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.
OBJECTIVE
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.


CONCLUSIONS
Although the TIC regimen showed good efficacy, its value regarding managing XDR-Ab ventilator-associated pneumonia bacteremia needs further evaluation.
Emergency Medicine, Department of Emergency and Critical Care Medicine, Wan Fang Hospital, Taipei Medical University, Taipei, Taiwan. Electronic address: jeanshioshin168@gmail.com.
Shio-Shin
SS
Jean
Division of Infectious Diseases, Department of Internal Medicine, Wan Fang Hospital, Taipei Medical University, Taipei, Taiwan.
Tai-Chin
TC
Hsieh
Emergency Medicine, Department of Emergency and Critical Care Medicine, Wan Fang Hospital, Taipei Medical University, Taipei, Taiwan.
Chin-Wan
CW
Hsu
Division of Infectious Diseases, Department of Internal Medicine, Wan Fang Hospital, Taipei Medical University, Taipei, Taiwan.
Wen-Sen
WS
Lee
Emergency Medicine, Department of Emergency and Critical Care Medicine, Wan Fang Hospital, Taipei Medical University, Taipei, Taiwan.
Kuan-Jen
KJ
Bai
Emergency Medicine, Department of Emergency and Critical Care Medicine, Wan Fang Hospital, Taipei Medical University, Taipei, Taiwan.
Carlos
C
Lam
D000151:Acinetobacter Infections / Q000188:drug therapy*; D040981:Acinetobacter baumannii / Q000187:drug effects* / Q000302:isolation & purification; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000900:Anti-Bacterial Agents / Q000627:therapeutic use*; D016470:Bacteremia / Q000188:drug therapy* / Q000382:microbiology; D015377:Cilastatin / Q000627:therapeutic use*; D000077728:Cilastatin, Imipenem Drug Combination; D004338:Drug Combinations; D024901:Drug Resistance, Multiple, Bacterial; D004357:Drug Synergism; D004359:Drug Therapy, Combination / Q000379:methods; D005260:Female; D017052:Hospital Mortality; D006801:Humans; D015378:Imipenem / Q000627:therapeutic use*; D008297:Male; D008826:Microbial Sensitivity Tests; D008875:Middle Aged; D008911:Minocycline / Q000031:analogs & derivatives* / Q000627:therapeutic use; D053717:Pneumonia, Ventilator-Associated / Q000188:drug therapy* / Q000382:microbiology; D016879:Salvage Therapy; D013407:Sulbactam / Q000627:therapeutic use*; D013624:Taiwan; D000078304:Tigecycline; D016896:Treatment Outcome
D000900:Anti-Bacterial Agents; D004338:Drug Combinations; D015377:Cilastatin; D000078304:Tigecycline; D015378:Imipenem; D000077728:Cilastatin, Imipenem Drug Combination; D008911:Minocycline; D013407:Sulbactam
combination regimen; extensively drug-resistant Acinetobacter baumannii; imipenem; sulbactam; tigecycline; ventilator-associated pneumonia