BJH - volume 15, issue 8, december 2024
Y. Vanbiervliet MD, R. Aerts MD, K. Lagrou MD, PhD, PharmD, A. Verlinden MD, PhD, J. Maertens MD, PhD, A. Schauwvlieghe MD, PhD
Background: Febrile neutropenia (FN) is an important complication in high-risk haematological patients, occurring in 80–90% of cases. While rapid initiation of broad-spectrum antibiotics has improved FN-related mortality, the optimal duration of treatment remains controversial. Prolonged use of antibiotics not only leads to resistance and toxicity but also to increased mortality and GVHD in allogeneic stem cell transplantation recipients due to disruption of the microbiome. Different guidelines provide different recommendations, leading to inconsistent practice and the ECIL guidelines are not widely implemented.
Methods: A national survey was conducted in Belgium to assess current practices for the management of FN in high-risk haematological patients. The electronic survey, consisting of 40 questions, was distributed to haematology centres via the newsletter of the Belgian Society of Haematology in January 2023. Responses from seventeen large haematology centres, including university hospitals, were analysed.
Results: Prophylactic measures such as germ-free diets and fluoroquinolone use were common, with 13/17 centres implementing germ-free diets and 11/17 centres using fluoroquinolone prophylaxis. Empirical broad-spectrum antibiotic treatment (EBAT) was initiated as monotherapy in 15/17 centres, predominantly with piperacillin-tazobactam (8/17) or third-/fourth-generation cephalosporins (7/17). Escalation to broader-spectrum antibiotics was common when FN persisted, with 9/17 centres using this approach. De-escalation practices varied, with 12/17 centres de-escalating if the patient showed improvement despite a severe initial presentation. Withdrawal of EBAT before neutrophil recovery occurred in 15/17 centres in stable, afebrile patients.
Discussion: The survey revealed partial compliance with the ECIL guidelines, with variations in escalation and de-escalation practices. While most centres followed recommended empirical treatments, de-escalation and early cessation remain difficult. The findings highlight the need for further research to optimise antibiotic use, reduce associated risks and reduce healthcare costs.
Conclusions: Although Belgian centres show better adherence to ECIL guidelines compared to other regions, challenges remain in de-escalation and early cessation of EBAT. A multicentre randomised controlled trial is needed to establish the safety of shorter EBAT durations and to improve antimicrobial stewardship.
(BELG J HEMATOL 2024;15(8):307–12)
Read moreBJH - volume 12, issue 3, may 2021
T. Mercier MD, PhD, K. Lagrou MD, PhD, PharmD, J. Maertens MD, PhD
Invasive mould infections such as invasive aspergillosis or mucormycosis remain an important infectious complication in haematology patients, especially in those undergoing intensive chemotherapy for acute myeloid leukaemia or undergoing allogeneic stem cell transplantation. An early diagnosis and timely initiation of antifungal therapy improves outcomes. In this thesis, we therefore looked at new possible diagnostic tools to aid in a rapid diagnosis, such as lateral flow assays, PCR tests, or a novel beta-D-glucan assay. Furthermore, we explored how we could get the maximum out of existing tests such as galactomannan, by optimising their use after therapy in an effort to assess the response to therapy.
(BELG J HEMATOL 2020;12(3):138-40)
Read moreBJH - volume 10, issue 4, june 2019
B. Calcoen MD, S. van Hecke MD, K. Lagrou MD, PhD, PharmD, J. Maertens MD, PhD
Letermovir (AIC246, MK-8228) is a novel anti-cytomegalovirus (CMV) agent that inhibits CMV replication by targeting the viral terminase complex. In December 2017, letermovir was approved by the Food and Drug Administration (FDA) for the prophylaxis of CMV infection and disease in adult CMV-seropositive recipients of an allogenic haematological stem cell transplantation. Letermovir shows a favourable pharmacokinetic profile in haematological stem cell transplantation recipients after oral administration. The recommended dose for CMV-prophylaxis is once daily 480 mg (oral or intravenous). Letermovir demonstrated superiority in a placebo (plus polymerase chain reaction-monitoring and pre-emptive therapy)-controlled phase III randomised clinical trial. Letermovir is an inhibitor of the cytochrome P450 (CYP)3A family, CYP2B8 and an inducer of the CYP2C9/19. Dose-adjustments (240 mg/day) are necessary when letermovir is combined with cyclosporine. Combinations of letermovir with either voriconazole, midazolam and rosiglitazone require close monitoring of the plasma levels of the latter agents. Letermovir-resistant CMV mutants share mutations that are mostly located between the codon range 230–370 of the UL56 gene. Letermovir is not nephrotoxic nor myelotoxic, but slightly higher rates of atrial fibrillation and tachycardia have been described. In conclusion, letermovir is the first FDA approved anti-CMV agent for prophylaxis in haematological stem cell transplantation patients.
(BELG J HEMATOL 2019;10(4):136–45)
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