title: Dual beta-lactam therapy for serious Gram-negative infections: is it time to revisit?
abstract: 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.
authors.affiliation: Albany College of Pharmacy and Health Sciences, Albany, NY, USA.
authors.forename: Christine
authors.initials: C
authors.lastname: Rahme
authors.affiliation: Albany College of Pharmacy and Health Sciences, Albany, NY, USA.
authors.forename: Jill M
authors.initials: JM
authors.lastname: Butterfield
authors.affiliation: Albany College of Pharmacy and Health Sciences, Albany, NY, USA.
authors.forename: Anthony M
authors.initials: AM
authors.lastname: Nicasio
authors.affiliation: Albany College of Pharmacy and Health Sciences, Albany, NY, USA. Electronic address: Thomas.lodise@acphs.edu.
authors.forename: Thomas P
authors.initials: TP
authors.lastname: Lodise
mesh_terms: D000617:Aminoglycosides / Q000494:pharmacology / Q000627:therapeutic use; D000818:Animals; D000900:Anti-Bacterial Agents / Q000627:therapeutic use*; D024881:Drug Resistance, Bacterial / Q000187:drug effects; D004359:Drug Therapy, Combination; D004755:Enterobacteriaceae / Q000187:drug effects; D016905:Gram-Negative Bacterial Infections / Q000188:drug therapy* / Q000382:microbiology; D006801:Humans; D046915:Penicillin-Binding Proteins / Q000378:metabolism; D011550:Pseudomonas aeruginosa / Q000187:drug effects; D047090:beta-Lactams / Q000009:adverse effects / Q000494:pharmacology / Q000627:therapeutic use*
chemical_list: D000617:Aminoglycosides; D000900:Anti-Bacterial Agents; D046915:Penicillin-Binding Proteins; D047090:beta-Lactams
keywords: Beta-lactam; Combination; Efficacy; In vitro; Outcomes; Review; Treatment