Thaís Guimarães

Epidemiologia das infecções hematogênicas por Candida spp

Candida spp is associated to almost 80% of all nosocomial fungal infections and is considered a major cause of blood stream infections. Candida spp is the fourth most common cause of blood stream infections in the United States, where this agent is responsible for 8% of all invasive infections documented in this site. At the present, non-albicans species are related to at least 50% of all invasive infections due to Candida spp and they present differences in terms of clinical outcome as well as susceptibility to antifungal drugs. The crude mortality rate of candidemia is between 40 and 60% which makes this infection an important challenge for all clinicians from tertiary care hospitals of diverse different countries.

Prospective observational study of candidemia in São Paulo, Brazil: incidence rate, epidemiology, and predictors of mortality.

BACKGROUND Studies conducted in tertiary care hospitals of different European countries and the United States have shown incidence rates of candidemia ranging from 0.17 to 0.76 and 0.28 to 0.96 per 1,000 admissions, respectively. So far, only 1 study has evaluated the incidence rates of candidemia in tertiary care hospitals in Latin American countries. OBJECTIVE To evaluate the epidemiology of candidemia in 4 tertiary care hospitals in São Paulo, Brazil. DESIGN Multicenter, laboratory-based surveillance of candidemia. RESULTS A total of 7,038 episodes of bloodstream infection were identified, and Candida species accounted for 282 cases (4%). The incidence rate of candidemia was 1.66 candidemic episodes per 1,000 hospital admissions. Candida albicans was the most frequently isolated Candida species in all hospitals, but Candida species other than C. albicans accounted for 62% of isolates, including predominantly Candida parapsilosis and Candida tropicalis. Azole resistance was restricted to only 2% of all Candida isolates (1 isolate of Candida glabrata and 4 isolates of Candida rugosa). Candidemia was mostly documented in surgical patients with long durations of hospital stay. The crude mortality rate was 61%, and advanced age and high Acute Physiology and Chronic Health Evaluation II score were both conditions independently associated with risk of death. CONCLUSIONS We observed in our series a higher incidence rate of candidemia than that reported in European countries and the United States. Advanced age and a high Acute Physiology and Chronic Health Evaluation II score were factors associated with a higher probability of death in candidemic patients. Fluconazole-resistant Candida strains are still a rare finding in our case-based study of candidemia.

Clinical and microbiological aspects of candidemia due to Candida parapsilosis in Brazilian tertiary care hospitals

In order to characterize the epidemiology, microbiology and outcome of candidemia due to Candida parapsilosis, we examined a database of 282 episodes of candidemia prospectively collected from four tertiary care hospitals in São Paulo, Brazil between March 2002 and February 2003, and compared the characteristics of patients with candidemia due to C. parapsilosis (n=64) with those caused by Candida albicans (n=107). C. parapsilosis candidemia was associated with neutropenia (p=0.005), tunneled central venous catheter (p=0.005) and cancer chemotherapy (p=0.03). By multivariate analysis, candidemia due to C. parapsilosis was associated with the presence of a tunneled central venous catheter (relative risk 3.71, 95% confidence interval 1.28-10.70). Except for a single isolate of C. parapsilosis that exhibited MIC >1 microg/ml to amphotericin B, no resistance was observed in 166 isolates tested against fluconazole, itraconazole, 5-flucytosine and amphotericin B. The caspofungin MIC values of C. parapsilosis isolates were significantly higher than those exhibited by C. albicans isolates (p<0.001). The overall mortality of patients with candidemia due to C. parapsilosis was significantly lower (45% vs. 62%, p=0.03). The association between C. parapsilosis candidemia and a tunneled central venous catheter supports the idea that the main mode of acquisition of C. parapsilosis is from an external source.

Brazilian guidelines for the management of candidiasis - a joint meeting report of three medical societies: Sociedade Brasileira de Infectologia, Sociedade Paulista de Infectologia and Sociedade Brasileira de Medicina Tropical.

Candida infections account for 80% of all fungal infections in the hospital environment, including bloodstream, urinary tract and surgical site infections. Bloodstream infections are now a major challenge for tertiary hospitals worldwide due to their high prevalence and mortality rates. The incidence of candidemia in tertiary public hospitals in Brazil is approximately 2.5 cases per 1000 hospital admissions. Due to the importance of this infection, the authors provide a review of the diversity of the genus Candida and its clinical relevance, the therapeutic options and discuss the treatment of major infections caused by Candida. Each topography is discussed with regard to epidemiological, clinical and laboratory diagnostic and therapeutic recommendations based on levels of evidence.

