Adecuación de la prescripción de antibióticos antipseudomónicos tras los cambios en los criterios EUCAST 2019 / Adequacy of the consumption of antipseudomonal antibiotics after changes in the 2019 EUCAST criteria

Introducción. En 2019, el Comité Europeo para el estudio de la sensibilidad antibiótica modificó las categorías de los test de sensibilidad antibiótica incluyendo el término “sensible con exposición incrementada”. Tras la difusión de protocolos locales recogiendo estas modificaciones, el objetivo de nuestro estudio fue analizar si los prescriptores se han adecuado a los mismos y el posible impacto clínico en los casos de inadecuación. Material y métodos. Estudio observacional y retrospecti vo de los pacientes con infección por pseudomonas aeruginosa y que hayan recibido antibiótico antipseudomónico desde ene ro a octubre de 2021 en un hospital terciario. Resultados. La inadecuación a las recomendaciones de la guía fueron un 57,6% en planta y un 40,4% en UCI (p<0,05). Tanto en planta como en UCI el grupo con más prescripción no ajustada a las recomendaciones de la guía fueron los amino glucósidos (92,9% y 64,9% respectivamente) por utilizar dosis subóptimas, seguido de los carbapenémicos (89,1% y 53,7% respectivamente) por no administrarlo en perfusión extendida. En planta, la tasa de mortalidad durante el ingreso o a los 30 días en el grupo de terapia inadecuada fue de 23,3% vs 11,5% en los que recibieron los tratamientos de forma adecuada (OR: 2,34; IC 95% 1,14-4,82); en UCI no hubo diferencias estadísti camente significativas. Conclusiones. Los resultados muestran la necesidad de implementar medidas para garantizar una mejor difusión y co nocimiento de los conceptos claves en el manejo de los antibió ticos, con el objetivo de garantizar exposiciones incrementadas y poder ofrecer una mejor cobertura de la infección, así como de evitar la amplificación de cepas resistente (AU)

Introduction. In 2019, the European Committee for the Study of Antibiotic Susceptibility modified the categories of antibiotic susceptibility tests to include the term “susceptible with increased exposure”. Following the dissemination of local protocols reflecting these modifications, the aim of our study was to analyse whether prescribers have adapted to them and the clinical impact in cases of inadequacy. Material and methods. Observational and retrospective study of patients with infection who received antipseudomonal antibiotics from January to October 2021 in a tertiary hospital.Results. Non adherence to the guideline recommendations was 57.6% in the ward and 40.4% in the ICU (p<0.05). In both the ward and ICU, the group with the most prescriptions not by the guideline ecommendations were aminoglycosides (92.9% and 64.9% respectively) for using suboptimal doses, followed by carbapenems (89.1% and 53.7% respectively) for not administering an extended infusion. On the ward, the mortality rate during admission or at 30 days in the inadequate therapy group was 23.3% vs 11.5% in those who received adequate treatment (OR: 2.34; 95% CI 1.14-4.82); in ICU there were no statistically significant differences.Conclusions. The results show the need to implement measures to ensure better dissemination and knowledge of key concepts in antibiotic management, to ensure increased exposures, and to be able to provide better infection coverage, as well as to avoid amplifying resistant strains (AU)

Recommended doses of endovenous vancomycin are insufficient to achieve therapeutic concentrations in paediatric patients.

OBJECTIVES: Vancomycin therapeutic drug monitoring is challenging, especially in the paediatric population where evidence is scarce. The main objective of this study was to analyse the achievement of therapeutic concentrations of vancomycin in paediatric patients and to evaluate the current monitoring method (trough levels), doses used, and the time required to achieve target concentrations. METHODS: Paediatric patients on treatment and monitored with vancomycin from November 2019 to December 2021 were included. Those with only one determination of serum vancomycin concentration were excluded. Demographic variables, analytical and microbiological parameters and toxicity data were collected. Pharmacokinetic parameters were assessed at baseline and during treatment. RESULTS: 225 patients (40.9% female; 108 neonates, 49 infants and 68 children or adolescents) were included in the study. The main indications for vancomycin treatment were sepsis (33.9%) and fever of unknown origin (29.3%). Microbiological cultures were positive in 71.1%, mostly with Gram-positive bacteria (60.4%). Therapeutic levels of vancomycin were reached in only 20.1% of the participants in the first determination. After pharmacokinetic monitoring, 81.7% of patients reached therapeutic concentrations, requiring a 23% increase in the initial dose, a 2-day lag time and 1-2 dosage adjustments until the therapeutic concentration was reached. Of the total patients, 13 developed nephrotoxicity, nine neutropenia and one patient developed red man syndrome. CONCLUSIONS: In our sample of paediatric patients, the recommended doses of vancomycin were insufficient to achieve therapeutic concentrations. Revision of the recommendations and/or a change in the method of pharmacokinetic monitoring is crucial to optimise treatment in this population.

