Glabrata Candidemia Research Articles

Epidemiology and susceptibility of Nakaseomyces (formerly Candida) glabrata bloodstream isolates from hospitalised adults in South Africa.

During 2016-2017, Nakaseomyces glabrata (formerly Candida glabrata) caused 14% of cases of candidaemia in South Africa. We aimed to describe the clinical characteristics of adults with N. glabrata candidaemia at 20 sentinel hospitals (accounting for 20% (172/917) of cases) and the antifungal susceptibility of the corresponding isolates. A higher proportion of patients with N. glabrata candidaemia were older (median age: 55 years [interquartile range (IQR): 41-65 years] vs. 49 years [IQR: 35-63 years]; p=0.04), female (87/164, 53% vs. 283/671, 42%; p=0.01), admitted to a public-sector hospital (152/172, 88% vs. 470/745, 63%; p<0.001), treated with fluconazole only (most with suboptimal doses) (51/95, 54% vs. 139/361, 39%; p<0.001), and had surgery (47/172, 27% vs. 123/745, 17%; p=0.001) and a shorter hospital stay (median 7 days [IQR: 2-20 days] vs. 13 days [IQR: 4-27 days]; p<0.001) compared to patients with other causes of candidaemia. Eight N. glabrata isolates (6%, 8/131) had minimum inhibitory concentrations in the intermediate or resistant range for≥1 echinocandin and a R1377K amino acid substitution encoded by the hotspot 2 region of the FKS2 gene. Only 11 isolates (8%, 11/131) were resistant to fluconazole. Patients with confirmed N. glabrata candidaemia are recommended to be treated with an echinocandin (or polyene), thus further guideline training is required.

Bittersweet: infective complications of drug-induced glycosuria in patients with diabetes mellitus on SGLT2-inhibitors: two case reports

BackgroundSodium-glucose co-transporter 2 (SGLT2) inhibitors are novel hypoglycemic agents which reduce reabsorption of glucose at the renal proximal tubule, resulting in significant glycosuria and increased risk of genital mycotic infections (GMI). These infections are typically not severe as reported in large systematic reviews and meta-analyses of the medications. These reviews have also demonstrated significant cardiovascular benefits through other mechanisms of action, making them attractive options for the management of Type 2 diabetes mellitus (T2DM). We present two cases with underlying abnormalities of the urogenital tract in which the GMI were complicated and necessitated cessation of the SGLT2 inhibitor.Case presentationsBoth cases are patients with T2DM on empagliflozin, an SGLT2 inhibitor. The first case is a 64 year old man with Candida albicans balanitis and candidemia who was found to have an obstructing renal calculus and prostatic abscess requiring operative management. The second case describes a 72 year old man with Candida glabrata candidemia who was found to have prostatomegaly, balanitis xerotica obliterans with significant urethral stricture and bladder diverticulae. His treatment was more complex due to fluconazole resistance and concerns about urinary tract penetration of other antifungals. Both patients recovered following prolonged courses of antifungal therapy and in both cases the SGLT2 inhibitor was ceased.ConclusionsDespite their cardiovascular benefits, SGLT2 inhibitors can be associated with complicated fungal infections including candidemia and patients with anatomical abnormalities of the urogenital tract may be more susceptible to these infections as demonstrated in these cases. Clinicians should be aware of their mechanism of action and associated risk of infection and prior to prescription, assessment of urogenital anatomical abnormalities should be performed to identify patients who may be at risk of complicated infection.

Acquired multidrug‐resistant Candida glabrata in Australia: a case report

AbstractBackgroundCandida glabrata is the second most common cause of candidaemia in Australia, and echinocandins remain the first‐line choice for empirical treatment. There have been increasing reports of multidrug‐resistant (MDR) C. glabrata worldwide. To date, there have been no documented cases of MDR C. glabrata in Australia. This paper describes a case of C. glabrata resistant to azole antifungals and echinocandins in Australia.Clinical detailsA 47‐year‐old male was admitted for management of acute graft‐versus‐host disease (GVHD) of the gastrointestinal tract on Day 129 after allogeneic haematopoietic stem cell transplant for chronic lymphocytic leukaemia. On Day 38 of admission, the patient developed C. glabrata candidaemia that was susceptible to echinocandins but resistant to azole antifungals. The patient received a 17‐day course of intravenous (IV) caspofungin with subsequent negative blood cultures. However, on Day 67, the patient again developed C. glabrata candidaemia that now exhibited resistance to echinocandins and azole antifungals.OutcomesThe patient was commenced on liposomal amphotericin B (3 mg/kg, IV, daily) by the infectious diseases unit. A literature search by the pharmacist prompted a recommendation of a dose increase to 5 mg/kg, IV, daily given this isolate had a high minimum inhibitory concentration of 1 microgram/mL. Liposomal amphotericin B continued for 14 days with no further positive blood cultures. Unfortunately the patient died on Day 92 of admission secondary to severe treatment‐refractory GVHD.ConclusionThis case highlights a case of MDR C. glabrata in Australia, which is of concern given the recommended empirical use of echinocandins for candidaemia.

