Six-year experience with GM test in hematological patients in a public Brazilian tertiary hospital

Abstract Invasive fungal infection (IFI) is frequent in patients with hematologic malignancies or submitted hematopoietic stem cell transplantation (HSCT). Objectives To evaluate the role of the GM (galactomannan) test in prescribing therapeutic antifungals; to determine invasive aspergillosis (IA) frequency, the factors associated with positive GM test, and the in-hospital mortality. Methods We conducted a retrospective observational study including patients aged 18 or over with hematological malignancy or submitted to HSCT. GM test was measured twice weekly. The hypothesis of IFI was considered in patients with neutropenia and persistent fever despite broad-spectrum antibiotics. Results A total of 496 patients were evaluated; the mean of GM tests performed per patient was 4.2 (+3.1), and 86 (17.3 %) had positive results. IFI was diagnosed in 166 (33.5 %) and IA in 22 (24.6 %) patients. Positive GM test was more frequent in patients with IFI (72.2 % and 25.1 %; OR 8.1; 95 % CI 4.8 - 13.8), and was associated with therapeutic antifungals prescription (52, 9 % and 20.5 %; OR 4.3, 95CI% 2.0 - 9.4), as well as lung abnormalities on HRCT (45.3% vs. 21.5 %; OR 3.0, 95 %CI 1.4 - 6.5). Mortality was 31.6 %. In the multivariate analysis, the variables associated with mortality were the hypothesis of IFI (OR 6.35; 95 % CI 3.63-11.12.0), lung abnormalities on HRCT (57.9 % and 26.9 %; OR 2 0.6; 95 % CI 1.5 - 4.4), and positive GM test (57.9 % and 26.9 %; OR 2.7 95 % CI 1.6 - 4.5). Conclusions Positive GM test was associated with lung abnormalities on HRCT and with the introduction of therapeutic antifungals. If adequate anti-mold prophylaxis is available, the GM test should not be used as screening, but to investigate IFI in high-risk patients. The diagnosis of IFI, positive GM test and lung abnormalities on HRCT were predictors of hospital mortality in patients with hematological malignancies or undergoing HSCT.

Clinical diagnostic value of combined detection of serum and bronchoalveolar lavage fluid galactomannan for invasive pulmonary aspergillosis in non-neutropenic children / 中华微生物学和免疫学杂志

Objective:To investigate the clinical diagnostic value of combined detection of serum and bronchoalveolar lavage fluid (BALF) galactomannan (GM) for invasive pulmonary aspergillosis (IPA) in children with non-neutropenia.Methods:An analysis was made on 100 children with non-neutropenia suspected of invasive pulmonary aspergillosis in the respiratory ward of the Children′s Hospital Affiliated to Capital Institute of Pediatrics from January 2019 to March 2020. All of them were tested by serum and BALF GM tests as well as sputum and BALF culture for fungi. The sensitivity, specificity and accuracy of serum and BALF GM in the diagnosis of IPA in non-neutropenic children were analyzed. The receiver operating characteristic (ROC) curve and the area under the ROC curve (AUC) were used to evaluate the clinical diagnostic value of serum and BALF GM tests for IPA in children with non-neutropenia.Results:The recruited 100 cases included one confirmed case, 85 clinically diagnosed cases and two suspected cases, while the 12 cases were excluded. The accuracy and 95% confidence interval (95%CI) of serum and BALF GM tests used alone and in combination in the clinical diagnosis of IPA in non-neutropenic children were 29.0% (95%CI: 20.1%-37.9%), 75.0% (95%CI: 66.5%-83.5%) and 81.0% (95%CI: 73.3%-88.7%), respectively. The AUC and 95%CI were 0.645 (95%CI: 0.513-0.778), 0.785 (95%CI: 0.644-0.926) and 0.819 (95%CI: 0.681-0.953), respectively.Conclusions:The combined detection of serum and BALF GM was better than a single indicator in the clinical diagnosis of IPA in non-neutropenic children, suggesting the combined detection was of great value in clinical diagnosis.

