The escalating global burden of antimicrobial resistance constitutes a public health crisis. The World Health Organization reports that epidemiological models project 10 million deaths attributable to this issue annually by 2050. Among resistant pathogens, metallo-β-lactamase (MBL)-producing organisms represent a clinical challenge, given their consistent association with high rates of morbidity and mortality. This review summarizes effective treatment options against MBL-producing Enterobacterales. In clinical practice, a pragmatic therapeutic decision rule can be applied: when aztreonam–avibactam (ATM–AVI) is accessible and in vitro susceptibility is confirmed, it should be regarded as the preferred targeted regimen for infections caused by MBL-producing Enterobacterales. In settings where ATM–AVI is unavailable, the combination of ceftazidime–avibactam with aztreonam (CAZ–AVI + ATM) remains the treatment of choice, an approach endorsed by current recommendations from the Infectious Diseases Society of America (IDSA) and the European Society of Clinical Microbiology and Infectious Diseases (ESCMID). Critical evaluation of the published evidence is essential to inform the selection of optimal therapeutic regimens for affected patients. Novel antimicrobial agents are currently under clinical development and may broaden the therapeutic toolkit in the near future.

The increasing prevalence of antimicrobial resistance has stimulated interest in non-antibiotic small molecules that can restore or potentiate the activity of established antibacterial agents. In this study, a focused series of low-molecular-weight chromene derivatives was synthesized, structurally characterized, and evaluated primarily as antibacterial adjuvants rather than as stand-alone antibiotics. The experimental strategy was designed to distinguish intrinsic antibacterial activity from potentiating activity in combination with a partner antibiotic. Initial susceptibility testing was followed by combination experiments in selected bacterial strains, with particular emphasis on changes in the minimum inhibitory concentration (MIC) of meropenem or doripenem in the presence of each test compound. Broth microdilution combination assays demonstrated that compound 3a significantly reduced the MIC of meropenem and doripenem against methicillin-resistant Staphylococcus aureus (MRSA). The observed adjuvant effect suggests that chromene scaffolds may serve as promising candidates for the development of next-generation β-lactam enhancers aimed at overcoming carbapenem resistance.