Interacción paradójica entre nirmatrelvir/ritonavir y voriconazol en un paciente con COVID-19 / Paradoxical interaction between nirmatrelvir/ritonavir and voriconazole in a patient with COVID-19

Presentamos el caso de una interacción farmacológica entre nirmatrelvir/ritonavir (fármaco aprobado para la infección por COVID-19) y voriconazol, derivada del efecto bidireccional del ritonavir sobre las 2 principales enzimas metabolizadoras del voriconazol (citocromo P450 3A y 2C19) de forma que, ritonavir inhibe la primera e induce la segunda.De acuerdo con las principales bases de datos de información farmacoterapéutica, en la interacción entre ambos fármacos, se espera una disminución en el área bajo la curva del voriconazol por el efecto inductor de su metabolismo, sin embargo, en el caso que presentamos ha ocurrido el efecto opuesto, se dan niveles supraterapéuticos de forma mantenida, lo cual es un efecto paradójico según la literatura.Dado el corto periodo de tratamiento con nirmatrelvir/ritonavir (5 días), no llega a manifestarse el efecto inductor del ritonavir propuesto en los estudios en los que se basan las recomendaciones, donde el tratamiento con ritonavir es más prolongado. (AU)

This case is based on a drug interaction between nirmatrelvir/ritonavir (approved drug for COVID-19) and voriconazole is presented, possibly derived from the bidirectional effect of ritonavir on the 2 main voriconazole metabolising enzymes (cytochrome P450 3A and 2C19) ritonavir inhibits the former and induces the latter respectively.According to the main pharmacotherapeutic information databases, in the interaction between both drugs, a decrease in the area under the curve of voriconazole is expected due to the.inducing effect of its metabolism; however, in the case we present, unexpectedly, a paradoxical effect occurs, according to what is described in literature, with the result of sustained supratherapeutic levels of voriconazole.Given the short treatment period with nirmatrelvir/ritonavir (5 days), the induction effect of ritonavir proposed in the studies on which the recommendations are based, where treatment with ritonavir is longer, does not occur. (AU)

[Translated article] Paradoxical interaction between nirmatrelvir/ritonavir and voriconazole in a patient with COVID-19.

This case is based on a drug interaction between nirmatrelvir/ritonavir (approved drug for COVID-19) and voriconazole is presented, possibly derived from the bidirectional effect of ritonavir on the 2 main voriconazole metabolizing enzymes (cytochrome P450 3A and 2C19) ritonavir inhibits the former and induces the latter respectively. According to the main pharmacotherapeutic information databases, in the interaction between both drugs, a decrease in the area under the curve of voriconazole is expected due to the inducing effect of its metabolism; however, in the case we present, unexpectedly, a paradoxical effect occurs, according to what is described in literature, with the result of sustained supratherapeutic levels of voriconazole. Given the short treatment period with nirmatrelvir/ritonavir (5 days), the induction effect of ritonavir proposed in the studies on which the recommendations are based, where treatment with ritonavir is longer, does not occur.

Paradoxical interaction between nirmatrelvir/ritonavir and voriconazole in a patient with COVID-19. / Interacción paradójica entre nirmatrelvir/ritonavir y voriconazol en un paciente con COVID-19.

This case is based on a drug interaction between nirmatrelvir/ritonavir (approved drug for COVID-19) and voriconazole is presented, possibly derived from the bidirectional effect of ritonavir on the 2 main voriconazole metabolising enzymes (cytochrome P450 3A and 2C19) ritonavir inhibits the former and induces the latter respectively. According to the main pharmacotherapeutic information databases, in the interaction between both drugs, a decrease in the area under the curve of voriconazole is expected due to the. inducing effect of its metabolism; however, in the case we present, unexpectedly, a paradoxical effect occurs, according to what is described in literature, with the result of sustained supratherapeutic levels of voriconazole. Given the short treatment period with nirmatrelvir/ritonavir (5 days), the induction effect of ritonavir proposed in the studies on which the recommendations are based, where treatment with ritonavir is longer, does not occur.

Survival of Patient With Hemorrhagic Meningitis Associated With Inhalation Anthrax.

