Abstract

IntroductionCurrent 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.MethodsA 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 high-risk 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 30-day mortality, ICU admittance within 30 days after start of EAT and positive blood cultures with carbapenem-susceptible microorganisms.ResultsThree 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.ConclusionThe introduction of a protocol promoting restrictive use of EAT resulted in reduction of carbapenem and vancomycin use and appears to be safe in AML or high-risk MDS patients with febrile neutropenia during chemotherapy or SCT.

Highlights

  • Current guidelines advocate empirical antibiotic treatment (EAT) in haematological patients with febrile neutropenia

  • Vancomycin use decreased with a step change of − 13.7 days of therapy (DOT)/100 neutropenic days and an overall reduction of 54.7% (14.6 DOT/100 neutropenic days)

  • The introduction of a protocol promoting restrictive use of EAT resulted in reduction of carbapenem and vancomycin use and appears to be safe in acute myeloid leukaemia (AML) or high-risk myelodysplastic syndrome (MDS) patients with febrile neutropenia during chemotherapy or stem cell transplantation (SCT)

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Summary

Introduction

Current guidelines advocate empirical antibiotic treatment (EAT) in haematological patients with febrile neutropenia. This study assesses the effect of introducing this protocol on carbapenem and vancomycin use in high-risk haematological patients and its safety. Patients with acute myeloid leukaemia (AML) or high-risk myelodysplastic syndrome (MDS) are treated with intensive chemotherapy and, if indicated, an allogenic stem cell transplantation (SCT). This treatment results in periods of neutropenia with mucositis, making patients vulnerable to severe infections. When a patient develops fever during neutropenia, broad spectrum empirical antibiotic treatment (EAT) is started immediately to rapidly and adequately treat a bacterial infection. Used EAT regimes are a carbapenem, piperacillin/tazobactam, ceftazidime or cefepime with or without an aminoglycoside [1, 3]

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