Unmonitored and Untreatable: The Neonatal Antimicrobial Resistance Crisis in Pakistan

A BSTRACT Neonatal sepsis remains a leading cause of neonatal mortality in low- and middle-income countries (LMICs), where increasing antimicrobial resistance (AMR) is undermining the effectiveness of commonly used empirical antibiotic regimens. In Pakistan, antibiotic-resistant bacterial infections are estimated to contribute to approximately 25,000 neonatal deaths annually, yet consolidated national data to guide antimicrobial therapy remain limited. This review synthesizes contemporary evidence on pathogen distribution and antimicrobial resistance patterns in culture-confirmed neonatal sepsis across Pakistani neonatal intensive care units (NICUs). A PRISMA-guided systematic search identified studies published between 2017 and 2024, of which 20 met inclusion criteria. Isolate-weighted analyses were performed to determine pooled pathogen frequencies and resistance patterns, including regional comparisons. Among 7,613 specimens evaluated, 2,161 (28.3%) yielded positive cultures, with Gram-negative organisms accounting for 67.5% of isolates. The most frequently identified pathogens were Klebsiella spp. (29.5%), Escherichia coli (13.1%), Acinetobacter spp. (11.5%), and Pseudomonas aeruginosa (9.8%). Resistance rates exceeded 70% for ampicillin, gentamicin, and third-generation cephalosporins across most studies, while substantial carbapenem resistance was observed among Acinetobacter spp. Marked regional variation in pathogen prevalence and resistance profiles was also identified. These findings demonstrate that multidrug-resistant Gram-negative organisms predominate in neonatal sepsis in Pakistan and render many standard empirical antibiotic regimens inadequate. The review highlights the urgent need for updated evidence-based treatment guidelines, routine NICU-specific antibiograms, and strengthened neonatal AMR surveillance systems in Pakistan and other comparable LMIC settings.