Breakthrough Candidemia Research Articles

Risk factors and outcome for nosocomial breakthrough candidaemia

To describe all cases of nosocomial candidaemia that occurred in patients in use of anti-fungals. Retrospective cohort study (1995-2003). Breakthrough candidaemia was defined as the occurrence of candidaemia in a patient receiving at least 3 days of systemic anti-fungal therapy. Patients with breakthrough candidaemia were compared to patients with non-breakthrough candidaemia. During the period of study, 20 patients had breakthrough candidaemia, and 40% of them had cancer. While most of these episodes occurred with amphotericin B, some patients received low-dose regimens of fluconazole or ketoconazole in association with ranitidine. Non-Candida albicans species caused 75% of these infections, mainly Candida parapsilosis (30%). When compared to controls (n=171), the breakthrough group had more frequently mucositis, longer stay in the intensive care unit, and longer periods of hyperalimentation, mechanical ventilation, urinary catheter and broad-spectrum antibiotics. Candida isolation from sites other than blood occurred more frequently in the breakthrough group. Mortality rate and Candida species distribution were similar among groups. C. parapsilosis was the main aetiology of breakthrough candidaemia. Common risk factors included mucositis, isolation of Candida from sites other than blood, use of broad-spectrum antibiotics, and invasive medical procedures. No difference in the mortality rate was observed.

Breakthrough Candida Infection in a Preterm Infant with Congenital CutaneousCandida albicansInfection

Amphotericin B is the primary antifungal agent used for candida sepsis in neonates. Breakthrough candidemia was not reported in neonates during either amphotericin B or liposomal amphotericin B (AmBisome) treatment. We describe a case of a premature infant with congenital cutaneous candida infection, who had two episodes of breakthrough infection, from Candida albicans and Candida parapsilosis, while he was treated with amphotericin B and AmBisome, respectively. We discuss the pathogenesis of breakthrough infections, and the relevance of antifungal resistance and sensitivities testing.

Epidemiology, presentation, management and outcome of candidemia in a tertiary care teaching hospital in the United Arab Emirates, 1995-2001.

Sixty episodes of candidemia among hospitalized patients in the United Arab Emirates (0.77/1000 discharges) in 1995-2001 were identified through case retrieval. All patients had malignancy (65%) or serious non-malignant disease (35%). Candida albicans accounted for 45% of isolates. Non-C. albicans Candida species occurred more frequently than C. albicans in adults (67%), hematologic-malignancy patients (58%), and cases of breakthrough candidemia (83%) and were prevalent overall in 2000-2001 (67-73%). C. tropicalis was identified in 15% of cases, C. glabrata in 5%, C. parapsilosis in 5%, C. inconspicua in 2%, C. famata in 2% and C. lusitaniae in 1%. Delayed diagnosis or treatment was common, as was Karnofsky scale < or = 40%, septic shock, and inadequate dosage or duration of antifungal drug therapy. Crude mortality was 50%, and mortality attributable to candidemia was 30%. Univariate analysis indicated patients were more likely to die (odds ratio for death [95% CI]) if they had been stationed in the intensive care unit (ICU) (4.76 [1.31-17.2]), had a Karnofsky scale < or = 40% (38.76 [4.66-322.47]), or suffered septic shock (9.88 [2.9-33.65]). They were more likely to survive in cases with concomitant bacteremia (0.25 [0.07-0.91]), adequate antifungal dose (0.28 [0.08-0.94]), and removal of central lines (0.26 [0.07-0.95]). The high association of bacteremia with candidemia (70% of cases) is unusual. The apparent survival benefit experienced by patients who had bacteremia (odds ratio for survival on multivariate analysis = 2.40 [0.28-20.17], P < 0.03) is novel.

Breakthrough candidemia in patients with cancer differs from de novo candidemia in host factors and Candida species but not intensity.

To evaluate the risk factors associated with breakthrough candidemia in patients with cancer and to compare them with those of de novo candidemia in this patient population. Retrospective case series of 120 episodes of candidemia, 90 de novo and 30 breakthrough candidemias. University-affiliated, tertiary-care cancer center in Houston, Texas. All patients with cancer who acquired candidemia between January 1993 and December 1998 were included if they had non-catheter-related candidemia and information about quantitative blood cultures. Although less frequent, breakthrough candidemia was seen more often in neutropenic patients with leukemia. The intensity of breakthrough candidemia was comparable to that of de novo candidemia. Most (70%) of the breakthrough candidemias were due to Candida glabrata or C. krusei. In breakthrough candidemia, the same risk factors seen in de novo candidemia were encountered, although more frequently. C. glabrata and C. krusei are the leading causes of breakthrough candidemia in patients with cancer.

