Non-albicans Candida Infections Research Articles

A Chart Review for Epidemiology and Outcome of Fungal Bloodstream Infections Among Neonates in a Tertiary Care Hospital at North India

Background and Aims The risk of fungal bloodstream infection (BSI) and accompanying mortality in neonates varies widely in between centres depending on the region, the population characteristics and the risk factors. Methods This chart review of neonatal cases with fungal BSI admitted in a tertiary care teaching hospital in North India aimed to comprehensively investigate the epidemiology, profile of fungal species (and their susceptibility to various antifungal agents), risk factors, clinical profile and outcomes in these neonates. The study spanned over a one-year period, from September 2022 to August 2023, included all symptomatic neonates with positive blood cultures for fungal pathogen. Results Over one year, 24 out of 1,174 neonates at risk were diagnosed with fungal BSI, with a cumulative risk of 2.0 per 100 neonates. A peak in cases occurred in February. Candida pelliculosa was the predominant species (75% of isolates), while Candida albicans constituted 4.2%. Most isolates were sensitive to fluconazole, except for some fluconazole-resistant Candida pelliculosa (5.5%) and Candida tropicalis (25.0%), which remained susceptible to amphotericin-B and voriconazole. Around 60% of neonates were preterm, 40% had very low birth weight and 37% were small for gestational age. Nearly all had received prior broad-spectrum antibiotics, with 92% receiving prolonged courses over five days. Respiratory support, including intubation and mechanical ventilation, was used in 83% before onset of fungal sepsis. Intriguingly, all neonates had some invasive device in place for more than seven days. Mortality rate of 25% was observed, with preterm birth and gastrointestinal anomalies contributing to adverse outcomes. Conclusions This study confirms the ongoing shift in trend from albicans to non-albicans Candida infections in our region as well. A seasonal peak of fungal sepsis noted in the month of February hinted at potential seasonal variation or lapses in infection control practices during colder months. The analysis of trends in fungal BSI might hold a significance within neonatal intensive care units (NICUs) for the prompt detection of outbreaks. Simultaneously, understanding and analysing risk factors associated with fungal BSI are essential for targeted prevention.

Virulence-Related Genes Expression in Planktonic Mixed Cultures of Candida albicans and Non-Albicans Candida Species

Introduction: Candida albicans is the most common opportunistic pathogen causing fungal infections worldwide, especially in high-risk patients. Its pathogenicity is related to virulence factors gene expression, such as hyphal growth (HWP1), cell adhesion (ALS3), and protease secretion (SAP1) during infection spreading mechanisms. In recent years, an increase in non-albicans Candida infections has been reported, which may present coinfection or competitive interactions with C. albicans, potentially aggravating the patient’s condition. This study aims to evaluate the expression of genes related to virulence factors of C. albicans and non-albicans Candida during planktonic stage. Methods: C. albicans (ATCC MYA-3573) as well as with three clinical strains (C. albicans DCA53, C. tropicalis DCT6, and C. parapsilosis DCP1) isolated from blood samples, were grown in 24-well plates at 37°C for 20 h, either in monocultures or mixed cultures. Quantitative real-time polymerase chain reaction was used to evaluate the expression levels of the genes HWP1, ALS3, and SAP1 in cells collected during the planktonic stage. In addition, hyphal filamentation was observed using a Scanning Electron Microscope. Results: The overexpression of HWP1 and ASL3 genes in mixed growth conditions between C. albicans and non-albicans Candida species suggests a synergistic relationship as well as an increased capacity for hyphal growth and adhesion. In contrast, C. parapsilosis versus C. tropicalis interaction shows an antagonistic relationship during mixed culture, suggesting a decreased virulence profile of C. parapsilosis during initial coinfection with C. tropicalis. Conclusion: The expression of HWP1, ALS3, and SAP1 genes associated with virulence factors varies under competitive conditions among species of the genus Candida during planktonic stage.

Antifungal Resistance and Genotyping of Clinical Candida parapsilosis Complex in Japan.

