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.

中文翻译：

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在具有挑战性的耐药情况下，针对革兰氏阴性感染保留基于β-内酰胺的日益减少的经验疗法选择：经验教训和前进方向。

适当的经验治疗可降低与严重革兰氏阴性感染相关的死亡率和发病率。由于其安全性，功效和覆盖范围广，β-内酰胺（BLs）是最优选的经验性药物。不适当使用较老的青霉素和头孢菌素会导致抗性克隆的选择和传播。结果，这些有价值的药物失去了可靠性，迫使临床医生经常使用以前的最后一线疗法，例如碳青霉烯。过量的碳青霉烯类药物会通过选择难以治疗的耐碳青霉烯类生物而造成附带损害。制药业意识到缺乏适用于当代病原体感染的经验性治疗选择，这导致人们在发现新型抗生素方面付出了巨大的努力。这些努力导致批准了更新的β-内酰胺和β-内酰胺酶抑制剂（BL-BLI）组合。这篇综述详细阐述了BL经验性使用的过去趋势以及随之而来的革兰氏阴性菌耐药性出现的模式。此外，已经提出了对较新的BL-BLI的严格评估，以鉴定其使用的合适临床情况，以确保临床疗效以及最小的耐药性选择。这些学习是从较早的经验疗法的临床使用的过去趋势中得出的，因此随着全球抗生素管道的减少，新药的治疗效用得以长期保留。已经提出了对新型BL-BLI的严格评估，以鉴定其使用的合适临床情况，以确保临床疗效以及最小的耐药性选择。这些学习是从较早的经验疗法的临床使用的过去趋势中得出的，因此随着全球抗生素管道的减少，新药的治疗效用得以长期保留。已经提出了对新型BL-BLI的严格评估，以鉴定其使用的合适临床情况，以确保临床疗效以及最小的耐药性选择。这些学习是从较早的经验疗法的临床使用的过去趋势中得出的，因此随着全球抗生素管道的减少，新药的治疗效用得以长期保留。