Disseminated Lomentospora prolificans infection that could have been predicted: A case report.

Lomentospora prolificans is a rare, filamentous fungus, that causes a disseminated infection in immunocompromised individuals. Disseminated infections caused by the fungus are difficult to diagnose early. It is resistant to multiple antifungal agents and has a high mortality rate. We encountered a case in which the involvement of this fungus was indicated by a history of antifungal prophylaxis and an elevated serum 1,3-beta-D-glucan (BDG) level. A 76-year-old female with myelodysplastic syndrome that developed into overt leukemia was administered oral posaconazole as antifungal prophylaxis. She was admitted to the hospital to determine the cause of her fever, where no new abnormalities other than an elevated serum BDG level were observed. Unfortunately, the patient died due to acute respiratory failure on the same day of admission. The day after her death, L. prolificans was detected in a blood culture taken upon her admission. L. prolificans should be suspected based on the history of antifungal prophylaxis and an elevated serum BDG level, as these are risk factors for infection by this pathogen. Blood cultures are useful to provide a diagnosis. If treated early, before it is detected in culture, the mortality rate can be decreased.

Case report: Chronic Candida albicans meningitis: a rare entity diagnosed by metagenomic next-generation sequencing.

The aetiology of chronic aseptic meningitis is difficult to establish. Candida meningitis in particular is often diagnosed late, as cerebrospinal fluid (CSF) work-up and imaging findings are nonspecific. A 35-year-old patient with chronic aseptic meningitis, for which repeated microbiological testing of CSF was unrevealing, was finally diagnosed with Candida albicans (C. albicans) meningitis with cauda equina involvement using metagenomic next-generation sequencing (mNGS). This report highlights the diagnostic challenges and the difficulties of treating shunt-associated fungal meningitis.

Negative serum (1,3) -ß-D-glucan has a low power to exclude Pneumocystis jirovecii pneumonia (PJP) in HIV-uninfected patients with positive qPCR.

OBJECTIVE: The current study evaluated the diagnostic performance of serum (1,3)-beta-D Glucan (BDG) in differentiating PJP from P. jirovecii-colonization in HIV-uninfected patients with P. jirovecii PCR-positive results. METHODS: This was a single-center retrospective study between 2019 and 2021. The diagnosis of PJP was based on the following criteria: detection of P. jirovecii in sputum or BAL specimen by qPCR or microscopy; Meet at least two of the three criteria: (1) have respiratory symptoms of cough and/or dyspnea, hypoxia; (2) typical radiological picture findings; (3) receiving a complete PJP treatment. After exclusion, the participants were divided into derivation and validation cohorts. The derivation cohort defined the cut-off value of serum BDG. Then, it was verified using the validation cohort. RESULTS: Two hundred and thirteen HIV-uninfected patients were enrolled, with 159 PJP and 54 P. jirovecii-colonized patients. BDG had outstanding specificity, LR, and PPV for PJP in both the derivation (90.00%, 8.900, and 96.43%) and the validation (91.67%, 9.176, and 96.30%) cohorts at ≥ 117.7 pg/mL. However, it had lower sensitivity and NPV in the derivation cohort (89.01% and 72.97%), which was even lower in the validation cohort (76.47% and 57.89%). Of note, BDG ≥ 117.7 pg/mL has insufficient diagnostic efficacy for PJP in patients with lung cancer, interstitial lung disease (ILD) and nephrotic syndrome. And although lymphocytes, B cells, and CD4+ T cells in PJP patients were significantly lower than those in P. jirovecii-colonized patients, the number and proportion of peripheral blood lymphocytes did not affect the diagnostic efficacy of serum BDG. CONCLUSIONS: Serum BDG ≥ 117.7 pg/mL could effectively distinguish P. jirovecii-colonization from infection in qPCR-positive HIV-uninfected patients with infectious diseases, solid tumors (excluding lung cancer), autoimmune or inflammatory disorders, and hematological malignancies. Of note, for patients with lung cancer, ILD, and nephrotic diseases, PJP should be cautiously excluded at BDG < 117.7 pg/mL.

Use of 1,3-Beta-D-Glucan concentration in peritoneal fluid for the diagnosis of intra-abdominal Candidiasis in Critically-ill patients.