Non-albicans Candida infections have recently gained worldwide attention due to their intrinsic resistance to different antifungal agents and the limited therapeutic options for treating them. Although the Candida parapsilosis complex is reported to be the second or third most prevalent Candida spp., little information is available on the prevalence of antifungal resistance along with genotyping of the C. parapsilosis complex. In this study, we aimed to evaluate the prevalence of antifungal resistance, the genetic basis of such resistance, and the genotyping of C. parapsilosis complex isolates that were recovered from hospitalized patients in Japan from 2005 to 2019. Our results indicated that, with the exception of one single C. metapsilosis isolate that was dose-dependently susceptible to fluconazole, all other isolates were susceptible or showed wild phenotypes to all tested antifungals, including azoles, echinocandins, amphotericin B, and flucytosine. Molecular analyses for azole and echinocandin resistance via evaluating ERG11 mutation and FKS1 hotspot one (HS1) and hotspot two (HS2) mutations, respectively, confirmed the phenotypic results. Genotyping of our isolates confirmed that they belong to 53 different but closely related genotypes, with a similarity percentage of up to 90%. Our results are of significant concern, since understanding the genetic basis of echinocandin resistance in the C. parapsilosis complex as well their genotyping is essential for directing targeted therapy, identifying probable infection sources, and developing strategies for overcoming epidemic spread.

Dual Organism Periprosthetic Joint Infection Following Total Knee Arthroplasty: A Case Report and One Year Follow-Up

Abstract Periprosthetic joint infections (PJI) of the knee are mostly due to a single organism, very rarely, it is due to dual organisms, and even rarer are dual Gram-negative bacilli and fungal infections. Most fungal infections are caused by Candida albicans; however, very few case reports are available for nonalbicans Candida in immunocompetent patients. We report an unusual case of nonalbicans Candida infection with Gram-negative bacilli in the knee joint with no predisposing risk factors. A 59-year-old man reported following mild pain, swelling, and restricted knee movements in a case of a primary total knee arthroplasty. The patient had minimal symptoms but had gross lysis around implants on imaging. His inflammatory markers were significantly high and knee aspiration was turbid, with raised polymorphs without any conclusive staining result. The culture reports revealed a fungal and Gram-negative organism infection. The patient was managed by debridement, prosthesis removal and antibiotic-loaded cement spacer insertion, and culture-specific antibiotics, followed by revision TKA and oral fluconazole therapy. The patient had a good clinical performance at 3 months and 1-year follow-up visits, with a painless range of motion of 10°–90° and there was no evidence of recurrence of infection. Dual Gram-negative and fungal prosthetic joint infection is a rare but serious complication. In the presence of mild clinical symptoms, but extensive lysis around the implant, fungal pathology should be considered irrespective of the immune status of the patient.

Prevalence of Candida species and their Susceptibility to Triazoles in Clinical Isolates from a Tertiary Care Hospital

In the recent past, the incidence of Candidiasis has witnessed a concerning upsurge, resulting in a significant healthcare challenge. These infections are further exacerbated by factors like the widespread use of broad-spectrum antimicrobials, chemotherapy-induced neutropenia, and the presence of medical devices. The present study is designed to address the critical need for identifying the Candida species responsible for clinical infections and assessing their susceptibility to key antifungal drugs Fluconazole, Voriconazole, and Itraconazole. Two hundred clinical samples from Rohilkhand Medical College & Hospital, Bareilly were analyzed. Using Vitek-2 Compact (Biomerieux, France), the Candida spp. and the antifungal drug sensitivities were identified for Fluconazole and Voriconazole. E-test was done to identify Itraconazole sensitivity. This study found that C. albicans accounted for 21.5% while Non-albicans Candida (NAC) constituted 78.5%. Prolonged medication was the most common factor making susceptible for Candidiasis (43.5%), followed by indwelling biomedical devices (23%), Diabetes mellitus (16%), surgical causes (5.5%), trauma (5%), pregnancy (5%), and HIV (2%). Antifungal susceptibility testing showed that 68.5%, 72%, and 69.5% of Candida spp. isolates were sensitive to Fluconazole, Voriconazole, and Itraconazole, respectively. In conclusion, non-albicans Candida infections are increasing due to predisposing conditions, and some of these species are inherently resistant to the routinely used antifungal drugs. The study emphasizes the importance of identifying Candida spp. and their susceptibility to antifungals. This can limit the indiscriminate use of antifungal drugs, aid in selecting appropriate treatments, and reduce treatment costs, hospital stays, and patient morbidity and mortality.

