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.

La docencia de la patología infecciosa en los estudios de grado de medicina / Teaching of Infectious Diseases in Medical Degree Studies

Definimos la docencia de la patología infecciosa en losestudios de grado de medicina como el conjunto deactividades destinadas a proporcionar al alumno un nivelde competencia en esta área (conocimientos, habilidades yactitudes) adecuado para un médico recién licenciado, asícomo a dotarle de una base sólida para poder adquirir enel futuro las competencias propias de un especialista.En el momento actual, la ubicación, la dimensión y lascompetencias de la patología infecciosa en el grado demedicina son muy heterogéneas en las distintas facultadesespañolas. La próxima incorporación al espacio europeo deeducación superior, con la necesaria adecuación de losplanes de estudio, comportará una mejor definición de loscontenidos y objetivos docentes de esta materia. El últimodocumento de la Conferencia de Decanos de Facultades deMedicina identifica claramente la asignatura de patologíainfecciosa y la sitúa en el módulo de patologías médicasdentro del bloque de formación clínica humana. En nuestraopinión, la patología infecciosa debe plantearse como unaasignatura troncal situada preferentemente en el segundosemestre del quinto curso y disponer de un mínimo de 6 yun máximo de 9 créditos ECTS, entre teóricos y prácticos,distribuidos equitativamente en créditos presenciales,semipresenciales y de formación autónoma. La asignaturadebe tener una integración horizontal con la mayoría deasignaturas que conforman el bloque clínico y unaintegración vertical con la asignatura de microbiología. Lacoordinación de la asignatura y la impartición de la mayorparte de los créditos deben corresponder a especialistascon actividad clínica en enfermedades infecciosas(AU)

The teaching of the infectious diseases in the Bachelor ofMedicine degree consists of activities aimed at providingthe student with levels of competence in this area(knowledge, abilities, attitudes) appropriate for a generalphysician, and to give them a solid base to achieve theskills and abilities for becoming a specialist in this area.Currently, the location, the amount and quality ofinfectious diseases studies in the Bachelor of Medicinedegree are very disparate between the different SpanishMedical Schools. The incorporation into the EuropeanHigher Education Area, with the necessary adaptation ofcurricula, will enable the contents and the teachingobjectives in this field to be better defined. The latestdocument from the Medical Schools Deans Conferenceclearly identifies the studies of the infectious diseases intothe Medical Diseases module and in the area of humanclinical training. In our opinion, infectious diseases must beconsidered as a major subject, preferably in the secondsemester of the fifth year, and having a minimum of 6 anda maximum of 9 ECTS, theoretical and practical,distributed equally among attendance, part-attendanceand self-teaching credits. Infectious diseases pathologymust be horizontally integrated with most of the othersubjects in the clinical module and vertically integratedwith the subject of microbiology. The coordination andmost of the teaching of the credits in the infectiousdiseases subject must be done by specialists with clinicalactivity in infectious diseases(AU)

La docencia de la patología infecciosa en los estudios de grado de medicina / Teaching of Infectious Diseases in Medical Degree Studies

Definimos la docencia de la patología infecciosa en losestudios de grado de medicina como el conjunto deactividades destinadas a proporcionar al alumno un nivelde competencia en esta área (conocimientos, habilidades yactitudes) adecuado para un médico recién licenciado, asícomo a dotarle de una base sólida para poder adquirir enel futuro las competencias propias de un especialista.En el momento actual, la ubicación, la dimensión y lascompetencias de la patología infecciosa en el grado demedicina son muy heterogéneas en las distintas facultadesespañolas. La próxima incorporación al espacio europeo deeducación superior, con la necesaria adecuación de losplanes de estudio, comportará una mejor definición de loscontenidos y objetivos docentes de esta materia. El último documento de la Conferencia de Decanos de Facultades de Medicina identifica claramente la asignatura de patología infecciosa y la sitúa en el módulo de patologías médicas dentro del bloque de formación clínica humana. En nuestra opinión, la patología infecciosa debe plantearse como unaasignatura troncal situada preferentemente en el segundosemestre del quinto curso y disponer de un mínimo de 6 yun máximo de 9 créditos ECTS, entre teóricos y prácticos,distribuidos equitativamente en créditos presenciales,semipresenciales y de formación autónoma. La asignaturadebe tener una integración horizontal con la mayoría deasignaturas que conforman el bloque clínico y unaintegración vertical con la asignatura de microbiología. La coordinación de la asignatura y la impartición de la mayor parte de los créditos deben corresponder a especialistas con actividad clínica en enfermedades infecciosas

The teaching of the infectious diseases in the Bachelor of Medicine degree consists of activities aimed at providing the student with levels of competence in this area (knowledge, abilities, attitudes) appropriate for a general physician, and to give them a solid base to achieve the skills and abilities for becoming a specialist in this area. Currently, the location, the amount and quality of infectious diseases studies in the Bachelor of Medicine degree are very disparate between the different Spanish Medical Schools. The incorporation into the European Higher Education Area, with the necessary adaptation of curricula, will enable the contents and the teaching objectives in this field to be better defined. The latest document from the Medical Schools Deans Conference clearly identifies the studies of the infectious diseases into the Medical Diseases module and in the area of human clinical training. In our opinion, infectious diseases must be considered as a major subject, preferably in the second semester of the fifth year, and having a minimum of 6 anda maximum of 9 ECTS, theoretical and practical,distributed equally among attendance, part-attendanceand self-teaching credits. Infectious diseases pathologymust be horizontally integrated with most of the othersubjects in the clinical module and vertically integratedwith the subject of microbiology. The coordination andmost of the teaching of the credits in the infectiousdiseases subject must be done by specialists with clinical activity in infectious diseases (AU)

[Teaching of infectious diseases in medical degree studies]. / La docencia de la patología infecciosa en los estudios de grado de medicina.

The teaching of the infectious diseases in the Bachelor of Medicine degree consists of activities aimed at providing the student with levels of competence in this area (knowledge, abilities, attitudes) appropriate for a general physician, and to give them a solid base to achieve the skills and abilities for becoming a specialist in this area. Currently, the location, the amount and quality of infectious diseases studies in the Bachelor of Medicine degree are very disparate between the different Spanish Medical Schools. The incorporation into the European Higher Education Area, with the necessary adaptation of curricula, will enable the contents and the teaching objectives in this field to be better defined. The latest document from the Medical Schools Deans Conference clearly identifies the studies of the infectious diseases into the Medical Diseases module and in the area of human clinical training. In our opinion, infectious diseases must be considered as a major subject, preferably in the second semester of the fifth year, and having a minimum of 6 and a maximum of 9 ECTS, theoretical and practical, distributed equally among attendance, part-attendance and self-teaching credits. Infectious diseases pathology must be horizontally integrated with most of the other subjects in the clinical module and vertically integrated with the subject of microbiology. The coordination and most of the teaching of the credits in the infectious diseases subject must be done by specialists with clinical activity in infectious diseases.

Endocarditis tricuspídea en válvulanativa por Enterococcus faecalis / An unusual case of tricuspid endocarditis by Enterococcus faecalis in native valve

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