Diagnosis Of Invasive Candidiasis Research Articles

Evaluation of colonization index and (1,3)- ß- D glucan as diagnostic tools of invasive candidiasis in a pediatric Intensive Care Unit

PurposeThe study aimed to evaluate the corrected colonization index (CCI) and (1, 3)-ß-D Glucan (BDG) in diagnosis of Invasive Candidiasis (IC) in critically ill pediatric patients. MethodsA prospective observational study in a tertiary care (PICU) were surveyed for Candida colonization and CCI was calculated. For cases with suspicious clinical presentation, samples were cultured, and double(1,3) ß-D- glucan (BDG) performed. ResultsAccording to the European Organization for Research and Treatment of Cancer EORTC case definition for critically ill non-neutropenic patients, only 7.14 % (9/188) were diagnosed as IC (4 proven and 5 probable cases). The combined use of CCI with BDG proved to have excellent discriminative power AUC= 0.946, improved sensitivity 87.5 % and specificity 85.71 %. ConclusionThe key in diagnosis of IC relies in compiling proofs from the clinical context, high CCI (≥ 0.4) and BDG.

A novel quantitative double antigen sandwich ELISA for detecting total antibodies against Candida albicans enolase 1.

This study aimed to develop a double antigen sandwich ELISA (DAgS-ELISA) method for more efficient, accurate, and quantitative detection of total antibodies against Candida albicans enolase1 (CaEno1) for diagnosing invasive candidiasis (IC). DAgS-ELISA was developed using recombinant CaEno1 and a monoclonal antibody as the standard. Performance evaluation included limit of detection, accuracy, and repeatability. Dynamic changes in antibody levels against CaEno1 in serum from systemic candidiasis mice were analyzed using DAgS-ELISA. Patient serum samples from IC, Candida colonization, bacterial infections, and healthy controls were analyzed with DAgS-ELISA and indirect ELISA. DAgS-ELISA outperformed indirect ELISA in terms of linear range and test background. In systemic candidiasis mice, a distinctive 'double-peak' pattern in dynamic antibody levels was observed. Additionally, there was a high level of consistency in the positive rates of CaEno1 antibodies detected by both DAgS-ELISA and indirect ELISA. While the positivity rates differed among patient groups, no significant variations in antibody levels were detected among the various positive patient groups. DAgS-ELISA offers a reliable novel approach for IC diagnosis, enabling rapid, accurate, and quantitative detection of CaEno1 antibodies. Further validation and optimization are needed for its clinical application and effectiveness.

Candida albicans cDNA library screening reveals novel potential diagnostic targets for invasive candidiasis

The detection of patterns associated with the invasive form of Candida albicans, such as Candida albicans germ tube antibodies (CAGTA), is a useful complement to blood culture for Invasive Candidiasis (IC) diagnosis. As CAGTA are detected by a non-standardisable and non-automatable technique, a Candida albicans cDNA expression library was screened with CAGTA isolated from serum of an animal model of invasive candidiasis, and five protein targets were identified: hyphally regulated cell wall protein 1 (Hyr1), enolase 1 (Eno1), coatomer subunit gamma (Sec21), a metallo-aminopeptidase (Ape2) and cystathionine gamma-lyase (Cys3). Homology with proteins from other organisms rules out Cys3 as a good biomarker while Sec21 results suggest that it is not in the germ tubes surface but secreted to the external environment. Our analysis propose Ape2, Sec21 and a region of Hyr1 different from the one currently being studied for immunoprotection as potential biomarker candidates for the diagnosis of IC.

Stewardship-Guided T2Candida Testing Shortens Time to Antifungal Treatment and Reduces Antifungal Usage Among Medical Intensive Care Unit Patients With Septic Shock.