High prevalence of hepatitis C infection in a Brazilian prison: identification of risk factors for infection

Hepatitis C virus (HCV) causes infectious hepatitis worldwide. It is transmitted mainly by blood products and sharing of intravenous paraphernalia during illicit drug use. High prevalence rates have been described among specific groups considered to be at higher risk for HCV infection, including prison inmates. The objectives of this study were: to determine the HCV seroprevalence among inmates of Casa de Detenção de São Paulo; to identify risk factors for HCV infection; and to compare the seroprevalence of HCV to other blood borne or sexually transmitted diseases. From December, 1993, to January, 1994, a total of 779 inmates were interviewed to collect information on sociodemographic status, sexual behavior, and past experience with illicit drugs. Blood samples were obtained from 756 inmates for serological tests. 310 (41%) blood samples were positive for anti-HCV, 425 (56.2%) were negative, and 21 (2.8%) showed indeterminate results. In this population, we found a seroprevalence of 13.7% for HIV, 3.3% for syphilis (VDRL), and 68.1% for hepatitis B virus previous infection. Four variables were each identified as associated with a positive anti-HCV serologic test: a positive VDRL (OR = 2.63 IC 95% 1.08 to 6.36); a time of current imprisonment longer than 130 months (OR = 2.44 IC 95% 1.04 to 5.71); previous incarceration at Casa de Detenção de São Paulo (OR = 1.73 IC 95% 1.19 to 2.52) and; illicit drug use before admission to the Casa de Detenção de São Paulo (OR = 1.64 IC 95% 1.15 to 2.33). The seroprevalence of HCV antibodies among the study population was high (41%), indeed, one of the highest clusters of HCV infection recorded until now. Four variables were each shown to be associated with HCV infection. The simultaneous presence of these 4 variables is associated with an 82% probability of being anti-HCV positive. Although risk factor analysis indicates most HCV infections occur prior to inprisonment, initiation of control measures to prevent continued transmission after incarceration should be done.

Epidemiology and predictors of a poor outcome in elderly patients with candidemia

BACKGROUND Candidemia affects patient populations from neonates to the elderly. Despite this, little information is available about the epidemiology of candidemia in elderly patients. METHODS We performed a retrospective analysis of 987 episodes of candidemia in adults (>14 years of age) from the databases of three laboratory-based surveys of candidemia performed at 14 tertiary care hospitals. Patients aged ≥60 years were considered elderly (group 1, n=455, 46%) and were compared to younger patients (group 2, n=532, 54%) regarding demographics, underlying diseases, comorbidities, exposure to medical procedures, species, treatment, and outcome. RESULTS The median APACHE II score was significantly higher in the elderly patients (19 vs. 15, p=0.03). Variables that were observed significantly more frequently in elderly patients included admission to an intensive care unit, diabetes mellitus, renal failure, cardiac disease, lung disease, receipt of antibiotics or H2 blockers, insertion of a central venous catheter, mechanical ventilation, and candidemia due to Candida tropicalis. The 30-day mortality of elderly patients was significantly higher than that of younger patients (70% vs. 45%, p<0.001). Factors associated with higher mortality by multivariate analysis included APACHE II score and being in group 1 (elderly). Factors associated with mortality in elderly patients were lung disease and the receipt of mechanical ventilation. CONCLUSIONS Elderly patients account for a substantial proportion of patients with candidemia and have a higher mortality compared to younger patients.

Historical trends in the epidemiology of candidaemia: analysis of an 11-year period in a tertiary care hospital in Brazil

Candida species are an important cause of bloodstream infections (BSI). To evaluate the epidemiological, clinical and microbiological aspects of two cohorts {1994-1999 [period 1 (P1) ]; 2000-2004 [period 2 (P2) ]} of candidaemic patients, we performed a retrospective analysis from a laboratory-based survey. A total of 388 candidaemias were identified, with an incidence of 0.20/1,000 patient-days and a significant increase in P2 vs. P1 (0.25 vs. 0.15, p = 0.04). Cancer and prior antibiotic use were frequent and Candida albicans was the most prevalent species found (42.4%). Resistance to fluconazole was found in 2.47% of the strains. No differences were observed in the species distribution of Candida during the study periods. In the P2 cohort, there were higher prevalence of elderly individuals, cardiac, pulmonary and liver diseases, renal failure, central venous catheters and antibiotic therapy. In P1, there were higher prevalence of neurological diseases and chemotherapy. The crude mortality was 55.4%. In conclusion, our incidence rates remained high. Furthermore, the distribution pattern of Candida species and the fluconazole resistance profile remained unchanged. Moreover, we found a clear trend of higher prevalence of candidaemia among the elderly and among patients with comorbidities. Finally, it is necessary to discuss strategies for the prevention and control of Candida BSI in Brazil.

