Cause Of Candidemia Research Articles

Candida rugosa: a possible emerging cause of candidaemia in trauma patients

Candida rugosa appears to be emerging as a distinctive cause of candidaemia in recent years. Candidaemia due to this species is important to recognise because of its decreased susceptibility to azoles. We retrospectively evaluated a cluster of C. rugosa candidaemia occurring in critically ill trauma patients from a level I trauma centre of India. During the period from July 2008 to September 2009, a total of 28 blood samples from 19 patients were found to be positive for C. rugosa. Genetic relatedness among 17 C. rugosa isolates were characterised by the random amplified polymorphic DNA (RAPD) assay using M13 primers. These isolates were also characterised for their susceptibility to four antifungal agents, amphotericin B, fluconazole, flucytosine and voriconazole. In our study, 21% of C. rugosa isolates were resistant to fluconazole, whereas 100% susceptibility to amphotericin B, flucytosine and voriconazole was noted. Thirteen out of the 19 patients (68.4%) with C. rugosa candidaemia died. Of these, six had received antifungal therapy after confirmation of fungaemia. Prior to this cluster, C. rugosa had never been identified as a cause of infection at our centre. Due to the retrospective nature of the evaluation of these cases, the source of this possible outbreak could not be traced. Nevertheless, to the best of our knowledge, this is the largest cluster of cases of C. rugosa candidaemia reported from a single institution in the English literature.

Candida isolates in tertiary hospitals in northeastern Brazil

Candida is an opportunistic pathogen that affects high-risk patients who are either immunocompromised or critically ill and is associated with almost 80% of all nosocomial fungal infections, representing the major cause of fungemia with high mortality rates (40%). Candida albicans is the main cause of candidemia and among the non-albicans species C. parapsilosis, C. glabrata and C. tropicalis are the most frequent agents. The aim of this study was to evaluate the distribution of Candida species in two tertiary hospitals in Recife, Northeastern Brazil. It began by surveying all positive Candida cultures processed by the microbiology laboratory from September 2003 to September 2006. The cultures, originated from various types of biological material (blood, urine, tracheal, catheter and others), were processed by Vitec (®) system (Biomerieux SA, France). A total of 1.279 (hospital A: 837; hospital B: 442) sample isolates were positive for Candida. The most frequent species in both hospitals were: C. albicans (367), C. tropicalis (363), C. parapsilosis (147), C. glabrata (81), C. krusei (30) and C. guillermondii (14). The isolates were obtained from 746 hospitalized patients. A total of 221 positive hemocultures were detected in 166 different patients in both hospitals, and 113 (68.1%) of these patients with positive hemocultures presented Candida in other body sites. This study shows that Candida non-albicans was the main isolated agent and evidences the importante of C. tropicalis in nosocomial fungal infections.

Risk Factors for Fluconazole-Resistant

Candida glabrata is the second leading cause of candidemia in U.S. hospitals and is more likely than other common Candida species to be fluconazole

Candida rugosa: a distinctive emerging cause of candidaemia. A case report and review of the literature

Candida rugosa is a rare cause of candidaemia, but important to recognize because of frequent azole-resistance and its association with catheters and total parenteral nutrition. Recommended therapy is an echinocandin or amphotericin, and catheter discontinuation. Fluconazole might be substituted based on susceptibility testing and a clinical response to initial therapy.

Candida rugosa: a distinctive emerging cause of candidaemia. A case report and review of the literature

Candida rugosa: a distinctive emerging cause of candidaemia. A case report and review of the literature