Intra-Abdominal Candidiasis (IAC) is frequent and associated with high mortality in intensive care unit (ICU) patients. Antifungal treatments may be overused due to a lack of diagnostic tools to rule out IAC. Serum 1,3-Beta-D-Glucan (BDG) concentrations are used to diagnose Candida infections, its concentration in peritoneal fluid (PF) may help to confirm or invalidate the diagnosis of IAC. We performed a non-interventional, prospective, multicenter study, at the Hospices Civils de Lyon, France, in seven ICU located in three different hospitals from December 2017 to June 2018. IAC was defined as the isolation of Candida in a sample collected from the intra-abdominal cavity under sterile conditions in patients displaying clinical evidence of intra-abdominal infection. Among the 113 included patients, 135 PF samples corresponding to 135 intra-abdominal infection episodes were collected and BDG concentrations were assessed. IAC accounted for 28 (20.7%) of the intra-abdominal infections. Antifungals were administered empirically to 70 (61.9%) patients; among them, 23 (32.9%) had an IAC. The median [IQR] BDG value was significantly higher in IAC (8100 [3000;15000] pg/mL) than in non-IAC samples (1961 [332;10650] pg/mL). BDG concentrations were higher in PF with Fecaloid aspect and in case of positive bacterial culture. For a BDG threshold of 125 pg/mL, the negative predictive value to assess IAC was 100%. In conclusion, low BDG PF concentrations could be used to rule out IAC. https://clinicaltrials.gov/ct2/show/NCT03469401.

Intra-Abdominal Candidiasis (IAC) is associated with a high mortality in Intensive Care Unit (ICU) patients. 1,3-Beta-D-Glucan (BDG), a component of Candida cell wall, was prospectively measured in peritoneal fluid from ICU patients Low peritoneal BDG concentrations may be used to rule out IAC.

The Diagnostic Values of Peptidoglycan, Lipopolysaccharide, and (1,3)-Beta-D-Glucan in Patients with Suspected Bloodstream Infection: A Single Center, Prospective Study.

This study aimed to assess the diagnostic values of peptidoglycan (PGN), lipopolysaccharide (LPS) and (1,3)-Beta-D-Glucan (BDG) in patients with suspected bloodstream infection. We collected 493 heparin anticoagulant samples from patients undergoing blood culture in Peking Union Medical College Hospital from November 2020 to March 2021. The PGN, LPS, and BDG in the plasma were detected using an automatic enzyme labeling analyzer, GLP-F300. The diagnostic efficacy for PGN, LPS, and BDG were assessed by calculating the sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV). This study validated that not only common bacteria and fungi, but also some rare bacteria and fungi, could be detected by testing the PGN, LPS, and BDG, in the plasma. The sensitivity, specificity, and total coincidence rate were 83.3%, 95.6%, and 94.5% for PGN; 77.9%, 95.1%, and 92.1% for LPS; and 83.8%, 96.9%, and 95.9% for BDG, respectively, which were consistent with the clinical diagnosis. The positive rates for PGN, LPS, and BDG and the multi-marker detection approach for PGN, LPS, and BDG individually were 11.16%, 17.65%, and 9.13%, and 32.86% significantly higher than that of the blood culture (p < 0.05). The AUC values for PGN, LPS, and BDG were 0.881 (0.814−0.948), 0.871 (0.816−0.925), and 0.897 (0.825−0.969), separately, which were higher than that of C-reactive protein (0.594 [0.530−0.659]) and procalcitonin (0.648 [0.587−0.708]). Plasma PGN, LPS, and BDG performs well in the early diagnosis of bloodstream infections caused by Gram-positive and Gram-negative bacterial and fungal pathogens.

Highly Conserved gsc1 Gene of Pneumocystis jirovecii in Patients with or without Prior Exposure to Echinocandins.

