Clinical usefulness of therapeutic drug monitoring of voriconazole in a university hospital / / Utilidad clínica de la determinación de concentraciones plasmáticas de voriconazol en un hospital universitario

INTRODUCTION: The aim of this study was to assess the clinical usefulness of therapeutic drug monitoring (TDM) of voriconazole (VOR) in a university hospital. METHODS: A retrospective review was conducted on the clinical records of 52 patients treated with VOR and on whom TDM was performed. Steady-state trough plasma VOR concentration was measured at least 5 days after starting treatment. The therapeutic range of plasma VOR concentration was defined as 1-5.5 μg/mL. RESULTS: The most frequent underlying conditions in the study population were lung transplant (48.1%) and hematological malignancies (26.9%). At the first TDM in each patient, VOR levels were outside the therapeutic range in 16 (30.7%) cases: <1 µg/mL in 10 (19.2%) and >5.5 µg/mL in 6 (11.5%). Eleven patients (21.2%) experienced severe muscle weakness and had considerable difficulty walking. All these patients were receiving concomitant treatment with corticosteroids. Age younger than 30 years (p = .005) and cystic fibrosis as the underlying disease (p = .04) were factors associated with low VOR levels. Almost all patients who had VOR concentrations >1 µg/mL at the first TDM had a successful outcome (96%). CONCLUSIONS: Plasma VOR concentrations were outside the therapeutic range at the first TDM in 30% (16/52) of patients. Age younger than 30 years and cystic fibrosis were factors associated with low VOR levels. The potential interactions between corticosteroids and VOR should be highlighted, as they could be responsible for a high rate of muscle weakness observed in our patients. Prospective trials are needed to investigate VOR TDM and corticosteroid pharmacokinetics

INTRODUCCIÓN: Nuestro objetivo fue evaluar la utilidad clínica de la monitorización de la concentración plasmática (TMD) de voriconazol (VOR) en un hospital universitario. MÉTODOS: Revisión retrospectiva de las historias clínicas de 52 pacientes tratados con VOR en los que se realizó TDM. El intervalo terapéutico de la concentración plasmática de VOR fue definida entre 1 μg/mL y 5.5 μg/mL. RESULTADOS: Las condiciones subyacentes más frecuentes en la población de estudio fueron trasplante de pulmón (48,1%) y neoplasias hematológicas (26,9%). En la primera determinación de TMD de VOR estaban fuera del intervalo en 16 (30,7%) casos: < 1 µg/mL en 10 (19,2%) y > 5,5 µg/mL en 6 (11,5%). Once pacientes (21,2%) experimentaron debilidad muscular, éstos pacientes recibían tratamiento concomitante con corticosteroides. Los Factores asociados con bajos niveles de VOR observados fueron la edad menor a 30 años (p= 0,005) y la fibrosis quística (p = 0,04). Casi todos los pacientes que tenían concentraciones VOR > 1 µg/mL en la primera TDM tuvieron un resultado satisfactorio (96%). CONCLUSIONES: En 30% (16/52) de los pacientes, las concentraciones plasmáticas de VOR estaban fuera del intervalo terapéutico en la primera TDM. La edad menor a 30 años y la fibrosis quística fueron factores asociados con niveles bajos de VOR. Observamos una posible interacción entre corticoesteroides y voriconazol con debilidad muscular asociada en los pacientes tratados con ambos fármacos. Se necesitan estudios clínicos prospectivos en relación a las interacciones entre corticoesteroides y voriconazol

Clinical usefulness of therapeutic drug monitoring of voriconazole in a university hospital.

INTRODUCTION: The aim of this study was to assess the clinical usefulness of therapeutic drug monitoring (TDM) of voriconazole (VOR) in a university hospital. METHODS: A retrospective review was conducted on the clinical records of 52 patients treated with VOR and on whom TDM was performed. Steady-state trough plasma VOR concentration was measured at least 5 days after starting treatment. The therapeutic range of plasma VOR concentration was defined as 1-5.5µg/mL. RESULTS: The most frequent underlying conditions in the study population were lung transplant (48.1%) and hematological malignancies (26.9%). At the first TDM in each patient, VOR levels were outside the therapeutic range in 16 (30.7%) cases: <1µg/mL in 10 (19.2%) and >5.5µg/mL in 6 (11.5%). Eleven patients (21.2%) experienced severe muscle weakness and had considerable difficulty walking. All these patients were receiving concomitant treatment with corticosteroids. Age younger than 30 years (p=.005) and cystic fibrosis as the underlying disease (p=.04) were factors associated with low VOR levels. Almost all patients who had VOR concentrations >1µg/mL at the first TDM had a successful outcome (96%). CONCLUSIONS: Plasma VOR concentrations were outside the therapeutic range at the first TDM in 30% (16/52) of patients. Age younger than 30 years and cystic fibrosis were factors associated with low VOR levels. The potential interactions between corticosteroids and VOR should be highlighted, as they could be responsible for a high rate of muscle weakness observed in our patients. Prospective trials are needed to investigate VOR TDM and corticosteroid pharmacokinetics.

