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.

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.

Continuous infusion of antibiotics using elastomeric pumps in the hospital at home setting.

OBJECTIVE: To describe the avoided costs and to analyze the effectiveness of intravenous antibiotic treatment in continuous perfusion in patients at Hospital at Home Units (HHU) administered using elastomeric infusion pumps (EIP) prepared in a Hospital Pharmacy Service (HPS). METHODS: Retrospective observational study of the number and type of EIP prepared in the HPS and of the treated patients. Study period: January 2017-December2018. Analyzed data: demographic data of patients, location of infection, responsible microorganism, medication and type of EIP, dose and duration of treatment and its effectiveness in terms of cure or non-cure or patient's death. Economic valuation considering: costs of EIP, nursing time needed for preparation and cost of HHU care. RESULTS: A total of 1,688 EIP to treat 102 patients resulted in 106 episodes of outpatient treatment of parenteral antibiotic therapy (OPAT) for 1,409 days, thereby avoiding 1,409 days of hospital admission. A total of 59.8% of the patients were men and the mean age was 70.5 ± 17 years. A 31.1% and 68.9% of the cases were empirical and pathogen-directed treatments, respectively. The most used antimicrobials were piperacillin/tazobactam (42.7%), ceftazidime (24.5%), meropenem (19.8%), ceftolozane/tazobactam (2.8%), and cloxacillin (1.9%). Mean duration of treatment was 13.29 ± 8.60 days. Location of infection: respiratory (42.5%), urinary (17.9%), skin and soft tissue (12.3%), bacteraemia (11.3%), osteomyelitis (7.5%), abdominal (3.8%) and 4.7% in other locations. The cure rate was 84%. Total avoided cost: 580,788.28€ in the 24 months studied. CONCLUSIONS: This program represents very important economic savings for the health system, and the effectiveness of the antibiotic treatment has not been compromised.

Effectiveness and safety of daclatasvir/sofosbuvir with or without ribavirin in genotype 3 hepatitis C virus infected patients. Results in real clinical practice.

OBJECTIVE: Direct-acting antivirals have shown high efficacy in all hepatitis C virus (HCV) genotypes, but genotype 3 (G3) treatments continue to be a challenge, mainly in cirrhotic patients. The aim of this study is to analyse effectiveness and safety of daclatasvir associated with sofosbuvir with or without ribavirin in G3-HCV infected patients in real clinical practice. METHODS: An observational, prospective, cohort study over 2.5 years, in G3-HCV infected adult patients, in all fibrosis stages including patients with decompensated cirrhosis. Treatment was a combination of sofosbuvir 400 mg/day + daclatasvir 60 mg/day, with or without a weight-adjusted dosing of ribavirin for 12 or 24 weeks. The primary efficacy endpoint was sustained virologic response rates 12 weeks after therapy (SVR12). The primary safety endpoint was treatment withdrawal rates secondary to severe adverse events. RESULTS: A total of 111 patients were enrolled, 32.4% cirrhotics and 29.9% treatment-experienced. The global SVR12 rate was 94.6%, while the SVR12 rate in F3-4 fibrosis stage patients was 90.8% versus 100% in patients with F0-2 fibrosis (p=0.03). In cirrhotic patients, SVR12 was 100% versus 40% depending on whether ribavirin was added or not to daclatasvir/sofosbuvir (p=0.001). No other patient or treatment basal variables influenced the treatment effectiveness. No patient treatment withdrawal secondary to severe adverse events was observed. CONCLUSIONS: Daclatasvir/sofosbuvir ± ribavirin is highly effective in G3-HCV infected patients. Advanced degrees of fibrosis significantly decrease the effectiveness of this treatment, which motivates the need for the addition of ribavirin in cirrhotic patients. The regimen was safe and well tolerated.

[The prophylaxis and treatment of c virus liver disease in the liver transplantation setting. Narrative review]. / Profilaxis y tratamiento de la hepatopatía por virus C en el entorno del trasplante hepático. Revisión narrativa.