1698. Epidemiology and Antifungal Susceptibility of Candidemia Among Adult Patients at a Tertiary Care Hospital in South Korea During an 8-Year Period

BackgroundCandidemia continues to contribute to significant morbidity and mortality in the hospital. This study aimed to evaluate the epidemiology and antifungal susceptibility at a tertiary care hospital in South Korea during an 8-year period.MethodsAdult patients ≥19 years with candidemia at a tertiary care hospital in South Korea from 2006 to 2018 were reviewed, and cases of candidemia with antifungal susceptibility data were included for the analysis.ResultsThere were 270 cases of candidemia with fluconazole susceptibility data from 2011 to 2018. Overall, fluconazole resistance rate of candidemia was 8.5%. Between period 1 (2011–2015) and period 2 (2016–2018), fluconazole resistance rate was significantly higher in the period 2 (14.3%) than in the period 1 (0.9%), P < 0.001. Among candidemia caused by different Candida spp., a significant increase of fluconazole-resistant C. parapsilosis candidemia was noted in the period 2 (12 out of 34 cases; 35.3%) when compared with the period 1 (0 out of 17 cases; 0.0%), P = 0.004. Although there was a trend of higher fluconazole resistance rate for candidemia caused by C. albicans (9.1% vs. 1.8%), C. tropicalis (2.7% vs. 0.0%), and C. glabrata (11.1% vs. 0.0%) in the period 2 than in the period 1, no statistical significance was observed. Echinocandin (caspofungin and micafungin) susceptibility data were available for 211 cases of candidemia from 2013 to 2018. There were no cases of caspofungin-resistant candidemia except for 2 cases of C. utilis candidemia. However, there were 9 cases of micafungin-resistant candidemia (1 case of C. tropicalis candidemia out of 51 cases [2.0%], 6 cases of C. glabrata candidemia out of 18 cases [33.3%], and 2 cases of C. utilis candidemia out of 2 cases [100.0%]). Micafungin-resistant C. tropicalis and C. glabrata candidemia cases were susceptible to caspofungin.ConclusionA significant increase of fluconazole-resistant candidemia in recent years was noted, particularly among C. parapsilosis candidemia cases. Echinocandin resistance among candidemia cases is rare. However, close monitoring needs to be considered for the possible emergence of differential echinocandin resistance.Disclosures All authors: No reported disclosures.

The association between fluconazole dose and MIC with mortality and persistence in candidemia.

To evaluate the association between fluconazole exposure parameters and clinical outcomes in patients with candidemia. We retrospectively included all adults with candidemia in a single center from January 2009 to December 2017, treated initially with fluconazole for fluconazole-susceptible candidemia. We assessed the association between fluconazole exposure parameters and 30-day mortality or 14-day clinical failure, a composite of mortality at day 14 or persistent candidemia ≥ 72h, in all patients and in patients with C. glabrata candidemia. During the study period, 158 patients fulfilled the inclusion criteria. Main species were C. albicans 66 (41.8%), C. glabrata 35 (22.2%), and C. parapsilosis 31 (19.6%). Sixty patients (38%) died within 30days. Sixty-one patients (38.6%) experienced 14-day failure. In 30-day survivors, the median AUC24/MIC was 2279 [398, 5989] versus 1764 [238, 6714]h in non-survivors, p = 0.75. Median fluconazole MIC was 0.75 [0.25, 4] and 1 [0.22, 5.50]mg/L, p = 0.54, respectively. Similar non-significant differences were found for other fluconazole exposure parameters and in the 14-day clinical failure analysis. For C. glabrata, a higher AUC24/MIC was observed among 30-day survivors with a median of 230 [77, 539] compared to 96 [75, 164]h in non-survivors, p = 0.008, in parallel with a trend for lower MIC values (median 7 [1, 2] versus 16 [8, 24] mg/L, p = 0.06, respectively). Currently used fluconazole dosing has no association with clinical outcome in Candida with low MIC values. For Candida species with high MICs, attention to dosing is needed.

