Carbapenems-resistant Pseudomonas aeruginosa bloodstream infection in Hematopoietic stem cell transplant patients: in vitro synergy and clinical outcome
Abstract Summary Bloodstream infection (BSI) caused by Pseudomonas aeruginosa has high mortality in hematopoietic stem cell transplant (HSCT) recipients. Objectives: To evaluate clinical, in vitro synergy and molecular features of 30 BSI caused by carbapenems-resistant P. aeruginosa (CRPA) in HSCT patients. Methods: Demographic and clinical data including treatment were collected and a database was built using EPIINFO, bivariate and multivariate analysis were run to assess outcome using SPSS. In vitro synergy using time-kill assays, pulsed-field electrophoresis (PFGE) and PCR for carbapenemases and virulence genes were performed for all isolates. Whole genome sequence (WGS) of main clones was done by Nextera XT, using Illumina MiSeq technology. Results: Mortality was 71%; most patients who died were allogeneic HSCT (78%) (p=0.02). Clinical isolates showed a high resistance level to meropenem: 50% had a MIC of 512 µg/mL; two thirds were susceptible to amikacin (MIC 2-512 µg/mL) and 100% to colistin. Many (17/30) isolates achieved synergistic effect with meropenem plus colistin but not with amikacin. None antagonism was observed. The presence of synergy by time-kill between colistin and meropenem showed a tendency towards a better outcome (HR 0.68 95%CI 0.02-1.02; p=0.06). The most frequent carbapenemase gene identified was blaSPM, and six co-harboured both blaKPC and blaSPM. Isolates presented genes related with virulence factors such as toxA, exoS and more patients with BSI caused by P. aeruginosa harbouring gene lasB evolved to death. The WGS showed that all five clones harboured SPM-1, Tn4371 and belonged to ST277; however, the resistance and virulence genes differ among the clones. Conclusion: CRPA BSI showed high mortality in HSCT patients. All clones carried SPM-1, Tn4371 and belonged to ST277. Synergy by time-kill between colistin and meropenem showed a tendency towards a better outcome