Synergistic combination of carbapenems and colistin against P. aeruginosa and A. baumannii

Abstract

Background: Intubated patients are particularly at risk of developing infections caused by these pathogens, specifically, P. aeruginosa and A. baumannii. In the past fifteen years, Carbapenems were known to be the drugs of choice for these bacteria. With the increase in the use and misuse of antibiotics, these bacteria became highly resistant, and almost all available antibiotics, including Carbapenems, became inefficient. Synergistic combination therapy may be a useful strategy in slowing as well as overcoming the emergence of resistance. The aim of this study was to evaluate the anti-bacterial activity on P. aeruginosa and A. baumannii of the combination of two antibiotics: Colistin and a Carbapenem (Meropenem or Imipenem). Methods: The antibacterial activity was assessed by determining the MIC. Then, the effect of combining the antibiotics was studied using the Checkerboard Technique described by White et al., 1996. The Fractional Inhibitory Concentration (FIC) for each strain was then calculated and classified as synergy, additive, indifference or antagonism. 11 strains of A. baumannii and 11 strains of P. aeruginosa were tested in the presence of Meropenem combined with Colistin or Imipenem combined with Colistin. Results: For the combination of Meropenem and Colistin, 6 strains of A. baumannii and 3 strains of P. aeruginosa showed synergy while 5 strains of A. baumannii and 7 strains of P. aeruginosa showed additive effect, only 1 strain of P. aeruginosa showed antagonism. For Imipenem and Colistin, only 1 strain of A. baumannii and 3 strains of Pseudomonas showed synergy while 8 strains of Acinetobacter and 8 strains of Pseudomonas showed additive effect. Conclusion: The "in vitro" combination Colistin-Carbapenem is associated with an improvement in MIC. In the majority of the cases, this improvement suggests a synergistic combination or an additive effect.