OBJECTIVE: To review the use of antiviral therapy as prophylaxis or treatment of virus C liver disease in the liver transplantation setting. METHOD: A search was made of the literature in PubMed with the strategy liver transplantation AND hepatitis C AND (interferon OR peginterferon OR ribavirin) from 1966 to June 2007 and a manual search of the journals Gastroenterología y Hepatología, Journal of Hepatology and Hepatology between 2001 and June 2007, to identify publications and communications to congresses relating to the subject. The studies identified were selected and evaluated. RESULTS: A total of 48 articles were chosen for review. Hepatitis C virus is one of the main indications for liver transplantation. Post-transplant re-infection is immediate and almost universal, and results, in many cases, in a recurrent liver disease that reduces the patients survival. Four basic therapeutic strategies have been studied: pre-transplant anti-viral treatment, prophylaxis, early or preventative treatment and treatment of acute or chronic recurrent hepatitis C. CONCLUSIONS: Currently, the hepatitis C treatment in the liver transplantation setting is based on the use of peginterferon associated with ribavirin as pre-transplant treatment in selected patients or as treatment of recurrent post-transplant hepatitis C, achieving sustained virological responses of around 20% and 35% respectively. The main limitation of these treatments is the high frequency of the adverse effects and interruptions to treatment, meaning it is important to carry out strict follow-up of the treatment safety.

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

Objetivo:El uso de sirolimus en anomalías vasculares es una in-dicación especial no autorizada en ficha técnica. El objetivo de esteestudio es incrementar la evidencia del empleo por vía oral o tópica desirolimus en esta indicación en población pediátrica. Método. Estudio observacional retrospectivo de pacientes meno-res de 18 años tratados con sirolimus oral o tópico para anomalíasvasculares recogiendo: diagnóstico y ubicación de lesiones, forma deadministración y dosificación de sirolimus, niveles sanguíneos de fár-maco en los pacientes con tratamiento oral, duración del tratamiento,respuesta y toxicidad. Resultados: Se incluyeron 18 pacientes (7 con tratamiento oral y11 tópico). Con sirolimus oral, la tasa de respuesta global fue 85,7%.Se interrumpió sirolimus en 2 casos: por resolución completa y porprogresión. El 57,1% experimentó algún efecto adverso, en su mayoríaleves; siendo la dislipemia el efecto adverso más frecuente. La moni-torización de niveles sanguíneos fue empleada en todos los pacientespara el ajuste de dosis. Con el tratamiento tópico, la tasa de respuestaglobal fue 72,7%. Se interrumpió sirolimus en 3 casos: progresión en2 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 siroli-mus en nuestros pacientes parecen confirmar la efectividad y seguridaddel fármaco en anomalías vasculares y lo posicionan como una opciónterapéutica en pacientes pediátricos. Aun así, parece necesaria mayorinvestigación que trate de aclarar, entre otros, el régimen óptimo deltratamiento, la duración del mismo y los potenciales efectos adversosa largo plazo.(AU)

Objective: The use of sirolimus in vascular anomalies is a specialindication not authorized in its data sheet. The objective of this studywas to increase the evidence of oral or topical use of sirolimus for thisindication in the pediatric population. Materials and methods: An observational, retrospective study ofpatients under 18 years of age treated with oral or topical sirolimus forvascular anomalies was carried out. Diagnosis and location of lesions,administration route and dosage of sirolimus, blood levels of sirolimusin patients who received oral treatment, treatment duration, response,and toxicity were collected. Results: 18 patients –7 with oral treatment and 11 with topicaltreatment– were included. With oral sirolimus, the overall responserate was 85.7%. Sirolimus was discontinued in 2 cases –as a result offull resolution and progression. 57.1% of patients had adverse effects,most of which were mild. Dyslipidemia was the most frequent adverseeffect. Blood levels were monitored in all patients for dose adjustmentpurposes. With topical treatment, the overall response rate was 72.7%.Sirolimus was discontinued in 3 cases –due to progression in 2 casesand to stability in 1. 27.3% of patients had adverse effects, with itchingstanding out as the most frequent one. Conclusions: The favorable results of sirolimus treatment in ourpatients seem to confirm its effectiveness and safety in vascular anom-alies, which make it stand as a therapeutic option in pediatric patients.However, further research is required to establish the optimal treatmentregimen, treatment duration, and potential long-term adverse effects.(AU)