Adherence of Candida Species Isolated from Patients with Head and Neck Cancer Presented for Radiation Therapy and its Correlation with Hemogram

The objective of the current study was to quantify the adherence property of Candida species causing infections in head and neck cancer patients on radiation therapy (RT) or chemoradiotherapy (CRT). Additionally, the study aimed to establish a correlation between adherence properties and patients’ hemograms. A prospective cohort study was done on head and neck cancer (HNC) patients with oropharyngeal candidiasis. All patients received radiation doses ranging from 60 to 70 Gy using Intensity Modulated Radiation Therapy. Inoperable patients received concurrent chemotherapy with cisplatin 40mg/m2 once weekly during the course of RT. Swabs were collected from patients with signs and symptoms of candidiasis and microbiological confirmation and speciation were done according to standard protocol. An in vitro adherence test was done. Hemogram of all the patients at the start of infection was compared with the adherence. Candidiasis was detected in 58(35.3%) out of a total of 164 patients (Age 36-85). Candida albicans was the most prevalent 39(67.2%) species isolated. C.albicans showed the highest adherence which was statistically significant. The hemogram at the start of treatment and with C. albicans infection showed a statistically significant decrease in the absolute lymphocyte count (p-value 0.0001), RBC count (p-value 0.004) and haemoglobin level (p-value 0.003). Less adherence was seen with non-albicans Candida infection when compared to C.albicans (Odds 0.894, 95% CI -0.818-0.977), significant at 5 % (0.013). C. albicans showed significant adherence, which indicates the severity of infection. The occurrence of oral candidiasis is strongly associated with low lymphocyte count and severity of mucositis. Absolute lymphocyte count needs to be monitored in HNC patients who are undergoing RT or CRT.

Profile of neonatal candidiasis in tertiary neonatal intensive care unit: A report from a developing country.

Systemic candidiasis is an important nosocomial infection in neonatal intensive care units. The objective of this study was to identify the change in the profile of neonatal candidiasis in a tertiary neonatal intensive care unit (NICU) in eastern India in recent times. It was a retrospective review of case records from 2014 to 2019 from a tertiary NICU of eastern India. Data of the fungal sepsis, demographic details, risk factors of fungal sepsis and mortality were collected from 103 neonates. One hundred and three neonates had blood culture positive for fungal species of which 91 (88.3%) infants weighed ≥1500 g and 66 (64%) infants were term. There was significant higher incidence of candidiasis among outborn (Relative risk of outborn 18.84, 95% CI 10.74-33.05). Prolonged antibiotic usage (>14 days), meropenem usage (>5 days), central catheterization (>5 days), invasive mechanical ventilation (>5 days), surgical intervention were found in 64 (62.1%), 46 (44.6%), 31(30.0%), 40 (38.8%) and 39 (37.8%) infants. Non albicans candida (NAC) was isolated as the predominant species (82/103, 79.6%). Resistance to both of fluconazole and amphotericin B were found in 19 (18.4%) babies. Presence of NAC infection and resistance to both amphotericin B and fluconazole were independent predictors of candida associated mortality in NICU. Neonatal candidiasis is found among outborn infants with higher birth weight and gestational age. NAC species are predominant organisms with resistance to common antifungal drugs.

Invasive Fungal Breakthrough Infections under Targeted Echinocandin Prophylaxis in High-Risk Liver Transplant Recipients

Invasive fungal infections (IFIs) are frequent and outcome-relevant complications in the early postoperative period after orthotopic liver transplantation (OLT). Recent guidelines recommend targeted antimycotic prophylaxis (TAP) for high-risk liver transplant recipients (HR-LTRs). However, the choice of antimycotic agent is still a subject of discussion. Echinocandins are increasingly being used due to their advantageous safety profile and the increasing number of non-albicans Candida infections. However, the evidence justifying their use remains rather sparse. Recently published data on breakthrough IFI (b-IFI) raise concerns about echinocandin efficacy, especially in the case of intra-abdominal candidiasis (IAC), which is the most common infection site after OLT. In this retrospective study, we analyzed 100 adult HR-LTRs undergoing first-time OLT and receiving echinocandin prophylaxis between 2017 and 2020 in a tertiary university hospital. We found a breakthrough incidence of 16%, having a significant impact on postoperative complications, graft survival, and mortality. The reasons for this may be multifactorial. Among the pathogen-related factors, we identified the breakthrough of Candida parapsilosis in 11% of patients and one case of persistent IFI due to the development of a secondary echinocandin resistance of an IAC caused by Candida glabrata. Consequently, the efficacy of echinocandin prophylaxis in liver transplantation should be questioned. Further studies are necessary to clarify the matter of breakthrough infections under echinocandin prophylaxis.