Echinocandins are noncompetitive inhibitors of the GSC1 subunit of the enzymatic complex involved in synthesis of 1,3-beta-d-glucan, a cell wall component of most fungi, including Pneumocystis spp. Echinocandins are widely used for treating systemic candidiasis and rarely used for treating Pneumocystis pneumonia. Consequently, data on P. jirovecii gsc1 gene diversity are still scarce compared to that for the homologous fks1 gene of Candida spp. In this study, we analyzed P. jirovecii gsc1 gene diversity and the putative selection pressure of echinocandins on P. jirovecii. gsc1 gene sequences of P. jirovecii specimens from two patient groups were compared. One group of 27 patients had prior exposure to echinocandins, whereas the second group of 24 patients did not, at the time of P. jirovecii infection diagnoses. Two portions of the P. jirovecii gsc1 gene, HS1 and HS2, homologous to hot spots described in Candida spp., were sequenced. Three single-nucleotide polymorphisms (SNPs) at positions 2204, 2243, and 2303 close to the HS1 region and another SNP at position 4540 more distant from the HS2 region were identified. These SNPs represent synonymous mutations. Three gsc1 HS1 alleles, A, B, and C, and two gsc1 HS2 alleles, a and b, and four haplotypes, Ca, Cb, Aa, and Ba, were defined, without significant difference in haplotype distribution in both patient groups (P = 0.57). Considering the identical diversity of P. jirovecii gsc1 gene and the detection of synonymous mutations in both patient groups, no selection pressure of echinocandins among P. jirovecii microorganisms can be pointed out so far.

Low cut-off value of serum (1,3)-beta-D-glucan for the diagnosis of Pneumocystis pneumonia in non-HIV patients: a retrospective cohort study.

BACKGROUND: Non-human immunodeficiency virus (HIV) Pneumocystis pneumonia (PCP) is a fulminant disease with an increasing incidence. The serum beta-D-glucan (BDG) assay is used as an adjunct to the diagnosis of PCP; however, the cut-off value for this assay is not well-defined, especially in the non-HIV PCP population. Therefore, we aimed to identify the assay cut-off value for this population. METHODS: In this retrospective observational study, we reviewed the medical records of all patients (≥ 18 years old) with clinical suspicion of PCP who underwent evaluation of respiratory tract specimens between December 2008 and June 2014 at Kameda Medical Center. We created a receiver operating characteristic curve and calculated the area under the curve to determine the cut-off value for evaluating the inspection accuracy of the BDG assay. RESULTS: A total of 173 patients were included in the study. Fifty patients showed positive results in specimen staining, loop-mediated isothermal amplification assay, and polymerase chain reaction test, while 123 patients showed negative results. The receiver operating characteristic analyses suggested that the BDG cut-off level was 8.5 pg/mL, with a sensitivity and specificity of 76% and 76%, respectively. CONCLUSIONS: The Wako-BDG cut-off value for the diagnosis of non-HIV PCP is 8.5 pg/mL, which is lower than the classical cut-off value from previous studies. Clinicians should potentially consider this lower BDG cut-off value in the diagnosis and management of patients with non-HIV PCP. TRIAL REGISTRATION:  The participants were retrospectively registered.

Temozolomide is a risk factor for invasive pulmonary aspergillosis: A case report and literature review.

BACKGROUND: Temozolomide is an oral alkylating agent incorporated in the treatment of glioblastoma multiforme (GBM) that can lead to lymphopenia. The standard treatment of GBM involves temozolomide chemotherapy with radiation, often with addition of corticosteroids for symptomatic management of cerebral edema. Some studies have reported an increased risk of opportunistic infections. CASE PRESENTATION: A 72-year-old man receiving Temozolomide for treatment of newly diagnosed GBM associated with radiotherapy and corticosteroids was admitted in an intensive care unit because a rapid deterioration of consciousness associated with acute respiratory failure. The diagnosis of invasive pulmonary aspergillosis (IPA) was made. The patient was successfully treated with voriconazole alone. CONCLUSIONS: This case shows that Temozolomide can be associated with severe invasive aspergillosis, which is in all likelihood associated with T lymphocyte immune dysfunction. Physicians should be aware of possible opportunistic infections when managing patients with glioblastoma, and patients exposed to this agent should be carefully monitored.

Diagnostic value of serum human Galactomannan aspergillus antigen and 1,3-beta-D-glucan in immunocompromised patient suspected fungal infection.