Candidemia in an intensive care unit

Candidemia is becoming more actual because of better survival of even critically ill patients, wide use of antimicrobials, and increased numbers of invasive procedures and manipulations. Diagnosis of candidemia remains complicated, and costs of treatment and mortality rates are increasing. OBJECTIVE. To evaluate the pathogens of candidemia, risk factors and their influence on outcome. MATERIAL AND METHODS. Data of 41 patients with positive blood culture for Candida spp., who were treated in the intensive care units at the Hospital of Kaunas University of Medicine, were analyzed retrospectively. RESULTS. Candidemia was caused by Candida albicans (C. albicans) in 48.8% (n=20) of patients and by non-albicans Candida in 51.2% (n=21) of patients. The main cause of candidemia was C. albicans in 2004 (83.3%, n=5), but in 2005 (63.6%, n=7), in 2006 (57.1%, n=4), and in 2007 (52.9%, n=9), the main cause was non-albicans Candida spp. The number of candidemia cases caused by C. albicans was decreased in 2005, 2006, and 2007 as compared with 2004, and the number of candidemia caused by non-albicans Candida spp. was decreased, respectively (P<0.05). More than 65% (n=34) of patients had severe disease (P<0.05). Lethal outcome was recorded in 58.5% of patients with candidemia. Mechanical ventilation was used in 76.9% (n=20) and urinary bladder catheter in 72.1% (n=19) of non-survivors and in 23.1% (n=6) and 26.9% (n=7) of survivors, respectively (P<0.05). CONCLUSIONS. There is an increase in the prevalence of candidemia in the intensive care units during the 4-year period; half of candidemia cases were caused by non-albicans Candida spp., and patients with candidemia caused by non-albicans Candida spp. are at higher risk of mortality. Therefore, for the empirical treatment of septic conditions in an intensive care unit, when invasive fungal infection is suspected, we recommend using an antifungal agent of non-azole class until a pathogen of candidemia is determined. Severe disease is evaluated as a risk factor for candidemia. Patients with oncological diseases are at significantly higher risk for candidemia caused by non-albicans Candida spp. Use of mechanical ventilation and urinary bladder catheter is a risk factor for lethal outcome.

The changing epidemiology of invasive candidiasis

The objective of the current retrospective study was to compare the epidemiology of candidemia and its risk factors in patients who had hematologic malignancies(HM) with those in patients who had solid tumors (ST). The medical and electronic records of all patients with cancer who had candidemia at the authors' institution from 1993 to 2003 were reviewed for demographic data and clinical information, including the use of prophylactic fluconazole, the infecting Candida species, and the source of candidemia (catheter-related vs other apparent sources). Six hundred thirty-five patients with candidemia were analyzed. C. glabrata and C. krusei were the leading causes of candidemia in 31% and 24% of patients with HM, respectively, and in 18% and 2% of patients with ST, respectively (P < .001). A catheter was the source of candidemia in 36% of the patients with ST and in 12% of the patients with HM (P < .001). Response to antifungal therapy occurred in 73% of the ST group compared with 49% of the HM group (P < .001). Multivariate logistic regression analysis revealed that fluconazole prophylaxis was a risk factor for both C. glabrata and C. krusei candidemia. The analysis also identified neutropenia as a risk factor for all candidemia and catheter-related infection as a risk factor for C. parapsilosis candidemia. The results of this study indicated that C. glabrata and C. krusei were the leading causes of candidemia in patients with HM. Neutropenia was the leading risk factor for all candidemia, whereas the catheter was the leading risk factor for C. parapsilosis candidemia.

Candida lusitaniaefungemia in cancer patients: risk factors for amphotericin B failure and outcome

Candida lusitaniae, a Candida species frequently resistant to amphotericin B (AMB), is a rare cause of candidemia. The clinical significance of this in vitro resistant phenotype, the risk factors for, and the clinical presentation of C. lusitaniae fungemia in comparison with those of Candida albicans have not been completely characterized. We reviewed 13 consecutive cases of C. lusitaniae fungemia in cancer patients and compared them with 41 consecutive cases of C. albicans fungemia (1990-2004). The AMB mutational frequency and rate of fungicidal activity was compared between a bloodstream, AMB-susceptible C. lusitaniae isolate associated with clinical failure and reference C. albicans and Candida glabrata strains. In multivariate analysis, patients having C. lusitaniae fungemia were more likely to have neutropenia (p=0.001), stem cell transplantation (p=0.014) and to have received prior antifungals (p=0.04). Mutational frequencies at clinically-achievable AMB exposures were 8 x 10(5) for C. lusitaniae and <1 x 10(9) for C. albicans and C. glabrata reference strains. Compared to C. albicans and C. glabrata, AMB had much less fungicidal activity against C. lusitaniae in time-kill curve analysis. Clinically, C. lusitaniae fungemia was more frequently associated with stem cell transplant and neutropenia. C. lusitaniae, even originally susceptible to AMB, might be less amenable to AMB therapy.

