treatment strategies: a review of therapeutic challenges and considerations.

Antimicrobial resistance poses a major challenge in the treatment of spp. are intrinsically resistant to a number of commonly used antibiotics. Over the past 3 years, the European and American Professional Societies have provided important guidelines on the treatment options for carbapenem-resistant (CRAB). Here, we review the recent literature on combination regimens for CRAB as well as carbapenem-susceptible infections. We discuss the strengths and weaknesses of various agents used in combination, depending on the site of infection and their pharmacokinetic properties. Consistent with the 2024 Infectious Diseases of America (IDSA) update, sulbactam-durlobactam, in combination with background carbapenem therapy, remains the combination with the greatest reduction in mortality for pulmonary infections and has promising outcomes in bloodstream infections with CRAB. Sulbactam-based combination therapy remains an ideal part of targeted strategies and has been shown to be associated with reduced mortality. Certain agents have been highlighted in the literature for suboptimal outcomes, primarily pulmonary infections treated with cefiderocol, tigecycline, and eravacycline. Studies including non-pulmonary infections, specifically bacteremia and central nervous system (CNS) infections, are overall limited to case series and subgroup analyses. Important areas for further research include breakpoint evaluations for eravacycline and minocycline as well as subclinical resistance in cefiderocol.