Methods: A retrospective cohort study was conducted at Assaf Harofeh Medical Center (AHMC) from 01/2010 to 08/2014. Adult patients with PA-BSI with minimal inhibitory concentration (MIC) > 2 to either meropenem or imipenem, but with MIC < 16 to ceftazidime, or <32 to piperacillin, or < 32/4 to piperacillin-tazobactam were enrolled. We compared the outcomes of patients who got (≥2 doses) an appropriate (per in-vitroreport) beta-lactam agent (“cases”) to those who got (≥2 doses) appropriate non-beta-lactam regimens (“controls”). Patients who received agents from both study arms were excluded. Whole genome sequencing for one representative blood isolate was executed, and mechanisms of carbapenem resistance and genotyping (MLST) were queried.
Results: There were 26 patients with PA BSI who met the inclusion criteria: 18 were treated with a beta-lactam (7 cephalosporin, 5 penicillins with/out beta-lactamase inhibitor, and 6 combinations) and 8 were treated with a non-beta-lactam (4 fluoroquinolones, 2 colistin, 1 fluoroquinolone with aminoglycoside and 1 colistin with aminoglycoside). Patients’ characteristics were similar between groups (prediction score to control for biases associated with being a “case” in not presented due to model instability). All clinical outcomes were similar between groups: e.g., 1) 30-day mortality (57% among cases vs. 50% among controls, OR=1.2, p<0.99), 2) median length of stay from infection to discharge after excluding the dead (11 days among cases and controls, p=0.3). There were huge variations in phenotypic susceptibilities of strains. Detailed molecular investigation of a representative isolate revealed a strain that belonged to MLST-175 with OXA-28 and OXA-19 present.
Conclusion: Even for invasive BSI, when the PA is non-susceptible to carbapenems, it is reasonable to choose another “appropriate” (per MIC breakpoints) non-carbapenem-beta-lactam agent. However, larger confirmatory studies are needed.
R. Zaidenstein, None
M. Dadon, None
D. Marchaim, Merck: Grant Investigator and Speaker's Bureau , Research grant and Speaker honorarium
Pfizer: Scientific Advisor , payment for participating in advisory board