[The influence of antiretroviral-resistance tests on treatment effectiveness in patients with HIV and virological failure]. / Influencia de las pruebas de resistencias a antirretrovirales sobre la efectividad del tratamiento en pacientes con infección por VIH y fracaso virológico.

OBJECTIVE: The objective of this study is to determine the influence of antiretroviral-resistance tests on the suppression of HIV (< 400 copies/mL) in patients with virological failure who require an alternative antiretroviral treatment. METHOD: A retrospective observational study on cohorts of adult patients. Two groups were defined: cases in which the prescription of antiretrovirals was based on resistance tests (group A), and controls in which no such test was performed (group B). Each group was divided into two sub-groups according to the number of changes in treatment: first treatment change (A1 and B1); a subsequent change (A2 and B2). The main variable was defined as the proportion of patients with negative viral load (< 400 copies/mL) at the third month of treatment; secondary variables were the proportion of patients with negative viral load at the sixth month and an average variation in the CD4 level at the third and sixth months after this change. RESULTS: A total of 152 patients were included in this study, 59 in group A and 93 in group B (control). No differences were found in the stage of the disease at the time of administering an alternative treatment. 59.3% of the patients in group A and 47.3% of the patients in group B had suppressed the HIV viral load at the third month, although this difference was not statistically significant (p = 0.149). No statistically significant differences were found in the secondary variables. CONCLUSIONS: The use of antiretroviral-resistance tests increased effectiveness in the response to the selected antiretroviral treatment in the study group, although we did not obtain significant differences for the group of patients in which these tests were not performed.

[Carbamazepine-induced aplastic anaemia: a case report]. / Anemia aplasica inducida por carbamacepina. A proposito de un caso.

INTRODUCTION: The widespread use of carbamazepine in multiple neurological disorders makes it a drug whose most frequent side effects are well known and controlled. Aplastic anaemia is a very rare side effect, although it is the most serious since it presents a high mortality rate. CASE REPORT: We report the case of a 51 year old male patient who suffered brain injury that required daily treatment with 600 mg of carbamazepine. In the sixth month of treatment he was found to have a decrease in the number of platelets, which was confirmed a month later. He was admitted to hospital and diagnosed as having a medullar aplasia. Despite therapy with immunosuppressants, he died 12 weeks later. DISCUSSION: The appearance of aplastic anaemia does not seem to be related to age, the disease treated or to be dose dependent. Most cases are seen 3 4 months after treatment and the risk period is the first year. The choice treatment is a bone marrow transplant in patients under the age of 50; in older patients the recommended treatment is immunosuppressant therapy. The early diagnosis of aplastic anaemia is essential, although the difficulty lies in determining how often haematological controls are to be performed, since some cases have appeared a few days after beginning treatment. The frequency of the controls must be based on the clinical judgement of the doctor with regular check ups to detect haematological problems (infections, high temperature, ecchymosis) and to warn the patient and relatives should any of the symptoms appear.

[Phenytoin: paradoxical toxicity; a discussion of 4 cases]. / Fenitoína: intoxicación paradójica; descripción de 4 casos.

