Fidaxomicin monotherapy versus standard therapy combined with bezlotoxumab for treating patients with Clostridioides difficile infection at high risk of recurrence: a matched cohort study.

BACKGROUND: Both fidaxomicin and bezlotoxumab (used in combination with an antibiotic against Clostridioides difficile) achieve reductions in recurrence rates of C. difficile infection (CDI). However, the two strategies have never been compared. METHODS: Data from two retrospective cohorts of 'real-life' use of fidaxomicin and bezlotoxumab in combination with a standard anti-C. difficile antibiotic were used to compare the rates of recurrence of both strategies. Since the two cohorts were not identical, we used a propensity score analysis. RESULTS: Three hundred and two patients were included: 244 in the fidaxomicin cohort and 78 in the bezlotoxumab cohort. A history of renal failure or immunosuppression was more frequent in patients receiving bezlotoxumab (39.7% and 66.7% versus 26.6% and 38.9%; P = 0.03 and P < 0.001, respectively), but the severity and number of previous CDI episodes were similar in both cohorts. We observed that 19.3% of the patients in the fidaxomicin cohort experienced recurrence, compared with 14.1% in the bezlotoxumab cohort (OR 1.45; 95% CI 0.71-2.96; P = 0.29) but the difference remained non-significant after propensity score matching using previously defined variables (OR 1.24; 95% CI 0.50-3.07; P = 0.64). Moreover, the multivariate analysis did not show differences depending on the drug used. CONCLUSIONS: We observed that fidaxomicin and bezlotoxumab are prescribed in similar clinical scenarios, although those treated with bezlotoxumab have greater comorbidity. The proportion of recurrences was numerically lower in those treated with bezlotoxumab, although the propensity analysis did not find significant differences between the two drugs.

Real-World Experience with Bezlotoxumab for Prevention of Recurrence of Clostridioides difficile Infection.

Bezlotoxumab is marketed for the prevention of recurrent Clostridioides difficile infection (rCDI). Its high cost could be determining its prescription to a different population than that represented in clinical trials. The objective of the study was to verify the effectiveness and safety of bezlotoxumab in preventing rCDI and to investigate factors related to bezlotoxumab failure in the real world. A retrospective, multicentre cohort study of patients treated with bezlotoxumab in Spain was conducted. We compared the characteristics of cohort patients with those of patients treated with bezlotoxumab in the pivotal MODIFY trials. We assessed recurrence rates 12 weeks after completion of treatment against C. difficile, and we analysed the factors associated with bezlotoxumab failure. Ninety-one patients were included in the study. The cohort presented with more risk factors for rCDI than the patients included in the MODIFY trials. Thirteen (14.2%) developed rCDI at 12 weeks of follow-up, and rCDI rates were numerically higher in patients with two or more previous episodes (25%) than in those who had fewer than two previous episodes of C. difficile infection (CDI) (10.4%); p = 0.09. There were no adverse effects attributable to bezlotoxumab. Despite being used in a more compromised population than that represented in clinical trials, we confirm the effectiveness of bezlotoxumab for the prevention of rCDI.

Resultados de la implementación de un programa multidisciplinar de trasplante de microbiota fecal por colonoscopia para el tratamiento de la infección recurrente por Clostridium difícil / Results of the implementation of a multidisciplinary programme of faecal microbiota transplantation by colonoscopy for the treatment of recurrent Clostridium difficile infection

