Rahme Christine, Butterfield Jill M, Nicasio Anthony M, Lodise Thomas P
Albany College of Pharmacy and Health Sciences, Albany, NY, USA.
Albany College of Pharmacy and Health Sciences, Albany, NY, USA.
Diagn Microbiol Infect Dis. 2014 Dec;80(4):239-59. doi: 10.1016/j.diagmicrobio.2014.07.007. Epub 2014 Jul 31.
We are rapidly approaching a crisis in antibiotic resistance, particularly among Gram-negative pathogens. This, coupled with the slow development of novel antimicrobial agents, underscores the exigency of redeploying existing antimicrobial agents in innovative ways. One therapeutic approach that was heavily studied in the 1980s but abandoned over time is dual beta-lactam therapy. This article reviews the evidence for combination beta-lactam therapy. Overall, in vitro, animal and clinical data are positive and suggest that beta-lactam combinations produce a synergistic effect against Gram-negative pathogens that rivals that of beta-lactam-aminoglycoside or beta-lactam-fluoroquinolone combination therapy. Although the precise mechanism of improved activity is not completely understood, it is likely attributable to an enhanced affinity to the diverse penicillin-binding proteins found among Gram negatives. The collective data indicate that dual beta-lactam therapy should be revisited for serious Gram-negative infections, especially in light of the near availability of potent beta-lactamase inhibitors, which neutralize the effect of problematic beta-lactamases.
我们正迅速面临抗生素耐药性危机，尤其是在革兰氏阴性病原体中。这一点，再加上新型抗菌药物研发缓慢，凸显了以创新方式重新部署现有抗菌药物的紧迫性。一种在20世纪80年代曾被大量研究但后来逐渐被放弃的治疗方法是双重β-内酰胺疗法。本文综述了联合β-内酰胺疗法的证据。总体而言，体外、动物和临床数据都是积极的，表明β-内酰胺联合用药对革兰氏阴性病原体产生的协同作用可与β-内酰胺-氨基糖苷类或β-内酰胺-氟喹诺酮联合疗法相媲美。尽管活性提高的确切机制尚未完全了解，但这可能归因于对革兰氏阴性菌中发现的多种青霉素结合蛋白的亲和力增强。总体数据表明，对于严重的革兰氏阴性感染，应重新审视双重β-内酰胺疗法，特别是考虑到强效β-内酰胺酶抑制剂即将问世，这些抑制剂可中和有问题的β-内酰胺酶的作用。