Diagnosis of invasive candidiasis (IC) is limited by insensitivity and slow turnaround of cultures. Our objectives were to define the performance of T2Candida, a nonculture test, under guidance of a diagnostic stewardship program, and evaluate impact on time to antifungal initiation and antifungal utilization. This was a retrospective study of adult medical intensive care unit (MICU) patients with septic shock for whom T2Candida testing was performed from March 2017 to March 2020. Patients with positive T2Candida results during this period were compared to MICU patients who did not undergo T2Candida testing but had septic shock and blood cultures positive for Candida from January 2016 through March 2020. Overall, 155 T2Candida tests from 143 patients were included. Nine percent of T2Candida tests were positive compared to 4.5% of blood cultures. Sensitivity, specificity, positive predictive value, and negative predictive value of T2Candida for proven and probable IC were 78%, 95%, 50%, and 99%, respectively. Patients who tested positive for T2Candida (n = 14) were diagnosed earlier and initiated on antifungal therapy sooner than patients with IC (n = 14) diagnosed by blood culture alone (median, 5.6 vs 60 hours; P < .0001). Median antifungal days of therapy/1000 patient-days were 23.3/month preimplementation and 15/month postimplementation (P = .007). Following a negative T2Candida result, empiric antifungals were either not administered in 58% or discontinued within 72 hours in 96% of patients. Diagnostic stewardship guided T2Candida testing resulted in reduced time to IC diagnosis, faster initiation of antifungal therapy, and lower antifungal usage among MICU patients with septic shock.

The association between Geriatric Nutritional Risk Index and the risk of Invasive Candidiasis in critically ill older adults

BackgroundInvasive candidiasis is the most common hospital-acquired fungal infection in intensive care units (ICU). The Geriatric Nutritional Risk Index (GNRI) score was developed to evaluate the nutritional status of elderly adults. We aimed to assess the association between the GNRI score and the risk of invasive candidiasis in elderly patients admitted to ICU.MethodsHospitalization information of elderly patients with invasive candidiasis was collected retrospectively from Medical Information Mart for Intensive Care (MIMIC) IV and MIMIC-III Clinical Database CareVue subset from 2001 to 2019. The main outcome of this study was the diagnosis of invasive candidiasis in patients. We employed a multivariable Cox regression and propensity score matching to balance the influence of confounding factors on the outcome. Furthermore, we conducted sensitivity analyses by categorizing the GNRI into classes based on thresholds of 98, 92, and 81.ResultsA total of 6739 patients were included in the study, among whom 134 individuals (2%) were diagnosed with invasive candidiasis. The GNRI scores of patients with invasive candidiasis upon admission to the ICU were significantly lower, measuring 88.67 [79.26–98.27], compared to the control group with a score of 99.36 [87.98-110.45] (P < 0.001). The results of the multivariable Cox regression analysis demonstrated a strong association between higher GNRI scores and a decreased risk of invasive candidiasis infection (HR: 0.98, 95% CI: 0.97–0.99, P = 0.002). Consistently, similar results were obtained when analyzing the propensity score-matched cohort (HR: 0.99, 95% CI: 0.98-1, P = 0.028). Sensitivity analyses further confirmed a significantly increased risk of invasive candidiasis infection with lower GNRI scores. Specifically, the following associations were observed: GNRI ≤ 98 (HR: 1.83, 95% CI: 1.23–2.72, P = 0.003), GNRI ≤ 92 (HR: 1.68, 95% CI: 1.17–2.4, P = 0.005), 82 ≤ GNRI ≤ 92 (HR: 1.63, 95% CI: 1.01–2.64, P = 0.046), GNRI ≤ 81 (HR: 2.31, 95% CI: 1.44–3.69, P < 0.001).ConclusionsLower GNRI score was significantly associated with an increased risk of invasive candidiasis in elderly patients in ICU. Further research is needed to validate whether improving nutrition can prevent invasive candidiasis.

Comparison of Three β-Glucan Tests for the Diagnosis of Invasive Candidiasis in Intensive Care Units.