INTRODUCTION: Phenytoin overdosing results in a wide variety of signs and symptoms - ataxia, nistagmus, loss of consciousness. On occasions increased frequence of seizures may be seen in patients with high phenytoin serum levels and no evidence of standard toxicity symptoms - paradoxical toxicity. OBJECTIVE: To study the frequency of phenytoin paradoxical toxicity, and to analyze patients" clinical status. PATIENTS AND METHOD: Prospective study of 100% of patients monitored by the Pharmacy Department during August-December, 1998 and who had phenytoin serum levels above therapeutic range and seizures. Laboratory determinations in samples was performed by polarized immunofluorescence analysis. The outcome of each patient was monitored through their pharmacotherapeutic record and clinical history. RESULTS: The number of patients was 1706; 124 of wich had serum levels above the therapeutic range. Out of this group, 3 males and 1 female, with ages ranging from 17 to 73, a diagnosis of epilepsy, and chronic therapy using phenytoin, come to our Emergency Department because of convulsions. Serum levels of phenytoin were ordered due to suspected lack of compliance or underdosing. In all 4 patients phenytoin was discontinued until the therapeutic range was reached, to be then reset with plasma level-adjusted dosages. CONCLUSIONS: Paradoxical toxicity may lead to errors, and therefore we should rule out such possibility in patients with exacerbated epilepsy undergoing treatment with phenytoin.

[Analysis of initial antiretroviral therapy in HIV-infected patients]. / Análisis del tratamiento antirretroviral inicial en pacientes VIH.

INTRODUCTION: The timing of highly active antiretroviral therapy (HAART) initiation and regimen combination treatment for HIV-infected patients are parameters requiring assessment, since they decisively influence results. The aim of the study was to evaluate initial HAART in HIV-infected patients in our hospital. MATERIALS AND METHODS: Retrospective study of the first 6 months after initiation of HAART in all treatment-naive adult patients so treated from January 2001 to June 2002. Baseline plasma viral load (PVL) and CD4+ count and HAART combination regimens were analyzed as well as therapy effectiveness and safety at 12 and 24 weeks after initiation of treatment. RESULTS: HAART was initiated in 85 patients, 45 of which met the inclusion criteria. Eighty seven percent (87%) of the patients had a baseline CD4+ count < 350 cells/microl. Fifty-nine percent of treatments consisted of regimens based on non-nucleoside analogs, 34% were based on protease inhibitors, and 7% on nucleosides. The CD4+ count increased in 78 and 73% of patients at the 12th and 24th week respectively, and the percentage of patients with no detectable PVL was 67 and 71%, respectively. No significant differences in effectiveness were seen between the different combination regimens. CONCLUSIONS: In most cases HAART may recover immune status and control PVL in treatment-naive HIV-infected patients. No differences were seen between combination regimens at the initiation of therapy.

[Change of antiretroviral therapy in HIV-infected patients]. / Cambio del tratamiento antirretroviral en el paciente VIH.

INTRODUCTION: Antiretroviral therapy adherence plays a vital role in treatment onset and in the durability of antiviral response. In addition, clinical status, plasma viral load, and CD4+ cell count are essential in making therapeutic change decisions in various clinical situations. The aim of our study was to assess the reasons for therapy change in both treatment-naive and treatment-experienced patients, and to know the casuistry of antiretroviral therapy change. PATIENTS AND METHODS: A retrospective study of 100% of patients who underwent at least one antiretroviral treatment change from January to December 2002. The type of antiretroviral therapy before and after change was analyzed, as were the causes leading to treatment change. RESULTS: During year 2002, 131 patients (20.15%) had their antiretroviral therapy modified, and the total number of treatment changes in these patients was 151. An analysis of treatment changes revealed that 69 modifications resulted from intolerance/toxicity (45%), 51 from therapeutic failure (34%), 14 from lack of adherence (9%), 10 from therapy simplification (7%), 1 from therapy enhancement (1%), and 6 from other causes (4%). CONCLUSIONS: Adverse events such as (resulting from) intolerance, renal colic, lipodystrophy, pancreatitis, etc., are responsible for a high incidence of therapy changes, mostly in treatment-naive patients. Therapeutic failure and lack of adherence are further causes of medically-relevant therapy modifications.