Candida glabrata colonizes but does not often disseminate from the mouse caecum

Candida glabrata is the second or third most frequent cause of candidaemia. The gastrointestinal tract is considered to be a major portal of entry for systemic candidiasis, but relatively few studies have investigated the pathogenesis of C. glabrata. Experiments were designed to clarify the ability of C. glabrata to disseminate from the mouse intestinal tract. Following oral inoculation, C. glabrata readily colonized the caeca [approx. 10(7) cells (g caecum)(-1)] of antibiotic-treated mice, but extraintestinal dissemination was not detected. Superimposing several mouse models of trauma and/or immunosuppression known to induce dissemination of Candida albicans and other intestinal microbes did not cause C. glabrata to disseminate often, although one exception was mice given high doses of dexamethasone for 4 days. These data support the hypothesis that the antibiotic-treated mouse intestine may be an epidemiological reservoir for C. glabrata and that this yeast tends to disseminate under specific clinical conditions.

An ectophosphatase activity inCandida parapsilosisinfluences the interaction of fungi with epithelial cells

This study describes the biochemical characterization of a phosphatase activity present on the cell surface of Candida parapsilosis, a common cause of candidemia. Intact yeasts hydrolyzed p-nitrophenylphosphate to p-nitrophenol at a rate of 24.30+/-2.63 nmol p-nitrophenol h(-1) 10(-7) cells. The cell wall distribution of the Ca. parapsilosis enzyme was demonstrated by transmission electron microscopy. The duration of incubation of the yeast cells with the substrate and cell density influenced enzyme activity linearly. Values of V(max) and apparent K(m) for p-nitrophenylphosphate hydrolysis were 26.80+/-1.13 nmol p-nitrophenol h(-1) 10(-7) cells and 0.47+/-0.05 mM p-nitrophenylphosphate, respectively. The ectophosphatase activity was strongly inhibited at high pH as well as by classical inhibitors of acid phosphatases, such as sodium orthovanadate, sodium molybdate, sodium fluoride, and inorganic phosphate, the final product of the reaction. Only the inhibition caused by sodium orthovanadate was irreversible. Different phophorylated amino acids were used as substrates for the Ca. parapsilosis ectoenzyme, and the highest rate of phosphate hydrolysis was achieved using phosphotyrosine. A direct relationship between ectophosphatase activity and adhesion to host cells was established. In these assays, irreversible inhibition of enzyme activity resulted in decreased levels of yeast adhesion to epithelial cells.

Candidemia due to Candida tropicalis: clinical, epidemiologic, and microbiologic characteristics of 188 episodes occurring in tertiary care hospitals

Candida tropicalis is the 2nd most frequent agent of candidemia in Brazil (20–24%). We attempted to characterize the epidemiology, microbiology, and outcome of candidemia due to C. tropicalis by comparing patients with candidemia due to C. tropicalis with those with candidemia due to Candida albicans. Among the 924 episodes of candidemia, 188 (20%) were caused by C. tropicalis. These cases were compared with 384 candidemias due to C. albicans. C. tropicalis was the 2nd most frequent species in adults (21.6%) and elderly patients (23.2%), and 3rd in neonates (11.9%) and children (18.5%). Cancer was the most frequent underlying disease, and in adults and elderly patients, diabetes was the 2nd most frequent underlying disease. The only difference between C. tropicalis and C. albicans candidemia was a higher proportion of neutropenic patients in C. tropicalis candidemia. C. tropicalis is a leading cause of candidemia in Brazil, and its epidemiology is similar to that of C. albicans.

