Combination of Carbapenams with Fluoroquinolones for Gram-Negative Infections

Rationale Combination therapy

• likelihood that empiric antimicrobial therapy will provide adequate coverage for potential pathogens causing an infection is increased with the use of two antimicrobial agents compared to a single agent

In-Vitro Synergy

• data on synergistic activity have emerged for combinations of β-lactams and fluoroquinolones
• In vitro synergy between β-lactams and fluoroquinolones against Gram-negative organisms has ranged from 17% to 82%
• concluded that synergy between ciprofloxacin and β-lactams was sporadic and was not consistent across drug concentrations or sampling times

Clinical Evidence

• Fluoroquinolones are recognized for excellent tissue penetration into lung, meninges, and bone, and they have minimal nephrotoxicity compared with aminoglycosides
• According to the available evidence, in vitro synergy does not necessarily translate into a clinical benefit
• Several studies assessing the efficacy of fluoroquinolone monotherapy compared with combination therapy showed no difference in treatment effect between fluoroquinolone monotherapy and combination therapy

Additional disadvantages

• A substantial advantage can be gained with a simple antibiotic regimen with one agent, provided the agent is effective (including appropriate dosage, interval, and route of administration) and well tolerated
• broader spectrum of activity of carbapenems may have contributed to the improved response in these studies and suggests that the use of an appropriately broad β-lactam agent may invalidate the need for the addition of an aminoglycoside

Reference:

1. Combination Therapy for Treatment of Infections with Gram-Negative Bacteria. 2012 http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3416487/