PS1268 CEFTAZIDIME/AVIBACTAM AND CEFTOLOZANE/TAZOBACTAM FOR THE TREATMENT OF FEBRILE NEUTROPENIA IN ALLOGENEIC TRANSPLANT RECIPIENTS
Authors: Clerici D. , Oltolini C. , Greco R. , Pavesi F. , Giglio F. , Mastaglio S. , Lorentino F. , Lazzari L. , Scarpellini P. , Bernardi M. , Peccatori J. , Corti C. , Castagna A. , Ciceri F. 
Published: June 2019

Background:Febrile neutropenia (FN) is a common life‐threatening complication in allogeneic HSCT recipients. The growing incidence of multi‐drug resistant Gram‐negative bacteria (MDR‐GNB) is a public health challenge worldwide. Two new antibiotics [ceftazidime/avibactam (C/A), ceftolozane/tazobactam (C/T)], active against carbapenem‐resistant (CR) GNB, have been introduced in clinical practice.Aims:Within an antimicrobial stewardship program, we aim to analyze the place in therapy of C/A and C/T, splinted up by indication [definite therapy (DT) of MDR‐GNB pre‐engraftment bloodstream infection (PE‐BSI) in MDR‐GNB carriers, empirical therapy (ET) of FN in MDR‐GNB carriers, ET of clinically documented infection (CDI) in non‐carriers]. Secondly, we describe PE‐BSI.Methods:From January to December 2018, we conducted a retrospective study on consecutive adult patients affected by high‐risk hematological diseases who received allogeneic HSCT in the Hematology and BMT Unit of our institute. According to institutional guidelines, all patients received levofloxacin prophylaxis and active weekly surveillance for MDR‐GNB colonization by rectal swab.Results:Seventy patients underwent HSCT, mainly for acute myeloid leukemia (55%): HLA‐matched related donor (n = 12), HLA‐matched unrelated donor (n = 33), haploidentical donor (n = 23) and cord blood (n = 2). The graft source was unmanipulated peripheral blood, using myeloablative conditioning and post‐transplant cyclophosphamide GvHD prophylaxis.Overall, 8/70 patients (11%) were MDR‐GNB carriers before HSCT [5 CR‐Klebsiella pneumoniae (Kp; 4/5 KPC producer), 3 CR‐Pseudomonas aeruginosa (Pa; 0/3 MBL producer, 2/3 resistant to C/T)] and 9/62 non‐carriers (15%) acquired colonization after HSCT [5 CR‐ Kp (4/5 KPC producer), 3 CR‐ Pa (0/3 MBL producer, 1/3 resistant to C/T), 1 CR‐Enterobacter cloacae MBL‐producer].Nine patients received C/A. Among pre‐HSCT CR‐Kp carriers, 3/5 (60%) developed KPC‐Kp PE‐BSI, receiving a combination DT with C/A [tigecyclin (n = 2), gentamycin (n = 1)], and 2/5 (40%) received C/A in the pre‐engraftment phase as ET for FN with a median time to de‐escalation of 8 days. Among post‐HSCT CR‐Kp carriers, 1/5 (20%) developed KPC‐Kp PE‐BSI, receiving C/A plus fosfomycin as DT, and 2/5 (40%) received C/A in the post‐engraftment phase as ET for FN (n = 1) and severe pneumonia (n = 1). Among non‐carriers, 1 patient received C/A in the post‐engraftment phase as ET for CDI (septic shock).Three patients received C/T, none as DT of PE‐BSI. Among pre‐HSCT CR‐Pa carriers, 1/3 (33%) developed CR‐Pa PE‐BSI resistant to C/T and 1/3 (33%) received C/T in the post‐engraftment phase as DT of CR‐Pa intra‐abdominal infection. Two non‐carriers received C/T in the post‐engraftment phase as ET for severe pneumonia.Overall, 22 PE‐BSI episodes occurred in 21 patients (30%): 10/22 by GNB [4 E. coli (50% ESBL‐producer), 4 Kp (100% KPC‐producer), 2 Pa (50% CR)] and 12/22 by gram‐positive bacteria (GPB) [3 E. faecalis, 7 E. faecium, 2 S. epidermidis].While infection‐related mortality (IRM) at 30 days was 0% among patients with GPB PE‐BSI, it was 30% in patients with GNB PE‐BSI (3/10): 2/4 patients with KPC‐Kp PE‐BSI died, in addition to the patient with CR‐Pa PE‐BSI resistant to C/T.Summary/Conclusion:A longitudinal monitoring of MDR‐GNB colonization, allow us to select carriers who benefit a prompt administration of new antibiotics, improving the outcome of HSCT procedure in a high‐risk population. MDR‐GNB PE‐BSI are the main determinant of IRM at 30 days and C/A is safe and effective in its containment.