[Daptomycin dosing greater than 6 mg/kg/day depending on pharmacokinetic and pharmacodynamic parameters infections by Staphylococcus aureus]. / Dosis superior a 6 mg/kg/día de daptomicina según parámetros farmacocinéticos/farmacodinámicos en infecciones por Staphylococcus aureus.

Daptomycin is a cyclic lipopeptide antibiotic whose approved dose is 4 to 6 mg/kg/day. Today it is a matter of controversy the use of higher doses of daptomycin in a range of 8-12 mg/kg/ day, for the treatment of Staphylococcus aureus infections, justified by its concentration-dependent action and its tolerability and safety profile, but the available studies are inconclusive. Stratification is performed by groups of patients, on the recommendation of using doses above 6 mg/kg/day based on the PK/PD parameters predictive of efficacy and safety. We conclude that doses of 8-12 mg/kg/day may be beneficial in patients with severe sepsis, patients with hypoalbuminemia and infections involving potentially high bacterial load or where there is a bacterial kidnapping. However it is not suitable exceed the dose of 6 mg/kg/day in patients with obesity and/or creatinine clearance less than 50 ml/min.

Daptomicina es un antibiótico lipopéptido cíclico cuya dosis autorizada es de 4 a 6 mg/Kg/día. Actualmente se debate la utilización de dosis mayores de daptomicina, en un rango de 8 a 12 mg/Kg/día, para el tratamiento de infecciones producidas por Staphylococcus aureus, justificado por su acción concentración dependiente y su perfil de tolerancia y seguridad, pero los estudios disponibles no son concluyentes. Se realiza una estratificación, por grupos de pacientes, de la recomendación de utilizar dosis superiores a 6 mg/Kg/día en función de los parámetros pk/pd predictores de eficacia y seguridad. Se concluye que dosis de 8 a 12 mg/Kg/día pueden ser beneficiosas en pacientes con sepsis grave, pacientes con hipoalbuminemia y en infecciones que conlleven una carga bacteriana potencialmente elevada o en las que se produzca un secuestro bacteriano. Sin embargo no es adecuado sobrepasar la dosis de 6 mg/Kg/día en pacientes con obesidad y/o con aclaramiento de creatinina inferior a 50 ml/min.

Dosis superior a 6 mg/kg/día de daptomicina según parámetros farmacocinéticos/farmacodinámicos en infecciones por Staphylococcus aureus / Daptomycin dosing greater than 6 mg/kg/day depending on pharmacokinetic and pharmacodynamic parameters infections byStaphylococcus aureus

Daptomicina es un antibiótico lipopéptido cíclico cuya dosis autorizada es de 4 a 6 mg/Kg/día. Actualmente se debate la utilización de dosis mayores de daptomicina, en un rango de 8 a 12 mg/Kg/día, para el tratamiento de infecciones producidas por Staphylococcus aureus, justificado por su acción concentración dependiente y su perfil de tolerancia y seguridad, pero los estudios disponibles no son concluyentes. Se realiza una estratificación, por grupos de pacientes, de la recomendación de utilizar dosis superiores a 6 mg/Kg/día en función de los parámetros pk/pd predictores de eficacia y seguridad. Se concluye que dosis de 8 a 12 mg/Kg/día pueden ser beneficiosas en pacientes con sepsis grave, pacientes con hipoalbuminemia y en infecciones que conlleven una carga bacteriana potencialmente elevada o en las que se produzca un secuestro bacteriano. Sin embargo no es adecuado sobrepasar la dosis de 6 mg/Kg/día en pacientes con obesidad y/o con aclaramiento de creatinina inferior a 50 ml/min (AU)

