TY - JOUR
T1 - In vitro activity of doripenem in combination with various antimicrobials against multidrug-resistant acinetobacter baumannii
T2 - Possible options for the treatment of complicated infection
AU - Principe, Luigi
AU - Capone, Alessandro
AU - Mazzarelli, Antonio
AU - D'Arezzo, Silvia
AU - Bordi, Eugenio
AU - Di Caro, Antonino
AU - Petrosillo, Nicola
PY - 2013/10/1
Y1 - 2013/10/1
N2 - Aims: The aim of this study was to evaluate the in vitro activity of doripenem (DOR) alone and in combination with a variety of commonly used anti-Acinetobacter chemotherapeutic agents against 22 primary multidrug-resistant (MDR) Acinetobacter baumannii isolates (including 17 isolates that were resistant to DOR) from Intensive Care Unit patients. Antibiotic interactions were evaluated using the chequerboard method and the time-kill assay. Results: Considering all antimicrobials in combination with DOR, chequerboard analysis showed synergy in 13 A. baumannii strains (54.2%). Seven strains (29.2%) showed ≥2 synergistic interactions. DOR showed synergy in combination with tigecycline (TIG) (eight strains), colistin (COL) (eight strains), amikacin (AMK) (four strains), ampicillin/sulbactam (two strains), and rifampicin (one strain). Remarkably, synergistic effects were detected only in DOR nonsusceptible strains. Time-kill assays confirmed synergy in eight isolates (giving 10 synergistic interactions) for DOR in combination with TIG (n=4), COL (n=5), and AMK (n=1). No antagonistic interactions were observed with both methods. Conclusions: This study demonstrates the in vitro synergistic activity of DOR in combination with TIG, COL, and AMK against DOR-resistant A. baumannii strains, opening the way to in vivo assessment of novel combination therapies for treatment of infections caused by MDR A. baumannii.
AB - Aims: The aim of this study was to evaluate the in vitro activity of doripenem (DOR) alone and in combination with a variety of commonly used anti-Acinetobacter chemotherapeutic agents against 22 primary multidrug-resistant (MDR) Acinetobacter baumannii isolates (including 17 isolates that were resistant to DOR) from Intensive Care Unit patients. Antibiotic interactions were evaluated using the chequerboard method and the time-kill assay. Results: Considering all antimicrobials in combination with DOR, chequerboard analysis showed synergy in 13 A. baumannii strains (54.2%). Seven strains (29.2%) showed ≥2 synergistic interactions. DOR showed synergy in combination with tigecycline (TIG) (eight strains), colistin (COL) (eight strains), amikacin (AMK) (four strains), ampicillin/sulbactam (two strains), and rifampicin (one strain). Remarkably, synergistic effects were detected only in DOR nonsusceptible strains. Time-kill assays confirmed synergy in eight isolates (giving 10 synergistic interactions) for DOR in combination with TIG (n=4), COL (n=5), and AMK (n=1). No antagonistic interactions were observed with both methods. Conclusions: This study demonstrates the in vitro synergistic activity of DOR in combination with TIG, COL, and AMK against DOR-resistant A. baumannii strains, opening the way to in vivo assessment of novel combination therapies for treatment of infections caused by MDR A. baumannii.
UR - http://www.scopus.com/inward/record.url?scp=84884568940&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84884568940&partnerID=8YFLogxK
U2 - 10.1089/mdr.2012.0250
DO - 10.1089/mdr.2012.0250
M3 - Article
C2 - 23659601
AN - SCOPUS:84884568940
VL - 19
SP - 407
EP - 414
JO - Microbial Drug Resistance
JF - Microbial Drug Resistance
SN - 1076-6294
IS - 5
ER -