PFM-002 - Escalation in Non-albicans Candida infection in intensive care unit patients with emphasis on use of automated methods for expeditious diagnosis and management

PFM-002 - Escalation in Non-albicans Candida infection in intensive care unit patients with emphasis on use of automated methods for expeditious diagnosis and management

Risks for Recurrent Vulvovaginal Candidiasis Caused by Non-Albicans Candida Versus Candida Albicans.

Background: Vulvovaginal candidiasis (VVC) is the second most common vulvovaginitis (VV). About 20% of women will experience recurrent infections in their lifetime with non-albicans Candida (NAC) species being one of the causative agents. Although studies have looked at risk factors for recurrent VVC they are limited in scope. In this study, we explore whether risks of recurrent VVC are increased with NAC infections compared to Candida albicans infections. Methods: Through an institutional review board-approved retrospective chart review, we identified 174 women with positive yeast cultures and followed their charts to assess recurrent visits and treatments. We also assessed several baseline variables such as race, age, body mass index (BMI), obstetric history, probiotic use, contraceptive use, mycological therapy, steroid use, hormone replacement therapy, menopausal status, and medical comorbidities. Results: Women with NAC VV were more likely to have multiple visits for recurring infections compared to women who had C. albicans VV (66% vs. 34%). The women with multiple recurrences were younger, had a lower BMI, had lower parity, and endorsed higher use of probiotics. Conclusion: Women with positive NAC cultures were more likely to have multiple visits to their physicians for VV complaints. Identifying the causative species using vaginal fungal cultures can more accurately guide therapy and lead to better outcomes for these patients.

In vitro activities of the tetrazole VT-1161 compared with itraconazole and fluconazole against Cryptococcus and non-albicans Candida species

ABSTRACT Recently, Cryptococcus and non-albicans Candida (NAC) have emerged as health-threatening pathogens for clinical fungal infections. Due to their increased resistance to existing antifungal drugs, novel antifungals are urgently needed. In this study, we evaluated the antifungal effect of VT-1161 and its comparators itraconazole and fluconazole against common fluconazole-sensitive or -resistant Cryptococcus and NAC strains. The tested strains were obtained from Chinese patients by the Invasive Fungal Infection Group within the past 2 years. The minimum inhibitory concentrations (MICs) of VT-1161 and other triazoles were measured according to the Clinical and Laboratory Standards Institute (CLSI) M27-Ed4 guidelines. We found that VT-1161 exhibited strong in vitro activity against Cryptococcus spp.. VT-1161 (geometric mean MIC = 0.024 μg/mL) was 21.7-fold and 104.5-fold more potent than itraconazole and fluconazole, respectively. Against the seven Cryptococcus neoformans isolates with higher fluconazole MICs (≥8 μg/mL based on the MIC90 value of this azole), VT-1161 maintained potent activities, with MICs ranging between 0.031 and 0.5 μg/mL. For NAC spp., VT-1161 (geometric mean MIC = 0.099 μg/mL) was 6.0-fold and 11.4-fold more effective than itraconazole and fluconazole, respectively. There is a positive correlation of the MICs between VT-1161 and itraconazole/fluconazole. The MIC values of VT-1161 against Candida glabrata and Candida tropicalis were significantly lower than those of fluconazole, whereas for Candida parapsilosis the differences in the MIC values between VT-1161 and fluconazole were not statistically significant. The results showed that tetrazole VT-1161 might be a promising candidate for treating Cryptococcus and NAC infections.

Therapeutic implications of candida phenotypes, virulence factors and antifungal sensitivity in Oral leukoplakia

