The place in therapy of ceftazidime/avibactam and ceftolozane/tazobactam in hematological patients with febrile neutropenia

Int J Antimicrob Agents. 2021 Apr 7:106335. doi: 10.1016/j.ijantimicag.2021.106335. Online ahead of print.


OBJECTIVES: We evaluate ceftazidime/avibactam (C/A) and ceftolozane/tazobactam (C/T) use in hematological patients with febrile neutropenia (FN) receiving high-dose chemotherapy and HSCT.

METHODS: Between January-December 2018, we conducted a retrospective study to assess C/A and C/T efficacy through infection-related mortality (IRM) and bacteremia clearance for carbapenem-resistant Gram-negative bacteria (CR-GNB) pre-engraftment blood-stream infections (PE-BSIs).

RESULTS: Seventy patients underwent allogeneic HSCT: C/A and C/T were dispensed in 13% and 3%, respectively. C/A was administered as definite therapy for CR-Klebsiella pneumoniae (CR-Kp) PE-BSI in four carriers (bacteremia clearance in 5-days), empirical therapy for clinically-documented infection (CDI) in two patients (one carrier with pneumonia, one non-carrier with shock) and empirical therapy for fever of unknown origin in three CR-Kp carriers. C/T was administered as definite therapy for CR-Pseudomonas aeruginosa (CR-Pa) intra-abdominal infection in one carrier and empirical therapy for CDI (pneumonia) in one non-carrier. Among patients without PE-BSIs and with Gram-positive bacteria PE-BSIs, IRM was 0% at +30-day; conversely, it was 30% in GNB PE-BSIs (two CR-Kp PE-BSIs, one CR-Pa C/T-resistant PE-BSI). Thirty-nine patients underwent autologous HSCT: C/A and C/T were administered, respectively, as definite therapy for CR-Kp PE-BSI in one carrier (bacteremia clearance in 3-days) and for Pa PE-BSI (three strains, one CR-Pa) in one non-carrier (bacteremia clearance in 2-days). Overall, IRM at +30-day was 0%.

CONCLUSIONS: Monitoring MDR-GNB colonization allowed us to select carriers who benefit a prompt administration of new antibiotics, improving HSCT outcome in a high-risk population. C/A and C/T are effective in bacteremia clearance; unfortunately, MDR-GNB PE-BSIs still burden IRM.

PMID:33838223 | DOI:10.1016/j.ijantimicag.2021.106335