Appropriate empiric therapy reduces mortality and morbidity associated with serious Gram-negative infections. β-lactams (BLs) owing to their safety, efficacy, and coverage spectrum are the most preferred agents for empiric use. Inappropriate use of older penicillins and cephalosporins led to selection and spread of resistant clones. As a result, these valuable agents have lost their reliability compelling clinicians to often use erstwhile last-line therapies such as carbapenems. Excessive carbapenems use imposed collateral damage by selecting difficult-to-treat carbapenem-resistant organisms. Lack of empiric therapeutic options amenable for use in infections caused by contemporary pathogens was realized by the pharmaceutical industry leading to intensive efforts in discovering novel antibiotics. These efforts led to the approval of newer β-lactams and β-lactamase inhibitor (BL-BLI) combination. This review elaborates the past trends in empirical use of BLs and ensuing patterns of resistance emergence in Gram-negatives. Furthermore, a critical appraisal of newer BL-BLIs has been presented to identify the appropriate clinical situations for their use to ensure clinical efficacy coupled with minimal resistance selection. These learning have been derived from past trends of clinical usage of older empiric therapies so that the therapeutic utility of newer agents is preserved for long in light of dwindling global antibiotics pipeline.
Keywords: Gram-negative; empiric therapy; multidrug resistance; β-lactam and β-lactamase inhibitor.