Multilocus Sequence Typing (MLST) Genotypes of Candida glabrata Bloodstream Isolates in Korea: Association With Antifungal Resistance, Mutations in Mismatch Repair Gene (Msh2), and Clinical Outcomes.

Candida glabrata bloodstream infection (BSI) isolates from a particular geographic area have been reported to comprise a relatively small number of the major sequence types (STs) by multilocus sequence typing (MLST) analysis. Yet little is known about the characteristics of major ST strains of C. glabrata. To address this question in Korea, we investigated antifungal resistance and non-synonymous mutations of the mismatch repair gene (msh2 mutations) in C. glabrata BSI isolates, as well as associated clinical characteristics, and compared the results according to MLST genotype. We assessed a total of 209 C. glabrata BSI isolates from seven hospitals in Korea for 2 years (2009 and 2014). Clinical features of candidemia and their outcomes were analyzed for 185 available cases. According to MLST, ST7 (47.8%) was the most common type, followed by ST3 (22.5%); the remainder represented 28 types of minor STs (29.7%). Fluconazole-resistance (FR) rates for ST7, ST3, and other strains were 9.0% (9/100), 8.5% (4/47), and 4.8% (3/62), respectively, and all were susceptible to amphotericin B and micafungin. All ST7 isolates harbored the V239L mutation in msh2, known to confer hypermutability, while 91.5% of ST3 isolates did not harbor the msh2 mutation. Overall, isolates of the same ST had identical msh2 mutations, with the exception of nine isolates. The msh2 mutations were identified in 68.8% (11/16) of the FR isolates and 67.4% (130/193) of the fluconazole susceptible-dose dependent isolates. There was no significant difference in all clinical characteristics between ST3 and ST7. However, the 30-day mortality of C. glabrata candidemia due to the two major ST (ST3 or ST7) strains was significantly higher than that of candidemia due to other minor ST strains (45.1 vs. 25.0%, p < 0.05). Multivariate logistic regression analysis also showed that two major STs (ST3 and ST7) were independent predictors of 30-day mortality. This study showed for the first time that two STs (ST7 and ST3) were predominant among BSI isolates in Korea, and that C. glabrata BSI isolates belonging to two major MLST genotypes are characterized by higher mortality. In addition, most msh2 mutations align with MLST genotype, irrespective of FR.

Diabetes, malignancy and age as predictors of Candida glabrata bloodstream infection: A re-evaluation of the risk factors

ObjectiveEchinocandins and azoles are widely used in the treatment of candidaemia. Guidelines of the Infectious Diseases Society of America recommend commencing treatment with an echinocandin in candidaemic patients with risk factors for Candida glabrata i.e. patients who are elderly, or who have diabetes or malignancy, or those with recent prescription of azoles. We attempted to validate whether age, diabetes and malignancy are associated with C. glabrata candidaemia. Patients, materials and methodsInformation in relation to demographics, patient associated risk factors, and laboratory parameters were collected from the casenotes and the laboratory information system. We then analysed the distribution of the risk factors (age, diabetes, and malignancy) in candidaemic patients with C. glabrata and patients with species other than C. glabrata (excluding Candida krusei). ResultsOver a 42-month period (April 2011–September 2017), 124 patients had candidaemia. We analysed data for 119 patients of whom 33 (27.7%) had C. glabrata and the remaining 86 (72.2%) were infected with other species. Sixty-five patients were elderly (age≥65), 40 had some form of malignancy, 34 had diabetes, and 4 patients were prescribed azoles in the 30 days prior to candidaemia (many patients had multiple risk factors). Comparing patients with C. glabrata to patients infected with other species, we found no association with diabetes (39.3% vs. 24.4%, P=0.1), malignancy (36.3 vs. 32.5%, P=0.69), and age (54.5% vs. 54.6%, P=0.99). ConclusionsDiabetes, malignancy and age are not reliable predictors of candidaemia due to C. glabrata.

Detecting Infections Rapidly and Easily for Candidemia Trial, Part 2 (DIRECT2): A Prospective, Multicenter Study of the T2Candida Panel.

