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 three days in most patients and discouraging the standard use of vancomycin as EAT.[NF1] This study assesses the effect of this protocol on carbapenem and vancomycine 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 2011-2014 (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 to evaluate the overall antibiotic use[NF2] . Safety measurements included 30-day mortality, ICU admittance within 30 days after start of EAT and blood cultures positive for microorganisms sensitive to a carbapenem.Results: 362 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 (CI -26.73 to -1.41) and an overall reduction of 21.6% (8.7 DOT/100 neutropenic days). [NF3] Vancomycin use decreased with a step change of 13.7 DOT/100 neutropenic days (95% CI -23.66 to -2.90) and an overall reduction of 54.7% (14.6 DOT/100 neutropenic days). [NF4] There were no striking differences in other therapeutically used broad-spectrum antibiotics. No deaths were directly related to early discontinuation of EAT, also no notable difference in ICU-admission (n=9 in period I, n=9 in period II) and positive blood cultures (n=4 in period I, n=2 in period II) [NF5] was detected.Conclusion: The 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.

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].…”

Oncologic emergencies and urgencies: A comprehensive review

“…Table 4 summarizes the most common complications observed with these therapeutic modalities and the current standards for their management. 90,91,110,[115][116][117][118][119][120][121][122][123][124][125][126][127][128][129][130][131][132] Targeted Therapeutic-Related Complications Targeted therapies represent the subclass of antineoplastic agents deliberately engineered to interfere with oncogenic signal transduction pathways and are divided into smallmolecule inhibitors, monoclonal antibody-based pharmaceuticals, and cell-based agents. In general, targeted agents are less toxic than nonspecific cytotoxic chemotherapeutics; however, because many agents require long-term use, both acute and chronic treatment-related toxicities should be considered (Fig.…”

“…• Vancomycin, linezolid, or daptomycin should be given only when either methicillin-resistant Staphylococcus aureus or indwelling catheter infections are likely and should be discontinued once these are ruled out (Niessen 2020 118 ).…”

“…Both IgE‐mediated allergic and anaphylactoid mechanisms are noted. Table 4 summarizes the most common complications observed with these therapeutic modalities and the current standards for their management 90,91,110,115‐132 …”