Teste de galactomanana para o diagnóstico de aspergilose invasiva: uma revisão / Galactomannan test for the diagnosis of invasive aspergillosis: a review

As doenças fúngicas invasivas têm sido um problema crescente em ambientes hospitalares, sobretudo nas últimas duas décadas. A aspergilose invasiva (AI), ocasionada pelo gênero Aspergillus, está entre as principais causas de morte em pacientes gravemente imunocomprometidos, com mortalidade que varia de 70 a 90%. O padrão de referência para o diagnóstico de AI é o cultivo do micro-organismo e a análise histopatológica dos órgãos afetados. Estes procedimentos são dificilmente realizados na maioria dos casos, e apresentam baixa sensibilidade (<50%), além de as amostras serem habitualmente obtidas em estados avançados da infecção. O teste de detecção de galactomanana tem sido objeto de estudo para o diagnóstico de AI, por representar uma promissora ferramenta e por ser uma técnica sorológica rápida e não invasiva. A presente revisão tem por objetivo fazer levantamento de estudos que utilizaram o teste de galactomanana em amostras de pacientes com quadros clínicos distintos, porém com suspeita e/ou com comprovada AI, bem como as atuais tendências de conhecimento, aplicação e utilidade do ensaio laboratorial.

Invasive fungal diseases represent an increasing problem in the hospital environments, predominantly in the last two decades. The invasive aspergillosis (IA), induced by Aspergillus species, has been the main cause of death in severely immunocompromised patients, with mortality varying from 70 to 90%. Difficulties are found for diagnosing the IA. In vitro culture of biological material shows low sensitivity (<50%), besides the positivity usually occurs at the advanced stages of the infection. The test for detecting galactomannan has been the object of the present study, seeing that it represents a promising diagnostic tool, as a fast and non-invasive serological procedure. The objective of the present review is to survey the studies which have been performed by using methods for detecting galactomannan in samples from patients with distinct clinical pictures. Patients presenting suspicion and/or confirmed IA were also included, as well as the up-to-date trends in knowledge, application and utility of the test.

G-test and GM-test combined with sputum fungal culture for the early diagnosis of invasive fungal infection in intensive care unit patients / 中国感染控制杂志

Objective To evaluate the detection value of serum (1,3)-β-D glucan (G-test) and galactomannan (GM-test) combined with sputum fungal culture in the early diagnosis of invasive fungal infection(IFI) in intensive care unit(ICU) patients.Methods Inpatients with high risk factors for IFI in the ICU of the Affiliated Hospital of Xuzhou Medical University between January 2015 and December 2016 were chosen,they were divided into 3 groups according to the diagnostic criteria of IFI:IFI group(including confirmed and clinically diagnosed cases),suspected IFI group,and non-IFI group.The results of serum G-test,GM-test,and sputum fungal culture in three groups of patients were analyzed,early diagnostic value in IFI with combined three tests was evaluated.Results A total of 264 ICU patients were investigated,IFI group,suspected IFI group,and non-IFI group were 56,43,and 165 cases respectively.Among 56 cases of confirmed IFI,46,39,and 34 were positive for G-test,GM-test,and fungal culture respectively.The sensitivity,specificity,positive predictive value,and negative predictive value of combined three detection were 98.2％,82.4％,65.5％,and 99.3％ respectively,positive likelihood ratio,negative likelihood ratio,and Youden index were 5.58,0.02,and 0.98 respectively.The sensitivity and negative predictive values of combined three detection were both higher than those of single G-test,GM-test,and sputum fungal culture (all P＜0.05);but specificity and positive predictive value of combined three detection were not significantly different from single G-test,GM-test,and sputum fungal culture(all P＞0.05).Conclusion The combination of G-test,GM-tests,and sputum fungal culture can improve the sensitivity of early diagnosis of IFI in ICU patients,and guide the clinicians in the early treatment of IFI.

Serum galactomannan levels in the diagnosis of invasive aspergillosis

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.

Success Rate and Risk Factors for Failure of Empirical Antifungal Therapy with Itraconazole in Patients with Hematological Malignancies: A Multicenter, Prospective, Open-Label, Observational Study in Korea

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)