- It is unknown as to whether other beta-lactams can be used for bloodstream infections (BSI) resulting from Pseudomonas aeruginosa (PA) which are non-susceptible to one or more carbapenem. We conducted a retrospective cohort study at the Assaf Harofeh Medical Center (AHMC) from January 2010 to August 2014. Adult patients with PA-BSI non-susceptible to a group 2 carbapenem but susceptible to ceftazidime or piperacillin (with or without tazobactam), were enrolled. We compared the outcomes of patients who received an appropriate beta-lactam antibiotic ("cases") to those who received an appropriate non-beta-lactam antibiotic ("controls"). Whole genome sequencing was performed for one of the isolates. Twenty-six patients with PA-BSI met inclusion criteria: 18 received a beta-lactam and 8 a non-beta-lactam (three a fluoroquinolone, two colistin, one a fluoroquinolone and an aminoglycoside, one a fluoroquinolone and colistin, and one colistin and an aminoglycoside). All clinical outcomes were similar between the groups. There were large variations in the phenotypic susceptibilities of the strains. A detailed molecular investigation of one isolate revealed a strain that belonged to MLST-137, with the presence of multiple efflux pumps, OXA-50, and a chromosomally mediated Pseudomonas-derived cephalosporinase (PDC). The oprD gene was intact. Non-carbapenem-β-lactams may still be effective alternatives for short duration therapy (up to 14 days) for BSI caused by a carbapenem non-susceptible (but susceptible to ceftazidime, piperacillin, and/or piperacillin-tazobactam) PA strain. This observation requires further confirmatory analyses. Future molecular investigations should be performed, in order to further analyze additional potential mechanisms for this prevalent phenotype.