Activity of imipenem-relebactam, ceftolozane-tazobactam and comparators against clinical isolates of Enterobacterales and Pseudomonas aeruginosa causing severe infections in hematological and oncological patients: A prospective multicenter study

Abstract

Objectives: Studies regarding the activity of antimicrobials against isolates causing severe infections in oncological and hematological patients are scarce. Ceftolozane-tazobactam (TOL/TAZ) and imipenem-relebactam (IMP/REL) are among the new antimicrobials active against multiresistant gramnegative microorganisms. We evaluate the in vitro activity of these antimicrobials and comparators against recent clinical isolates from hematology and oncology patients in Spain.

Methods: A total of 55 centers participated in a nationwide study. The isolates were prospectively recovered from patients with bacteremia, lower respiratory tract infections (LRTIs), complicated urinary infections (cUTI), and complicated intra-abdominal infections (cIAIs). The activities of TOL/TAZ, IMP/REL, imipenem (IMP), meropenem (MER), ceftazidime (CAZ), cefepime (FEP), piperacillin-tazobactam (PIP/TAZ), levofloxacin (LEV), and amikacin (AK) were studied following the EUCAST guidelines. Resistance mechanisms were detected by standard methods.

Results: A total of 997 isolates (563 Enterobacterales (EB) and 434 Pseudomonas aeruginosa (PA)) were collected. The source of EB/PA were: bacteremia (n = 347/182), LRT (n = 51/139), urine (n = 95/64), and intraabdominal samples (n = 70/49). Among EB, 93.6%, 98.9%, 98.6%, 87.4%, 82.2%, 93.6%, 98.6%, 73.7%, and 97.3% were susceptible to TOL/TAZ, IMP/REL, MER, FEP, CAZ, PIP/TAZ, IMP, LEV, and AK, respectively. The corresponding values for PA were 92.2%, 90.1%, 87.8%, 81.9%, 81.7%, 75.7%, 75.2%, 63.3%, and 96.1%, respectively. A total of 14/17 isolates (EB/PA) were carbapenenase-producers, and 82 EB isolates were ESBL-producers. IMP/REL restored the activity of IMP in 14,7% of IMP-resistant PA.

Conclusions: TOL/TAZ and IMP/REL were the most active of the beta-lactams against PA. IMP/REL was the most active agent against EB; 30% of the isolates were resistant to levofloxacin.

Keywords: Ceftolozane-tazobactam oncology; Hematology; Imipenem-relebactam; Immunocompromised patients; Levofloxacin.