Fluconazole and Itraconazole Resistance of Yeasts Isolated from the Bloodstream and Catheters of Hospitalized Pediatric Patients

Background: In critically ill children, Candida species and other yeasts appear as an important nosocomial pathogen. The emerging fungal pathogens are usually less susceptible to azole compounds, and the management of such infections could be problematic. Methods: 6,065 bloodstream cultures and 627 catheters from intensive care units and hospitalized oncology pediatric patients were studied. Antifungal susceptibility testing of isolates was performed according to the reference broth microdilution method describedby the National Committee for Clinical Laboratory Standards (M27-A). Results: We found a low activity of fluconazole (FCZ) and itraconazole (ITZ) against Candida glabrata, C. albicans, C. tropicalis and C. haemulonii. Resistant strains to FCZ and ITZ were detected. Conclusion: Results reveal the emergence of antifungal-resistant species and a change in the predominant role of C. albicans as a cause of candidemia in hospitalized children.

Candida guilliermondii fungemia in patients with hematologic malignancies.

The microbiological, clinical, and epidemiological features of most non-Candida albicans Candida species are well known, but much less is known about species such as Candida guilliermondii, an uncommon pathogen causing a variety of deep-seated infections in immunocompromised hosts. To characterize C. guilliermondii fungemia in patients with hematological malignancies and its susceptibility to antifungal drugs, all cases of C. guilliermondii fungemia diagnosed in our department between 1983 and 2005 were retrospectively analyzed and the literature was reviewed. C. guilliermondii caused 29/243 (11.7%) candidemia episodes diagnosed during the study period. Central venous catheters were the documented sources of candidemia in 19/29 episodes (65.5%), and invasive tissue infections were documented in 2 (6.9%). In the remaining eight, the catheter was not removed and the source of the fungemia remained obscure. Seven episodes ended in death, but only one could be attributed to invasive C. guilliermondii infection. Molecular typing data reveal no evidence of common infection sources. Isolates displayed high rates of in vitro susceptibility to amphotericin B (100%), voriconazole (95%), and fluconazole (90%) and lower rates of in vitro susceptibility to flucytosine (86%), itraconazole (76%), and caspofungin (33%). Our literature review confirms that C. guilliermondii is a significantly more frequent cause of candidemia among cancer patients compared with the general hospital population. It accounted for <1% of the total number of Candida bloodstream isolates reported in the articles we reviewed, with higher rates in Europe (1.4%) and Asia (1.8%) compared with North America (0.3%).

LPS-INDUCED MACROPHAGE (M??) ACTIVATION AUGMENTS PHAGOCYTOSIS OF CANDIDA GLABRATA

Candida glabrata is now the 2nd or 3rd most frequent cause of candidemia (after C. albicans) in trauma patients, but little is known about its pathogenesis. Others have reported that systemic injection with Escherichia coli (or its LPS) augments systemic C. albicans infection, but the opposite may be true for C. glabrata. Fourteen days after 108 intravenous C. glabrata, mice were injected intraperitoneally (ip) with 108E. coli (live or heat-killed), 100 μg E. coli LPS, or saline, and sacrificed 16 hr later. Numbers of C. glabrata recovered from the kidneys were consistently decreased in mice given E. coli or its LPS.TableTo clarify the role of LPS-induced MØ activation in clearance of C. glabrata, glass-adherent mouse peritoneal exudate cells (>90% positive for the F4/80 MØ antigen) were incubated with 0 or 100 μg/ml LPS for 24 hr, with MØ activation confirmed by increased fluorescent intensity to rat-anti-mouse MARCO (MØ receptor with collagenous structure) antibody (687 versus 2664 fluorescent intensity units, Metamorph software, P < 0.01, t-test). After 30 min incubation with 106C. glabrata, LPS-activated MØs had increased numbers of cell-associated C. glabrata, measured by light microscopy of Wright-Giemsa stained cultures (avg of 6.4 versus 3.7 C. glabrata per MØ incubated with and without LPS, P < 0.01, t-test, three experiments containing observations from 450 MØs). Thus, LPS-induced MØ activation was associated with a nearly 2-fold increase in C. glabrata phagocytosis. These data indicate that clinical conditions, or therapeutic agents, that increase MØ activation may help ameliorate systemic infection with C. glabrata.