Risk factors for breakthrough candidemia.

In order to assess the risk factors for breakthrough candidemia (candidemia occurring in patients receiving at least 3 days of systemic fluconazole or amphotericin B), 270 cases of candidemia occurring in two tertiary hospitals were analyzed. Using multivariate analysis, profound neutropenia (<100/mm(3)) (odds ratio [OR], 9.14), use of corticosteroids (OR, 3.17), and heavy antibiotic exposure (previous use of 2 or more antibiotics for at least 14 days) (OR, 2.93) were identified as risk factors. Neither the susceptibility of the isolates nor the presence of a catheter was found to be a risk factor. These data suggest that gastrointestinal colonization plays a major role in the development of breakthrough candidemia.

Risk factors and predictors of outcome in patients with cancer and breakthrough candidemia.

Hematogenous candidiasis adds substantially to the morbidity and mortality rates of patients with cancer. Little is known about the risk factors and outcome in patients with breakthrough (BT) candidemia while on systemic antifungal therapy. All 479 episodes of candidemia in 474 consecutive patients with candidemia that was diagnosed at M. D. Anderson Cancer Center from 1988 through 1992 were studied retrospectively. A total of 49 patients had BT candidemia, defined as candidemia that developed after at least 5 days of systemic antifungal therapy. Risk factors for BT candidemia and predictors of mortality were investigated. Multivariate analysis revealed that intensive care unit stay, neutropenia, use of corticosteroids, and duration of neutropenia as significant risk factors for BT candidemia. Seventy-six percent of patients with BT candidemia died, compared with 50% of patients with non-BT infection. In multivariate analysis, intensive care unit stay, being and remaining neutropenic, APACHE III score, and disseminated disease were independent prognostic factors. In conclusion, identification of risk factors and predictors of a poor outcome in patients with cancer with BT candidemia may have important implications in early diagnosis and appropriate therapy of these patients.

Breakthrough candidemia in neutropenic patients.

Breakthrough candidemia in neutropenic patients.

Fatal Candida tropicalis fungaemia in a leukaemic patient receiving fluconazole prophylaxis

A 50-year-old man with newly diagnosed acute myeloid leukaemia developed breakthrough candidaemia while receiving fluconazole as antifungal prophylaxis during remission-inducing chemotherapy. Candida tropicalis was isolated; the strain was resistant to fluconazole on in vitro sensitivity testing, a phenomenon which has not been previously reported in this setting.

The changing face of candidemia: emergence of non- Candida albicans species and antifungal resistance

To assess the changing epidemiology of candidemia in the 1990s, to evaluate the clinical implications for the presence of non-Candida albicans in blood, and to evaluate the presence of antifungal resistance in relation to prior antifungal administration. Multicenter prospective observational study of patients with positive blood cultures for Candida species or Torulopsis glabrata. Four tertiary care medical centers. Four hundred twenty-seven consecutive patients were enrolled. The frequency of candidemia due to non-C. albicans species significantly increased in each hospital throughout the 3.5-year study period (P = 0.01). Thirteen percent of candidemias occurred in patients who were already receiving systemic antifungal agents. Candidemias developing while receiving antifungal therapy were more likely caused by non-C. albicans species than by C. albicans species (P = 0.0005). C. parapsilosis and C. krusei were more commonly seen with prior fluconazole therapy, whereas T. glabrata was more commonly seen with prior amphotericin B therapy. Candida species isolated during episodes of breakthrough candidemia exhibited a significantly higher MIC to the antifungal agent being administered (P < 0.001). In this large scale study, the non-C. albicans species, especially T. glabrata, emerged as important and frequent pathogens causing fungemia. This finding has major clinical implications given the higher complication and mortality rate associated with the non-C. albicans species. The change in the pattern of candidemia might be partly attributed to the increase in number of immunocompromised hosts and the widespread use of prophylactic or empiric antifungal therapy. This is an ominous sign given the in vitro resistance of the non-C. albicans species to currently available antifungal agents.

Breakthrough Candidemia During Antifungal Treatment With Fluconazole in Patients With Hematologic Malignancies

Breakthrough Candidemia During Antifungal Treatment With Fluconazole in Patients With Hematologic Malignancies