Evaluación de los efectos adversos por antifúngicos en pacientes con candidemia y aspergilosis en un hospital de tercer nivel

Resumen

Objectives To describe the clinical and epidemiological characteristics of patients diagnosed with candidemia and invasive aspergillosis (IA) in a third level hospital. To study the frequency, severity and causality of adverse events (AE) described and to compare the safety profile of the different antifungal agents. To determine the predictive factors of adverse events in patients receiving antifungal treatment. Material and methods Retrospective observational study of adult patients who received echinocandins, fluconazole, voriconazole or amphotericin B liposomal, with a duration of ≥5 days, who had at least one positive blood culture for Candida spp or IA according to EORTC/ MSG criteria. It was collected: age, sex, baseline pathology, Charlson comorbidity index, Winston severity criteria, Pitt prognosis index, risk factors for candidemia and aspergillosis, antifungal used, route of administration, dose and duration of treatment. Outcome variables included AE, drug causality, degree of AE, outcome of AE and clinical evolution (cure, relapse of infectious process and death related to or not with the infectious process). The Naranjo algorithm was used to estimate the causality of AE (possible, probable or definite) and Common Terminology Criteria for Adverse Events to classify their severity. A multivariate logistic regression analysis was performed to adjust for various variables of the patients and their relation to the presence of AE. Results A total of 306 patients were included, 241 with candidemia and 63 with IA, with a mean age of 63.1 ±14.2 years. The main underlying diseases were cancer (53.9%), hypertension (48.7%), diabetes mellitus (22.4%) and renal failure (20.4%). The most frequent risk factors were antibiotic use (97.7%), previous abdominal surgery (84.1%), previous use of corticosteroids (73.0%), parenteral nutrition (47.0%) and immunosuppressive treatment (32.6%). Greater initial clinical severity was found in candidemias compared to IA (<0.0001). The most used antifungals agents were echinocandins (40.1%), followed by fluconazole (24.0%), voriconazole (22.0%) and liposomal amphotericin B (10.2%). The overall cure was obtained in 195 patients (64.1%), indicating the change in antifungal agent in 87 patients (28.6%). The main adverse effects were elevated liver enzymes (14.8%), increased plasma creatinine (11.4%), hypokalemia (8.6%) and hyperbilirubinemia (8.3%). A greater weight was found in the use of liposomal amphotericin B and the occurrence of AE (p=0.001), severe AE (p=0.031) and suspension rate due to AE (p=0.002). Micafungin was the antifungal that was less related to the presence of AE (p=0.0002) and suspension due to AE (p=0.002), while fluconazole had lower severe AE rate (p=0.04). The predictive factors independently associated with the development of AE were liposomal amphotericin B treatment (OR =4.63) and the Pitt score ≥3 (OR =1.84). Conclusions The main underlying diseases are cancer, hypertension and diabetes mellitus. The most frequent predisposing factors are antibiotic use, previous abdominal surgery and previous use of corticosteroids. The most commonly used antifungals have been echinocandins. The main adverse effects reported are increased liver enzymes, increased plasma creatinine and hypokalemia. Echinocandins have been the agents that presented a better safety profile. Liposomal amphotericin B treatment and the Pitt score ≥3 are associated with the development of higher AE rates.