RESUMEN
Little information on the efficacy and pharmacokinetics of letermovir among immunocompromised children is currently available. We describe here the use of letermovir in a 2-year-old immunocompromised child with ganciclovir-resistant cytomegalovirus disease who required extracorporeal membrane oxygenation. Detailed information on therapeutic-drug-monitoring measures and dosage adjustments for letermovir is provided.
Asunto(s)
Acetatos/administración & dosificación , Antivirales/administración & dosificación , Infecciones por Citomegalovirus/tratamiento farmacológico , Citomegalovirus , Monitoreo de Drogas/métodos , Huésped Inmunocomprometido , Neumonía Viral/tratamiento farmacológico , Quinazolinas/administración & dosificación , Acetatos/farmacocinética , Acetatos/uso terapéutico , Antivirales/farmacocinética , Antivirales/uso terapéutico , Preescolar , Ensayos de Uso Compasivo , Citomegalovirus/genética , Citomegalovirus/aislamiento & purificación , Infecciones por Citomegalovirus/inmunología , Infecciones por Citomegalovirus/virología , ADN Viral/sangre , Relación Dosis-Respuesta a Droga , Oxigenación por Membrana Extracorpórea/efectos adversos , Resultado Fatal , Femenino , Ganciclovir/uso terapéutico , Hepatitis Viral Humana/tratamiento farmacológico , Hepatitis Viral Humana/inmunología , Humanos , Infecciones Oportunistas/tratamiento farmacológico , Neumonía Viral/inmunología , Neumonía Viral/virología , Reacción en Cadena de la Polimerasa , Quinazolinas/farmacocinética , Quinazolinas/uso terapéutico , Insuficiencia del Tratamiento , Carga ViralRESUMEN
Since the beginning of the severe SARS-CoV-2 pandemic, an increasing number of countries reported cases of a systemic hyperinflammatory condition defined as multi-system inflammatory syndrome in children (MIS-C). The clinical features of MIS-C can be an overlap of Kawasaki Disease (KD), Toxic Shock Syndrome (TSS), Macrophage Activation Syndrome (MAS), or have often an acute abdominal presentation. Intravenous immunoglobulin (IVIG) is recommended as first line therapy in KD. Recent evidence suggests intravenous immunoglobulins (IVIG) resistance in some cases of SARS-CoV-2 related MIS-C, thereby questioning the benefit of immunomodulators such as IL-1 or IL-6 blocking agents. We report on a cohort of 6 Swiss children with SARS-CoV2 related MIS-C presenting with clinical features compatible with Incomplete KD and Toxic Shock Syndrome associated to a cytokine storm. Serum cytokine profile investigations showed increased IL1RA levels (8 to 22-fold) in 5 of the 6 patients (one patient had not been tested), whereas, IL-6 serum levels were increased only in the 3 patients of the 6 who were tested. With exception of one patient who had only benefited by Anakinra, all patients received at least one dose of IVIG. One patient has only received Anakinra with favorable evolution, and three patients had also a steroid treatment. In addition to all this anti-inflammatory medication two patients have also received one dose of anti-IL6. In conclusion, our case series reports on clinical and laboratory findings of most of Swiss cases with MIS-C and suggests the use of Anakinra as an alternative to steroids in these children, most of whom presented with high IL-1RA levels.
RESUMEN
BACKGROUND: Congenital cytomegalovirus (cCMV) infections are the leading nongenetic cause of congenital sensorineural hearing loss (SNHL); however the true impact of cCMV infections remains unknown. AIMS OF THE STUDY: (1) To identify the number of asymptomatic and symptomatic cCMV infections diagnosed between 1999 and 2014 at the Lausanne University Hospital; (2) to describe the audiological and neurodevelopmental outcomes of infants with cCMV infection; and (3) to compare clinical outcomes between infants born to mothers with primary versus nonprimary infection. METHODS: This was a single-centre, observational, exploratory, retrospective study of newborns diagnosed with cCMV infection at the Lausanne University Hospital between 1999 and 2014. RESULTS: Fifty newborns with cCMV infection were identified; 39 (78%) were symptomatic at birth, of whom 29 (74%) were neurologically symptomatic. Twelve children (24%) presented with subsequent abnormal audiological and/or neurodevelopmental outcomes. Newborns born to mothers with a nonprimary infection were more often symptomatic at birth than those born to mothers with a primary infection. CONCLUSIONS: All infants with subsequent SNHL or abnormal neurodevelopment were symptomatic at birth. Similar long-term neurodevelopmental and audiological outcomes were observed in infants born to mothers with a primary and nonprimary infection.