• Candidemia
• Catheter tip
• Catheter-Related Bloodstream Infections
• Endovascular catheter
• catheter related candidemia

• Humans
• Candidemia/microbiology
• Pandemics
• Candida
• Candidiasis/drug therapy
• Catheters
• Antifungal Agents/therapeutic use

• Candida
• Fungitell
• Platelia
• biomarker
• glucan
• mannan
• sepsis

• Adult
• Humans
• Candidemia/diagnosis
• Candidemia/drug therapy
• Candidemia/microbiology
• Mannans
• Glucans/therapeutic use
• Prospective Studies
• beta-Glucans
• Sensitivity and Specificity
• Antigens, Fungal
• Biomarkers
• Recurrence

• WI179471 Pfizer (Pfizer Inc.)
• HE 8209/1-1 Deutsche Forschungsgemeinschaft (DFG)

• Candida infection
• antibiotic stewardship
• antifungal therapy
• biomarker
• candidemia
• candidosis
• discontinuation
• fungal infection

• Adult
• Humans
• Antifungal Agents/therapeutic use
• Mannans
• Glucans
• Prospective Studies
• beta-Glucans
• Candidiasis, Invasive/drug therapy
• Intensive Care Units
• Biomarkers

• HE 8209/1-1 Deutsche Forschungsgemeinschaft (DFG)

• Beta-d-glucan
• continuous renal replacement therapy
• critical care
• invasive candidiasis
• invasive fungal infection

• Adult
• Humans
• Retrospective Studies
• Glucans
• Cohort Studies
• Critical Illness/therapy
• Continuous Renal Replacement Therapy
• Propensity Score
• beta-Glucans
• Renal Replacement Therapy

• Humans
• Inflammasomes/metabolism
• Interleukin-18
• HIV Infections/complications
• HIV Infections/drug therapy
• NLR Family, Pyrin Domain-Containing 3 Protein/genetics
• NLR Family, Pyrin Domain-Containing 3 Protein/metabolism
• Cytokines/metabolism
• Inflammation

• Candida albicans enolase1
• double antibody sandwich enzyme-linked immunosorbent assay
• invasive candidiasis
• laboratory diagnosis
• rabbit model

• Pediatrics
• biomarkers
• invasive candidiasis

Precision medicine risk stratification is desperately needed to both avoid systemic antifungals treatment delay and over prescription in the critically ill with risk factors. The aim of the present study was to explore the combination of host immunoparalysis biomarker (monocyte human leukocyte antigen-DR expression (mHLA-DR)) and Candida sp wall biomarker β-d-glucan in risk stratifying patients for secondary invasive Candida infection (IC).

Prospective observational study. Two intensive care units (ICU). All consecutive non-immunocompromised septic shock patients. Serial blood samples (n = 286) were collected at day 0, 2 and 7 and mHLA-DR and β-d-glucan were then retrospectively assayed after discharge. Secondary invasive Candida sp infection occurrence was then followed at clinicians’ discretion.

Fifty patients were included, 42 (84%) had a Candida score equal or greater than 3 and 10 patients developed a secondary invasive Candida sp infection. ICU admission mHLA-DR expression and β-d-glucan (BDG) failed to predict secondary invasive Candida sp infection. Time-dependent cause-specific hazard ratio of IC was 6.56 [1.24–34.61] for mHLA-DR < 5000 Ab/c and 5.25 [0.47–58.9] for BDG > 350 pg/mL. Predictive negative value of mHLA-DR > 5000 Ab/c and BDG > 350 pg/mL combination at day 7 was 81% [95% CI 70–92].

This study suggests that mHLA-DR may help predicting IC in high-risk patients with septic shock. The added value of BDG and other fungal tests should be regarded according to the host immune function markers.

• Beta D-glucan
• Candidiasis
• Septic shock
• mHLA-DR

• Candida spp
• multiplex PCR
• peritonitis

We aimed to assess the prognostic value of repeated measurements of serum (1–3)-β-D-glucan (BDG), mannan-antigen (mannan-Ag), and antimannan antibodies (antimannan-Ab) for the occurrence of invasive candidiasis (IC) in a high-risk nonimmunocompromised population.

This was a preplanned ancillary analysis of the EMPIRICUS Randomized Clinical Trial, including nonimmunocompromised critically ill patients with intensive care unit–acquired sepsis, multiple Candida colonization, and multiple organ failure who were exposed to broad-spectrum antibacterial agents. BDG (>80 and >250 pg/mL), mannan-Ag (>125 pg/mL), and antimannan-Ab (>10 AU) were collected repeatedly. We used cause-specific hazard models. Biomarkers were assessed at baseline in the whole cohort (cohort 1). Baseline covariates and/or repeated measurements and/or increased biomarkers were then studied in the subgroup of patients who were still alive at day 3 and free of IC (cohort 2).