Introducción: La recurrencia de la infección por Clostridium difficile (ICD) es frecuente y a menudo difícil de controlar. El trasplante de microbiota fecal (TMF) es una opción terapéutica avalada en estos casos, aunque se desconoce su aplicabilidad y efectividad en nuestro medio. Objetivos: Analizar los aspectos técnicos, seguridad y efectividad del primer programa consolidado de TMF en España. Métodos: Estudio retrospectivo descriptivo de todos los pacientes con ICD recurrente tratados mediante TMF por colonoscopia en un hospital de tercer nivel tras la implantación de un protocolo multidisciplinar entre marzo de 2015 y septiembre 2016. Resultados: Se realizaron 13 TMF en 12 pacientes (11/12; 91,7% mujeres) con una mediana de edad de 84,6 años (rango: 38,2-98,2). En todos los casos la indicación fue la recurrencia de la ICD. Los pacientes habían presentado una mediana de 3 episodios previos de ICD (rango: 2-6) y en todos había fracasado el tratamiento con fidaxomicina. Todos los procedimientos se realizaron mediante colonoscopia. La efectividad con una sesión de TMF fue del 91,7% (11/12; IC 95%: 64,6-98,5%). En la paciente no respondedora se realizó un segundo TMF a los 17 días con desaparición de la sintomatología. No se registraron efectos adversos secundarios al procedimiento endoscópico ni al TMF tras una mediana de seguimiento de 6,5 meses (rango: 1-16 meses). Dos pacientes fallecieron durante el seguimiento por causas no relacionadas con el TMF. Conclusiones: El TMF por colonoscopia es una alternativa terapéutica efectiva y segura en la recurrencia de la ICD. Se trata de un procedimiento sencillo que debería implementarse en más centros en nuestro entorno (AU)

Introduction: Recurrent Clostridium difficile infection (CDI) is common and often difficult to manage. Faecal microbiota transplant (FMT) is an effective therapeutic tool in these cases, although its applicability and effectiveness in Spain is currently unknown. Aim: To analyse the technical aspects, safety and effectiveness of the first consolidated FMT programme in Spain. Methods: Retrospective descriptive study of all patients with recurrent CDI treated with FMT performed by colonoscopy in a tertiary centre after the implementation of a multidisciplinary protocol between March 2015 and September 2016. Results: A total of 13 FMT were performed in 12 patients (11/12; 91.7% women) with a median age of 84.6 years (range: 38.2-98.2). Recurrence of CDI was the indication for FMT in all cases. Patients had suffered a median of 3 previous episodes of CDI (range: 2-6) and all had failed treatment with fidaxomicin. All procedures were performed by colonoscopy. Effectiveness with one session of FMT was 91.7% (11/12; 95% CI: 64.6 to 98.5%). In the non-responder patient, a second FMT was performed 17 days after the first procedure, with disappearance of symptoms. No side effects related to the endoscopic procedure or the FMT were recorded after a median follow-up of 6.5 months (range: 1-16 months). Two patients died during follow-up due to causes unrelated to FMT. Conclusion: FMT by colonoscopy is an effective and safe therapeutic alternative in recurrent CDI. It is a simple procedure that should be implemented in more centres in Spain (AU)

Farmacocinética y farmacodinamia de ceftazidima/avibactam / Pharmacokinetics and pharmacodynamics of ceftazidime/avibactam

Ceftazidima y avibactam presentan una farmacocinética lineal. Se unen poco a proteínas y no sufren metabolismo hepático; tampoco se han demostrado interacciones entre ellas. La excreción es mayoritariamente renal, por lo que la dosificación debe ajustarse a la función renal. La semivida de ambos fármacos es de aproximadamente 2 h (algo superior si se administran en una infusión de 2 h) y su volumen de distribución de unos 20 l. Los estudios farmacocinéticos realizados no demuestran diferencias relevantes en función de la edad (por encima de 3 meses), el sexo o la raza. El tiempo durante el cual las concentraciones en sangre permanecen por encima de la CMI (%fT>CMI) es el índice farmacocinético/farmacodinámico (PK/PD) relacionado con la eficacia de ceftazidima. En el caso de avibactam, el índice PK/PD relacionado con la eficacia es el tiempo durante el cual las concentraciones en sangre están por encima de la concentración crítica o umbral (CT), que es la concentración mínima de avibactam, por debajo de la cual no se produce inhibición de betalactamasas in vivo (%fT > CT). Se ha estimado que la CT de avibactam es de 0,5 mg/l para Enterobacteriaceae y 1 mg/l para Pseudomonas aeruginosa. Para la situación más desfavorable (que fT>CMI y fT>CT sean el 50% del intervalo de dosificación y CT 1 mg/l), con la dosis estándar (2/0,5 g cada 8 h administrada en perfusión de 2 h), la probabilidad de alcanzar el objetivo farmacodinámico o PTA es superior al 98% para CMI ≤ 8 mg/l (AU)

