Treatment with oral or topical sirolimus in complex vascular anomalies in pediatrics. Experience in a third-level hospital. / Tratamiento con sirolimus oral o tópico en anomalías vasculares complejas en pediatría. Experiencia en un hospital terciario.

OBJECTIVE: The use of sirolimus in vascular anomalies is a special indication not authorized in its data sheet. The objective of this study was to increase the evidence of oral or topical use of sirolimus for this indication in the pediatric population. MATERIALS AND METHODS: An observational, retrospective study of patients under 18 years of age treated with oral or topical sirolimus for vascular anomalies was carried out. Diagnosis and location of lesions, administration route and dosage of sirolimus, blood levels of sirolimus in patients who received oral treatment, treatment duration, response, and toxicity were collected. RESULTS: 18 patients - 7 with oral treatment and 11 with topical treatment - were included. With oral sirolimus, the overall response rate was 85.7%. Sirolimus was discontinued in 2 cases - as a result of full resolution and progression. 57.1% of patients had adverse effects, most of which were mild. Dyslipidemia was the most frequent adverse effect. Blood levels were monitored in all patients for dose adjustment purposes. With topical treatment, the overall response rate was 72.7%. Sirolimus was discontinued in 3 cases -due to progression in 2 cases and to stability in 1. 27.3% of patients had adverse effects, with itching standing out as the most frequent one. CONCLUSIONS: The favorable results of sirolimus treatment in our patients seem to confirm its effectiveness and safety in vascular anomalies, which make it stand as a therapeutic option in pediatric patients. However, further research is required to establish the optimal treatment regimen, treatment duration, and potential long-term adverse effects.

OBJETIVO: El uso de sirolimus en anomalías vasculares es una indicación especial no autorizada en ficha técnica. El objetivo de este estudio es incrementar la evidencia del empleo por vía oral o tópica de sirolimus en esta indicación en población pediátrica. METODO: Estudio observacional retrospectivo de pacientes menores de 18 años tratados con sirolimus oral o tópico para anomalías vasculares recogiendo: diagnóstico y ubicación de lesiones, forma de administración y dosificación de sirolimus, niveles sanguíneos de fármaco en los pacientes con tratamiento oral, duración del tratamiento, respuesta y toxicidad. RESULTADOS: Se incluyeron 18 pacientes (7 con tratamiento oral y 11 tópico). Con sirolimus oral, la tasa de respuesta global fue 85,7%. Se interrumpió sirolimus en 2 casos: por resolución completa y por progresión. El 57,1% experimentó algún efecto adverso, en su mayoría leves; siendo la dislipemia el efecto adverso más frecuente. La monitorización de niveles sanguíneos fue empleada en todos los pacientes para el ajuste de dosis. Con el tratamiento tópico, la tasa de respuesta global fue 72,7%. Se interrumpió sirolimus en 3 casos: progresión en 2 casos y estabilidad en 1. El 27,3% experimentó algún efecto adverso, siendo el prurito el más frecuente. CONCLUSIONES: Los resultados favorables del tratamiento con sirolimus en nuestros pacientes parecen confirmar la efectividad y seguridad del fármaco en anomalías vasculares y lo posicionan como una opción terapéutica en pacientes pediátricos. Aun así, parece necesaria mayor investigación que trate de aclarar, entre otros, el régimen óptimo del tratamiento, la duración del mismo y los potenciales efectos adversos a largo plazo.

Incidence and risk factors for mortality in patients treated with combined ceftaroline for Gram-positive infective endocarditis.

BACKGROUND: Ceftaroline is a fifth-generation cephalosporin and represents an alternative in the treatment of infective endocarditis (IE). The main objective of this study was to describe the incidence of in-hospital and 42-day mortality in patients with IE treated with ceftaroline. METHODS: An observational retrospective study included adult patients with IE admitted during a 3.5-year period (January 2018-June 2021) and treated with ceftaroline in a single center. All cases were definite or possible IE according to the modified Duke criteria. RESULTS: Seventy cases were analyzed. The mean age was 67.35 ± 16.62 (16-89) and 39 (55.7%) were males. The mean number of days of treatment with ceftaroline was 21.26 ± 16.17 (1-75). Overall mortality at 42 days was 30%, 20.7% in the first line, and 36.6% in rescue therapy. Predictors of 42 days-mortality were increased Charlson comorbidity index (CCI) (OR of 1.7 per 1 point increment, 95% CI 1.2-2.4, P 0.001), presence of methicillin-resistance (OR 6.8, 95% CI 1.3-36.8, P 0.026) and evidence of septic shock (OR 8.6 95% CI 1.7-44.2, P 0.01). Predictors of 42 days of therapeutic failure were the increase in the CCI (OR of 1.6 per 1 point increment, 95% CI 1.3-2.1, P 0.000) and septic shock (OR 4.5 95% CI 1.1-18 P 0.036). Adverse effects were described in 6/70 (8.6%) of the patients, precipitating in 4/70 (5.7%) the definitive withdrawal of the antibiotic. CONCLUSIONS: The incidence of in-hospital and 42 day-mortality of IE patients treated with ceftaroline remains similar to literature data. Increased CCI, septic shock, and methicillin resistance are associated with poor prognosis.