Blood cultures are approximately 50% sensitive for diagnosing invasive candidiasis. The T2Candida nanodiagnostic panel uses T2 magnetic resonance and a dedicated instrument to detect Candida directly within whole blood samples. Patients with Candida albicans, Candida glabrata, Candida parapsilosis, Candida tropicalis, or Candida krusei candidemia were identified at 14 centers using diagnostic blood cultures (dBCs). Follow-up blood samples were collected concurrently for testing by T2Candida and companion cultures (cBCs). T2Candida results are reported qualitatively for C. albicans/C. tropicalis, C. glabrata/C. krusei, and C. parapsilosis. T2Candida and cBCs were positive if they detected a species present in the dBC. Median time between collection of dBC and T2Candida/cBC samples in 152 patients was 55.5 hours (range, 16.4-148.4). T2Candida and cBCs were positive in 45% (69/152) and 24% (36/152) of patients, respectively (P < .0001). T2Candida clinical sensitivity was 89%, as positive results were obtained in 32/36 patients with positive cBCs. Combined test results were both positive (T2+/cBC+), 21% (32/152); T2+/cBC-, 24% (37/152); T2-/cBC+, 3% (4/152); and T2-/cBC-, 52% (79/152). Prior antifungal therapy, neutropenia, and C. albicans candidemia were independently associated with T2Candida positivity and T2+/cBC- results (P values < .05). T2Candida was sensitive for diagnosing candidemia at the time of positive blood cultures. In patients receiving antifungal therapy, T2Candida identified bloodstream infections that were missed by cBCs. T2Candida may improve care by shortening times to Candida detection and species identification compared to blood cultures, retaining sensitivity during antifungal therapy and rendering active candidemia unlikely if results are negative. NCT01525095.

Risk Factors Predicting Candida glabrata Bloodstream Infection

Background Increased incidence of Candida glabrata (CG) infection is a growing concern in recent years due to the higher rates of fluconazole resistance associated with C. glabrata . This study aimed to create a risk predictive model for C. glabrata in patients with culture-positive candidemia.Methods Demographic data, risk factors, laboratory parameters, and outcomes were retrospectively collected on all cases of candidemia occurring at a large tertiary referral hospital between January 2002 and January 2015. Between-group differences were compared using 2 square tests. A risk predictive model was built using multivariate logistic regression.ResultsOf 1,913 subjects with candidemia, 398 (21%) had C. glabrata isolated. Those with C. glabrata were older (mean [SD] 61 [23] vs. 58 [23] years; P < 0.001) and more often female (231 (58%) vs. 681 (45%); P < 0.001). On univariate analysis, age (OR 1.01 [95% CI 1.01,1.02]), gender (0.6 [0.5, 0.7]), history of rectal cancer (2.00 [1.2, 3.5]), other GI malignancy (3.0 [1.5, 6.2]), breast cancer (1.8 [1.1, 3.0]), enteral and parenteral feeding (1.9 [1.2, 3.2]), bowel resection (3.0 [1.4, 6.2]), temperature (0.9 [0.8, 1.0], recent fluconazole use (2.0 [1.4, 2.9]), and The presence of urinary catheter (2.3 [1.4, 3.6]), central line (1.4 [1.1, 1.7) or ventilator (2.2 [1.3, 3.8]) were all associated with C. glabrata infection (P < 0.05) and included in the multivariate modeling. Age, gender, history of rectal malignancy, other GI malignancies, use of enteral or parenteral feeding and recent fluconazole use remained significant (effect size 1.2 [95% CI 1.1, 1.3]; 1.8 [1.4, 2.3]; 2.0 [1.1, 3.6]; 3.0 [1.3, 6.9]; 1.9 [1.0, 3.3]; 2.0 [1.3, 3.0], respectively). The final model had a c-statistic of 0.66 [95% CI 0.63–0.69]). Ninety-day mortality in the C. glabrata group was not significantly different from the non-C. glabrata group (40% (158/398) vs. 42.5% (644/1515).Conclusion Underlying bowel pathology was more commonly associated with C. glabrata candidemia than with other candida species. Further exploration of the direct association between C. glabrata and GI malignancy and indirect effects of prior surgery or antifungal use on risk of C. glabrata candidemia are required. Interestingly, mortality did not differ between groups with glabrata and non-glabrata candida blood stream infections. This may reflect increasing empiric use of echinocandin therapy.Disclosures A. Spec, Astellas Pharma US, Inc.: Grant Investigator, Research grant

Revisiting Species Distribution and Antifungal Susceptibility of Candida Bloodstream Isolates from Latin American Medical Centers.