The (1→3)-β-d-glucan (BDG) is a marker of invasive fungal infection that can be detected in serum by different commercial kits. In this study, we compared the performance of the Fungitell assay (FA), the Fungitell STAT assay (STAT), and the Wako β-glucan test (WA) for the diagnosis of invasive candidiasis (IC) in the intensive care unit (ICU). Patients for whom at least one BDG testing was required for a clinical suspicion of IC were retrospectively enrolled. A total of 85 serum samples from 56 patients were tested by the three BDG tests. The rate of IC was 23% (13/56) with a predominance of noncandidemic (intra-abdominal) IC. STAT and WA results exhibited overall good correlation with those obtained by FA (Spearman's coefficient R = 0.90 and R = 0.89, respectively). For the recommended cutoffs of positivity, sensitivity and specificity for IC diagnosis were 77%/51% (FA, 80 pg/mL), 69%/53% (STAT, ratio 1.2), and 54%/65% (WA, 7 pg/mL), respectively. Optimal performance was obtained at 50 pg/mL (FA), ratio 1.3 (STAT), and 3.3 pg/mL (WA) with sensitivity/specificity of 85%/51%, 69%/57%, and 77%/58%, respectively. Overall, the three BDG tests showed comparable but limited performance in this setting with positive and negative predictive values for an estimated IC prevalence of 20% that were in the range of 30 to 35% and 85 to 95%, respectively.

Investigation of the location and secretion features of Candida albicans enolase with monoclonal antibodies

PurposeThe glycolytic enzyme enolase plays important role in the pathogenesis of Candida albicans infection and has been also considered as a promising molecular marker for the diagnosis of invasive candidiasis. This study aimed to investigate the location and secretion features of Candida albicans enolase (CaEno) with a couple of specific monoclonal antibodies (mAbs).MethodsTwo mAbs named 9H8 and 10H8 against CaEno were generated by fusing SP2/0 myeloma cell with the spleen lymphocytes from CaEno immunized mice. The specificity of the mAbs was then validated by Western blot and liquid chromatography-mass spectrometry (LC–MS/MS). A diverse set of experiments were conducted based on the pair of mAbs which involved immunohistochemical staining analysis, whole cell enzyme-linked immunosorbent assay (ELISA), double antibody sandwich ELISA, and confocal microscopy to analyze the possible location and secretion features of CaEno.ResultsCaEno is abundantly expressed in the cytoplasm of C. albicans blastospores and is distributed in a ring-shaped pattern along the cell wall. CaEno appeared in the hyphal C. albicans as just a “mushroom” form. CaEno was found to be weakly expressed on the surface of blastospores but constantly expressed at various stages of growth. CaEno concentrations in C. albicans blastospores culture supernatant are considerably higher than in C. albicans hyphae culture supernatant. The dynamic changes of supernatant CaEno concentration in blastospores and hyphal C. albicans exhibit distinct features, although both appear to be associated with the C. albicans growth state. When cultivated under normal circumstances, however, no apparent CaEno degradation was seen in the cell-free supernatant.ConclusionOur results implied that CaEno was constantly expressed on the cell surface and its secretion features varied according to the growth stage of C. albicans. However, further experimental and theoretical studies are needed in future to identify the specific mechanisms by which this phenomenon can arise.

Development and Validation of a Risk Score for Predicting Invasive Candidiasis in Intensive Care Unit Patients by Incorporating Clinical Risk Factors and Lymphocyte Subtyping.

ObjectiveTo develop and validate a rapid invasive candidiasis (IC)-predictive risk score in intensive care unit (ICU) patients by incorporating clinical risk factors and parameters of lymphocyte subtyping.MethodsA prospective cohort study of 1054 consecutive patients admitted to ICU was performed. We assessed the clinical characteristics and parameters of lymphocyte subtyping at the onset of clinical signs of infection and their potential influence on IC diagnosis. A risk score for early diagnosis of IC was developed and validated based on a logistic regression model.ResultsSixty-nine patients (6.5%) had IC. Patients in the cohort (N=1054) were randomly divided into a development (n=703) or validation (n=351) cohorts. Multivariate logistic regression identified that CD8+ T-cell count ≤143 cells/mm3, receipt of high-dose corticosteroids (dose ≥50 mg prednisolone equivalent), receipt of carbapenem/tigecycline, APACHE II score≥15, (1,3)-β-D-glucan (BDG) positivity and emergency gastrointestinal/hepatobiliary (GIT/HPB) surgery were significantly related with IC. IC risk score was calculated using the following formula: CD8+ T-cell count ≤143 cells/mm3 + receipt of high-dose corticosteroids + receipt of carbapenem/tigecycline + APACHE II score ≥15 + BDG positivity + emergency GIT/HPB surgery ×2. The risk scoring system had good discrimination and calibration with area under the receiver operating characteristic (AUROC) curve of 0.820 and 0.807, and a non-significant Hosmer-Lemeshow test P=0.356 and P=0.531 in the development and validation cohorts, respectively. We categorized patients into three groups according to risk score: low risk (0-2 points), moderate risk (3-4 points) and high risk (5-7 points). IC risk was highly and positively associated with risk score (Pearson contingency coefficient=0.852, P for trend=0.007). Candida score had a moderate predicting efficacy for early IC diagnosis. The AUROC of the risk score was significantly larger than that of Candida score (0.820 versus 0.711, Z=2.013, P=0.044).ConclusionsThe predictive scoring system, which used both clinical factors and CD8+ T cell count, served as a clinically useful predictive model for rapid IC diagnosis in this cohort of ICU patients.Clinical Trial Registrationchictr.org.cn, identifier ChiCTR-ROC-17010750.