BACKGROUND: The prevalence of fungal infection (FI) in developing countries is high, but the diagnosis of FI is still challenging to determine, so it is needed evaluation of biomarkers other than microbiological culture, because the culture has low sensitivity, high cost, not available in every laboratory and needs a long time. The detection of human galactomannan Aspergillus antigen (GAL) and 1,3-beta-D-glucan (BDG) on the fungal cell wall could be the promising biomarkers for fungal infection. Neutropenia, lymphopenia and CD4T cells in the immunocompromised patients are essential factors, but these cell associations with BDG and GAL levels have not been evaluated yet. The study aimed to evaluate GAL and BDG for detecting fungal infection and their association with total leucocyte count, neutrophil, monocyte, lymphocyte and CD4T cells. METHOD: A cross-sectional study was conducted among 86 patient with suspected FI. Fungal infection established using EORTC/MSG criteria. Serology test performed using ELISA. Leucocyte cells were measured using a haematology autoanalyser, and CD4T cells were analysed using BD FACSPresto. Statistical analysis obtained using Spearman's correlation coefficient, ROC curve analysis and 2 × 2 contingency table. RESULTS: Serum Galactomannan and BDG had a significant correlation with CD4T cells and total lymphocyte count (p < 0.05). The cut-off OD GAL >0.3 had sensitivity 54.6%, specificity 87.5% and AUC 0.71; meanwhile, the BDG cut-off >115.78 pg/ mL had sensitivity 71.2%, specificity 52.4% and AUC 0.63 for detecting fungal infection. CONCLUSIONS: The immunocompromised patients can undergo GAL for determining the diagnose of FI. The lower the CD4T cells and total lymphocyte count, the higher the GAL and BDG serum levels.

Glucan rich nutrition does not increase gut translocation of beta-glucan.

BACKGROUND: (1-3)-b-D-glucan (BDG) is a fungal cell wall component and, in the absence of invasive fungal infection, a novel biomarker for microbial translocation of endogenous fungal products from the gastrointestinal tract into systemic circulation. However, its value as a marker of fungal translocation is limited by a concern that plant BDG-rich food influences blood BDG levels. METHODS: We conducted a pilot clinical trial to evaluate the impact of a standardised oral BDG challenge on blood BDG levels in participants with and without elevated microbial translocation. We enrolled 14 participants including 8 with HIV infection, 2 with advanced liver cirrhosis, and 4 healthy controls. After obtaining a baseline blood sample, participants received a standardised milkshake containing high levels of BDG followed by serial blood samples up to 8 hours after intake. RESULTS: The standardised oral BDG challenge approach did not change the blood BDG levels over time in all participants. We found consistently elevated blood BDG levels in one participant with advanced liver cirrhosis and a single person with HIV with a low CD4 count of 201 cells/mm3 . CONCLUSION: Our findings indicate that BDG blood levels were not influenced by plant origin BDG-rich nutrition in PWH, people with advanced liver cirrhosis, or healthy controls. Future studies are needed to analyse gut mycobiota populations in individuals with elevated blood BDG levels.

Duration of posaconazole therapy for Aspergillus fumigatus osteomyelitis dictated by serial monitoring of 1,3-beta-D glucan.

Here, we present a case of an immunocompetent 37-year old male who developed Aspergillus fumigatus osteomyelitis 16 years after extensive chest wall reconstructive surgery for Ewing sarcoma. His treatment course was complicated by a severe adverse drug reaction to voriconazole, requiring the use of oral posaconazole therapy. Serum 1,3-beta-D glucan assay was utilized to dictate the duration of posaconazole therapy. The patient successfully completed 9 months of oral posaconazole therapy and has not had clinical recurrence for 9 months off antifungal therapy.

Efficacy of Cerebrospinal Fluid Beta-d-Glucan Diagnostic Testing for Fungal Meningitis: a Systematic Review.