The epidemiology of candidemia varies geographically, and there is still scarce data on the epidemiology of candidemia in Latin America (LA). After extensive revision of medical literature, we found reliable and robust information on the microbiological aspects of candidemia in patients from 11 out of 21 medical centers from LA countries and 1 out of 20 from Caribbean countries/territories. Based on 40 papers attending our search strategy, we noted that C. albicans remains the most common species causing candidemia in our region, followed by C. parapsilosis and C. tropicalis. In Argentina, Brazil, and Colombia, a trend towards an increase in frequency of C. glabrata candidemia was observed. Although resistance rates to fluconazole is under 3%, there was a slight increase in the resistance rates to C. albicans, C. parapsilosis and C. tropicalis isolates. Echinocandin resistance has been reported in a few surveys, but no single study confirmed the resistant phenotype reported by using molecular methods. We highlight the importance of conducting continuous surveillance studies to identify new trends in terms of species distribution of Candida and antifungal resistance related to episodes of candidemia in LA. This information is critical for helping clinicians to prevent and control Candida bloodstream infections in their medical centers.

Changing epidemiology of candidaemia in Australia.

Knowledge of contemporary epidemiology of candidaemia is essential. We aimed to identify changes since 2004 in incidence, species epidemiology and antifungal susceptibilities of Candida spp. causing candidaemia in Australia. These data were collected from nationwide active laboratory-based surveillance for candidaemia over 1 year (within 2014-2015). Isolate identification was by MALDI-TOF MS supplemented by DNA sequencing. Antifungal susceptibility testing was performed using Sensititre YeastOne™. A total of 527 candidaemia episodes (yielding 548 isolates) were evaluable. The mean annual incidence was 2.41/105 population. The median patient age was 63 years (56% of cases occurred in males). Of 498 isolates with confirmed species identity, Candida albicans was the most common (44.4%) followed by Candida glabrata complex (26.7%) and Candida parapsilosis complex (16.5%). Uncommon Candida species comprised 25 (5%) isolates. Overall, C. albicans (>99%) and C. parapsilosis (98.8%) were fluconazole susceptible. However, 16.7% (4 of 24) of Candida tropicalis were fluconazole- and voriconazole-resistant and were non-WT to posaconazole. Of C. glabrata isolates, 6.8% were resistant/non-WT to azoles; only one isolate was classed as resistant to caspofungin (MIC of 0.5 mg/L) by CLSI criteria, but was micafungin and anidulafungin susceptible. There was no azole/echinocandin co-resistance. We report an almost 1.7-fold proportional increase in C. glabrata candidaemia (26.7% versus 16% in 2004) in Australia. Antifungal resistance was generally uncommon, but azole resistance (16.7% of isolates) amongst C. tropicalis may be emerging.

Epidemiology and Risk Factors for Echinocandin Nonsusceptible Candida glabrata Bloodstream Infections: Data From a Large Multisite Population-Based Candidemia Surveillance Program, 2008-2014.

Background. Echinocandins are first-line treatment for Candida glabrata candidemia. Echinocandin resistance is concerning due to limited remaining treatment options. We used data from a multisite, population-based surveillance program to describe the epidemiology and risk factors for echinocandin nonsusceptible (NS) C glabrata candidemia.Methods. The Centers for Disease Control and Prevention's Emerging Infections Program conducts population-based laboratory surveillance for candidemia in 4 metropolitan areas (7.9 million persons; 80 hospitals). We identified C glabrata cases occurring during 2008–2014; medical records of cases were reviewed, and C glabrata isolates underwent broth microdilution antifungal susceptibility testing. We defined echinocandin-NS C glabrata (intermediate or resistant) based on 2012 Clinical and Laboratory Standards Institute minimum inhibitory concentration breakpoints. Independent risk factors for NS C glabrata were determined by stepwise logistic regression.Results. Of 1385 C glabrata cases, 83 (6.0%) had NS isolates (19 intermediate and 64 resistant); the proportion of NS isolates rose from 4.2% in 2008 to 7.8% in 2014 (P < .001). The proportion of NS isolates at each hospital ranged from 0% to 25.8%; 3 large, academic hospitals accounted for almost half of all NS isolates. In multivariate analysis, prior echinocandin exposure (adjusted odds ratio [aOR], 5.3; 95% CI, 2.6–1.2), previous candidemia episode (aOR, 2.5; 95% CI, 1.2–5.1), hospitalization in the last 90 days (aOR, 1.9; 95% CI, 1.0–3.5, and fluconazole resistance [aOR, 3.6; 95% CI, 2.0–6.4]) were significantly associated with NS C glabrata. Fifty-nine percent of NS C glabrata cases had no known prior echinocandin exposure.Conclusion. The proportion of NS C glabrata isolates rose significantly during 2008–2014, and NS C glabrata frequency differed across hospitals. In addition to acquired resistance resulting from prior drug exposure, occurrence of NS C glabrata without prior echinocandin exposure suggests possible transmission of resistant organisms.