ObjectivesTo determine the association of Candida phenotypes, virulence factors, antifungal sensitivity and clinical response to Fluconazole in Oral leukoplakia (OL). MethodsSterile swabs were obtained from oral lesions in immunocompetent subjects [30 Homogenous (HOL), 31 Non- Homogenous (NHOL] and normal buccal mucosa in 30 age and sex-matched healthy controls (C). Candida phenotypes, virulence factors (Secreted Aspartyl Proteinase (SAP), Phospholipase (PL), Biofilm formation (BF) and antifungal sensitivity were determined. Clinical features (Size, Erythema, thickness, oral burning sensation (VAS scores) before and after Fluconazole therapy in OL were recorded by two calibrated observers. ResultsCandida was associated with OL (p ​< ​0.01). Candida albicans was the most common phenotype sensitive to Fluconazole. SAP, PL and BF activity was significantly high in NHOL. Strong positive correlation was seen between SAP, and PL activity and pre-treatment VAS scores in NHOL. There was significant reduction in VAS scores, size of lesion [HOL (p ​< ​0.001) NHOL (p ​< ​0.05)], erythematous areas (67.8%) in NHOL and thickness of lesions (42.6%) in both types OL after Fluconazole therapy with substantial inter-observer agreement. Non albicans candida (NAC) species had similar virulence profiles but resistant to Fluconazole and showed minimal clinical improvement. ConclusionsVirulence activity of Candida in OL increases severity of lesions. Fluconazole is effective against virulent Candida albicans, causes clinical improvement and down-staging from high –risk NHOL to low-risk HOL which can reduce risk of malignant transformation. Detection of highly virulent NAC infection and antifungal sensitivity is recommended in OL recalcitrant to Fluconazole therapy.

743. Characteristics of Candidemia in a Coccidioidomycosis Endemic Region: The impact of Increased Azole Use in the Selection of Candida species

BackgroundThe incidence of invasive candidiasis secondary to non-albicans Candida species is on the rise. In Arizona, azoles are used for coccidioidomycosis treatment and prophylaxis in immunosuppressed population. Therefore, we intended to describe the characteristics and outcomes of non-albicans Candidemia in our area.MethodsWe conducted an IRB approved multicenter study evaluating patients from October 1, 2017 to January 1, 2020. Patient demographics, medical history, procedures, antifungal use, and laboratory data were collected. Episode per patient was included in the statistical analysis.ResultsIn the study period, there were 145 patients with 151 candidemia episodes. For the episode-per-patient, median age was 51 (IQR 37-62), 45% were female, and 86% were Caucasian. 10% had a history of transplantation (40% HSCT and 60% SOT), and 22.5% had a history of cancer. 78% had another concomitant systemic infection. 4/80 (5%) and 12/102 (12%) had infective endocarditis. Only 5 (3.3%) had a history of coccidioidomycosis and 37 (24.5%) had exposure to azole therapy in the prior 3 months. 60% of the candidemia episodes were due to non-albicans Candida species, 27/37 (73%) had a prior history of azole therapy, 12/15 (80%) were transplant recipients, and 23/34 (80%) had cancer. The majority (71%) of patients initially received an echinocandin without a significant difference in mortality. Of all the admission episodes, there were 45/151 (29%) deaths and 7/151 (4.5%) were discharged to hospice. Not removing central catheters was associated with 60% of deaths (P=0.002). Infectious diseases consult was associated with lower mortality (OR 0.25, 95% CI 0.087-0 .70) and higher rates of catheter removal (OR 8, 95% 2.2-29.5). There was no difference in mortality between non-albicans versus albicans Candidemia (28.6% vs. 32%, P=0.7).ConclusionOur study found higher rates of non-albicans Candidemia that are more eminent in transplant recipients and those with prior azole use, but this was not statistically significant. The removal of the central line and ID consultations was associated with a significant reduction in mortality. In Coccidioidomycosis endemic regions, the risk of non-albicans candida infections can be higher with the use of azoles; however, further studies are recommended.Disclosures All Authors: No reported disclosures

Distribution of invasive fungal infections: Molecular epidemiology, etiology, clinical conditions, diagnosis and risk factors: A 3-year experience with 490 patients under intensive care

Recently, the prevalence of invasive fungal infections (IFIs) is rising. The global mortality rate of IFIs is 10–49%. This study aimed to determine the prevalence, the causative agents, and the risk factors associated with the invasive fungal infections in a tertiary health center to provide valid decision-grounds for healthcare professionals to effectively prevent, control, and treat fungal infections. The current study was conducted on 1477 patients suspected to have systemic fungal infections from different units of the hospital. After screening using routine mycological examination, the patients were confirmed with complementary mycological and molecular methods. Patients were included based on the confirmed diagnosis of IFI and excluded based on lack of a microbiologically and histologically proven diagnosis of IFI. Of the 1477 patients recruited in this study, confirmed cases of fungal infection were 490 (169 proven; 321 cases probable). Among the fungi recovered, Candida species had the highest frequency 337 (68.8%) followed by Aspergillus species 108 (22.1%), Zygomycetes species 21 (4.3%), non-Candida yeast 9 (1.8%). Others were black fungi 5 (1%), mycetoma agents 5 (1%), Fusarium 4 (0.8%), and Trichoderma (0.2%). Hematologic malignancies and diabetes mellitus were the most common underlying diseases among IFI-confirmed patients. This study observed an increased frequency of invasive candidiasis with non-albicans Candida and other invasive saprophytic fungal infections. The increased rate of invasive candidiasis with non-albicans agents highlights a new perspective in the epidemiology and treatment of invasive fungal infections.