Ceftazidime and avibactam show linear pharmacokinetics. Both drugs bind only weakly to proteins and lack liver metabolism and mutual drug-drug interactions. Because ceftazidime/avibactam are excreted mainly by the kidney, the dosing regimen must be adjusted to renal function. Both molecules have an elimination half-life of around 2 hours (somewhat higher if they are infused in 2 hours) and their volume of distribution is approximately 20 litres. Pharmacokinetic studies have not shown significant differences due to sex, age (over 3 months) or race. The percentage of time that the free drug concentration is above the MIC (%fT>MIC) is the parameter that best characterizes the pharmacodynamic profile of ceftazidime. For avibactam, the pharmacokinetic/ pharmacodynamic (PK/PD) index that most closely correlates with efficacy is the percentage of time that the free drug concentration is above the threshold concentration (CT) (%fT>CT), CT being the concentration of avibactam below which betalactamases are no longer effectively inhibited in vivo (0.5 mg/L for Enterobacteriaceae and 1 mg/L for Pseudomonas aeruginosa). For the most conservative target (50% fT>MIC for ceftazidime, and 50% fT>CT and CT of 1 mg/L for avibactam), with the standard dosing regimen (with a 2 hours infusion of 2/0.5 g every 8 hours), the probability of target attainment (PTA) is higher than 98% for MICs ≤ 8 mg/L (AU)

Results of the implementation of a multidisciplinary programme of faecal microbiota transplantation by colonoscopy for the treatment of recurrent Clostridium difficile infection. / Resultados de la implementación de un programa multidisciplinar de trasplante de microbiota fecal por colonoscopia para el tratamiento de la infección recurrente por Clostridium difficile.

INTRODUCTION: Recurrent Clostridium difficile infection (CDI) is common and often difficult to manage. Faecal microbiota transplant (FMT) is an effective therapeutic tool in these cases, although its applicability and effectiveness in Spain is currently unknown. AIM: To analyse the technical aspects, safety and effectiveness of the first consolidated FMT programme in Spain. METHODS: Retrospective descriptive study of all patients with recurrent CDI treated with FMT performed by colonoscopy in a tertiary centre after the implementation of a multidisciplinary protocol between March 2015 and September 2016. RESULTS: A total of 13 FMT were performed in 12 patients (11/12; 91.7% women) with a median age of 84.6 years (range: 38.2-98.2). Recurrence of CDI was the indication for FMT in all cases. Patients had suffered a median of 3 previous episodes of CDI (range: 2-6) and all had failed treatment with fidaxomicin. All procedures were performed by colonoscopy. Effectiveness with one session of FMT was 91.7% (11/12; 95% CI: 64.6 to 98.5%). In the non-responder patient, a second FMT was performed 17 days after the first procedure, with disappearance of symptoms. No side effects related to the endoscopic procedure or the FMT were recorded after a median follow-up of 6.5 months (range: 1-16 months). Two patients died during follow-up due to causes unrelated to FMT. CONCLUSION: FMT by colonoscopy is an effective and safe therapeutic alternative in recurrent CDI. It is a simple procedure that should be implemented in more centres in Spain.

