Comparison of the clinical efficacy between tigecycline plus extended-infusion imipenem and sulbactam plus imipenem against ventilator-associated pneumonia with pneumonic extensively drug-resistant Acinetobacter baumannii bacteremia, and correlation of clinical efficacy with in vitro synergy tests

作者：Jean Shio Shin^*; Hsieh Tai Chin; Hsu Chin Wan; Lee Wen Sen; Bai Kuan Jen; Lam Carlos

来源：Journal of Microbiology, Immunology, and Infection, 2016, 49(6): 924-933.

DOI：10.1016/j.jmii.2015.06.009

• combination regimen
• extensively drug-resistant Acinetobacter baumannii
• imipenem
• sulbactam tigecycline
• ventilator-associated pneumonia

Background/Purpose: To compare the clinical efficacy between salvage antimicrobial regimen consisting of tigecycline plus extended-infusion imipenem/cilastatin (TIC) and regimen of sulbactam plus imipenem/cilastatin (SIC) for patients with ventilator-associated pneumonia and pneumonic bacteremia due to extensively drug-resistant (XDR) Acinetobacter baumannii (Ab) isolates, and determine the correlation of results of in vitro tigecycline -imipenem synergy test with clinical efficacy.
Methods: The comparative survey was conducted at a medical center in Taiwan in 2013. Patients comprising the TIC group (n = 28) received tigecycline plus extended-infusion imipenem/cilastatin following unresponsiveness to 3-day sulbactam-imipenem/cilastatin therapy, and those in the SIC group (n = 56) received sulbactam-imipenem/cilastatin throughout the course. Univariate and multivariate analyses were applied to explore 30-day case-fatality independent predictors. Additionally, the checkerboard test and time-kill analysis were performed for the bloodstream XDR-Ab isolates from patients in the TIC group, and molecular characterization was done for the bloodstream XDR-Ab strains of all patients.
Results: We found that the TIC scheme has a significant benefit on improving patients' survival status (the mortality rate of TIC and SIC group patients was 14.3% and 64.3%, respectively), corresponding well with in vitro synergy or additivity results by the checkerboard test. Twenty TIC group cases had monomicrobial XDR-Ab cultured from tracheal aspirates after 10 days of tigecycline-imipenem/cilastatin therapy, but none developed subsequent pneumonia. However, breakthrough primary Burkholderia cepacia (n = 3) and Pseudomonas aeruginosa (n = 1) bacteremias were attributed to four TIC case fatalities. Shock, SIC regimen usage, and development of breakthrough bacteremia were independent predictors of 30-day in-hospital mortality.
Conclusion: Although the TIC regimen showed good efficacy, its value regarding managing XDR-Ab ventilator-associated pneumonia bacteremia needs further evaluation.

• 出版日期2016-12