Several case reports and cohort studies have examined the use of (1,3)-beta-d-glucan measurement with cerebrospinal fluid to diagnose fungal meningitis. This systematic review aims to characterize the evidence regarding cerebrospinal fluid (1,3)-beta-d-glucan measurement to detect fungal meningitis. We searched PubMed for (1,3)-beta-d-glucan and each of several distinct fungi, cerebrospinal fluid, and meningitis. Summary data including diagnostic performance (where applicable) were recorded. A total of 939 records were examined via a PubMed search. One hundred eighteen records remained after duplicates were removed, and 104 records were excluded, as they did not examine cerebrospinal fluid, included animals, or focused on nonfungal infections. Fourteen studies were included in this systematic review. A variety of fungi, including species of Candida, Aspergillus, Exserohilum, Cryptococcus, Histoplasma, and Coccidioides, were studied, although most were case reports. Diagnostic accuracy was examined in 5 studies. Cerebrospinal fluid (CSF) (1,3)-beta-d-glucan measurement showed >95% sensitivity in the corticosteroid injection-related outbreak of Exserohilum rostratum One study in Histoplasma meningitis found 53% (53/87) sensitivity and 87% (133/153) specificity, while another study of Cryptococcus meningitis found 89% (69/78) sensitivity and 85% (33/39) specificity. CSF (1,3)-beta-d-glucan testing may be useful, primarily as a nonspecific marker of fungal meningitis. Although the FDA black box warning states that Cryptococcus spp. do not make (1,3)-beta-d-glucan, the current evidence shows that (1,3)-beta-d-glucan is detectable in cryptococcal meningitis. Organism-specific testing should be used in conjunction with (1,3)-beta-d-glucan measurement.

Diagnostic accuracy of serum (1,3)-beta-d-glucan for neonatal invasive candidiasis: systematic review and meta-analysis.

OBJECTIVES: Neonatal invasive candidiasis (NIC) is a leading cause of infection-related morbidity and mortality in preterm neonates. Several studies have shown that (1,3)-Beta-d-glucan (BDG) was accurate in detecting invasive fungal infection in adults, but studies in neonates are scarce. The aim was to obtain summary estimates of the accuracy of BDG detection in serum for the diagnosis of NIC. METHODS: We searched Medline, Embase, Clinicaltrials.gov, and Google Scholar (inception to July 2019). We checked the reference lists of included studies, clinical guidelines, and review articles. We included studies that assessed the accuracy of BDG against a reference standard that defined groups of patients with ordinal levels of NIC probability (e.g. proven, probable, possible) and included fungal blood culture. Participants were neonates suspected of having NIC. The intervention was BDG measurement in serum (Fungitell® assay). We assessed risk of bias and applicability using QUADAS-2. We used bivariate meta-analysis to produce summary estimates of diagnostic accuracy at prespecified positivity thresholds of 80 and 120 pg/mL. This study was registered with PROSPERO (CRD42018089545). RESULTS: We included eight studies (465 participants). Of these, two were judged at low overall risk of bias. There was substantial variability across studies in the reference standards used. At a positivity threshold of 80 pg/mL, summary estimates of sensitivity and specificity of BDG were 89% (95% CI: 80-94%) and 60% (53-66%), respectively; summary sensitivity for detecting proven cases of NIC was 99% (93-100%). At a positivity threshold of 120 pg/mL, summary estimates of sensitivity and specificity were 81% (71-88%) and 80% (67-88%), respectively. CONCLUSIONS: Because of high sensitivity, BDG seems promising to rule-out NIC. It might be too early to recommend its use because of the scarcity of reliable clinical data, heterogeneity in case definitions, and unstable accuracy estimates.

Comparative sensitivity of 1,3 beta-D-glucan for common causes of candidaemia in South Africa.

