Should Antibiotic Combinations Be Used to Treat Ventilator-Associated Pneumonia?

Abstract

This review summarizes the rationale for using or not using combinations of antibiotics to treat ventilator-associated pneumonia (VAP). Patients suffering from VAP require empirical antibiotic treatment before the identification of an etiologic agent. Most treatment failures are related to inappropriate initial antibiotic treatment with insufficient coverage of multidrug-resistant (MDR) pathogens. Guidelines require initial (empirical) treatment of VAP with a combination of antibiotics. However, this contributes to overexposure to antibiotics and further emergence of MDR microorganisms. We review the rationale for using combinations of antibiotics to cover MDR gram-negatives. However, clinical data supporting this strategy are limited. In fact, systematic combination therapy may have contributed to the overuse of antibiotics and to the emergence of MDR microorganisms. Nevertheless, combination therapy is our best strategy to treat severe infections due to suspected MDR microorganisms. Optimally, therapeutic strategies should be sufficiently broad to cover relevant pathogens while minimizing the risk for emergence of antimicrobial resistance.

Pseudomonas aeruginosa: resistance and therapeutic options at the turn of the new millennium

“…As no evidence‐based guidelines are available, the antibiotic selection should be adapted on a case‐by‐case basis, taking into account the susceptibility testing results (preferably the MIC data). In such cases, combinations of several agents are usually recommended [96]. Among the various therapeutic alternatives, colistin has received renewed interest [119].…”

In vitro synergism of β-lactams with ciprofloxacin and moxifloxacin against genetically distinct multidrug-resistant isolates of Pseudomonas aeruginosa

“…This particularly applies when considering the underlying rationale for the prescription of a combination. More precisely, many authors suggest that the application of empirical therapy should provide as broad coverage as possible for the probably implicated pathogens, whereas no benefit is disclosed when P. aeruginosa is susceptible to both administered antimicrobials [4,5]. However, no data are available regarding how a pathogen resistant to both administered antimicrobials behaves when exposed to their combination.…”

Accelerated evolution of resistance in multidrug environments

“…Such interactions between drugs are classified as additive, synergistic, or antagonistic depending on whether their combined effect on bacterial growth is equal to, greater than, or less than expected based on the inhibitory abilities of the individual drugs (8,9). Two main goals of drug treatment are stopping bacterial growth and preventing the evolution of drug resistance (5,(10)(11)(12). Although synergistically interacting drugs are often favored because of their greater combined ability to inhibit growth (13), little direct evidence for their ability to suppress the evolution of resistance exists, and some studies even suggest the contrary (14)(15)(16)(17)(18).…”