Diagnosis and Management of Invasive Candida Infections in Critically Ill Patients.

Invasive candidiasis (IC) has become a serious problem in the intensive care unit patients with an attributable mortality rate that can reach up to 51%. Multiple global surveillance studies have shown an increasing incidence of candidemia. Despite their limited sensitivity (21-71%), cultures remain the gold standard for the diagnosis of IC associated with candidemia. Many adjunct laboratory tests exist to support or rule out the diagnosis, each with its indications and limitations, including procalcitonin, 1,3-β-D-glucan, mannan and anti-mannan antibodies, and Candida albicans germ tube antibody. In addition, polymerase chain reaction-based methods could expedite species identification in positive blood cultures, helping in guiding early empirical antifungal therapy. The management of IC in critically ill patients can be classified into prophylactic, preemptive, empiric, and directed/targeted therapy of a documented infection. There is no consensus concerning the benefit of prophylactic therapy in critically ill patients. While early initiation of appropriate therapy in confirmed IC is an important determinant of survival, the selection of candidates and drug of choice for empirical systemic antifungal therapy is more controversial. The choice of antifungal agents is determined by many factors, including the host, the site of infection, the species of the isolated Candida, and its susceptibility profile. Echinocandins are considered initial first-line therapy agents. Due to the conflicting results of the various studies on the benefit of preemptive therapy for critically ill patients and the lack of robust evidence, the Infectious Diseases Society of America (IDSA) omitted this category from its updated guidelines and the European Society of Intensive Care Medicine (ESICM) and the Critically Ill Patients Study Group of the European Society of Clinical Microbiology and Infectious Diseases (ESCMID) do not recommend it.

Identification of fungal trehalose for the diagnosis of invasive candidiasis by mass spectrometry

The rapidity of the diagnosis of invasive candidiasis (IC) is crucial to allow the early introduction of antifungal therapy that dramatically increases the survival rate of patients. Early diagnosis is unfortunately often delayed because Candida blood culture, the gold standard diagnostic test, is positive in only 50% of cases of IC and takes several days to obtain this result. Complementary non-culture-based methods relying on the detection of Candida cell wall polysaccharides in the serum, β-glucans and mannans, by enzymatic and immunological reagents have been successfully developed to allow a more efficient patients care. We have previously demonstrated that detection of circulating glycans by mass spectrometry could provide a reliable and cost-effective early diagnosis method called MS-DS for Mass Spectrometry of Di-Saccharide. Here, by comparing patient's sera and Candida albicans strains deficient in carbohydrates synthesis, we demonstrate that trehalose derived from fungal metabolism can be specifically targeted by MS-DS to allow early diagnosis. In particular, the use of C. albicans strains deficient in the synthesis of trehalose synthesizing enzymes Tps1 and Tps2 show that MS-DS results were correlated to the metabolism of trehalose. Finally, we demonstrate that the performance of the IC diagnosis can be significantly improved by using high resolution mass spectrometry, which opens new perspectives in the management of the disease.