Análisis farmacocinético-farmacodinámico en microbiología: herramienta para evaluar el tratamiento antimicrobiano / Pharmacokinetic/pharmacodynamic analysis in microbiology: a tool for the evaluation of the antimicrobial treatment

La selección de microorganismos multirresistentes, como efecto indeseable de la utilización de los antimicrobianos, y la escasez de novedades terapéuticas que se prevé para los próximos años obligan a una utilización racional de los antimicrobianos de uso habitual. La optimización de los regímenes terapéuticos mediante la utilización del análisis farmacocinético/farmacodinámico (PK/PD) sin duda contribuirá a alargar la vida útil de los antimicrobianos y a la contención de la resistencia bacteriana. Se revisa la importancia de la adecuada selección del régimen de dosificación de los antimicrobianos, la aplicación del análisis PK/PD en antibioterapia, la simulación de Montecarlo, los índices de eficacia y los puntos de corte PK/PD.El análisis PK/PD también se puede aplicar para la prevención de resistencias. Para estudiar los principios que predicen su aparición y difusión se pueden utilizar diferentes métodos: modelos in vitro, modelos animales y métodos para la evaluación de la prevención de resistencias (ventanas de selección de mutantes).Aunque el análisis PK/PD en antibioterapia es una herramienta muy útil que facilita la selección del tratamiento antimicrobiano más adecuado, presenta una serie de limitaciones para su aplicación en la práctica clínica

The selection of multiresistant microorganisms, as a side-effect of the use of antimicrobials, together with the lack of new therapeutic drugs expected in the near future, forces to a rational use of antibiotics. The optimisation of antibacterial treatments based on pharmacokinetic/pharmacodynamic analysis (PK/PD) may contribute to prolong the life of antibiotics and to contain the bacterial resistance to them. A review is made of the importance of the appropriateness of the dose regimen selected, the application of PK/PD analysis of antimicrobials, the Monte Carlo simulation, PK/PD indices for efficacy, and PK/PD cut-off points.PK/PD analysis is also applicable to the prevention of bacterial resistance. Different methods have been used to study the factors that lead to its emergence and spread, such as in vitro and animal models, and resistance prevention studies (mutant selection window).Although the PK/PD analysis is a very useful tool for the selection of the most appropriate dose regimen of antibiotics, several problems limit its use in clinical practice

[Pharmacokinetic/pharmacodynamic analysis in microbiology: a tool for the evaluation of the antimicrobial treatment]. / Análisis farmacocinético-farmacodinámico en microbiología: herramienta para evaluar el tratamiento antimicrobiano.

The selection of multiresistant microorganisms, as a side-effect of the use of antimicrobials, together with the lack of new therapeutic drugs expected in the near future, forces to a rational use of antibiotics. The optimisation of antibacterial treatments based on pharmacokinetic/pharmacodynamic analysis (PK/PD) may contribute to prolong the life of antibiotics and to contain the bacterial resistance to them. A review is made of the importance of the appropriateness of the dose regimen selected, the application of PK/PD analysis of antimicrobials, the Monte Carlo simulation, PK/PD indices for efficacy, and PK/PD cut-off points. PK/PD analysis is also applicable to the prevention of bacterial resistance. Different methods have been used to study the factors that lead to its emergence and spread, such as in vitro and animal models, and resistance prevention studies (mutant selection window). Although the PK/PD analysis is a very useful tool for the selection of the most appropriate dose regimen of antibiotics, several problems limit its use in clinical practice.

Utilidad potencial de ceftarolina fosamil en las infecciones osteoarticulares / Potential utility of ceftaroline fosamil in osteoarticular infections

Las infecciones osteoarticulares (IOA) abarcan un conjunto amplio de escenarios clínicos, habitualmente complejos, cuyo abordaje es frecuentemente medicoquirúrgico. A esta complejidad cabe añadir un bajo grado de evidencia en la literatura médica sobre estas infecciones. No obstante es posible -y necesario-integrar información microbiológica, farmacológica, experimental y clínica para conseguir los mejores resultados clínicos posibles. La elección del tratamiento antibiótico más conveniente dependerá sustancialmente del escenario clínico y, obviamente, de los microorganismos implicados. Dado el protagonismo de los estafilococos en las IOA es pertinente dilucidar el papel que puede desempeñar un nuevo fármaco antiestafilocócico en estas infecciones. La incorporación de ceftarolina supone, para el clínico que maneja IOA, la recuperación de un fármaco betalactámico para tratar estafilococos resistentes a la meticilina. Desde esta perspectiva es posible orientar el papel potencial de este nuevo antibiótico para el manejo de las IOA en sus diversos escenarios y la investigación clínica necesaria para su incorporación a la práctica clínica (AU)