Daptomycin is a cyclic lipopeptide antibiotic whose approved dose is 4 to 6 mg/kg/day. Today it is a matter of controversy the use of higher doses of daptomycin in a range of 8-12 mg/kg/ day, for the treatment ofStaphylococcus aureus infections, justified by its concentration-dependent action and its tolerability and safety profile, but the available studies are inconclusive. Stratification is performed by groups of patients, on the recommendation of using doses above 6 mg/kg/day based on the PK/PD parameters predictive of efficacy and safety. We conclude that doses of 8-12 mg/kg/day may be beneficial in patients with severe sepsis, patients with hypoalbuminemia and infections involving potentially high bacterial load or where there is a bacterial kidnapping. However it is not suitable exceed the dose of 6 mg/kg/day in patients with obesity and/or creatinine clearance less than 50 ml/min (AU)

Profilaxis y tratamiento de la hepatopatía por virus C en el entorno del trasplante hepático. Revisión narrativa / The prophylaxis and treatment of C virus liver disease in the liver transplantation setting. Narrative review

Objetivo: Revisar la utilización de terapia antiviral como profilaxis otratamiento de la hepatopatía por virus C en el entorno del trasplantehepático.Método: Se realizó una búsqueda bibliográfica en PubMed con laestrategia “liver transplantation” AND “hepatitis C” AND (“interferon”OR “peginterferon” OR “ribavirin”) desde 1966 hasta junio2007 y una búsqueda manual en las revistas Gastroenterología yHepatología, Journal of Hepatology y Hepatology desde 2001 hastajunio 2007, para identificar publicaciones y comunicaciones a congresosrelacionadas con el tema. Se seleccionaron y evaluaron losestudios identificados.Resultados: Se seleccionaron 84 trabajos para realizar la revisión.La hepatopatía por virus C es una de las principales indicaciones detrasplante hepático. La re-infección post-trasplante es inmediata ycasi universal, y deriva, en muchos casos, en una hepatopatía recurrenteque disminuye la supervivencia del paciente. Se han estudiadocuatro estrategias terapéuticas básicas: tratamiento antiviral pretrasplante,profiláctico, anticipado o preventivo y tratamiento de lahepatitis C aguda y crónica recurrente.Conclusiones: Actualmente el tratamiento de la hepatitis C en elentorno del trasplante hepático se basa en la utilización de peginterferónasociado a ribavirina como tratamiento pre-trasplante enpacientes seleccionados o como tratamiento de la hepatitis C recurrentepost-trasplante, alcanzándose respuestas virológicas sostenidasen torno al 20% y 35% respectivamente. La principallimitación de estos tratamientos es la alta frecuencia de efectosadversos y suspensiones de tratamiento, por lo que es muy importanterealizar un seguimiento estricto de la seguridad del tratamiento

Objective: To review the use of antiviral therapy as prophylaxis ortreatment of virus C liver disease in the liver transplantation setting.Method: A search was made of the literature in PubMed with thestrategy “liver transplantation” AND “hepatitis C” AND (“interferon”OR “peginterferon” OR “ribavirin”) from 1966 to June 2007 and amanual search of the journals Gastroenterología y Hepatología,Journal of Hepatology and Hepatology between 2001 and June2007, to identify publications and communications to congressesrelating to the subject. The studies identified were selected and evaluated.Results: A total of 48 articles were chosen for review. Hepatitis C virusis one of the main indications for liver transplantation. Post-transplantre-infection is immediate and almost universal, and results, inmany cases, in a recurrent liver disease that reduces the patient’s survival.Four basic therapeutic strategies have been studied: pre-transplantanti-viral treatment, prophylaxis, early or preventative treatmentand treatment of acute or chronic recurrent hepatitis C.Conclusions: Currently, the hepatitis C treatment in the liver transplantationsetting is based on the use of peginterferon associatedwith ribavirin as pre-transplant treatment in selected patients or astreatment of recurrent post-transplant hepatitis C, achieving sustainedvirological responses of around 20% and 35% respectively. Themain limitation of these treatments is the high frequency of the adverseeffects and interruptions to treatment, meaning it is importantto carry out strict follow-up of the treatment safety