STANDARDS OF MEDICAL CARE “INVASIVE CANDIDIASIS IN NEWBORNS”

Candida infection (candidiasis) is an important clinical problem in newborns who need treatment in modern intensive care units. Organ and/or systemic infections caused by these fungi are called invasive candidiasis (IC). Newborns are especially vulnerable to IC, and their incidence is 3-5 times higher than the corresponding rates in children or adults. Invasive fungal infections caused by Candida are the third most common late-onset infection in infants born with a birth weight &lt;1500 g. IC in newborns is associated with approximately 20% mortality, and about half of survivors have serious long- term neurological damage. In recent years, new data have been obtained on the diagnosis, prevention and treatment of IC in newborns, which has determined a change in treatment recommendations. Accordingly, the need arose to ensure the compliance of our clinical practice with modern evidence-based approaches. Early diagnosis of candidiasis and prompt treatment with effective antifungal agents such as fluconazole, amphotericin B, and micafungin, when indicated, are critical to improving outcomes.

Consensus guidelines for the diagnosis and management of invasive candidiasis in haematology, oncology and intensive care settings, 2021.

Patients with haematological malignancies, haemopoietic stem cell transplant recipients and patients requiring admission to intensive care settings are at high risk for invasive candidiasis (IC). Over the past decade, there has been increased reporting of non-albicans species and fluconazole resistance in Australia. These guidelines provide updated evidence-based recommendations for the diagnosis and management of IC in adult and paediatric haematology, oncology and intensive care settings. Optimal pharmacological and non-pharmacological management are discussed. Recent studies strengthen the recommendation for an echinocandin agent as first-line therapy for high-risk patients with IC. Mortality benefit has also been demonstrated for non-pharmacological management, including removal of central venous catheters, infectious diseases consultation and use of care bundles. Healthcare facilities managing immunocompromised patient populations should therefore adopt implementation strategies for these multimodal interventions.

Mortality Risk Factors for Invasive Candidiasis in Pediatric Intensive Care Unit

Invasive Candida infections are one of the most important risk factors for the increasing mortality of immunocompromised patients with comorbidities in intensive care units. In this study, it was aimed to evaluate the mortality rate and risk factors affecting mortality in patients followed up with the diagnosis of invasive candidiasis in our pediatric intensive care unit. Patients who were between the ages of 1 month and 18 years followed up in the paediatric intensive care unit with invasive candidiasis between 2014 and 2018, were included in the study. The demographic characteristics of the patients, fever and hypotension, the Candida species, use of broad-spectrum antibiotics, blood transfusion, parenteral nutrition, invasive interventions, use of mechanical ventilation and laboratory test results were retrospectively analyzed and the relationship with mortality was statistically determined. A total of 85 patients, 45 girls, and 40 boys were included in the study. The death rate was 38.8% (n= 33). Candida albicans (48%) was the most common species for all isolates followed by Candida parapsilosis (21%), Candida tropicalis (15%), and others (16%). No statistically significant relationship was detected between the central venous catheter, broad-spectrum antibiotic and corticosteroid treatment, parenteral nutrition, gender difference, surgical operation, patient culture samples, isolated Candida species, and mortality (p> 0.05). A statistically significant relationship was found between blood transfusion, thrombocytopenia, and leukopenia, the first positive culture time since hospitalization, and the duration of antibiotic treatment and mortality (p<0.05). A statistically significant correlation was found with the presence of hypotension, one of the clinical markers associated with mortality (p<0.05) but the same relationship was not found with the presence of fever (p> 0.05). The mortality rate is high in candidiasis patients in pediatric intensive care units. Blood transfusions, long-term use of broad-spectrum antibiotics, and hypotension increase mortality.

The importance of developing new mannan tests in the diagnosis of invasive candidiasis in oncology patients

The regimens of anticancer therapy have been intensified and methods of high-dose chemotherapy (HDCT) have been introduced for recent years which made it possible to achieve significant progress in the results of tumor treatments. Intensification of chemotherapy regimens in cancer patients leads to the emergence of risk factors of invasive candidiasis (IC) development: agranulocytosis, disruption of the integrity of the mucous membranes, prolonged use of CVC, repeated antibiotic therapy, long-term parenteral nutrition. Thus, intensification of anticancer therapy may be accompanied by an increase in infection-mediated mortality.IC is the most common invasive mycosis in Russia. More than 11 thousand cases of IC occur in our country every year. The frequency IC in Russia is 8.29 per 100 thousand of the population, which corresponds to the results of the LIFE study in European countries where this indicator varies from 2.2 to 11 per 100 thousand of the population. There are no clinical signs or symptoms specific for IC. It develops in patients with concomitant diseases, which significantly complicates the diagnosis. In this regard, an urgent issue is to improve the diagnosis of candidal infectious complications in cancer patients in order to optimize treatment by studying serological markers that have the greatest value in the diagnosis of infectious complications in cancer patients.