Long-term follow-up of jaw osteomyelitis associated with bisphosphonate use in a tertiary-care center

OBJETIVES: This study reviews our experience in bisphosphonate-associated jaw osteomyelitis (BJOM), focusing on the incidence, etiology, treatment, and long-term outcome. Methods Retrospective review of the clinical histories adult patients diagnosed with BJOM (1995-2008) in a tertiary hospital. Results BJOM was found in 30 of 132 (22.7%) consecutive patients with jaw osteomyelitis. The percentage of BJOM cases increased from 8.7% (4/46) in 1995-2005 to 30.2% (26/86) in 2005-2008. Symptoms appeared in a median of 2.5 years after intravenous use, and 4.5 years after oral exposure. Viridans group streptococci were isolated in 83.3% of cases. Actinomyces spp. was found in 16 (39.0%) of 41 bone histologies. All included patients received a median of 6 months of appropiate antibiotic therapy and a surgical procedure (debridament and/or sequestrectomy). Thirteen of 27 cases (48.1%) with long-term follow-up (median 22 months, IQR 25-75 17-28) failed. Clinical failure defined as, persistent infection or relapse, was more frequent in patients receiving intravenous than oral bisphosphonates (11/16 [68.8%] vs. 2/11 [18.2%]; P < .05) and in cases with Actinomyces spp. (7/10 [70.0%] vs6/17 [35.3%]; P = .08).Conclusions Bisphosphonate therapy is now a frequent cause of JO. BJOM is difficult to cure and relapses are common, particularly in patients exposed to intravenous bisphosphonates

OBJETIVOS: Analizar la incidencia, la etiología, el tratamiento y la evolución clínica a largo plazo de la osteomielitis maxilar (OM) asociada al tratamiento con bifosfonatos (OMAB). MÉTODOS: Estudio retrospectivo de pacientes adultos con diagnóstico de OMAB (1995-2008) en un hospital universitario. RESULTADOS: Fueron diagnosticadas 30OMAB de un total de 132OM. Desde el año 1995 al 2004 fueron diagnosticadas 4OMAB de 46OM (8,7%), y desde el año 2005 al 2008, 26 de 86 (30,2%). Los síntomas de osteomielitis aparecieron en una mediana de 2,5años en los pacientes que recibieron el tratamiento con bifosfonatos por vía intravenosa y una mediana de 4,5 años en los pacientes que lo recibieron por vía oral. En el 83,3% se aislaron Streptococcus del grupo viridans. En 16 (39%) de 41muestras enviadas para estudio histológico se constató la presencia de Actinomyces spp. Todos los pacientes fueron sometidos a desbridamiento quirúrgico y/o secuestrectomía y recibieron una mediana de 6meses de tratamiento antibiótico. Trece de los 27casos (48,1%) con seguimiento a largo plazo (mediana 22meses, IQR25-75 17-28) presentaron fracaso terapéutico. Estos fueron más frecuentes en pacientes que recibieron bifosfonatos por vía intravenosa en comparación con los que los recibieron por vía oral (11/16 [68,8%] vs 2/11 [18,2%], p < 0,05) y en los casos con Actinomyces spp. (7/10 [70,0%] vs 6/17 [35,3%], p = 0,08). CONCLUSIONES: Actualmente el tratamiento con bifosfonatos es causa frecuente de OM. Las recidivas son frecuentes en las OMAB, especialmente en pacientes expuestos a los bifosfonatos por vía intravenosa

Long-term follow-up of jaw osteomyelitis associated with bisphosphonate use in a tertiary-care center.

OBJECTIVES: This study reviews our experience in bisphosphonate-associated jaw osteomyelitis (BJOM), focusing on the incidence, etiology, treatment, and long-term outcome. METHODS: Retrospective review of the clinical histories adult patients diagnosed with BJOM (1995-2008) in a tertiary hospital. RESULTS: BJOM was found in 30 of 132 (22.7%) consecutive patients with jaw osteomyelitis. The percentage of BJOM cases increased from 8.7% (4/46) in 1995-2005 to 30.2% (26/86) in 2005-2008. Symptoms appeared in a median of 2.5 years after intravenous use, and 4.5 years after oral exposure. Viridans group streptococci were isolated in 83.3% of cases. Actinomyces spp. was found in 16 (39.0%) of 41 bone histologies. All included patients received a median of 6 months of appropiate antibiotic therapy and a surgical procedure (debridament and/or sequestrectomy). Thirteen of 27 cases (48.1%) with long-term follow-up (median 22 months, IQR 25-75 17-28) failed. Clinical failure defined as, persistent infection or relapse, was more frequent in patients receiving intravenous than oral bisphosphonates (11/16 [68.8%] vs. 2/11 [18.2%]; P < .05) and in cases with Actinomyces spp. (7/10 [70.0%] vs6/17 [35.3%]; P = .08). CONCLUSIONS: Bisphosphonate therapy is now a frequent cause of JO. BJOM is difficult to cure and relapses are common, particularly in patients exposed to intravenous bisphosphonates.