title: Use of the E test to assess synergy of antibiotic combinations against isolates of Burkholderia cepacia-complex from patients with cystic fibrosis.
abstract: Treatment of Burkholderia cepacia-complex infections in cystic fibrosis patients is problematic, since the microorganism is often resistant to most antimicrobial agents. In this study, the Epsilometer test, or E test, was used to assess the activity of antimicrobial combinations against Burkholderia cepacia-complex. In a preliminary evaluation, the E test was compared to the checkerboard method using 10 test organisms. Synergy testing by the E test was then performed on 131 clinical isolates of Burkholderia cepacia-complex using various combinations of antimicrobial agents. Agreement between the E test and the checkerboard method was 90%. The rate of resistance to individual agents ranged from 48% for meropenem to 100% for tobramycin, chloramphenicol, and rifampin. In 71.6%, 15.6%, and 12.6% of the test evaluations performed, the combinations tested resulted in additivity/indifference, synergism, and antagonism, respectively. The highest rates of synergy were observed with combinations of ciprofloxacin-piperacillin (44%), rifampin-ceftazidime (33%), chloramphenicol-ceftazidime (22%), cotrimoxazole-piperacillin/tazobactam (22%), and ciprofloxacin-ceftazidime (21%). Rates of antagonism for cotrimoxazole and chloramphenicol in combination with beta-lactam agents were higher than those observed for ciprofloxacin plus beta-lactam agents. These results suggest that the E test is a valuable and practical method to be considered for improving the identification of possible therapeutic options in cystic fibrosis patients infected with organisms belonging to the Burkholderia cepacia-complex.
authors.affiliation: Department of Paediatrics, Infectious Diseases Research and Diagnosis Laboratory, Gaslini Research Institute-Children's Hospital, University of Genoa, Largo G. Gaslini 5, 16147 Genoa, Italy. graziana@unige.it
authors.forename: G
authors.initials: G
authors.lastname: Manno
authors.forename: E
authors.initials: E
authors.lastname: Ugolotti
authors.forename: M L
authors.initials: ML
authors.lastname: Belli
authors.forename: M L
authors.initials: ML
authors.lastname: Fenu
authors.forename: L
authors.initials: L
authors.lastname: Romano
authors.forename: M
authors.initials: M
authors.lastname: Cruciani
mesh_terms: D001431:Bacteriological Techniques; D019121:Burkholderia Infections / Q000188:drug therapy* / Q000209:etiology; D016956:Burkholderia cepacia / Q000187:drug effects* / Q000302:isolation & purification; D002442:Ceftazidime / Q000494:pharmacology; D016009:Chi-Square Distribution; D002648:Child; D002675:Child, Preschool; D002939:Ciprofloxacin / Q000494:pharmacology; D003550:Cystic Fibrosis / Q000150:complications* / Q000188:drug therapy; D004352:Drug Resistance, Microbial; D004357:Drug Synergism; D004359:Drug Therapy, Combination / Q000494:pharmacology*; D005260:Female; D006801:Humans; D007769:Lactams / Q000494:pharmacology; D008297:Male; D008826:Microbial Sensitivity Tests / Q000379:methods*; D010878:Piperacillin / Q000494:pharmacology; D012293:Rifampin / Q000494:pharmacology; D012680:Sensitivity and Specificity
chemical_list: D007769:Lactams; D002939:Ciprofloxacin; D002442:Ceftazidime; D012293:Rifampin; D010878:Piperacillin