Open Journal of Medical Microbiology, 2013, 3, 253-258
Published Online December 2013 (http://www.scirp.org/journal/ojmm)
http://dx.doi.org/10.4236/ojmm.2013.34038
Open Access OJMM
Synergistic Combination of Carbapenems and Colistin
against P. aeruginosa and A. baumannii
Ziad Daoud
1,2*
, Najwa Mansour
1
, Khalil Masri
2
1
Clinical Microbiology Laboratory, Faculty of Medicine, University of Balamand, Tripoli, Lebanon
2
Infectious Diseases Department, Centre Hospitalier du Nord, Zgharta, Lebanon
Email:
*
ziad.daoud@balamand.edu.lb
Received October 24, 2013; revised November 22, 2013; accepted November 29, 2013
Copyright © 2013 Ziad Daoud et al. This is an open access article distributed under the Creative Commons Attribution License,
which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. In accor-
dance of the Creative Commons Attribution License all Copyrights © 2013 are reserved for SCIRP and the owner of the intellectual
property Ziad Daoud et al. All Copyright © 2013 are guarded by law and by SCIRP as a guardian.
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 Frac-
tional Inhibitory Concentration (FIC) for each strain was then calculated and classified as synergy, additive, indiffer-
ence or antagonism. 11 strains of A. baumannii and 11 strains of P. aeruginosa were tested in the presence of Mero-
penem 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 combina-
tion or an additive effect.
Keywords: Antibiotic Combination; Antibiotic Synergy; MIC; FIC; Acinetobacter baumannii;
Pseudomonas aeruginosa; Colistin; Meropenem; Imipenem
1. Introduction
Nosocomial infections are mostly encountered in patients
admitted to the intensive care units [1]. Among these,
catheterized or critically ill patients are considered as
number one group developing hospital acquired infec-
tions [2]. Gram positive as well as many gram negative
bacteria can be responsible for such infections [3,4]. P.
aeruginosa and A. baumannii are opportunistic patho-
gens that mostly cause hospital acquired pneumonia
(HAP) and ventilated associated pneumonia (VAP) [5].
They are usually more resistant than community acquired
pathogens due to extensive exposure to antibiotics in
hospitals.
Due to the lack or inefficiency of infection control
programs in many hospitals, random/extensive use of
antibiotics and many others reasons, resistance highly
emerged within these pathogens and they became known
as highly resistant microorganisms [6]. Carbapenem re-
sistant P. aeruginosa and A. baumannii are nowadays
widely spread. By nature, these pathogens are more re-
sistant than other Gram negative organisms because of
their outer membrane that is less permeable [7] and their
ability to form biofilm [8]. Furthermore, the main me-
chanisms of resistance acquired by these pathogens can
*
Corresponding author.