Two hundred thirty-four patients were included, and 215 were still alive and free of IC at day 3. IC developed in 27 patients (11.5%), and day 28 mortality was 29.1%. Finally, BDG >80 pg/mL at inclusion was associated with an increased risk of IC (CSHR[IC], 4.67; 95% CI, 1.61–13.5) but not death (CSHR[death], 1.20; 95% CI, 0.71–2.02).

Among high-risk patients, a first measurement of BDG >80 pg/mL was strongly associated with the occurrence of IC. Neither a cutoff of 250 pg/mL nor repeated measurements of fungal biomarkers seemed to be useful to predict the occurrence of IC. The cumulative risk of IC in the placebo group if BDG >80 pg/mL was 25.39%, which calls into question the efficacy of empirical therapy in this subgroup.

• (1,3)-β-D-glucan
• competing risk models
• invasive candidiasis

(1→3)-β-glucan (BDG) testing as an adjunct in the diagnosis of invasive fungal disease (IFD) has been in use for nearly three decades. While BDG has a very high negative predictive value in this setting, diagnostic false positives may occur, limiting specificity and positive predictive value. Although results may be diagnostically false positive, they are analytically correct, due to the presence of BDG in the circulation. This review surveys the non-IFD causes of elevated circulating BDG. These are in the main, iatrogenic patient contamination through the use of BDG-containing medical devices and parenterally-delivered materials as well as translocation of intestinal luminal BDG due to mucosal barrier injury. Additionally, infection with Nocardia sp. may also contribute to elevated circulating BDG. Knowledge of the factors which may contribute to such non-IFD-related test results can improve the planning and interpretation of BDG assays and permit investigational strategies, such as serial sampling and BDG clearance evaluation, to assess the likelihood of contamination and improve patient care.

• bacterial
• beta-glucan
• contamination
• diagnostic
• fungal
• parenteral

• (1,3)-β-D-Glucan
• candidemia
• fungal biomarker
• non-culture diagnostic assay
• prognostic factors
• sepsis

Patient: Male, 45-year-old

Final Diagnosis: Fungal endocarditis

Symptoms: Cough • fever • hemiplegia • malaise • shortness of breath

Medication: —

Clinical Procedure: Endarterectomy • valve replacement surgery

Specialty: Cardiology

The Fungitell assay (FA) and the Wako β-glucan test (GT) are employed to measure the serum/plasma 1,3-β-D-glucan (BDG), a well-known invasive fungal disease biomarker. Data to convincingly and/or sufficiently support the GT as a valuable alternative to the FA are yet limited. In this study, we evaluated the FA and the GT to diagnose invasive aspergillosis (IA), invasive candidiasis (IC), and Pneumocystis jirovecii pneumonia (PJP). The FA and GT performances were compared in sera of patients with IA (n = 40), IC (n = 78), and PJP (n = 17) with respect to sera of control patients (n = 187). Using the manufacturer’s cutoff values of 80 pg/mL and 11 pg/mL, the sensitivity and specificity for IA diagnosis were 92.5% and 99.5% for the FA and 60.0% and 99.5% for the GT, respectively; for IC diagnosis were 100.0% and 97.3% for the FA and 91.0% and 99.5% for the GT, respectively; for PJP diagnosis were 100.0% and 97.3% for the FA and 88.2% and 99.5% for the GT, respectively. When an optimized cutoff value of 7.0 pg/mL for the GT was used, the sensitivity and specificity were 80.0% and 97.3% for IA diagnosis, 98.7% and 97.3% for IC diagnosis, and 94.1% and 97.3% for PJP diagnosis, respectively. At the 7.0-pg/mL GT cutoff, the agreement between the assays remained and/or became excellent for IA (95.1%), IC (97.3%), and PJP (96.5%), respectively. In conclusion, we show that the GT performed as well as the FA only with a lowered cutoff value for positivity. Further studies are expected to establish the equivalence of the two BDG assays.