Clinical and therapeutic aspects of candidemia: a five year single centre study.

BackgroundCandida is an important cause of bloodstream infections (BSI) in nosocomial settings causing significant mortality and morbidity. This study was performed to evaluate contemporary epidemiology, species distribution, antifungal susceptibility and outcome of candida BSI in an Italian hospital.MethodsAll consecutive patients who developed candidemia at Santa Maria della Misericordia University Hospital (Italy) between January 2009 and June 2014 were enrolled in the study.ResultsA total of 204 episodes of candidemia were identified during the study period with an incidence of 0.79 episodes/1000 admissions. C. albicans was isolated in 60.3% of cases, followed by C. parapsilosis (16.7%), C. glabrata (11.8%) and C. tropicalis (6.4%). Of all Candida BSI, 124 (60.8 %) occurred in patients admitted to IMW, 31/204 (15.2 %) in ICUs, 33/204 (16.2%) in surgical units and 16/204 (7.8%) in Hematology/Oncology wards. Overall, 47% of patients died within 30 days from the onset of candidemia. C. parapsilosis and C. glabrata candidemia were associated with the lowest mortality rate (36%), while patients with C. tropicalis BSI had the highest mortality rate (58.3%). Lower mortality rates were detected in patients receiving therapy within 48 hours from the time of execution of the blood cultures (57,1% vs 38,9%, P <0.05). At multivariate analysis, steroids treatment (OR= 0.27, p=0.005) and CVC removal (OR=3.77, p=0.014) were independently associated with lower and higher survival probability, respectively. Candidemia in patients with peripherally inserted central catheters (PICC) showed to be associated with higher mortality in comparison with central venous catheters (CVC, Short catheters and Portacath) and no CVC use. For each point increase of APACHE III score, survival probability decreased of 2%. Caspofungin (OR=3.45, p=0.015) and Amphothericin B lipid formulation (OR=15.26, p=0.033) were independently associated with higher survival probability compared with no treatment.

Candida glabrata candidemia.

Candida glabrata candidemia.

Comments on "Candida glabrata candidemia; an emerging threat in critically ill patients".

Sir, The article “Candida glabrata candidemia; An emerging threat in critically ill patients” very well highlights the importance of this emerging species.[1] Due to delay in time to positivity for blood culture, empirical antifungal therapy is an important strategy in the management of invasive candidiasis, more so for C. glabrata infection. Appropriate empirical therapy requires identification of high risk group. In the present study, authors have reported broad spectrum antibiotic, mechanical ventilation, central venous catheter, diabetes mellitus and age >65 years as risk factors for C. glabrata candidemia. We agree with Chakrabarti's view that due to lack of control group in the study, it is difficult to draw any inference regarding the risk factors.[2] At least two authors have attempted to develop risk model to predict C. glabrata candidemia. Tapia et al. studied 246 cases of candidemia, out of which 68 cases were due to C. glabrata.[3] Four factors independently associated with C. glabrata candidemia were absence of renal failure, <7 days in the hospital, abdominal surgery and fluconazole use. The model had moderately good discriminating ability between C.glabarata candidemia and non C. glabrata candidemia (c-statistic value 0.727 [95% confidence interval: 0.635-0.775]). Another risk prediction model was developed by Cohen et al. in a study including 48 C. glabrata candidemia patients and 106 had nonglabrata fungemia.[4] The model identified six factors independently associated with C. glabrata candidemia. These were age >60 years, recent abdominal surgery, interval from intensive care unit admission to first positive blood culture <7 days, recent use of cephalosporins, solid tumor, and absence of diabetes mellitus. The model had good discriminating ability (c-statistics value 0.89). These models require external validation before they can be generalized in different cohorts. Both above described models have identified gastro surgery as an independent risk factor for C. glabrata candidemia.[3,4] C. glabrata is a frequent gut colonizer in hospitalized patients and can disseminate to cause candidemia in susceptible host. It has been shown in animal model that gut of antibiotic-treated mice can act as a reservoir for C. glabrata. It would be enlightening if the authors can report the data regarding, nature of surgeries done in the surgical group. Hospitalized patients are frequently colonized with Candida. Risk of candidemia increases with increase in density of colonization and number of colonized sites.[5] The method used for identifying urine as the most common source of C. glabrata candidemia needs to be mentioned in the study. Authors have stated that candiduria is a useful indicator for systemic candidiasis, but it is unclear from the results that what were the other sites looked for. Interpreting the source of candidemia without studying different sites for colonization and typing the strain can give misleading results. Local epidemiology is important to guide empirical antifungal therapy. More studies are needed to identify the risk factors for C. glabrata infection and colonization as well as to conduct external validation of already existing risk models.

