance patterns of MDR and XDR strains causing neonatal sepsis. Objectives: This study aimed to determine the prevalence of culture-positive neonatal sepsis, characterize the bacteriological profile and antimicrobial resistance patterns of multidrug-resistant (MDR) and extensively drug-resistant (XDR) pathogens, and assess clinical outcomes, specifically mortality, in neonates admitted to a tertiary care NICU. Methods: A prospective observational study was conducted from August 2020 to September 2022. Neonates with clinical signs of sepsis and positive blood cultures were enrolled. Bacterial identification and antibiotic susceptibility testing were performed using the VITEK 2 compact automated system (Marcy-l'Étoile, France: bioMérieux). Isolates were classified as MDR or XDR based on standardized international definitions. Results: Of 120 culture-positive neonates, 100 (83.3%) had bacterial sepsis. Gram-negative bacteria accounted for 67 of 100 bacterial isolates (67%); the most common pathogens were Klebsiella pneumoniae (19/67; 28.4%) and Acinetobacter species (10/67; 14.9%). Overall, 55 of 100 bacterial isolates (55.0%) were multidrug-resistant (MDR), and 19 of 100 (19.0%) were extensively drug-resistant (XDR). High resistance rates were observed for fluoroquinolones (59/98 tested; 60.2%), carbapenems (30/59 tested; 50.8%), and third-generation cephalosporins among Gram-negative isolates (42/66 tested; 63.6%). Among XDR isolates, resistance was 13/14 (92.9%) to piperacillin-tazobactam and 16/17 (94.1%) to cephalosporins. Mortality was higher in XDR cases (6/19; 31.6%) than in MDR cases (7/55; 12.7%). Conclusion: There is a high burden of MDR and XDR Gram-negative neonatal sepsis, predominantly due to K. pneumoniae and Acinetobacter species. The alarming resistance to last-resort antibiotics underscores the critical need for robust antibiotic stewardship programs and continuous surveillance to prevent the emergence of pan-drug-resistant strains.