When might we consider using the newer β-lactam agents as empirical therapy against presumed carbapenem-resistant gram-negative infections?

Background: Carbapenem-resistant Gram-negative (CRGN) pathogens-including Methods: In this review we evaluate epidemiological studies, randomized trials, comparative observational studies, international guidelines, microbiological surveillance data on CRGN infections and clinical factors supporting consideration of empirical use of newer β-lactam agents in patients with sepsis at risk for CRGN infection. Results: Carbapenem resistance epidemiology varies substantially across regions and strongly affects the likelihood of CRGN infection. Key risk factors include prior CRGN colonization or infection, recent broad-spectrum antibiotic exposure, prolonged hospitalization and healthcare contact in high-prevalence settings. In sepsis, delayed effective antimicrobial therapy-particularly in septic shock or severe immunosuppression-is associated with poorer outcomes. However, indiscriminate empirical use of newer β-lactam agents may promote resistance and compromise stewardship efforts. Direct evidence supporting empirical use of these agents remains limited and is based largely on observational data and extrapolation from targeted-therapy studies. Empirical use of newer agents may be appropriate for carefully selected patients with a high probability of CRGN infection and clinical scenarios where delayed active therapy could have serious consequences. Conclusion: A risk-stratified, stewardship-integrated approach incorporating local epidemiology, patient-level risk factors, illness severity and rapid diagnostics may optimize timely effective therapy while preserving the long-term utility of these agents.