Candida glabrata candidemia: An emerging threat in critically ill patients.

Background:Candidemia is an important nosocomial blood stream infection in critically ill patients. Although several studies have addressed candidemia, very few have reviewed the impact of Candida glabrata candidemia in Intensive Care Unit (ICU) patients.Materials and Methods:The medical records of ICU patients between 2006 and 2010 were reviewed retrospectively. The epidemiology, clinical features and mortality related risk factors among our adult ICU patients were seen.Results:Among 144 episodes of candidemia, C. glabrata (n = 26; 18.05%) was the third most common species isolated. The incidence of C. glabrata candidemia was 0.21/1000 ICU admissions. The most common risk factors were prior exposure to broad spectrum antibiotics (100%), central venous catheter (100%), mechanical ventilation (76.9%), diabetes mellitus (50%), age >65 years (46.15%). Urine (23%) was the most common source of C. glabrata candidemia. Overall in hospital 30 days mortality rate due to C. glabrata fungemia was 53.8%. Patients who were treated with fluconazole showed better outcome than patients treated with amphotericin B. Renal failure requiring hemodialysis was the significantly associated with mortality in our study.Conclusion:Candida glabrata was the 3rd most common Candida causing candidemia in our ICUs with a incidence of 0.21/1000 ICU admissions. The outcome of ICU acquired C. glabrata candidemia was poor with 30 days mortality rate of 53.8%. Renal failure requiring hemodialysis was the only risk factor associated with mortality. Further studies are required to identify the other risk factors associated with mortality in C. glabrata candidemia.

FKS Mutant Candida glabrata: Risk Factors and Outcomes in Patients With Candidemia

Echinocandins are recommended for Candia glabrata candidemia. Mutations in the FKS1 and FKS2 genes are associated with echinocandin resistance. Few studies have assessed risk factors for FKS mutant isolates and outcomes in patients receiving micafungin treatment. Patients with C. glabrata bloodstream infection admitted to a large, tertiary care hospital between 2009 and 2012 were included in this study. For each isolate, FKS1 and FKS2 genes were sequenced to identify mutations. Risk factors for FKS mutations and treatment outcomes in patients receiving an echinocandin were assessed using multivariate logistic regression. Seventy-two patients were included in the study of which 13 (18%) had an FKS mutant isolate. The only significant predictor for FKS mutations was prior echinocandin exposure (odds ratio [OR], 19.9; 95% confidence interval [CI], 4.7-84.7; P ≤ .01). Treatment failure occurred in 17 (30%) of 57 patients who received an echinocandin and was more common in patients with FKS mutants (6 of 10; 60%) compared with non-FKS mutants (11 of 47; 23%). Underlying gastrointestinal disorder (OR, 4.7; 95% CI, 1.1-20.9; P = .04) and prior echinocandin exposure (OR, 8.3; 95% CI, 1.7-40.4; P ≤ .01) were independent predictors of echinocandin treatment failure. Treatment response and echinocandin minimum inhibitory concentrations varied among specific FKS mutations. FKS mutations were identified in 18% of 72 patients with C. glabrata candidemia. Common risk factors for FKS mutant isolates included previous echinocandin exposure, which also influenced response rates.