This report describes a 49-year-old male construction worker who acquired a Bacillus anthracis infection after working on a sheep farm. He experienced a severe respiratory infection, septic shock, and hemorrhagic meningoencephalitis with severe intracranial hypertension. After several weeks with multiple organ dysfunction syndrome, he responded favorably to antibiotic treatment. Three weeks into his hospitalization, an intracranial hemorrhage and cerebral edema led to an abrupt deterioration in his neurological status. A single dose of raxibacumab was added to his antimicrobial regimen on hospital day 27. His overall status, both clinical and radiographic, improved within a few days. He was discharged 2 months after admission and appears to have fully recovered.

Sellado rotatorio del catéter vascular e instilaciones vesicales con anfotericina B liposomal para erradicar Candida parapsilosis / No disponible

No disponible

Equinocandinas: buscando diferencias. El ejemplo de su uso en pacientes sometidos a técnicas continuas de reemplazamiento renal / Echinocandins: searching for differences. The example of their use in patients requiring continuous renal replacement therapy

Las equinocandinas tienen un papel creciente en el tratamiento de las infecciones fúngicas, sobre todo por su novedoso mecanismo de acción. Esto se refleja en las guías de tratamiento recientemente publicadas, pero, ni los estudios "in vitro" o en animales, ni los estudios clínicos muestran diferencias claras entre las tres del grupo. Cuestiones sobre la eficacia clínica comparativa, el perfil farmacocinético en poblaciones especiales, la justificación de su coste o su papel en la terapéutica permanecen sin respuesta. Comparten muchas características comunes pero los tres proveedores mantienen estrategias de marketing que buscan su diferenciación. Aunque existen similitudes en aspectos de su farmacocinética (FC), los datos en pacientes sometidos a técnicas continuas de reemplazamiento renal (TCRR), son limitados. La FC de la eliminación de fármacos en pacientes críticos sometidos a TCRR es muy compleja, con muchas variables que afectan al aclaramiento. Esta revisión esboza los principios básicos que determinan si es necesario el ajuste de dosis y compara las dos publicaciones actualmente disponibles sobre la FC de micafungina y anidulafungina en pacientes sometidos a TCRR(AU)

The echinocandins have a growing role in the treatment of fungal infections because of their novel mechanism of action. This is reflected in recently published management guidelines, but available in vitro data, animal studies, and clinical studies do not clearly differentiate the three agents in class. Comparative clinical efficacy among agents within the class, pharmacokinetic profiles in special populations, pharmacoeconomics justifications, and place in therapy have been largely unanswered. They share many common properties but marketing strategies of drug manufacturers are engaged in product differentiation. Although exist similarities in the pharmacokinetic (PK) profiles of the echinocandins, limited data have been published regarding their pharmacokinetics in continuous renal replacement therapy (CRRT) patients. The pharmacokinetics of drug removal in critically ill patients receiving CRRT is very complex, with multiple variables affecting clearance. This review outlines the basic principles that determine whether a dose adjustment is required. Two studies with data on PK parameters of micafungin and anidulafungin in CRRT patients have been published and are compared following that basic principles in the review(AU)

[Echinocandins: searching for differences. The example of their use in patients requiring continuous renal replacement therapy]. / Equinocandinas: buscando diferencias. El ejemplo de su uso en pacientes sometidos a técnicas continuas de reemplazamiento renal.

The echinocandins have a growing role in the treatment of fungal infections because of their novel mechanism of action. This is reflected in recently published management guidelines, but available in vitro data, animal studies, and clinical studies do not clearly differentiate the three agents in class. Comparative clinical efficacy among agents within the class, pharmacokinetic profiles in special populations, pharmacoeconomics justifications, and place in therapy have been largely unanswered. They share many common properties but marketing strategies of drug manufacturers are engaged in product differentiation. Although exist similarities in the pharmacokinetic (PK) profiles of the echinocandins, limited data have been published regarding their pharmacokinetics in continuous renal replacement therapy (CRRT) patients. The pharmacokinetics of drug removal in critically ill patients receiving CRRT is very complex, with multiple variables affecting clearance. This review outlines the basic principles that determine whether a dose adjustment is required. Two studies with data on PK parameters of micafungin and anidulafungin in CRRT patients have been published and are compared following that basic principles in the review.

