Letermovir for Prophylaxis and Pre-emptive Therapy of Cytomegalovirus Infection in Paediatric Allogeneic Haematopoietic Cell Transplant Patients.

BACKGROUND: Cytomegalovirus (CMV) infection is a frequent event in patients undergoing allogeneic haematopoietic cell transplantation (HCT) and is associated with increased morbidity and mortality due to eventual progress to end-organ disease. Letermovir prophylaxis for CMV infections has become a standard of care in adult HCT recipients due to its efficacy and high tolerability. However, it is not yet approved for paediatric patients. OBJECTIVE: In a retrospective single-centre observational study we evaluated the use of letermovir for prophylaxis or pre-emptive treatment of cytomegalovirus (CMV) infection in seropositive paediatric HCT recipients receiving the compound outside of clinical trials. The primary endpoint was CMV reactivation requiring a change of medication. METHODS: A total of 17 patients (seven female/ten male; median age 12.2 [range 3.5-19] years, median body weight 39.5 [range 15-63] kg; median follow-up time 463.7 [range 41-1022] days) were identified who were started on oral (14) or intravenous (3) followed by oral (2) letermovir shortly after neutrophil engraftment at doses determined on the basis of age, weight, and concomitant cyclosporine use. RESULTS: Five patients had no evidence of viral replication (prophylactic use), while 12 patients had varying extents of viral replication (pre-emptive therapy). A change of therapy was required in one patient due to a sustained increase in CMV viral load, and in two patients, letermovir was stopped without later reactivation after initiation of palliative care for recurrent leukaemia. Of the 14 patients who completed treatment, 3 had evidence of transient viral replication after end of treatment that required no further antiviral treatment. No patients (of 17) discontinued letermovir due to an adverse event. CONCLUSION: Letermovir was effective in controlling CMV infection in seropositive paediatric allogeneic HCT recipients and was overall well tolerated. Pending completion of the still ongoing paediatric investigation plans, letermovir will be an important adjunct to our options for control of infectious complications in this special population.

Prospective surveillance of colonization and disease by methicillin-resistant Staphylococcus aureus (MRSA) at a European pediatric cancer center.

PURPOSE: Children and adolescents undergoing treatment for cancer or allogeneic hematopoietic cell transplantation are at increased risk for methicillin-resistant Staphylococcus aureus (MRSA). We therefore examined the occurrence and outcome of MRSA colonization and infection in patients of a large European pediatric cancer center. METHODS: In a prospective observational cohort study conducted between 2007 and 2018, nasopharyngeal swabs for culture of MRSA were obtained from all admitted patients. The primary endpoint of the study was the colonization rate over time. Secondary endpoints included genetic relatedness of isolates, time burden of isolation measures, and results of decolonization efforts. RESULTS: During the study period, MRSA screening identified 34 colonized patients (median age: 10 years; range: 0-21) without trends over time. MRSA colonization was associated with the presence of classical risk factors. There was no molecular evidence of patient-to-patient transmission. A standard MRSA eradication regimen led to a lasting eradication of the organism in 26 of 34 patients. MRSA infection occurred in two patients with no associated fatalities. CONCLUSION: Prospective monitoring revealed low rates of MRSA colonization and infection at our center. These low rates and the absence of patient-to-patient transmission support the effectiveness of the management bundle of MRSA identification, isolation, and decolonization.