Biomarkers for the diagnosis of invasive candidiasis in immunocompetent and immunocompromised patients

Blood culture methods show low sensitivity, so reliable non–culture diagnostic tests are needed to help clinicians with the introduction, de-escalation, and discontinuation of antifungal therapy in patients with suspected invasive candidiasis (IC). We evaluated different biomarkers for the diagnosis of IC in immunocompetent and immunocompromised patients at risk for developing invasive fungal diseases. The specificity of Candida albicans germ-tube antibodies (CAGTA) detection was high (89%−100%), but sensitivity did not exceed 61% even after raising the cut-off from 1/160 to 1/80. We developed enzyme-linked immunoassays detecting antibodies against C. albicans proteins (Als3-N, Hwp1-N, or Met6) that resulted more sensitive (66%−92%) but less specific than CAGTA assay. The combination of 1,3-beta-D-glucan (BDG) detection and CAGTA results provided the highest diagnostic usefulness in immunocompetent patients. However, in immunocompromised patients, anti–Met6 antibodies was the best biomarker, both, alone or in combination with BDG.

Invasive candidiasis in children

The prevalence of invasive candidiasis (IC) in pediatric hospitals is from 4,3 to 15,2 per 10,000 hospitalized, in ICU – from 3,5 to 7 cases per 1,000, with HSCT – 2,9%. The average length of stay of a patient in the hospital before the development of IC varies from 21 to 56 days, in the ICU – more than 15 days. Knowledge of risk factors (ICU stay for ≥15 days, use of antibacterial drugs and parenteral nutrition, active malignant neoplasm, etc.) makes it possible to identify patients with a high (10-46%) risk of developing IC. Candida albicans remains the leading causative agent of IC in children, but infections with non-albicans Candida spp. have increased and an increase in the resistance of IC pathogens to azole antimycotics was noted. The main clinical variant of IC in children is candidemia, other forms include the central nervous system, abdominal organs, eyes, heart, bones and joints, kidneys, skin and subcutaneous tissue involvement, as well as chronic disseminated (hepatolienal) candidiasis. Blood culture, the main method of laboratory diagnostics of IC, is characterized by low sensitivity and requires a long time. Methods of noncultural diagnostics of IC (1,3-β-D-glucan, mannan and antimannan antibodies, T2 Candida etc) in children have not been sufficiently studied. The main drugs for the treatment of IC in children are echinocandins (anidulafungin, etc.), and CVC removal/replacement is necessary. The overall mortality rate in pediatric patients within 30 days after the diagnosis of IC is 37% to 44%.

Clinical Profile of Non-neutropenic Patients with Invasive Candidiasis: A Retrospective Study in a Tertiary Care Center.

