Synergistic combination of carbapenems and colistin against Pseudomonas Aeruginosa and Acinetobacter Baumannii

Abstract

MDR organisms are highly encountered in hospitals and their settings especially in the critically ill patients and ICUs. Intubated patients are particularly at risk of developing different infections caused by different MDR pathogens. Of these pathogens, P.aeruginosa and A.baumannii are of a great interest. In the past fifteen years, Carbapenems were known to be the drugs of choice for these bacteria. Unfortunately, with the increase in the use and misuse of antibiotics, these bacteria became highly resistant and almost all the 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 combination of two bactericidal antibiotics: a polymyxin (colistin) with a carbapenem (Meropenem or Imipenem) in terms of antibacterial activity against P.aeruginosa and A. baumannii and to investigate which combination gives a better synergy. 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. In the combination of Meropenem and Colistin, 6 strains of A.baumannii showed synergy and 5 strains showed additive effect. The average of FICs was 0.5393. With the same combination, 3 strains of P.aeruginosa showed synergy, 7 strains showed additive effect and 1 strain showed antagonism. The average of FICs was 0.9342. For the second combination tested Imipenem and Colistin, only 1 strain of A.baumannii showed synergy while 8 strains showed additive effect and 2 showed antagonism. The average of FICs was 0.9619. Apparently, Meropenem combined with Colistin was better than Imipenem combined with Colistin in both types of bacteria; however the treatment cannot be generalized and the best combination remains strain specific.