Osteoarticular infections (OAI) include a wide-usually complex-spectrum of clinical scenarios. The approach is usually medical-surgical. In addition to this complexity, there is a low grade of evidence in the medical literature on these infections. Nevertheless, it is possible-and necessary-to integrate microbiological, pharmacological, experimental and clinical information to achieve the best possible clinical results. The most appropriate choice of antibiotic therapy largely depends on the clinical scenario and, obviously, on the microorganisms involved. Given the protagonism of staphylococci in OAI, it is appropriate to elucidate the role that could be played by a new antistaphylococcic agent in these infections. For clinicians who manage OAI, the incorporation of ceftaroline represents the recovery of a beta-lactam to treat methicillin-resistant staphylococci. This perspective can be used to guide the potential role of this new antibiotic for the management of OAI in various scenarios and the clinical research required for its introduction in clinical practice (AU)

Pancreatitis aguda inducida por doxiciclina / Doxycycline induced - acute pancreatitis

No disponible

No disponible

[Guidelines for the diagnosis and treatment of patients with bacteriemia. Guidelines of the Sociedad Española de Enfermedades Infecciosas y Microbiología Clínica]. / Guía para el diagnóstico y tratamiento del paciente con bacteriemia. Guías de la Sociedad Española de Enfermedades Infecciosas y Microbiología Clínica (SEIMC).

Bacteremia is a complex clinical syndrome in constant transformation that is an important, growing cause of morbidity and mortality. Even though there is a great deal of specific information about bacteremia, few comprehensive reviews integrate this information with a practical AIM. The main objective of these Guidelines, which target hospital physicians, is to improve the clinical care provided to patients with bacteremia by integrating blood culture results with clinical data, and optimizing the use of diagnostic procedures and antimicrobial testing. The document is structured into sections that cover the epidemiology and etiology of bacteremia, stratified according to the various patient populations, and the diagnostic work-up, therapy, and follow-up of patients with bacteremia. Diagnostic and therapeutic decisions are presented as recommendations based on the grade of available scientific evidence.

Guía para el diagnóstico y tratamiento del paciente con bacteriemia. Guías de la Sociedad Española de Enfermedades Infecciosas y Microbiología Clínica (SEIMC) / Guidelines for the diagnosis and treatment of patients with bacteriemia

La bacteriemia conforma un síndrome clínico complejo y en constante transformación que ocasiona una importante y creciente morbimortalidad. La información sobre la bacteriemia es abundante y específica, pero escasean los documentos que integren esa información de forma práctica. El principal objetivo de esta Guía, especialmente dirigida a los médicos de hospital, es mejorar la asistencia clínica a los pacientes con bacteriemia interpretando los resultados de los hemocultivos junto a los datos clínicos, y optimizando el uso de las pruebas diagnósticas y de los antimicrobianos. La Guía está estructurada en secciones que recogen la epidemiología y la etiología de las bacteriemias estratificadas por las principales poblaciones de pacientes, el manejo diagnóstico, el tratamiento y el seguimiento de los pacientes con bacteriemia. Las decisiones diagnósticas y terapéuticas se exponen en forma de recomendaciones que están basadas en el grado de evidencia científica disponible (AU)

Bacteremia is a complex clinical syndrome in constant transformation that is an important, growing cause of morbidity and mortality. Even though there is a great deal of specific information about bacteremia, few comprehensive reviews integrate this information with a practical aim. The main objective of these Guidelines, which target hospital physicians, is to improve the clinical care provided to patients with bacteremia by integrating blood culture results with clinical data, and optimizing the use of diagnostic procedures and antimicrobial testing. The document is structured into sections that cover the epidemiology and etiology of bacteremia, stratified according to the various patient populations, and the diagnostic work-up, therapy, and follow-up of patients with bacteremia. Diagnostic and therapeutic decisions are presented as recommendations based on the grade of available scientific evidence (AU)