G Model ANTAGE-4532; No. of Pages 2
ARTICLE IN PRESS International Journal of Antimicrobial Agents xxx (2015) xxx–xxx
Contents lists available at ScienceDirect
International Journal of Antimicrobial Agents journal homepage: http://www.elsevier.com/locate/ijantimicag
Letter to the Editor Synergistic interactions between colistin and meropenem against extensively drug-resistant and pandrug-resistant Acinetobacter baumannii isolated from ICU patients Sir, Over the last years, Acinetobacter baumannii has been recognised as a serious human pathogen because of its capacity to cause outbreaks and to acquire multiple resistance mechanisms. The European Centre for Disease Prevention and Control (ECDC) reported a large proportion of invasive multidrug-resistant (MDR) A. baumannii isolates for 2013 and, more worryingly, the emergence of colistin-resistant isolates, which results in extensive drug resistance or pandrug resistance and compromises the efficacy of this last-resort antibacterial against A. baumannii. Combination therapy is a common strategy against MDR infections, but there are few in vitro data regarding the effectiveness of antibacterial combinations against colistin-resistant and pandrug-resistant (PDR) A. baumannii [1]. In this study, the in vitro interactions of five two-drug combinations, comprising colistin plus ampicillin/sulbactam (COL + SAM), colistin plus tigecycline (COL + TGC), colistin plus meropenem (COL + MEM), ampicillin/sulbactam plus meropenem (SAM + MEM) and ampicillin/sulbactam plus tigecycline (SAM + TGC), against three extensively drug-resistant (XDR) and two PDR A. baumannii isolates from five intensive care unit (ICU) patients at a tertiary hospital were studied. The minimum inhibitory concentration (MIC) of each drug was determined according to Clinical and Laboratory Standards Institute (CLSI) guidelines [2], and combinations were tested using the chequerboard technique at concentrations ranging from 1/8× MIC to 4× MIC in 96-well microplates. All combinations were tested in triplicate. Drug interactions were assessed both by the Loewe additivitybased fractional inhibitory concentration index (FICI) model and the Bliss independence-based response surface (BIRS) analysis in order to reduce analytical bias and to increase sensitivity in detecting significant pharmacodynamic interactions, as previously found [3]. For the FICI, microplates were visually inspected after 24 h of incubation and the FICI was calculated using the equation FIC = CA /MICA + CB /MICB , where CA and CB are the concentrations of drugs A and B in combination, and MICA and MICB are the MICs of drug A and drug B alone, respectively. Synergy, additivity or antagonism were concluded when the FICI was ≤0.5, >0.50 to
ARTICLE IN PRESS International Journal of Antimicrobial Agents xxx (2015) xxx–xxx
Contents lists available at ScienceDirect
International Journal of Antimicrobial Agents journal homepage: http://www.elsevier.com/locate/ijantimicag
Letter to the Editor Synergistic interactions between colistin and meropenem against extensively drug-resistant and pandrug-resistant Acinetobacter baumannii isolated from ICU patients Sir, Over the last years, Acinetobacter baumannii has been recognised as a serious human pathogen because of its capacity to cause outbreaks and to acquire multiple resistance mechanisms. The European Centre for Disease Prevention and Control (ECDC) reported a large proportion of invasive multidrug-resistant (MDR) A. baumannii isolates for 2013 and, more worryingly, the emergence of colistin-resistant isolates, which results in extensive drug resistance or pandrug resistance and compromises the efficacy of this last-resort antibacterial against A. baumannii. Combination therapy is a common strategy against MDR infections, but there are few in vitro data regarding the effectiveness of antibacterial combinations against colistin-resistant and pandrug-resistant (PDR) A. baumannii [1]. In this study, the in vitro interactions of five two-drug combinations, comprising colistin plus ampicillin/sulbactam (COL + SAM), colistin plus tigecycline (COL + TGC), colistin plus meropenem (COL + MEM), ampicillin/sulbactam plus meropenem (SAM + MEM) and ampicillin/sulbactam plus tigecycline (SAM + TGC), against three extensively drug-resistant (XDR) and two PDR A. baumannii isolates from five intensive care unit (ICU) patients at a tertiary hospital were studied. The minimum inhibitory concentration (MIC) of each drug was determined according to Clinical and Laboratory Standards Institute (CLSI) guidelines [2], and combinations were tested using the chequerboard technique at concentrations ranging from 1/8× MIC to 4× MIC in 96-well microplates. All combinations were tested in triplicate. Drug interactions were assessed both by the Loewe additivitybased fractional inhibitory concentration index (FICI) model and the Bliss independence-based response surface (BIRS) analysis in order to reduce analytical bias and to increase sensitivity in detecting significant pharmacodynamic interactions, as previously found [3]. For the FICI, microplates were visually inspected after 24 h of incubation and the FICI was calculated using the equation FIC = CA /MICA + CB /MICB , where CA and CB are the concentrations of drugs A and B in combination, and MICA and MICB are the MICs of drug A and drug B alone, respectively. Synergy, additivity or antagonism were concluded when the FICI was ≤0.5, >0.50 to