Efectividad y seguridad de ranibizumab en degeneración macular neovascular asociada a la edad / Assessment of the effectiveness and safety of ranibizumab in neovascular agerelated macular degeneration

Fundamento y objetivos: La degeneración macular asociada a la edad (DMAE) neovascular es una enfermedad degenerativa y crónica. Los tratamientos actuales sólo han demostrado ralentizar la progresión de la DMAE. El objetivo del estudio es evaluar la efectividad y seguridad de ranibizumab en una serie de pacientes, así como describir sus características demográficas y clínicas. Pacientes y método: Se realizó un estudio observacional y retrospectivo, incluyendo todos los pacientes que iniciaron tratamiento desde el 1-12-2006 hasta el 31-12-2008, realizándose el seguimiento hasta el 31-03-2009. Se realizó un análisis bivariante y modelos de regresión logística para analizar la influencia de factores demográficos y clínicos en la efectividad y en la durabilidad del tratamiento. Se recogieron las reacciones adversas descritas en las historias clínicas para evaluar la seguridad.Resultados: Se incluyeron 112 pacientes con una media (DE) de edad de 77,7 (6,0) años. La media de durabilidad del tratamiento fue de 18,2 meses, siendo superior en el grupo de pacientes que iniciaron tratamiento con agudeza visual (AV) > 0,1 (p<0,001). Ranibizumab mantenía la AV por encima de los valores basales hasta los 18 meses. Ninguna de las variables estudiadas se asoció con la efectividad del tratamiento. La agudeza visual inicial influía en la duración del tratamiento, siendo superior en el grupo de pacientes con AV > 0,1.Conclusiones: Ranibizumab parece ser efectivo hasta los 18 meses. Un diagnóstico precoz de DMAE permitiría un inicio del tratamiento más temprano cuando los pacientes presentan valores superiores de AV, optimizando los beneficios del tratamiento. Ranibizumab fue bien tolerado y seguro en la mayoría de los pacientes (AU)

Background and objectives: Neovascular Age Related Macular Degeneration (ARMD) is a chronic and degenerative disease. Current treatment options are limited and have shown to slow diseaseprogression. The aim of this study was to assess Ranibizumab effectiveness and safety and to describe patients’ demographic and clinical characteristics. Patients and method: We conducted a retrospective observational study including all patients who had started treatment between 1/12/2006 and 31/12/2008, and were followed up until31/03/2009. A bivariate analysis on months 4, 12 and 18 and two logistic regression models were performed to analyze the influence of demographic and clinical factors on the effectiveness and durability of treatment. Adverse reactions were collected as described in themedical records to assess safetyResults: A total of 126 eyes of 112 patients were recruited. The mean age was 77.7 ( 6.0) years. The meandurability of treatment was 18.2 months, and it was higher in the group of patients who started treatment with visual acuity (VA) > 0.1 (p < 0.001). Ranibizumab therapy maintained AV over baseline at 18 months.None of the studied variables showed any influence on treatment effectiveness. However, baseline visual acuity influenced on reatment duration, being higher in the group of patients with AV > 0.1.Conclusions: Ranibizumab was shown to be effective until 18months. Early diagnosis of AMD could lead to an earlier treatment start, when patients present a higher AV, in order to optimize the benefits of treatment. Ranibizumab was well tolerated and safe in most patients (AU)

[Assessment of the effectiveness and safety of ranibizumab in neovascular age-related macular degeneration]. / Efectividad y seguridad de ranibizumab en degeneración macular neovascular asociada a la edad.

BACKGROUND AND OBJECTIVES: Neovascular Age Related Macular Degeneration (ARMD) is a chronic and degenerative disease. Current treatment options are limited and have shown to slow disease progression. The aim of this study was to assess Ranibizumab effectiveness and safety and to describe patients' demographic and clinical characteristics. PATIENTS AND METHOD: We conducted a retrospective observational study including all patients who had started treatment between 1/12/2006 and 31/12/2008, and were followed up until 31/03/2009. A bivariate analysis on months 4, 12 and 18 and two logistic regression models were performed to analyze the influence of demographic and clinical factors on the effectiveness and durability of treatment. Adverse reactions were collected as described in the medical records to assess safety. RESULTS: A total of 126 eyes of 112 patients were recruited. The mean age was 77.7 (± 6.0) years. The mean durability of treatment was 18.2 months, and it was higher in the group of patients who started treatment with visual acuity (VA) > 0.1 (p<0.001). Ranibizumab therapy maintained AV over baseline at 18 months. None of the studied variables showed any influence on treatment effectiveness. However, baseline visual acuity influenced on treatment duration, being higher in the group of patients with AV > 0.1. CONCLUSIONS: Ranibizumab was shown to be effective until 18 months. Early diagnosis of AMD could lead to an earlier treatment start, when patients present a higher AV, in order to optimize the benefits of treatment. Ranibizumab was well tolerated and safe in most patients.