• Adult
• Aged
• Aspergillosis/blood
• Aspergillosis/diagnosis
• Aspergillosis/microbiology
• Aspergillus/immunology
• Aspergillus/isolation & purification
• Candida albicans/immunology
• Candida albicans/isolation & purification
• Candidiasis, Invasive/blood
• Candidiasis, Invasive/diagnosis
• Candidiasis, Invasive/microbiology
• Diagnostic Tests, Routine/classification
• Diagnostic Tests, Routine/methods
• Female
• Humans
• Male
• Middle Aged
• Pneumocystis carinii/immunology
• Pneumocystis carinii/isolation & purification
• Pneumonia, Pneumocystis/blood
• Pneumonia, Pneumocystis/diagnosis
• Pneumonia, Pneumocystis/microbiology
• ROC Curve
• beta-Glucans/analysis

• Fujifilm Corporation (JP)

Candida is one of the most frequent pathogens of bloodstream infections, which is associated with high morbidity and mortality rates. Rapid immunological detection methods are essential in the early diagnosis of candidemia. Anti-mannan is one of host-derived biomarkers against cell wall components of Candida. We conducted this study to evaluate the diagnostic performance of two anti-mannan assays (IgM, IgG) for candidemia through the analysis of 40 candidemia patients, 48 participants with Candida colonization and 213 participants with neither Candida colonization nor Candida infections (13 patients with other bloodstream infections, 145 hospitalized patients and 55 healthy controls). The performance of the two assays were evaluated by calculating their sensitivity and specificity. The sensitivity ranged from 0.78 to 0.80 for the IgM assay and 0.68 to 0.75 for the IgG assay. The specificity ranged from 0.97 to 0.98 for the IgM assay and 0.91 to 0.94 for the IgG assay. The diagnostic performance of the anti-mannan IgM assay was better than that of IgG, with higher sensitivity and specificity. Combining the two assays (positive results of single or both assays are both considered as positive) could improve the sensitivity up to 0.93 (0.79-0.98) and only slightly reduce the specificity (0.93(0.89-0.95)). The anti-mannan IgM, IgG assays are rapid and cost-effective assays that may be probably useful in the diagnosis of candidemia.

• (1,3)-β-D-glucan (BDG)
• antimannan antibody
• diagnosis
• invasive candidiasis
• mannan

• T2 Candida
• fungi
• lateral flow assay
• next generation sequencing
• proximity ligation assay
• risk stratification

• Candida
• candidemia
• diagnosis
• proteomics
• sequencing
• yeast pathogens

• Antifungal Agents/pharmacology
• Antifungal Agents/therapeutic use
• Drug Resistance, Multiple, Fungal
• High-Throughput Nucleotide Sequencing/methods
• High-Throughput Nucleotide Sequencing/trends
• Humans
• Mycoses/diagnosis
• Mycoses/drug therapy
• Mycoses/microbiology
• Pathology, Molecular/methods
• Pathology, Molecular/trends
• Point-of-Care Systems/trends
• Polymerase Chain Reaction/trends
• Proteomics
• Whole Genome Sequencing/trends
• Yeasts/drug effects
• Yeasts/genetics
• Yeasts/pathogenicity

• MR/N006364/1 Medical Research Council
• W 1253 Austrian Science Fund FWF

Procalcitonin (PCT) is a biomarker used to assess systemic inflammation, infection, and sepsis and to optimize antimicrobial therapies. Its role in the in the differential diagnosis between candidemia and bacteremia is unclear. The aim of this systematic review was to summarize the current evidence about PCT values for differentiating candidemia from bacteremia.

PubMed and EMBASE were searched for studies reporting data on the diagnostic performance of serum PCT levels in intensive care unit (ICU) or non-ICU adult patients with candidemia, in comparison to patients with bacteremia.

We included 16 studies for a total of 45.079 patients and 785 cases of candidemia. Most studies claimed to report data relating to the use of PCT values for differentiating between candidemia and bacteremia in septic patients in the intensive care unit. However, the studies identified were all retrospective, except for one secondary analysis of a prospective dataset, and clinically very heterogeneous and involved different assessment methods. Most studies did show lower PCT values in patients with candidemia compared to bacteremia. However, the evidence supporting this observation is of low quality and the difference seems insufficiently discriminative to guide therapeutic decisions. None of the studies retrieved actually studied guidance of antifungal treatment by PCT. PCT may improve diagnostic performance regarding candidemia when combined with other biomarkers of infection (e.g., beta-d-glucan) but more data is needed.

PCT should not be used as a standalone tool for the differential diagnosis between candidemia and bacteremia due to limited supporting evidence.

The online version of this article (10.1186/s13054-019-2481-y) contains supplementary material, which is available to authorized users.