Usefulness of time-to-positivity in aerobic and anaerobic vials to predict the presence of Candida glabrata in patients with candidaemia

To determine whether time-to-positivity (TTP) in aerobic and anaerobic blood culture vials is useful to predict the presence of Candida glabrata in patients with candidaemia. TTP was recorded for both aerobic and anaerobic vials for each blood culture set of monomicrobial candidaemia. We considered TTP as the shortest time registered for any positive vial. Two diagnostic criteria were evaluated: the cut-off TTP value as obtained from a receiver operating characteristic curve and the detection of growth only or with a shorter TTP in anaerobic vials. A total of 157 episodes were analysed of which 19 (12.1%) were due to C. glabrata. The TTP for C. glabrata was longer than that for other species. C. glabrata grew more frequently than other species in anaerobic vials [9/19 (47%) versus 19/138 (14%); P = 0.001] and also more often exclusively or earlier in anaerobic vials [7/19 (37%) versus 5/138 (4%); P < 0.0001]. The sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) of a TTP >56.5 h for predicting the presence of C. glabrata were 47%, 88%, 36% and 92%, respectively. Growth detection only or earlier in anaerobic flasks had a sensitivity of 37%, a specificity of 96%, a PPV of 58% and an NPV of 92%. Using the BACTEC 9240 system, a TTP ≤ 56.5 h is useful to rule out C. glabrata. In addition, in settings with an ~12% prevalence of C. glabrata candidaemia, yeast detection exclusively or earlier in anaerobic vials increases the probability of the presence of C. glabrata to 58%, which may be useful for early treatment optimization.

Arteriovenous graft infection caused by Candida glabrata: A case report and literature review

The infection rate of arteriovenous (AV) grafts is high, but fungal etiology is rare. Only five cases of graft infection due to Candida albicans (C. albicans) or C. tropicalis have been described in the literature. Herein, we report the first case of AV graft infection caused by C. glabrata. A 60-year-old woman on maintenance hemodialysis for end-stage renal disease was admitted because of intermittent fever, for 10 days. Upon physical examination, tenderness over the AV graft site was noticed. Blood culture yielded C. glabrata and her clinical symptoms improved after she was treated with micafungin for 1 month. However, C. glabrata candidemia reoccurred 5 weeks later. Cure was achieved after removal of the AV graft and anidulafungin treatment. Pus was observed in the removed graft, from which C. glabrata was isolated. The outcome of our case and patients from the literature review suggest that removal of the infected graft is important for treatment success of AV graft Candida infection.

Is the incidence of candidemia caused byCandida glabrataincreasing in Brazil? Five-year surveillance ofCandidabloodstream infection in a university reference hospital in southeast Brazil

From 2006 to 2010, a retrospective study was conducted in a university referral tertiary care hospital to study the frequency and distribution of Candida species in different medical specialties. The use of mechanical ventilation, central venous catheter, and urinary catheter were recorded per 1,000 patient-days and the use of antifungals was calculated using defined daily dose (DDD). A total of 313 episodes were identified and the overall incidence was 0.54 (0.41-0.71) episodes per 1,000 patient-days. Candida albicans caused 44% of the overall episodes, followed by C. tropicalis (21.7%), C. parapsilosis (14.4%), C. glabrata (11.2%), and C. krusei (3.5%). The incidence of C. glabrata significantly increased from 2006-2010 (range: 4.8-23.5%) (P = 0.024). Candida glabrata was associated with malignancies (P = 0.004) and C. krusei with hematologic malignancies (P < 0.0001). The use of antifungals was higher in the hematology/bone marrow transplant units and represented 40% of all fluconazole prescription in the hospital. There was no correlation with the use of fluconazole and the increasing ratio of C. glabrata (r = 0.60). The use of invasive devices was significantly higher in the intensive care units (ICUs) than the medical and surgical emergencies units (P < 0.001). In contrast, the emergencies had higher incidence of candidemia (2-2.1 episodes/1,000 patient-days) than the ICUs (1.6 episodes 1,000 patient-days). Candida glabrata candidemia showed a significant increase in contrast to the current national literature where C. parapsilosis remained the most important non-C. albicans Candida species in Brazilian hospitals. Our findings suggested that the increasing incidence of C. glabrata was not associated with use of fluconazole and other risk factors might play an important role.