Meropenem response in neonatal carbapenem-resistant Klebsiella pneumoniae: a narrative review of in vitro-in vivo discordance.

backgroundNeonatal sepsis remains a major contributor to morbidity and mortality worldwide, particularly in low- and middle-income countries. gram-negative organisms, especially Klebsiella pneumoniae, are increasingly implicated in neonatal intensive care unit (NICU)-associated infections. The emergence of carbapenem-resistant Klebsiella pneumoniae (CRKP) has substantially limited therapeutic options. Although meropenem is widely used for severe gram-negative infections, clinical improvement has occasionally been observed despite documented in vitro resistance. This phenomenon suggests clinically important in vitro-in vivo discordance between antimicrobial susceptibility testing and therapeutic outcomes.

methodsA narrative literature review was conducted to evaluate clinical responses to meropenem in neonates with infections caused by carbapenem-resistant Klebsiella pneumoniae. To improve transparency and reporting rigor, the review incorporated PRISMA-informed methodological principles. Electronic databases including PubMed/MEDLINE, Embase, Scopus, Web of Science, and the Cochrane Library were searched from January 1990 to February 2025. Search terms included combinations of: ("neonate" OR "newborn") AND ("Klebsiella pneumoniae") AND ("meropenem resistance" OR "carbapenem-resistant") AND ("clinical outcome" OR "treatment response"). Two independent reviewers (M.M. and V.D.) conducted title/abstract screening and full-text assessment. Disagreements were resolved through consensus discussion. Eligible studies included neonates aged 0-28 days with confirmed K. pneumoniae infection treated with meropenem and reporting both antimicrobial susceptibility data and clinical outcomes. Systematic reviews were screened for contextual references only, while data extraction was limited to primary studies to avoid duplication.

resultsFollowing identification of 180 records and removal of duplicates, 13 articles were included in the final narrative synthesis, comprising primary neonatal clinical studies together with supporting mechanistic, pharmacokinetic/pharmacodynamic, and epidemiological literature relevant to in vitro-in vivo discordance. Meropenem monotherapy demonstrated inconsistent effectiveness against CRKP infections, particularly among carbapenemase-producing isolates such as New Delhi metallo-β-lactamase (NDM)-producing strains. However, partial clinical responses were occasionally observed despite in vitro resistance. Improved outcomes were reported in selected cases using pharmacokinetic/pharmacodynamic optimization strategies, including high-dose regimens, prolonged infusion, therapeutic drug monitoring, or combination antimicrobial therapy. Potential contributors to observed in vitro-in vivo discordance included neonatal pharmacokinetic variability, bacterial heteroresistance, inoculum effects, resistance mechanisms, and host-related factors such as prematurity and immune immaturity.

conclusionsAvailable evidence suggests that meropenem demonstrates variable and often limited clinical effectiveness in neonatal CRKP infections, and that conventional MIC-based antimicrobial susceptibility testing alone may inadequately predict therapeutic outcomes in this population. Management strategies should integrate resistance mechanism profiling, individualized pharmacokinetic/pharmacodynamic optimization, and host-specific clinical considerations rather than relying solely on laboratory susceptibility results.