OBJECTIVE: To evaluate the accuracy and diagnostic value of bronchoalveolar lavage fluid galactomannan test (BALF-GM) combined with serum GM test on invasive pulmonary aspergillosis (IPA). METHODS: 190 cases of BALF-GM and 4 787 cases of serum GM specimens suspected of fungal infection in patients admitted to Affiliated Hospital of Jining Medical University from January 2016 to June 2018 were enrolled and analyzed. All patients were classified into clinically confirmed IPA, clinically diagnosed IPA, suspected IPA and excluded IPA according to the classification standard of Expert consensus on diagnosis and treatment of pulmonary mycosis. The coincidence rate of BALF and serum GM test results with clinical diagnosis was analyzed. Receiver operating characteristic (ROC) curve was performed, and the diagnostic value of BALF and serum GM test alone or in combination for IPA was evaluated. Subgroup analysis was performed in patients with normal or abnormal immune function, and the sensitivity and specificity of BALF and serum GM test were compared separately or jointly. RESULTS: The positive rate of BALF-GM was 46.8% (89/190), and 10.4% (497/4 787) on serum GM. Among them, 156 patients were both tested on BALF and serum GM. There were 44 cases with both positive in BALF and serum GM, the coincidence rate of clinical definite was 93.2% (41/44). There were 34 cases with positive BALF-GM and negative GM test in serum, and the coincidence rate of clinical definite was 64.7% (22/34). There were 56 cases positive in serum GM and negative in BALF-GM, and the coincidence rate of clinical definite was 48.2% (27/56). BALF and serum GM tests were both negative in 22 cases, and the coincidence rate of exclusion diagnosis was 90.9% (20/22). ROC curve analysis showed that the diagnostic value of BALF-GM test combined with serum GM test for IPA was better than that of BALF-GM test or serum GM test alone [area under ROC curve (AUC): 0.992 vs. 0.983, 0.976]. The sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) were 95.3%, 87.0%, 93.2% and 90.9%, respectively. Subgroup analysis showed that among 89 patients with positive BALF-GM test, 85 cases (95.5%) had normal immune function and 4 cases (4.5%) had unknown condition. Among 497 patients with positive serum GM test, 12 cases (2.4%) had normal immune function, 372 cases (74.9%) had abnormal immune function and 113 cases (22.7%) were uncertain. It was shown by ROC curve analysis that the sensitivity of positive BALF-GM test in diagnosis of IPA in patients with normal immune function was higher than that of positive serum GM test (95.6% vs. 88.9%), while the sensitivity of positive serum GM test in patients with abnormal immune function was higher than that of positive BALF-GM test (91.8% vs. 89.9%). CONCLUSIONS The results of BALF and serum GM tests are in good agreement with clinical diagnosis, and the combined detection of BALF and serum GM is more valuable for IPA diagnosis than single detection, especially for patients with unknown immune function.
Bronchoalveolar Lavage Fluid/chemistry* ; Galactose/analogs & derivatives* ; Humans ; Invasive Pulmonary Aspergillosis/diagnosis* ; Mannans/blood* ; Sensitivity and Specificity

OBJECTIVETo evaluate the clinical value of serum 1,3-beta-D-glucan (BG) and galactomannan (GM) detection for early diagnosis of invasive aspergillosis (IA) in patients after renal transplantation.

METHODSBlood samples collected from 69 renal transplant recipients were divided into diagnosis group, clinical diagnosis group, suspected diagnosis group, and non-infected group for detection of serum BG and GM.

RESULTSThe mean serum levels of BG in the diagnosis group, clinical diagnosis group, and suspected diagnosis group were significantly higher than that in non-infected group (P<0.05). The sensitivity, specificity, and positive and negative predictive values of BG was 69.49%, 70%, 93.18% and 35.71% for IA diagnosis, respectively. The serum levels of GM in the 3 diagnosis groups were also significantly higher than that in the non-infected group (P<0.05) with the sensitivity, specificity, and positive and negative predictive values of 84.75%, 90%, 96.15% and 52.63% for IA diagnosis, respectively.

CONCLUSIONIncreased serum BG and GM levels can serve as the evidence for early diagnosis of IA with a high diagnostic sensitivity and specificity in renal transplant recipients.