Bioregulatory Role of Wickerhamomyces anomalus Killer Toxin against Pathogenic Members of the Genus Candida

Objectives: Candida species are endogenous fungus causing both mucosal and invasive infections. With the increasing rate of non-albicans Candida infections with varying susceptibilities, early and accurate species identification would help the clinician in befitting therapeutic management. So the interest in natural products secreted by a fungus Wickerhamomyces anomalus itself as an antimicrobial agent against pathogenic Candida species has evaluated in the present study. Methods: A total of 336 Candida species isolated from various clinical samples were included in the study. Candida identification, antifungal susceptibility was done by standard procedures. The environmental yeast killer toxin Wickerhamomyces anomalus was purified and the killer toxin assay against Candida species was done by standard procedures. Results: The predominant Candida species were Candida albicans (31%), but the emergence of non-albicans Candida also noted with 69%. Total antifungal resistance was 117 (35%) with fluconazole resistance in Candida albicans 13 (13%) and in non-albicans Candida were 50 (21%). The characterization of W. anomalus toxin has revealed that it is a glycoprotein of having 42.6 kDa active at pH 5.5 and temperatures 250 C. Candida isolates showed 292 (87%) sensitivity to the killer toxin. Conclusions: The study emphasizes the need for rapid and precise speciation and antifungal susceptibility of Candida isolates for effective treatment and management strategies.Our study proved the antifungal ability of W. anomalus and this resource can be used for alternative treatment of candidiasis with further assessments. J Microbiol Infect Dis 2019; 9(3):155-160.

2257. BDG-Guided Management of Empirical Antifungal Therapy: a Real-life Experience in a Hospital-Wide Context with High Incidence of Non-albicans Candida Infection

BackgroundBDG-guided management of empirical antifungal therapy (AT) has been suggested as a tool to rule out invasive candidiasis (IC) and discontinue AT in critically ill patients. However, some authors reported lower BDG sensibility for non-albicans Candida (NAC) infection. Impact of BDG use in a hospital wide setting has yet to be determined.MethodsWe performed a retrospective observational study of consecutive patients admitted to a 1535-bed teaching hospital from November 2015 to August 2017. Adult patients starting empirical AT and performing at least one BDG test for a suspected fungal infection were included. According to first BDG result and AT management, patients were classified in 3 groups: (G1) negative index BDG and early AT withdrawal; (G2) negative index BDG and AT continued; (G3) positive index BDG and AT continued. IC was defined as monomicrobial Candida spp. isolation from blood cultures and/or surgical specimen. Comparison of the 3 groups was made using post-hoc Bonferroni correction. Univariate and multivariate analyses of risk factors for all-cause 30 days mortality were performed using binary logistic regression model.ResultsStudy population consisted of 208 patients, of which 46 (22.1%) were included in G1, 79 (38.0%) in G2, and 83 (39.9%) in G3. NAC species were more commonly isolated from patients with IC and negative BDG (P = 0.005). IC was diagnosed in 2.2%, 13.9%, and 19.3% of G1, G2, and G3, respectively (P < 0.01 for G1 vs. G3). Median AT DDD were 8, 28, and 20 (P < 0.01 for G1 vs. G2 and G1 vs. G3) and 30-day mortality rate was 21.4%, 16.5%, and 30.1%, respectively. Factors associated with 30-day mortality were age, Charlson Comorbidity Index (CCI), ICU admission, SOFA score, septic shock, orotracheal intubation, CVVH and index BDG ≥ 80 pg/mL. At multivariate model, independent risk factors for 30-day mortality were CCI (OR 1.4, 95% CI 1.2–1.6, P < 0.001), SOFA score (OR 1.2, 95% CI 1.1–1.3, P < 0.001) and index BDG≥80 pg/mL (OR 2.4, 95% CI 1.2–4.8, p = 0.012). Model fit was P = 0.65 by Hosmer–Lemeshow test and accuracy according with ROC analysis was 0.82 (95% CI 0.76–0.88).ConclusionBDG positivity is a strong predictor of poor outcome, but its accuracy for NAC infection may be suboptimal. Caution may be necessary for AT discontinuation based on a negative BDG result in patients at high risk for NAC infection. Disclosures All authors: No reported disclosures.