Culture-based diagnosis of candidaemia suffers poor sensitivity and prolonged turnaround time. The 1,3-beta-D-glucan (BDG) assay is a non-culture-based broad fungal antigen with rapid turnaround time. To assess overall, species-specific and population-specific sensitivity of the BDG assay for candidaemia, to determine if the BDG assay is able to detect candidaemia prior to blood culture collection, and to evaluate the performance of the assay for the detection of Candida auris candidaemia. A retrospective review of all blood cultures (BC) with C albicans, C parapsilosis, C glabrata, C krusei and C auris was performed. A corresponding BDG result (Fungitell® ) within 10 days of the BC was sought on the laboratory information system. Overall sensitivity of the assay was 79% (95% CI 73-85; 173/218). Per species sensitivity was 81% (95% CI 72-90; 66/81) for C albicans, 72% (61-83; 60/83) for C parapsilosis, 90% (95% CI 79-100; 27/30) for C glabrata, 71% (95% CI 43-99; 10/14) C auris and 100% (10/10) for C krusei. No statistically significant difference in sensitivity between species was noted (P = .093). The assay demonstrated 92% (59/64) sensitivity in neonatal ICU (P = .047) compared to 94% (15/16) in surgery, 81% (59/73) in adult ICUs and 71% (15/21) in Oncology. BDG results were positive up to 10 days prior to blood culture collection with no significant difference in detection rate (P = .563). BDG results were positive up to 10 days prior to blood culture collection. BDG when collected a mean of 2.5 days (range 1-10 days) prior to blood culture collection were positive.

High initial (1, 3) Beta-d-Glucan concentration may be a predictor of satisfactory response of c aspofungin combined with TMP/SMZ for HIV-negative patients with moderate to severe Pneumocystis jirovecii pneumonia.

OBJECTIVES: The aim of this study was to investigate the efficacy of combination therapy of caspofungin and TMP/SMZ (trimethoprim/sulfamethoxazole) in moderate to severe pneumocystis jirovecii pneumonia (PJP) in patients without human immunodeficiency virus infection (HIV) and the relationship between therapeutic effect and plasma (1, 3) Beta-d-Glucan (BDG) levels. METHODS: We retrospectively reviewed HIV-negative patients with PJP diagnosed in our department, who were treated with combination therapy of caspofungin and TMP/SMZ or monotherapy of TMP/SMZ during a six and a half year period. RESULTS: A total of 126 moderate to severe PJP patients were enrolled in the study. In the multivariate analysis, low lymphocyte counts, high serum lactate dehydrogenase levels at the diagnosis of PJP and progression to shock were significant risk factors for death. In all patients, there was no significant difference in risk of death at 3 months. In the group of BDG≥800pg/m, patients receiving combination therapy was associated with a significantly decreased risk of death at 3 months, whereas in the group of BDG<800pg/ml, there were no statistically significant difference in survival rate between the two treatment regimens. CONCLUSION: High initial plasma (1, 3) Beta-d-Glucan concentration may be a predictor of satisfactory caspofungin response to HIV-negative patients with PJP. Based on our findings, we suggest the choice of combination therapy with caspofungin and TMP/SMZ as the initial treatment when BDG≥800pg/ml in moderate to severe HIV-negative patients with PJP.

Serum-based diagnosis of Pneumocystis pneumonia by detection of Pneumocystis jirovecii DNA and 1,3-ß-D-glucan in HIV-infected patients: a retrospective case control study.

BACKGROUND: Pneumocystis jirovecii pneumonia (PCP) is one of the most common HIV-related opportunistic infections. The diagnosis of PCP is based on analyses from respiratory tract specimens which may require the invasive procedure of a diagnostic bronchoscopy. The objective of this study was to evaluate the diagnostic potential of Pneumocystis jirovecii PCR in serum combined with the 1,3-ß-D-glucan (betaglucan) test for the diagnosis of PCP in HIV-infected patients. METHODS: This was a retrospective case-control study including serum samples from 26 HIV-infected patients with PCP collected within 5 days prior to the start of PCP treatment, 21 HIV-infected control subjects matched by blood CD4+ cell counts, and 18 blood donors. The serum samples were analyzed for Pneumocystis jirovecii PCR and betaglucan. The reference standard for PCP was based on previously described microbiological and clinical criteria. RESULTS: All patients with PCP had detectabe Pneumocystis jirovecii DNA in serum yielding a sensitivity for the Pneumocystis jirovecii PCR assay in serum of 100%. All blood donors had negative Pneumocystis PCR in serum. The specificity when testing HIV-infected patients was 71%, but with a PCR Cycle threshold (Ct) value of 34 as cut-off the specificity was 90%. At a putative pretest probaility of 20%, the negative and positive predictive value for the Pneumocystis PCR assay in serum was 0.99 and 0.71, respectively. Betaglucan with cut-off level 200 pg/ml combined with a positive Pneumocystis jirovecii PCR result had sensitivity and specificity of 92 and 90%, respectively. The concentration of Pneumocystis jirovecii DNA in serum samples, expressed by the PCR Ct values, correlated inversely to the betaglucan levels in serum. CONCLUSION: In this case-control study including 70% of all HIV-infected patients with PCP treated at Sahlgrenska University Hospital during a time period of 13 years, Pneumocystis PCR analysis on serum samples had a very high sensitivity and negative predictive value for the diagnosis of PCP in HIV-infected patients. A serum-based diagnostic procedure either based on Pneumocystis jirovecii PCR alone or in combination with betaglucan analysis may thus be feasible and would facilitate the care of HIV-infected patients with suspected PCP.

