Original Article
In vitro assessment of cefoperazone-sulbactam based combination therapy for multidrug-resistant Acinetobacter baumannii isolates in China
Abstract
Background: Multidrug-resistant Acinetobacter baumannii (MDRAB) has emerged as an important pathogen of nosocomial infections. Even though cefoperazone-sulbactam is frequently used to treat MDRAB infections, this single-drug therapeutic approach often results in antibiotic resistance. Thus, combination therapy is preferred over single-drug therapy, particularly in the case of carbapenemase-producing gram negative bacteria. The aim of this study was to investigate the efficacy of cefoperazone-sulbactam combined with either tigecycline or rifampicin against clinical isolates of MDRAB.
Methods: One hundred and three MDRAB bacteria were isolated from patients in two hospitals in China. The Epsilomer test (E test) was used to determine the minimum inhibitory concentration (MIC) values for amikacin, ceftazidime, cefepime, levofloxacin, rifampicin, cefoperazone-sulbactam, meropenem, tigecycline, and gentamicin against MDRAB isolates. In vitro effects of various antibiotic combinations were measured and the fractional inhibitory concentration index (FICI) was calculated for each drug combination.
Results: Approximately 17.5% of the isolates were resistant to tigecycline, whereas more than 84.2% isolates were resistant to other antimicrobial agents tested in this study. Cefoperazone-sulbactam revealed remarkable synergistic effects when used in combination with either tigecycline or rifampicin. However, for the isolates with MICs lower than blood peak concentration after combination therapy, the ratio was lower in highly resistant isolates compared to the least resistant bacteria.
Conclusions: In vitro cefoperazone-sulbactam in combination with tigecycline or rifampicin showed the highest synergistic or additive activity against MDRAB isolates. However, acquisition of highly antibiotic resistant bacteria may lessen the effectiveness of combination therapy.
Methods: One hundred and three MDRAB bacteria were isolated from patients in two hospitals in China. The Epsilomer test (E test) was used to determine the minimum inhibitory concentration (MIC) values for amikacin, ceftazidime, cefepime, levofloxacin, rifampicin, cefoperazone-sulbactam, meropenem, tigecycline, and gentamicin against MDRAB isolates. In vitro effects of various antibiotic combinations were measured and the fractional inhibitory concentration index (FICI) was calculated for each drug combination.
Results: Approximately 17.5% of the isolates were resistant to tigecycline, whereas more than 84.2% isolates were resistant to other antimicrobial agents tested in this study. Cefoperazone-sulbactam revealed remarkable synergistic effects when used in combination with either tigecycline or rifampicin. However, for the isolates with MICs lower than blood peak concentration after combination therapy, the ratio was lower in highly resistant isolates compared to the least resistant bacteria.
Conclusions: In vitro cefoperazone-sulbactam in combination with tigecycline or rifampicin showed the highest synergistic or additive activity against MDRAB isolates. However, acquisition of highly antibiotic resistant bacteria may lessen the effectiveness of combination therapy.