• Biomarker
• Candida
• Candidemia
• Fungal
• Fungi
• PCT
• Procalcitonin
• Sepsis

• Antifungal Agents/therapeutic use
• Aspergillus
• Candida
• Humans
• Incidence
• Invasive Fungal Infections/drug therapy

• Candida parapsilosis
• antifungal
• epidemiology
• experimental tools
• genome
• host response
• pathogenicity
• treatment
• virulence

Allogeneic hematopoietic stem cell transplantation (allo-HSCT) has become a widely used modality of therapy for a variety of malignant and nonmalignant diseases. Despite advances in pharmacotherapy and transplantation techniques, infection remains one of the most severe and frequently encountered complications of allo-HSCT.

This chapter will address the risk factors for development of infection following allo-HSCT, including those related to the host, the conditioning regimen, and the graft, as well as the timing of opportunistic infections after allo-HSCT. The most common bacterial, viral, fungal, and parasitic infections, as well as issues surrounding their diagnostics and treatment, will be discussed. Finally, this chapter will address vaccination and other preventative strategies to be utilized when caring for patients undergoing allo-HSCT.

• allogeneic hematopoietic stem cell transplantation (allo-hsct)
• opportunistic infection
• bacterial, viral, fungal, and parasitic infections
• vaccination
• preventative strategies

1,3-beta-D Glucan (BDG) assay has good accuracy for distinguishing patients with invasive fungal infections from patients without. Some procedures and medications affect BDG levels, resulting in false-positive BDG results. The extent of intestinal surgery on BDG kinetics is unknown. We evaluated the influence of laparoscopic and open intestinal surgery on peri- and postsurgical serum BDG values.

BDG was determined in 346 samples from 50 patients undergoing laparoscopic (24) or open (26) intestinal surgery at the following time points: after insertion of arterial but before skin incision, after skin incision but before dissection of the intestinal mucosa, after completion of anastomosis, after completion of skin sutures, in the evening after surgery, day 2 after surgery, 4–5 days after surgery.

BDG was positive (ie, concentration ≥80 pg/mL) in 54% to 61% of patients during laparoscopic and open surgery (highest rates after completion of skin sutures). BDG was still positive in 12% (open) to 17% (laparoscopic) of patients without any suspected or proven fungal infection or anastomotic leakage 4–5 days after surgery. After completion of gut anastomosis, the BDG increase was higher in open compared with laparoscopic intestinal surgery.

The value of positive BDG tests in the perioperative setting up to 5 days postsurgery seems to be limited due to BDG elevations from intestinal surgical procedures.

• 1,3-ß-D-Glucan
• Candida
• surgery

• BDG
• Beta-D-glucan
• Candidemia
• Mannan
• Serology

• cancer
• diagnosis
• fungal infections
• granulocytopenia
• haematology
• recommendations

• BDG
• Candida
• Fungitell
• PCP
• Wako
• beta-d-glucan
• biomarker
• candidiasis
• candidosis
• pneumocystis

• Antifungal Agents/therapeutic use
• Candida/classification
• Candida/drug effects
• Candida/isolation & purification
• Candidiasis, Invasive/diagnosis
• Candidiasis, Invasive/drug therapy
• Diagnostic Tests, Routine/methods
• Disease Management
• Drug Resistance, Fungal
• Drug Therapy/methods
• Drug Therapy/trends
• Echinocandins/therapeutic use
• Fluconazole/therapeutic use
• Humans

• UM1 AI104681 NIAID NIH HHS

• (1,3)-β-D-Glucan
• Antifungal
• Candida
• Critical illness
• Empirical
• Mannan

• Aged
• Algorithms
• Antibodies, Fungal/blood
• Antifungal Agents/therapeutic use
• Biomarkers/blood
• Candidiasis, Invasive/blood
• Candidiasis, Invasive/drug therapy
• Candidiasis, Invasive/immunology
• Critical Illness/therapy
• Drug Administration Schedule
• Female
• Humans
• Intensive Care Units
• Male
• Mannans/blood
• Middle Aged
• Predictive Value of Tests
• Prospective Studies
• Proteoglycans
• beta-Glucans/blood

• galactomannan
• invasive fungal disease
• mannan
• polymerase chain reaction
• β-D-glucan

• Antibodies, Fungal/analysis
• Antigens, Fungal/analysis
• Aspergillosis/diagnosis
• Aspergillus/genetics
• Biomarkers/blood
• Candida/genetics
• Candidiasis/diagnosis
• Child
• DNA, Fungal/analysis
• Galactose/analogs & derivatives
• Humans
• Immunoassay
• Invasive Fungal Infections/diagnosis
• Mannans/analysis
• Polymerase Chain Reaction
• beta-Glucans/analysis

