Candidemia em Hospital Universitário do Triângulo Mineiro: Estudo prospectivo

Abstract

Introduction: The number of fungal infections associated with health care has increased in recent decades, probably a consequence of advances in medical and surgical therapies. The wide use of aggressive treatment modalities has contributed to the increase in the number of patients at risk of developing invasive fungal infection, especially Candidiasis. Objectives: To evaluate the occurrence of Candidemia and its etiological agents, risk factors for the development of the disease and those associated with mortality in 30 days, investigate phenotypic characteristics such as biofilm production and to determine the antifungal susceptibility of Candida spp. isolated from the bloodstream of patients treated at Hospital de Clínicas de Uberlândia (HCU). Material and Methods: This was a two-year cohort study, conducted from July 2017 to July 2019 at HCU. Samples of Candida spp. and clinical and epidemiological data from patients (gender, age, comorbidities, time and place of hospital stay, medication for chronic use, invasive devices, antifungal treatment and duration of treatment, previous use of antimicrobials, disease outcome) with Candidemia were studied. The isolates were identified using three techniques: CHROMagarTM Candida Medium Chromogenic Agar, Automated Biochemical Tests (VITEK®-2) and Mass Spectrometry (MALDI-TOF/MS). The antifungal susceptibility test was performed using the cards from the automated VITEK®-2 system. The biofilm tests were conducted using conventional spectrophotometric techniques (Violet Crystal Staining and XTT Salt Reduction Assays) and Mass Spectrometry (MALDI-TOF/MS). Statistical analyzes of risk factors associated with 30-day mortality were performed using univariate and multiple logistic regressions, followed by the selection of variables using the Stepwise Method. The agreement between the techniques used for the identification of yeasts was made using the Kappa test. Patient survival curves were constructed using the Kaplan-Meier method; p≤0.05 values were statistically significant. Results: Most patients were male (65%), over 60 years old (45%). The presence of CVC (90%), bladder catheter (64%), mechanical ventilation (57%) and parenteral nutrition (55%) were the most commonly found invasive devices; previous use of antimicrobials (96%), chronic diseases such as neoplasia (27%), systemic arterial hypertension (20%) and previous abdominal surgery (43%) were the most frequent comorbidities. Antifungal treatment was performed in 85% of the patients, mainly with fluconazole. Candidemia mortality was 56%; age over 60 years, the presence of a bladder catheter and admission to the ICU were the independent risk factors for mortality in 30 days (p<0.05). Early treatment initiation contributed to lower mortality (p<0.0001); there was no statistical difference in patient survival with respect to Candida species. During the study period, 113 patients were diagnosed with Candidemia and 126 Candida spp. isolates were obtained; 41 were C. albicans; 27 C. tropicalis; 18 C. glabrata; 17 C. parapsilosis; 10 C. krusei; 3 C. kefyr; 3 C. lusitaneae; 2 C. pelliculosa; 2 C. guilliermondii; 2 C. orthopsilosis and 1 C. dubliniensis. The best correlation between the methodologies was between VITEK®-2 and MALDI-TOF/MS, being considered almost perfect (K = 0.833) and significant (p <0.0001). Most of the isolates (95%) were susceptible to the antifungals used and all were biofilm producers, most of them strongly producers, with high quantification of biomass (95%) and high metabolic activity (99%); MALDI-TOF / MS was able to detect specific biofilm proteins, since the proteomic profiles of biofilm-producing isolates were different from those of non-producing strains. Conclusion: Candidemia can reach high mortality rates; the knowledge of risk factors, early diagnosis, the correct identification of the species involved, virulence factors such biofilm-forming strains and the institution of therapy in a timely manner are fundamental for the management of the disease.