Aspergillosis ; diagnosis ; Early Diagnosis ; Humans ; Kidney Transplantation ; Mannans ; blood ; Sensitivity and Specificity ; beta-Glucans ; blood

BACKGROUND/AIMS: In this study, the sensitivity-specificity of galactomannan-enzyme immunoassay (GM-EIA) with a cut-off value of 0.5 for a single, two, or three consecutive positivity in the diagnosis of invasive pulmonary aspergillosis (IPA) in neutropenic patients with hematological malignancy was investigated. METHODS: IPA was classified as "proven," "probable," or "possible" as described in the guidelines prepared by the European Organization for Research and Treatment of Cancer and Mycoses Study Group." Serum samples were collected from the patients twice a week throughout their hospitalization. A total of 1,385 serum samples, with an average of 8.3 samples per episode, were examined. RESULTS: Based on the 165 febrile episodes in 106 patients, 80 (48.5%) were classified as IPA (4 proven, 11 probable, 65 possible) and 85 (51.5%) as non-IPA. The sensitivity/ specificity was 100%/27.1% for a single proven/probable IPA with the cut of value of GM-EIA > or = 0.5, 86.7%/71.8% for two consecutive positive results, and 73.3%/85.9% for three consecutive positive results. CONCLUSIONS: With the galactomannan levels measured twice a week, consecutive sensitivity decreased and specificity increased. Therefore, an increase may be obtained in sensitivity-specificity by more frequent monitoring of GM-EIA starting from the first day of positivity is detected.
Adult ; Aged ; Antineoplastic Agents/*adverse effects ; Biomarkers/blood ; Enzyme-Linked Immunosorbent Assay ; Female ; Hematologic Neoplasms/diagnosis/*therapy ; Hematopoietic Stem Cell Transplantation/*adverse effects ; Humans ; Immunocompromised Host ; Immunosuppressive Agents/*adverse effects ; Invasive Pulmonary Aspergillosis/*blood/diagnosis/immunology/microbiology ; Male ; Mannans/*blood ; Middle Aged ; Opportunistic Infections/*blood/diagnosis/immunology/microbiology ; Predictive Value of Tests ; Reproducibility of Results ; Time Factors

BACKGROUNDCritically ill chronic obstructive pulmonary disease (COPD) patients admitted to an intensive care unit (ICU) due to respiratory failure are at particularly high risk of Aspergillus infection. The serum galactomannan index (GMI) has proven to be one of the prognostic criteria for invasive pulmonary aspergillosis (IPA) in classical immunocompromised patients. However, the prognostic value of serum GMI in critically ill COPD patients needs evaluation. The purpose of this study is to investigate the prognostic value of serum GMI in patients with severe COPD.

METHODSIn this single-center prospective cohort study, serum samples for GMI assay were collected twice a week from the first day of ICU admission to the day of the patients' discharge or death. Patients were divided into two groups according to their clinical outcome on the 28th day of their ICU admission. Univariate analysis and survival analysis were tested in these two groups.

RESULTSOne hundred and fifty-three critically ill COPD patients were included and were divided into survival group (106 cases) and non-survival group (47 cases) according to their outcome. Univariate analysis showed that the highest GMI level during the first week after admission (GMI-high 1st week) was statistically different between the two groups. Independent prognostic factors for poor outcome in severe COPD patients were: GMI-high 1st week >0.5 (RR: 4.04, 95% CI: 2.17-7.51) combined with accumulative dosage of corticosteroids >216 mg before the RICU admission (RR: 2.25, 95% CI: 1.11-4.56) and clearance of creatinine (Ccr) ≤ 64.31 ml/min (RR: 2.48, 95% CI: 1.22 ± 5.07).

CONCLUSIONSThe positive GMI-high 1st week (>0.5) combined with an accumulative dosage of corticosteroids >216 mg before the ICU admission and a low Ccr may predicate a poor outcome of critically ill COPD patients.

Aged ; Aged, 80 and over ; Critical Illness ; Female ; Humans ; Invasive Pulmonary Aspergillosis ; blood ; complications ; pathology ; Male ; Mannans ; blood ; Middle Aged ; Prospective Studies ; Pulmonary Disease, Chronic Obstructive ; blood ; etiology ; pathology

We assessed the success rate of empirical antifungal therapy with itraconazole and evaluated risk factors for predicting the failure of empirical antifungal therapy. A multicenter, prospective, observational study was performed in patients with hematological malignancies who had neutropenic fever and received empirical antifungal therapy with itraconazole at 22 centers. A total of 391 patients who had abnormal findings on chest imaging tests (31.0%) or a positive result of enzyme immunoassay for serum galactomannan (17.6%) showed a 56.5% overall success rate. Positive galactomannan tests before the initiation of the empirical antifungal therapy (P=0.026, hazard ratio [HR], 2.28; 95% confidence interval [CI], 1.10-4.69) and abnormal findings on the chest imaging tests before initiation of the empirical antifungal therapy (P=0.022, HR, 2.03; 95% CI, 1.11-3.71) were significantly associated with poor outcomes for the empirical antifungal therapy. Eight patients (2.0%) had premature discontinuation of itraconazole therapy due to toxicity. It is suggested that positive galactomannan tests and abnormal findings on the chest imaging tests at the time of initiation of the empirical antifungal therapy are risk factors for predicting the failure of the empirical antifungal therapy with itraconazole. (Clinical Trial Registration on National Cancer Institute website, NCT01060462)
14-alpha Demethylase Inhibitors/adverse effects/therapeutic use ; Adolescent ; Adult ; Aged ; Antifungal Agents/adverse effects/*therapeutic use ; Aspergillosis/complications/*drug therapy ; Candidiasis/complications/*drug therapy ; Coccidioidomycosis/complications/drug therapy ; Febrile Neutropenia/complications/drug therapy ; Female ; Hematologic Neoplasms/complications/drug therapy/*microbiology ; Humans ; Itraconazole/adverse effects/*therapeutic use ; Male ; Mannans/blood ; Middle Aged ; Prospective Studies ; Treatment Outcome ; Young Adult