Probiotic Yeasts Inhibit Virulence of Non-albicans Candida Species.

Systemic infections of Candida species pose a significant threat to public health. Toxicity associated with current therapies and emergence of resistant strains present major therapeutic challenges. Here, we report exploitation of the probiotic properties of two novel, food-derived yeasts, Saccharomyces cerevisiae (strain KTP) and Issatchenkia occidentalis (strain ApC), as an alternative approach to combat widespread opportunistic fungal infections. Both yeasts inhibit virulence traits such as adhesion, filamentation, and biofilm formation of several non-albicans Candida species, including Candida tropicalis, Candida krusei, Candida glabrata, and Candida parapsilosis as well as the recently identified multidrug-resistant species Candida auris They inhibit adhesion to abiotic surfaces as well as cultured colon epithelial cells. Furthermore, probiotic treatment blocks the formation of biofilms of individual non-albicans Candida strains as well as mixed-culture biofilms of each non-albicans Candida strain in combination with Candida albicans The probiotic yeasts attenuated non-albicans Candida infections in a live animal. In vivo studies using Caenorhabditis elegans suggest that exposure to probiotic yeasts protects nematodes from infection with non-albicans Candida strains compared to worms that were not exposed to the probiotic yeasts. Furthermore, application of probiotic yeasts postinfection with non-albicans Candida alleviated pathogenic colonization of the nematode gut. The probiotic properties of these novel yeasts are better than or comparable to those of the commercially available probiotic yeast Saccharomyces boulardii, which was used as a reference strain throughout this study. These results indicate that yeasts derived from food sources could serve as an effective alternative to antifungal therapy against emerging pathogenic Candida species.IMPORTANCE Non-albicans Candida-associated infections have emerged as a major risk factor in the hospitalized and immunecompromised patients. Besides, antifungal-associated complications occur more frequently with these non-albicans Candida species than with C. albicans Therefore, as an alternative approach to combat these widespread non-albicans Candida-associated infections, here we showed the probiotic effect of two yeasts, Saccharomyces cerevisiae (strain KTP) and Issatchenkia occidentalis (ApC), in preventing adhesion and biofilm formation of five non-albicans Candida strains, Candida tropicalis, Candida krusei, Candida glabrata, Candida parapsilosis, and Candida auris The result would influence the current trend of the conversion of conventional antimicrobial therapy into beneficial probiotic microbe-associated antimicrobial treatment.

Resistance rates of non-albicans Candida infections in Taiwan after the revision of 2012 Clinical and Laboratory Standards Institute breakpoints.

PurposeIn 2012, the Clinical and Laboratory Standards Institute (CLSI) revised its breakpoints for drugs and species because of the increase in non-albicans Candida infections and their drug resistance. Following global trends, the non-albicans candidemia resistance rate has increased in Taiwan as well. To update the antifungal susceptibility of non-albicans candidemia isolates, we conducted a multicenter study using the revised break points.Patients and methodsPatients with non-albicans candidemia infections were identified at five tertiary hospitals in Taiwan from July 1, 2011, to June 30, 2014. The broth microdilution method using a Sensititre YeastOne system was performed for the determination of minimum inhibitory concentration (MIC). The susceptibility was interpreted based on the guidelines of the CLSI (CLSI M27-S4 and M27-S3).ResultsCandida tropicalis was the predominant non-albicans candidemia pathogen (42.4%), and it showed increased fluconazole non-susceptibility (36.3%) when compared to the results from previous studies. In particular, C. tropicalis showed high cross-resistance to azole agents. C. tropicalis isolates that were found to be resistant to fluconazole also showed increased resistance to voriconazole (82.2%) and posaconazole (100%). The increased non-susceptibility of Candida glabrata to multiple antifungal agents, based on the revised break points, resulted from an increase in dose-dependent susceptibility (94.4%) rather than from an increase in resistance (5.6%).ConclusionThe resistance rate of non-albicans candidemia isolates is increasing, particularly for C. tropicalis and C. glabrata.

