Early discontinuation of empirical antibiotic treatment in neutropenic patients with acute myeloid leukaemia and high-risk myelodysplastic syndrome

Abstract

Introduction: Current guidelines advocate empirical antibiotic treatment (EAT) in haematological patients with febrile neutropenia. However, the optimal duration of EAT is unknown. In 2011, we have introduced a protocol, promoting discontinuation of carbapenems as EAT after 3 days in most patients and discouraging the standard use of vancomycin. This study assesses the effect of introducing this protocol on carbapenem and vancomycin use in high-risk haematological patients and its safety. Methods: A retrospective before-after study was performed comparing a cohort from 2007 to 2011 (period I, before restrictive EAT use) with a cohort from 2011 to 2014 (period II, restrictive EAT use). Neutropenic episodes related to chemotherapy or stem cell transplantation (SCT) in patients with acute myeloid leukaemia (AML) or highrisk myelodysplastic syndrome (MDS) were analysed. The primary outcome was the use of carbapenems and vancomycin as EAT during neutropenia, expressed as days of therapy (DOT)/100 neutropenic days and analysed with interrupted time series (ITS). Also the use of other antibiotics was analysed. Safety measurements included 30day mortality, ICU admittance within 30 days after start of EAT and positive blood cultures with carbapenemsusceptible microorganisms. Results: Three hundred sixty-two neutropenic episodes with a median duration of 18 days were analysed, involving 201 patients. ITS analysis showed decreased carbapenem use with a step change of − 16.1 DOT/100 neutropenic days (95% CI − 26.77 to − 1.39) and an overall reduction of 21.6% (8.7 DOT/100 neutropenic days). Vancomycin use decreased with a step change of − 13.7 DOT/100 neutropenic days (95% CI − 23.75 to − 3.0) and an overall reduction of 54.7% (14.6 DOT/100 neutropenic days). The use of all antibiotics combined decreased from 155.6 to 138 DOT/100 neutropenic days, a reduction of 11.3%. No deaths directly related to early discontinuation of EAT were identified, also no notable difference in ICU-admission (9/116 in period I, 9/152 in period II) and positive blood cultures (4/116 in period I, 2/152 in period II) was detected.

Safety and Efficacy of Antibiotic De-escalation and Discontinuation in High-Risk Hematological Patients With Febrile Neutropenia: A Single-Center Experience

“…Implementation of ECIL-4 recommendations reduced the number of days on antibiotic therapy by a median of 2 days relative to a 27-day median duration of hospitalization, in line with previously published studies [ 9–11 , 14 , 17 ]. To account for the effect of combination therapy, we calculated total antibiotic exposure, which was more extensively reduced by a median of 7 daily doses.…”

New approaches to management of fever and neutropenia in high-risk patients

“…Most published studies are retrospective or prospective observational, and the de-escalation and continuation arms are often not well matched (Table 1). Within the limitations of these studies, most found similar outcomes including rates of ICU admission and mortality in the de-escalation arm to the continuing antibiotic arm [61,62,[77][78][79][80][81]. Some reduction in carbapenems and vancomycin use has also been shown [77,79].…”

“…Within the limitations of these studies, most found similar outcomes including rates of ICU admission and mortality in the de-escalation arm to the continuing antibiotic arm [61,62,[77][78][79][80][81]. Some reduction in carbapenems and vancomycin use has also been shown [77,79].…”

Neutropenia and antibiotics: when, what, how and why?

“…These studies further demonstrate that implementation of ECIL guidelines in high-risk neutropenic patients was safe and feasible. Several of these studies demonstrated a significant reduction in BSA use, yet no differences in ICU transfers, bacteremia incidence, infection relapses, or mortality [29–32]. While two studies observed a higher bacteremia incidence in patients that followed ECIL-guidelines [33 ▪ ,34], two also showed a decreased risk of ICU [35 ▪ ] admission and death [34,35 ▪ ].…”