• K08 DE026189 NIDCR NIH HHS
• R01 HD081044 NICHD NIH HHS

• Candida
• Critical illness
• Procalcitonin
• Sepsis

• Aged
• Aged, 80 and over
• Bacterial Infections/diagnosis
• Biomarkers/analysis
• Biomarkers/blood
• Calcitonin/analysis
• Calcitonin/blood
• Candida/pathogenicity
• Candidiasis/diagnosis
• Candidiasis/epidemiology
• Case-Control Studies
• Critical Illness/epidemiology
• Female
• Humans
• Intensive Care Units/organization & administration
• Intensive Care Units/statistics & numerical data
• Italy/epidemiology
• Male
• Middle Aged
• Retrospective Studies
• Sepsis/classification
• Sepsis/epidemiology

Sera from candidemic and non-candidemic subjects were examined for antibodies against the cell wall β1,3- and β1,6-glucans, as well as the β-glucan-associated protein MP65 of Candida species. Although antibodies against each of the above components were detected in all subjects, candidemic patients had lower antibody titers against β1,3-glucan, but higher antibody titers against β1,6-glucan and MP65, than non-candidemic subjects. The elevated levels of anti-β1,6-glucan and -MP65 antibodies found in candidemic patients were independent on the patient risk category, APACHE II score, presence of co-morbidities, β1,3-glucanemia level, Candida isolate, and antifungal treatment. Interestingly, however, the anti-MP65, but not the anti-β1,6-glucan antibodies, of candidemic patients had higher titers in survivors than in non-survivors, particularly in those subject categories with the highest mortality (>65-years old, diabetic, or septic shock patients). Thus, candidemic patients are capable of boosting anti-Candida immune responses upon infection, and some of these responses might be associated to the generation of protective immunity in patients with candidemia.

• Diagnostics
• Galactomannan
• Imaging
• Invasive fungal disease
• PCR
• Paediatric patients

• Wellcome Trust
• MR/N006364/1 Medical Research Council
• University of Aberdeen

• 1,3 β-D-glucan
• Fungal diagnosis
• T2Candida assay
• antigen galactomannan
• invasive fungal infections
• pediatrics

The extent of gut microbial translocation, which plays roles in HIV disease progression and non-AIDS comorbidities, appears to vary with the composition of the gut microbiome, particularly the presence of Lactobacillales, which reduce mucosal injury. While low proportions of Lactobacillales in the distal gut microbiome are a very promising indicator of microbial translocation, measurement is expensive and complicated and not feasible for clinical routine. (1→3)-β-d-Glucan (BDG) is a component of most fungal cell walls and might be a surrogate marker for Lactobacillales proportion in the gut and a useful indicator of HIV-associated gut injury. This study evaluated BDG as a biomarker of gut integrity in adults with acute or early HIV infection (AEH).

Study samples were collected longitudinally during study visits at weeks 0, 12, and 24 in a cohort of 11 HIV-infected men starting antiretroviral therapy during AEH. Blood plasma levels of BDG, soluble cluster of differentiation 14 (sCD14) and lipopolysaccharide (LPS) were measured and then correlated with the proportion of Lactobacillales in the distal gut microbiome, as measured by 16s rDNA sequencing by using mixed-effects models with random intercepts.

Mean BDG and sCD14 levels across subjects were associated with Lactobacillales after controlling for time effects and within-subjects correlations (p-values < 0.05), while LPS levels were not. Specifically, each point increase in mean BDG and sCD14 levels across participants was associated with 0.31 ± 0.14 and 0.03 ± 0.01 percent decrease in mean Lactobacillales proportions, respectively.

BDG and sCD14 may be indicators of low Lactobacillales in the gut in adults with acute or early HIV infection, and serve as biomarkers of gut integrity and microbial translocation in HIV infection. Larger studies are needed to confirm our findings.

• HIV
• Lactobacillales
• acute HIV infection
• beta-d-glucan
• microbial translocation
• microbiome

• (1 → 3)-ß-D-glucan
• Anti-mannan antibody
• Candida PCR
• Candida albicans germ tube antibody
• Candida spp. colonization
• Candidemia
• Intra-abdominal candidiasis
• Invasive candidiasis
• Mannan antigen

• BDG
• allogeneic
• antifungal prophylaxis
• autologous
• stem cell transplantation