False-positive elevation of 1,3-beta-D-glucan caused by continuous administration of penicillin G.

The 1,3-beta-D-Glucan (BDG) assay is widely used for the diagnosis of fungal infections, especially in patients with hematologic malignancies. Some antimicrobials have been reported to cause false-positive results for BDG, but there has been no report on the effect of penicillin G (PCG) on BDG levels. We experienced a patient who developed false-positive BDG elevation during the administration of PCG for osteomyelitis due to Streptococcus pneumoniae infection. The serum BDG level increased up to 81.0 pg/ml during the continuous administration of PCG at 24 million units per day. However, chest and paranasal CT scan showed no evidence of fungal infection. The BDG level decreased to 38.0 pg/ml at 14 hours after the discontinuation of PCG. The amount of BDG in one vial of PCG inferred from these serum BDG levels is very similar to the actual BDG concentration in a vial of PCG. Therefore, during the administration of PCG, elevated BDG levels should be interpreted with caution, as they may be false-positive results.

Prospective evaluation of a combination of fungal biomarkers for the diagnosis of invasive fungal disease in high-risk haematology patients.

We prospectively evaluated a combination of fungal biomarkers in adult haematology patients with focus on their clinical utility at different time points during the course of infection. In total, 135 patients were monitored once to twice weekly for serum (1-3)-ß-d-glucan (BG), galactomannan (GM), bis-methyl-gliotoxin and urinary d-arabinitol/l-arabinitol ratio. In all, 13 cases with proven or probable invasive fungal disease (IFD) were identified. The sensitivity of BG and GM at the time of diagnosis (TOD) was low, but within 2 weeks from the TOD the sensitivity of BG was 92%. BG >800 pg/mL was highly specific for IFD. At a pre-test probability of 12%, both BG and GM had negative predictive values (NPV) >0.9 but low positive predictive values (PPV). In a subgroup analysis of patients with clinically suspected IFD (pre-test probability of 35%), the NPV was lower, but the PPV for BG was 0.86 at cut-off 160 pg/mL. Among IFD patients, 91% had patterns of consecutively positive and increasing BG levels. Bis-methyl-gliotoxin was undetectable in 15 patients with proven, probable and possible IA. To conclude, BG was the superior fungal marker for IFD diagnosis. Quantification above the limit of detection and graphical evaluation of the pattern of dynamics are warranted in the interpretation of BG results.

Usefulness of 1,3 Beta-D-Glucan Detection in non-HIV Immunocompromised Mechanical Ventilated Critically Ill Patients with ARDS and Suspected Pneumocystis jirovecii Pneumonia.