Introduction: Invasive candidiasis (IC) is a major cause of morbidity and mortality in critically ill patients in the intensive care unit (ICU). In this study, we aim to analyze the clinical profile, species distribution, and susceptibility pattern of patients with IC.Methods: Case records of non-neutropenic patients ≥18 years of age with IC between January 2016 and June 2019 at a tertiary care referral hospital were analyzed. IC was defined as either candidemia or isolation of Candida species from a sterile site (such as CSF; ascitic, pleural, or pericardial fluid; or pus or tissue from an intraoperative sample) in a patient with clinical signs and symptoms of infection.Results: A total of 114 patients were analyzed, out of which 105 (92.1%) patients had bloodstream infection (BSI) due to Candida and 9 (7.9%) had IC identified from a sterile site. Central line-associated blood stream infection (27 patients, 23.6%) and a gastrointestinal source (30 patients, 26.3%) were the most common presumed sources for candidemia. The commonest species was Candida tropicalis 42 (36.8%), followed by Candida glabrata 20 (17.5%). Serum beta-D-glucan (BDG) was done only in 32 patients of the 114 (35.3%); among those who were tested, 5 (15.6%) had a BDG value of less than 80 pg/mL despite having Candida BSI. Fluconazole sensitivity was 69.5% overall. At 14 days after diagnosis of IC, 49.1% had recovered, with the remainder having an unfavorable outcome (32.4% had died and 18.4% had left against medical advice).Clinical significance: IC is a major concern in Indian ICUs, with a satisfactory outcome in only half of our patients. Serum BDG is a valuable test to diagnose blood culture-negative IC, but more studies are needed to determine its role in the exclusion of IC, as we had a small minority of patients with negative tests despite proven IC.Conclusion: We recommend sending two sets of blood cultures and serum BDG assay for all suspected patients. Initiating empiric antifungal therapy with an echinocandin is advisable, in view of increasing azole resistance and the emergence of Candida auris, with de-escalation to fluconazole for sensitive isolates after clinical stability and blood culture clearance.How to cite this article: Sridharan S, Gopalakrishnan R, Nambi PS, Kumar S, Sethuraman N, Ramasubramanian V. Indian J Crit Care Med 2021;25(3):267-272.

The role of combined use of mannan antigen and anti-mannan antibodies in the diagnosis of invasive candidiasis in pediatric intensive care unit

The role of combined use of mannan antigen and anti-mannan antibodies in the diagnosis of invasive candidiasis in pediatric intensive care unit

Identification and broth-microdilution antifungal susceptibility testing of yeast directly from automated blood cultures.

Aim: To standardize MALDI-TOF-MS based identification and antifungal susceptibility (AFST) for yeasts directly from automated blood cultures to reduce turnaround time. Materials & methods: Direct-ID after lysis-centrifugation (0.5% SDS) standardized in 40 and validated in 250 yeast positive samples. Direct-AFST was standardized with fluconazole (28 samples) and evaluated (70 samples) for seven antifungals. Results: Direct-ID had a high sensitivity (97.2%) and specificity (94.3%). Correct species-level identification showed 100% in C. tropicalis, C. krusei, C. parapsilosis. Direct-AFST had a 100% categorical agreementwith culture-AFST for posaconazole, anidulafungin and >90% categorical agreement for amphotericin B, voriconazole and fluconazole. Conclusion: Direct-ID and subsequent direct-AFST is a rapid and robust method to reduce the turnaround time for the diagnosis of invasive candidiasis.

The Presence of (1→3)-β-D-Glucan as Prognostic Marker in Patients After Major Abdominal Surgery.

While the serological detection of (1→3)-β-D-glucan (BDG) can indicate invasive fungal disease (IFD), false positivity occurs. Nevertheless, the presence of BDG can still be recognized by the host's innate immune system and persistent BDG antigenemia, in the absence of IFD, can result in deleterious proinflammatory immune responses. During the XXX (INTENSE) study into the preemptive use of micafungin to prevent invasive candidiasis (IC) after abdominal surgery, the serum burden of BDG was determined to aid diagnosis of IC. Data from the INTENSE study were analyzed to determine whether BDG was associated with organ failure and patient mortality, while accounting for the influences of IC and antifungal therapy. A BDG concentration >100 pg/mL was associated with a significantly increased Sequential Organ Failure Assessment score (≤100 pg/mL: 2 vs >100 pg/mL: 5; P < .0001) and increased rates of mortality (≤100 pg/mL: 13.7% vs >100 pg/mL: 39.0%; P = .0002). Multiple (≥2) positive results >100 pg/mL or a BDG concentration increasing >100 pg/mL increased mortality (48.1%). The mortality rate in patients with IC and a BDG concentration >100 pg/mL and ≤100 pg/mL was 42.3% and 25.0%, respectively. The mortality rate in patients without IC but a BDG concentration >100 pg/mL was 37.3%. The use of micafungin did not affect the findings. The presence of persistent or increasing BDG in the patient's circulation is associated with significant morbidity and mortality after abdominal surgery, irrespective of IC. The potential lack of a specific therapeutic focus has consequences when trying to manage these patients, and when designing clinical trials involving patients where host-associated BDG concentrations may be elevated. NCT01122368.