Fenitoína: intoxicación paradójica; descripción de 4 casos / Phenytoin: paradoxical toxicity; a discussion of 4 cases

Introducción: La sobredosificación con fenitoína origina una amplia variedad de signos y síntomas: ataxia, nistagmus, pérdida de la consciencia. Ocasionalmente se puede observar un incremento de la frecuencia de las convulsiones en pacientes con niveles séricos elevados de fenitoína y sin evidencia de síntomas habituales de sobredosificación: intoxicación paradójica. Objetivo: Estudio de la frecuencia de la intoxicación paradójica de fenitoína y análisis de la situación clínica del paciente. Pacientes y método: Estudio prospectivo del 100 por ciento de los pacientes monitorizados por el Servicio de Farmacia durante el periodo agosto-diciembre de 1998, con niveles séricos de fenitoína superiores al rango terapéutico y que presentaban convulsiones. La determinación analítica de las muestras se realizó mediante el análisis de inmunofluorescencia polarizada. De cada paciente se siguió su evolución a través de su ficha farmacoterapéutica e historia clínica. Resultados: El número de pacientes fue 1.706, 124 con niveles séricos superiores al rango terapéutico, de los cuales 3 hombres y 1 mujer, con un rango de edades entre 17 y 73 años, diagnosticados de epilepsia, en tratamiento crónico con fenitoína, acudieron a Urgencias por presentar cuadros convulsivos. Se solicita la determinación de niveles séricos de fenitoína por sospecha de incumplimiento terapéutico o infradosificación. En los 4 casos se suspendió la fenitoína hasta alcanzar niveles dentro de rango terapéutico; reiniciándose con pautas posológicas ajustadas a los niveles plasmáticos. Conclusiones: La intoxicación paradójica nos puede inducir a errores, por ello debemos descartar esta posibilidad en pacientes con exacerbación de crisis epilépticas a tratamiento con fenitoína (AU)

Anemia aplásica inducida por carbamacepina. A propósito de un caso / Carbamazepine-induced aplastic anaemia: a case report

Introducción. La amplia utilización de la carbamacepina en múltiples trastornos neurológicos hace que sea un medicamento cuyos efectos secundarios más frecuentes sean conocidos y controlados. La anemia aplásica es un efecto secundario muy raro, aunque es el más grave, ya que presenta un alto índice de mortalidad. Caso clínico. Se presenta el caso de un paciente varón de 51 años que sufre traumatismo craneoencefálico, que precisa tratamiento con carbamacepina, 600 mg/día. En el sexto mes de tratamiento se le detecta un descenso de plaquetas, que se confirma un mes más tarde, por lo que se decide su ingreso hospitalario, donde se le diagnostica una aplasia medular. A pesar de la terapia inmunosupresora fallece 12 semanas después. Discusión. La aparición de la anemia aplásica no parece guardar relación con la edad, la enfermedad tratada o ser dosisdependiente. La mayoría de los casos se presentan a los 3-4 meses de tratamiento, cuyo período de riesgo se da en el primer año. El tratamiento de elección es el trasplante de medula ósea en pacientes menores de 50 años; si se supera esta edad se recomienda como tratamiento la terapia inmunosupresora. El diagnóstico temprano de la anemia aplásica es esencial, aunque la dificultad estriba en determinar la periodicidad de los controles hematológicos, ya que han aparecido casos a los pocos días de comenzar el tratamiento. La frecuencia de los controles debe basarse en el juicio clínico del médico efectuando consultas periódicas, para descubrir problemas hematológicos (infecciones, fiebre, equimosis) y alertar al paciente y familiares ante la aparición de alguno de estos síntomas (AU)

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