INTRODUCTION: Pneumocystis jirovecii pneumonia (PCP) is a major cause of disease in immunocompromised individuals. Diagnosis is typically obtained by microscopy and/or PCR. For ambiguous PCR results, we evaluated the new biomarker 1,3-Beta-D-Glucan (BDG). METHODS: BDG serum levels were assessed and correlated to PCR results in immunosuppressed patients with ARDS. RESULTS: 11 (22%) out of 50 patients had suspected PCP. APACHE II (26 vs. 24; p < 0.002), SOFA score (16 vs. 14; p < 0.010) and mortality rate (34 vs. 69% p < 0.004; 34 vs. 80% p < 0.003) were significantly altered in patients with positive (pPCR) and slightly positive (spPCR) PCJ PCR as compared to patients with no-PCP (nPCP). BDG levels were significantly lower in patients with nPCP (86; 30-315 pg/ml) than in patients with pPCR (589; 356-1000 pg/ml; p < 0.001) and spPCP (398; 297-516 pg/ml; p < 0.004) referring to the cutoff in this study for PCP of 275 pg/ml. An overall sensitivity (S) of 92% (95% CI 86-96%) and specificity (SP) of 84% (95% CI 79-85%) for PCP were found for the BDG Fungitell assay. In detail, S of 98% (95% CI 94-100%) and SP of 86% (95% CI 82-92%) for pPCP and S of 98% (95% CI 96-100%) and SP of 88% (95% CI 86-96%) for spPCO were found. CONCLUSION: Serum BDG levels were strongly elevated in PCP, and the negative predictive value is high. BDG could be used as a preliminary test for patients with suspected PCP, especially in patients with slightly positive PCR results.

[Expression and differential diagnostic value of serum microRNA for invasive pulmonary aspergillosis].

Objective: To explore the expression and the clinical diagnostic value of serum miR-21 for invasive pulmonary aspergillosis (IPA). Methods: Outpatients and inpatients from the Fourth Affiliated Hospital of Guangxi Medical University were included in the study during June 2014 to September 2015. The IPA group had 40 patients, male 22, female 18, aged 55-68 years (mean 60 ), while the control groups included 50 patients with pulmonary tuberculosis [male 23, female 27, aged 50-62 years (mean 55 )], 50 patients with lung cancer [male 30, female 20, aged 55-70 years (mean 62)], and 50 healthy controls [male 25, female 25, aged 50-67 years (mean 60) ]. Serum were obtained and the levels of miR-21 and galactomannan (GM test) and (1, 3)-beta-D-glucan (G test) were measured. The related indexes were analyzed by logistic regression and ROC curves. Results: The serum miR-21 expression in IPA and lung cancer patients were increased, the median values (P(25) and P(75)) being 0.42(0.31, 0.62)and 0.80(0.65, 0.94) respectively, both of which were significantly higher than those of the healthy controls [ 0.09(0.04, 0.15)] and the tuberculosis cases [ 0.08(0.03, 0.16)], P<0.001. The AUCs of miR-21 in IPA group, when compared to healthy controls, tuberculosis cases and lung cancer cases were 0.914, 0.897 and 0.863 respectively, with the Youden index being 0.780, 0.700 and 0.605 respectively. The serum levels of miR-21 in between 0.198 and 0.723 had preferable diagnostic accuracy. ROC analysis for miR-21 in IPA compared to healthy controls showed that the AUCs of miR-21 combined with G test or GM test were 0.992 and 0.966 respectively, the sensitivity being 95% (38/40) and 93% (37/40) respectively, the specificity being 98% (49/50) and 96% (48/50) respectively, and the Youden index being 0.930 and 0.885 respectively. If miR-21 was combined with G test and GM test, the AUC was 0.994, the sensitivity and the specificity being 98% (38/40) and 96% (48/50) respectively, and the Youden index increased to 0.935. ROC analysis for miR-21 in IPA compared to tuberculosis cases showed that when miR-21, G test and GM test were combined, the AUC was 0.984, the sensitivity and the specificity being 98% (38/40) and 90% (45/50) respectively, and the Youden index being 0.875. ROC analysis for miR-21 in IPA compared to lung cancer cases showed that the AUC for miR-21 with G test and miR-21 with GM test were 0.948 and 0.979 respectively, the Youden index being 0.725 and 0.895 respectively. When miR-21, G test and GM test were combined, the AUC was 0.998, the sensitivity and the specificity being 100% (40/40) and 98% (49/50) respectively, and the Youden index increased to 0.980. Conclusions: The serum level of miR-21 in IPA and lung cancer patients were significantly elevated. The serum level of miR-21 between 0.198 and 0.723 had preferable differential diagnostic accuracy, and therefore miR-21 may be regarded as an independent potential diagnostic serum marker of IPA. The diagnostic efficiency of miR-21 combined with G test and GM test may be more preferable, and remarkably increase the differential diagnosis of IPA from tuberculosis and lung cancer.