Candidúria: uma abordagem clínica e terapêutica

Candiduria remains a controversial issue for clinicians once that it may represent a broad variety of possibilities including colonization, local or systemic infection. We will discuss the epidemiology, diagnosis and treatment of candiduria in different settings of patients, including renal transplant recipients. Definitions on therapy are mostly based on epidemiological and clinical data. Once antifungal therapy is required the following antifungal treatment may be used: intravenous amphotericin B, bladder irrigation with amphotericin B or fluconazole. Blood cultures may be required in patients with candiduria and high risk for developing hematogenous infection. Removal of the urinary catheter must be considered in order to avoid persistent candiduria and recurrence.

Multilocus sequence typing of sequential Candida albicans isolates from patients with persistent or recurrent fungemia

Multilocus sequence typing (MLST) is a useful tool to explore the phylogenetics and epidemiology of Candida albicans isolates recovered from cases of invasive candidiasis. The goal of this study was to determine whether the same or different strains were responsible for persistent or recurrent fungemia through the use of MLST and ABC typing on sequential C. albicans isolates from the same patient. We applied both typing methods to 21 C. albicans strains recovered from 8 patients with persistent or recurrent candidemia. The isolates were collected during a multicenter surveillance study in four public tertiary care hospitals in Brazil. Persistent candidemia was defined as two or more blood cultures positive for C. albicans on 2 or more separate days. Recurrent candidemia was defined as an episode of candidemia occurring at least 1 month after the apparent complete resolution of an infectious episode caused by Candida species. We observed that, except for one patient, all strains from the first and second samples of the same patient showed the same MLST diploid sequence type (DST), ABC type and susceptibility profile to antifungals. Three distinct strains, well discriminated by MLST, were found in the seven samples collected sequentially over 10 days from one patient. The strains from the first four samples were indistinguishable, the fifth and sixth were also indistinguishable but different from the first four and seventh samples. Significantly, the seventh strain was the only C. albicans clade 2 isolate found in our total collection involving 61 patients, although clade 2 is commonly found worldwide. To the best of our knowledge, this is the first study describing the recovery of three distinct C. albicans strains in the same patient with a persistent blood stream infection within a short period of time.

Discontinuation of empirical antifungal therapy in ICU patients using 1,3-β-d-glucan

BACKGROUND Empirical antifungal therapy in high-risk ICU patients is an attractive strategy, but overuse of antifungal agents is a potential problem. OBJECTIVES We evaluated if ICU patients at high risk to develop candidaemia identified by a prediction rule could discontinue empirical antifungal therapy on the basis of repeatedly negative 1-3-β-d-glucan (BDG) tests. METHODS We conducted a multicentre cohort study in 85 ICU patients receiving antibiotics or with central venous catheter plus two additional factors (dialysis, parenteral nutrition, surgery, pancreatitis or receipt of corticosteroids or other immunosuppressive agents) plus either fever, hypothermia, hypotension, acidosis, elevated C-reactive protein or leucocytosis. Blood cultures (days 1 and 2) and BDG (days 1-3, baseline period) were performed and anidulafungin was given. On day 4, patients with negative blood cultures and BDG discontinued antifungal therapy. Registered in ClinicalTrials.gov (NCT01734525). RESULTS The incidence of candidaemia was 8.2% in patients selected versus 0.5% in patients without entry criteria (16.9 times higher). Sixty-four patients (75.3%) had baseline positive BDG, including 7 with candidaemia. All 21 patients with baseline negative BDG discontinued anidulafungin on day 4. None developed candidaemia until day 30. CONCLUSIONS Early discontinuation of empirical echinocandin therapy in high-risk ICU patients based on consecutive negative BDG tests may be a reasonable strategy, with great potential to reduce the overuse of echinocandins in ICU patients. Prospective studies with a higher number of patients are needed.