Etiology of fungaemia and catheter colonisation in Argentinean paediatric patients

Yeast strains obtained from blood cultures and catheters from intensive care units (ICU) and hospitalised oncology paediatrics were studied. Yeast were the first cause of catheter colonisation (51/627), and the third cause of bloodstream infection (44/6065). In catheter, the most frequent species were Candida albicans (34%), C. parapsilosis (27.7%) and C. tropicalis (15%). In blood, C. albicans (40.8%), C. parapsilosis (26.6%), C. tropicalis (15%). Malassezia furfur and Malassezia sympodialis were isolated from catheters from ICU patients. All isolates were susceptible to amphotericin B, 88.8% to itraconazole and 91.9% to fluconazole. Candida albicans and C. tropicalis strains resistant to fluconazole and itraconazol were detected. These results reveal a change in the predominant role of C. albicans as cause of candidemia in hospitalised children and the emergence of antifungal resistant species. These variations emphasise the importance of performing a permanent surveillance to observe and assess them.

Candida species distribution in bloodstream cultures in Lyon, France, 1998–2001

In order to determine the types of Candida spp. isolated from bloodstream cultures in Lyon, France, a retrospective study of isolates collected at five different bacteriology laboratories from 1998 to 2001 was conducted. During this period Candida spp. were isolated from 190 patients hospitalized in the internal medicine (32%), hematology (23%) and surgery (23%) wards, and in intensive care units (22%). C. albicans was the leading cause of Candida infection (49.5%), followed by C. glabrata (12.6%) and C. parapsilosis (12.1%). Among the onco-hematology patients, the major cause of candidemia was C. krusei (34%), followed by C. albicans (19%), while these two species were identified in 4% and 59% of patients in the other wards, respectively. In the single onco-hematology ward that was specialized in treating acute myeloid leukemia, 14 C. krusei isolates were identified in this study, which contrasts with the single C. krusei isolate recorded between 1992 and 1996. Since C. krusei has inherent resistance to the antifungal agent fluconazole, prophylactic use of fluconazole in these patients was investigated, but no relationship between these two parameters was found.

Comparative abilities ofCandida glabrataandCandida albicansto colonize and translocate from the intestinal tract of antibiotic-treated mice

Candida albicans is the primary cause of candidemia in hospitalized patients, and the intestinal tract is considered the source of most systemic infections. C. glabrata has emerged as the second or third most frequent cause of candidemia, but little is known about its epidemiology and pathogenesis. Our goal was to compare the intestinal colonization and extra-intestinal dissemination of C. glabrata and C. albicans (wild type and filamentation-defective mutant). Mice were pretreated with antibacterial agents to alter their resident microflora, and then orally inoculated with C. glabrata and/or C. albicans . Elimination of detectable cecal bacteria facilitated colonization with both Candida species. Selective elimination of aerobic/ facultative gram-negative bacilli did not noticeably affect Candida colonization, but Escherichia coli overgrowth inhibited colonization. In all situations, C. glabrata colonized the cecum equally well or better than C. albicans , and the ability of C. albican s to form filaments did not facilitate colonization. In vitro generation times had little relevance to the resulting cecal population levels of C. glabrata and C. albicans , and neither species readily disseminated to mesenteric lymph nodes. Thus, like C. albicans , the intestinal tract may be an epidemiological reservoir for C. glabrata and antibiotic-induced alterations in intestinal bacteria may facilitate colonization. Key words: Candida glabrata, Candida albicans, in testine, yeast, mouse, translocation

