Articles

Faster to the fungus: rapid diagnostic and prognostic tests for invasive fungal diseases

BJH - volume 12, issue 3, may 2021

T. Mercier MD, PhD, K. Lagrou PhD, PharmD, J. Maertens MD, PhD

SUMMARY

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)

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Defeating cytomegalovirus, the transplantation troll: can letermovir do the job?

BJH - volume 10, issue 4, june 2019

B. Calcoen MD, S. van Hecke MD, K. Lagrou 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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