OBJECTIVETo explore the relationship between the optical density index of serum aspergillus galactomannan (GM) assay and invasive aspergillosis (IA).

METHODSFrom Jan 2008 to Dec 2011, 825 hematological diseases patients with neutrophil count <0.5×10⁹/L⁹ by continuous blood count tests were admitted into our hospital. The optical density index of GM assay was ≥0.5 at least once. Of 825 patients, 247 cases were manifested as fever during hospitalization. The optical density index of GM antigen was detected by enzyme-linked immunosorbent assay, and the sensitivity and specificity of optical density ranged in 0.5-1.5.

RESULTSIn this study, the sensitivity and specificity of GM assay with continuous twice samples (73% and 93%, respectively) were higher than single sample (66% and 80%, respectively) when optical density index ≥1.0. 69 cases were diagnosed as proven IA with the incidence rate of 8.36%.

CONCLUSIONThe cut-off level for serum GM antigen assay should be decided as optical density index in two continuous samples of ≥1.0.

Adolescent ; Adult ; Aged ; Antigens, Fungal ; blood ; Aspergillosis ; blood ; diagnosis ; etiology ; Enzyme-Linked Immunosorbent Assay ; Female ; Hematologic Diseases ; blood ; microbiology ; Humans ; Male ; Mannans ; blood ; immunology ; Middle Aged ; Sensitivity and Specificity ; Young Adult

OBJECTIVETo evaluate serum antigens assay combined with chest CT scan in the diagnosis of patients of invasive pulmonary aspergillosis (IPA) without neutropenia.

METHODSOne hundred and thirteen patients with suspected IPA admitted in Department of Respiratory Medicine, Infectious Diseased, Kidney Disease Centre and ICU were included in the study. Serum levels of 1-3-β-D-glucan (G) antigen and galactomannan antigen (GM) were assayed and chest CT scans were performed in all cases. Clinically invasive pulmonary aspergillosis was defined as proven, probable and possible. Treatment effectiveness was recorded.

RESULTSIn this series 4 proven IPA, 36 probable IPA, 16 possible IPA, and 57 non-aspergillosis infection were diagnosed. GM test was more sensitive than G test. The specificity of two serum test was 84.2% and 87.7%, respectively. The sensitivity of chest CT was 30.0 %. The specificity of GM assay combined with chest CT was 100.0 %, while the sensitivity was 47.5%.

CONCLUSIONThe GM assay combined with chest CT may increase the specificity of diagnosis for IPA patients without neutropenia.

Adult ; Aged ; Aged, 80 and over ; Female ; Humans ; Invasive Pulmonary Aspergillosis ; blood ; diagnosis ; diagnostic imaging ; Male ; Mannans ; blood ; Middle Aged ; Sensitivity and Specificity ; Tomography, X-Ray Computed ; Young Adult ; beta-Glucans ; blood

We report a case of pneumonia caused by Aspergillus terreus and cytomegalovirus (CMV) in a patient with acute myleogenous leukemia (AML) after remission induction chemotherapy. A 19-year-old woman underwent chemotherapy for AML. Twenty-three days after completing chemotherapy, she experienced a neutropenic fever with a rapidly-progressive pulmonary infiltration. In those days, her serum galactomannan immunoassay was 4.7 and she was treated with intravenous voriconazole (6 mg/kg q12h for 2 doses, followed by 4 mg/kg q12h) because of persistent fever and radiological worsening, despite the administration of amphotericin B deoxycholate (1 mg/kg q24h) for 7 days. A chest CT showed wedge-shaped consolidation with a central hypodense lesion and an air-crescent sign in the right middle lobe. With maintenance therapy of oral voriconazole for 10 weeks, a partial response was shown and neutrophil count was still less than 100/mm3. A lobectomy of the right middle lobe was performed. A. terreus was discovered from the lung tissue. At the same time, giant cells with intranuclear inclusions were found and immunohistochemical staining for CMV was positive. Ganciclovir (5 mg/kg q12h) was added to voriconazole therapy for 3 weeks after surgery, and then cord blood hematopoietic stem cell transplantation (HSCT) was performed. During HSCT, foscarnet (60 mg/kg q12h) was substituted for ganciclovir, and both antiviral agents were used alternatively due to CMV DNAemia. After 83 days from HSCT, the patient achieved successful engraftment and discharged without worsening the pneumonia.
Amphotericin B ; Antiviral Agents ; Aspergillus ; Cytomegalovirus ; Deoxycholic Acid ; Drug Combinations ; Female ; Fetal Blood ; Fever ; Foscarnet ; Ganciclovir ; Giant Cells ; Hematopoietic Stem Cell Transplantation ; Humans ; Immunoassay ; Intranuclear Inclusion Bodies ; Leukemia ; Leukemia, Myeloid, Acute ; Lung ; Mannans ; Neutrophils ; Pneumonia ; Pyrimidines ; Remission Induction ; Thorax ; Triazoles ; Young Adult