Risk Factors for Candidemia in Critically Ill Patients: A Systematic Review and Meta-Analysis

Background: To assess the risk factors for candidemia as well as for non-albicans Candida (NAC) infections compared with Candida albicans infections in critically ill patients. Methods: MEDLINE, EMBASE, EBSCOhost, Web of Science and the Cochrane Library were systematically searched on June 2019. The pooled odds ratios (ORs) with 95% confidence intervals (CIs) were calculated using the random effects generic inverse variance method. Results: Thirty studies with 259455 patients were included. The following factors were associated with candidemia in ICUs: sepsis [OR 5.03 (3.36-7.52)], acute renal failure [OR 3.70 (1.10-12.43)], Candida colonization [OR 3.49 (2.02-6.04)], neutropenia [OR 3.33 (2.54-4.38)], abdominal surgery [OR 2.81 (2.10-3.76)], hematological neoplasm [OR 2.49 (1.60-3.86)], malignancy [OR 1.80 (1.35-2.40)], chronic renal failure [OR 1.56 (1.01-2.43)], diabetes [OR 1.50 (1.14-1.99)], renal replacement therapy [OR 4.55 (2.90-7.15)], parenteral nutrition [OR 3.58 (1.88-6.80)], central venous catheters [OR 3.53 (2.28-5.45)], mechanical ventilation [OR 3.26 (1.79-5.95)], the use of broad-spectrum antibiotics [OR 3.12 (1.91-5.10)], antifungul drugs [OR 2.78 (1.51-5.12)] and steroids [OR 1.69 (1.24-2.30)]. Moreover, Neutropenia [OR 2.55 (1.33-4.91)], hematological neoplasm [OR 1.92 (1.03-3.55)]; malignancy [OR 1.67 (1.12-2.49)], the use of antifungul drugs [OR 2.34 (1.33-4.12)] and steroids [OR 1.90 (1.15-3.14)] were associated with a significantly higher risk of NAC infection than of C. albicans infection. Conclusions: This meta-analysis confirmed that sepsis, acute renal failure, Candida colonization, neutropenia, abdominal surgery, hematological neoplasm, malignancy, chronic renal failure, diabetes, renal replacement therapy, parenteral nutrition, central venous catheters, mechanical ventilation, the use of broad-spectrum antibiotics, antifungul drugs and steroids significantly increase the incidence of candidemia. Systematic review registration: PROSPERO registration number CRD42019122815. Funding: This project was funded by the National Natural Science Foundation of China (No.81571871 and 81770276), Nn10 program, Distinguished Young Scholars Fund of Harbin Medical University Cancer Hospital, the Yuweihan Fund for Distinguished Young Scholars of Harbin Medical University, Harbin Science and Technology Innovation Scholar Fund (2017RAXXJ087), Heilongjiang Province Postdoctoral Research Fund. Declaration of Interest: All authors declare they have no competing financial interests.

A study on biofilm production and antifungal drug resistance among Candida species from vulvovaginal and bloodstream infections.

IntroductionCandida species, one among the opportunistic fungi, has become a common pathogen causing vaginal thrush and nosocomial bloodstream infections (BSIs). This study aims to evaluate the prevalence and antifungal susceptibility of various Candida species and slime production by Candida species in BSIs and vulvovaginal candidiasis (VVC).Materials and methodsA total of 176 samples were collected for a period of 1 year. Anti-fungal susceptibility testing and biofilm production testing were performed by the Kirby-Bauer method and crystal violet assay, respectively.ResultsOut of 176 samples, 74 (42%) were from BSIs and 102 (58%) were from VVC. The biofilm production was comparatively high in blood isolates, 55 (74%), than cervical isolates, 45 (44%). Increase in the trends of non-albicans Candida (NAC) species was seen in our setup. Good susceptibility rates were seen among Candida species, 82.38% to voriconazole and an increasing resistance pattern of 26.13% to fluconazole.ConclusionSpeciation of Candida becomes important as the prevalence of NAC is increasing. Antifungal susceptibility testing by the disk diffusion method is cost effective and should be adopted in routine testing as there is an increasing azole resistance, especially in invasive NAC infections. In this study, there was no correlation of antifungal drugs with the biofilm production.