Candidemia in patients with diabetes mellitus: epidemiology and predictors of mortality

Candidemia is the fourth most frequent nosocomial bloodstream infection in the US. The clinical characteristics and outcome of candidemia in adult patients with diabetes mellitus (DM) have not been reported in the literature. The objective of the study was to determine the epidemiology and determinants of mortality in diabetic patients with candidemia. A retrospective cohort study among diabetic patients with candidemia was carried out at 2 medical centers. The primary outcome was death from any cause after the onset of candidemia until discharge from the hospital. A stepwise logistic regression analysis was performed to determine the predictors of mortality. From June 1995 to June 2003, 87 patients with both DM and candidemia were studied. Candida albicans was the most common (48/87, 55%) and Candida glabrata the second most common isolate of candidemia (18/87, 21%). Overall hospital mortality was 39% (34/87). Logistic regression analysis identified 3 independent determinants of death; Apache II score > or =23 (OR 8.3, 95% CI{2.7, 25.4}, p =0.0002), nosocomial candidemia (OR 10.2, 95% CI{1.1, 97.9}, p = 0.04), and mechanical ventilation (OR 3.6, 95% CI{1.1, 11.2}, p = 0.03). The study demonstrates the emergence of non-albicans species of Candida as major causes of candidemia among diabetic patients. The severity of illness reflected by Apache II was the most significant predictor of mortality among diabetic patients with candidemia.

Non-albicans Candida is the most common cause of candidemia in pediatric cancer patients.

Candidemia is a serious infection that can severely complicate the care of children with cancer. We sought to determine the spectrum of Candida species in children with cancer, since effective therapy may depend on the species involved. A retrospective review of candidemia episodes in our pediatric oncology patients over a 9-year period was conducted. During this period azole prophylaxis was not routine in this group. 38 episodes of candidemia were identified: C. albicans 29%, C. tropicalis 26%, C. parapsilosis 24%, C. krusei 8%, C. glabrata 8%, and C. lusitaniae 5%. Non-albicans Candida was common in patients not receiving azole prophylaxis. Species typically susceptible to azoles were common among patients not using azoles. Death attributed to the fungal infection occurred in 21% of episodes, with nearly all the deaths occurring in patients with C. albicans and C. tropicalis. C. albicans is not the predominant species in pediatric oncology patients experiencing candidemia, even in azole-naive patients.

Epidemiology of candidemia: 3-year results from the emerging infections and the epidemiology of Iowa organisms study.

Bloodstream infections due to Candida species cause significant morbidity and mortality. Surveillance for candidemia is necessary to detect trends in species distribution and antifungal resistance. We performed prospective surveillance for candidemia at 16 hospitals in the State of Iowa from 1 July 1998 through 30 June 2001. Using U.S. Census Bureau and Iowa Hospital Association data to estimate a population denominator, we calculated the annual incidence of candidemia in Iowa to be 6.0 per 100,000 of population. Candida albicans was the most common species detected, but 43% of candidemias were due to species other than C. albicans. Overall, only 3% of Candida species were resistant to fluconazole. However, Candida glabrata was the most commonly isolated species other than C. albicans and demonstrated some resistance to azoles (fluconazole MIC at which 90% of the isolates tested are inhibited, 32 microg/ml; 10% resistant, 10% susceptible dose dependent). C. glabrata was more commonly isolated from older patients (P = 0.02) and caused over 25% of candidemias among persons 65 years of age or older. The investigational triazoles posaconazole, ravuconazole, and voriconazole had excellent in vitro activity overall against Candida species. C. albicans is the most important cause of candidemia and remains highly susceptible to available antifungal agents. However, C. glabrata has emerged as an important and potentially antifungal resistant cause of candidemia, particularly among the elderly.