OBJECTIVETo evaluate the diagnostic value of serum galactomannan antigen (GM) and (1→3)-β-D-glucan antigen (BG) assay in invasive fungal infections (IFI) in the patients with hematologic malignancies and the role in monitoring therapeutic response.

METHODSFifty one patients with hematological malignancies met the criteria for inclusion: (1) body temperature above 38°C for 48 hours, (2) failure to respond to broad-spectrum antibiotic treatment, or (3) temperature rose again after the responded drop. Blood samples were collected twice at the first week, then once a week in at least four weeks. The double antibody sandwich enzyme-linked immunosorbent assay (ELISA) and colorimetric assay were used for detecting GM and BG. The positive GM test is defined as two consecutive tests at different time GM value > 0.5 or > 0.8 and the positive G test is defined as BG value > 80 pg/ml. The patients were assigned into four groups as proven, probable, possible, and non-fungal infection respectively, and 21 normal volunteers were as controls.

RESULTSTwo hundred and forty serum samples were collected from 51 patients including 2 of proven IFI, 26 probable IFI, 17 possible IFI and 6 non-fungal infection. The true-positive group including the proven and probable groups, and true negative group was the non-fungal infection group. GM tests were positive in 21 of 28 cases in true positive group, and only one of 6 cases in non-fungal infection. The sensitivity, specificity, positive predictive value and negative predictive value were 75%, 83.3%, 95.5% and 41.7%, respectively. G tests were positive in all 28 cases of the true positive group, and 4 in 6 non-fungal infection cases. The sensitivity, specificity, positive predictive value and negative predictive value were 100%, 33.3%, 87.5% and 100%, respectively. G test is more sensitive than GM test (P = 0.015), but there was no significant difference in specificity of the two tests (P = 0.242). In 19 of 21 patients with GM test positive, anti-fungal treatment was effective, and GM value gradually decreased to negative, two invalid patients were persistent with GM test positive. After two weeks treatment, the average GM value was significantly lower in the effective group than in the ineffective group (P < 0.05). BG values in the responded patients showed a gradual decline similar to that of GM values, but not to negative. The changes of BG value in ineffective group varied with a trend upward. The changes in BG value had no relation with treatment effectiveness.

CONCLUSIONSSerum GM and BG antigens detection provides strong evidence for early diagnosis of IFI. Combination of GM and G tests can improve the diagnostic specificity and reduce the false positive GM test seems superior to G test for monitoring GM and BG values during treatment.

Adult ; Aged ; Aged, 80 and over ; Antigens, Fungal ; blood ; immunology ; Female ; Hematologic Neoplasms ; immunology ; microbiology ; Humans ; Male ; Mannans ; immunology ; Middle Aged ; Mycoses ; blood ; immunology ; Young Adult ; beta-Glucans ; immunology

OBJECTIVETo explore the value of circulating galactomannan (GM) screening for early diagnosis and treatment monitoring of invasive aspergillosis (IA).

METHODSSerum samples from 141 IA patients for the detection of GM by Platelia Aspergillus (Bia-Rad) were collected before and after systematic anti-fungal therapy.

RESULTS(1) An increase in the clinical diagnosis rate of IA was obtained on the result of GM detection. The GM positivity appeared (10+/-4.1) (8-15) d before positive sputum culture, while (12.6+/-5.7) (6-22) d before the CT positive image. (2) Among the 62 patients with consecutive serum samples, 50 were success in treatment and 12 died. A progressive decrease of GM level was found in the former group, while the rising antigen titres were found in the latter.

CONCLUSIONCompared with other diagnostic test, GM test has an obvious advantage of higher positivity and earlier result. The anti-fungal effectiveness can be estimated by dynamic detection of serum GM.

Adolescent ; Adult ; Aged ; Aged, 80 and over ; Aspergillosis ; blood ; diagnosis ; Early Diagnosis ; Enzyme-Linked Immunosorbent Assay ; Female ; Humans ; Male ; Mannans ; blood ; Middle Aged ; Young Adult