Serum Galactomannan Assay Research Articles

Utility of the serum galactomannan assay for the diagnosis of invasive aspergillosis in children with acute lymphoblastic leukemia

Invasive aspergillosis (IA) is an important cause of mortality and morbidity in children with hematological malignancies. The monitoring of serum galactomannan (GM) antigen is considered useful in the diagnosis of IA . The aim of this study was to determine the utility of serum GM monitoring in the early diagnosis of IA and the role of positive antigenemia in the management of children with acute lymphoblastic leukemia (ALL). The cases of 141 children who were being treated for ALL in the Division of Pediatric Hematology of the Medical School of Ege University between January 2006 and February 2015 were reviewed retrospectively. Cases of proven and probable IA were defined according to the European Organization for the Research and Treatment of Cancer/Mycoses Study Group (EORTC/MSG) criteria. The incidence of proven and probable IA was 3.5% (5/141). The incidence of positive GM antigenemia among 3264 serum samples was 5.5% (n=179). Of the cases detected, 21.7% were true-positive, 52.1% were false-positive, and the remaining 26.1% were classified as 'undetermined.' An increase in the incidence of true-positive tests and induction of antifungal therapy was determined through multiple consecutive positive tests. GM may be detected in the serum before the clinical signs of IA appear, but its sensitivity and specificity are variable. False-positivity is a significant disadvantage, and consecutive positive GM must be taken into account in the case of clinical and imaging findings that are relevant to IA.

Role of galactomannan assay in bronchoalveolar lavage fluid in the diagnosis of invasive aspergillosis in high risk patients with hematological disorders

Introduction: Invasive aspergillosis (IA) is the most frequent invasive fungal infection occurring in high risk patients with haematological disorders and also an important cause of morbidity and mortality in them. Lungs comprise the primary site of IA in the vast majority of cases, and the most frequently occurring form of IA. Early diagnosis followed by early initiation of therapy improves outcome. The current culture based diagnostic methods are insensitive and slow. Detection of Aspergillus galactomannan (GM) in serum using the platelia Aspergillus enzyme immunoassay (GM EIA) represents sensitive, non-culture-based tool for the early diagnosis of IA. Recent studies have shown that during IPA, GM is released earlier and in higher concentration in the BAL fluid than in serum. Thus, an early and accurate diagnosis of IPA can be reached by detecting antigen in BAL samples. Materials and Methods: Thirty consecutive high risk patients with haematological disorders satisfying the inclusion and exclusion criteria according to EORTC-MSG diagnostic criteria and undergoing indoor treatment were recruited between November 2013 and December 2014 into the study. In all the patients, bronchoalveolar lavage (BAL) fluid GM and serum GM assays were assayed. Results: The diagnostic accuracy of the two tests was measured by calculating the sensitivity, specificity, predictive values and receiver operating characteristic curve (ROC). The optimal BAL GM index for diagnosing probable and possible IPA was >1.00 OD, resulting in a sensitivity and specificity of 93.75% and 78.57% respectively. As per ROC curve, when the optimal BAL GM index for the diagnosis of probable and possible invasive pulmonary aspergillosis (IPA) was OD >0.5, it resulted in sensitivity and specificity of 50% and 71.43% respectively. BAL GM was thus found to have a significantly higher sensitivity as compared to serum GM. Conclusion: In all high-risk patients with haematological disorders where the clinical and radiological findings favour the possibility of invasive pulmonary aspergillosis, conducting a GM assay in BAL fluid sample is far more rewarding than carrying out the traditional serum GM assay. BAL GM has a high diagnostic accuracy when correlated with the EORTC/MSG diagnostic criteria, and this high diagnostic yield is useful in obviating the unnecessary widespread use and abuse of empirical antifungal therapy in patients with IPA.

Serum Galactomannan Screening for Diagnosis of Invasive Pulmonary Aspergillosis in Children After Stem Cell Transplantation or with High-Risk Leukemia

Both transplanted and leukemia patients are at high risk (HR) for invasive pulmonary aspergillosis (IPA). Methods for rapid diagnosis are crucial. Our objective was to investigate the impact of serial serum galactomannan assay (GMA) screening on IPA diagnosis in children. Between January 2010 and December 2011, all children following stem cell transplantation (SCT) or with HR leukemia were prospectively included. Serum samples for GMA were taken once-twice weekly. Results >.5 were considered positive. Patients suspected of having IPA were stratified as possible, probable, and definite. Forty-six children (median age, 8 years) were included, 38 after SCT (32 allogeneic), 8 with HR leukemia. A total of 510 samples were taken; screening period was 1–6 months for 34 patients. GMA was negative in 28 patients, all but one without suspicion of IPA. Eighteen patients had positive GMA: while four (22%) were upgraded to probable IPA, fourteen (78%) were considered as false positives (FP), some associated with piperacillin-tazobactam treatment. GMA sensitivity and specificity were 0.8 and 0.66, respectively; positive- and negative-predictive values (PPV, NPV) were 0.22 and 0.96, respectively. GMA may have a role in evaluating HR children for IPA. Both NPV and FP rates are high. The cost benefit of early detection versus over-diagnosis should be further studied.

Prophylaxis of Invasive Pulmonary Aspergillosis with Nebulized Lipid Complex Amphotericin B Is Feasible, Well Tolerated and Safe in Children with Acute Leukemia. Results of a Phase II Open Trial

▪ BACKGROUNDAcute leukemia is the most frequent cancer in childhood. The use of dose-intensive chemotherapy regimens has significantly increased the overall survival of acute leukemia during the last years. As a result of more dose-intensive myelosuppressive and immunosuppressive therapies there is a higher risk of systemic fungal infections. Invasive pulmonary aspergillosis (IPA) represents a significant source of morbidity and mortality (>50%), and therefore measures that effectively prevent IPA are needed. Prophylaxis of IPA with anti-mold azoles is effective, but has adverse systemic effects and important drug interactions with some chemotherapeutic agents (i.e. vincristine). Currently there is no optimal prophylaxis for IPA in pediatric patients so new strategies are needed. Because IPA originates from the inhalation of conidia, a prophylactic approach is the topical administration of antifungals inside the lungs. Aerosolized lipid formulations of amphotericin B could prevent IPA and avoid systemic adverse events and drug interactions. There are no published studies reporting feasibility and safety of inhaled lipidic amphotericins in the pediatric population. PATIENTS AND METHODSThe safety, feasibility and tolerance of nebulized lipid complex amphotericin B (ABCL) was evaluated in a phase II open label single arm trial on the use in pediatric patients (3 to 18 year-old) with acute leukemia during intensive chemotherapy. Nebulized therapy was administered by a PARI eFlow®rapid nebulizer system twice weekly, at 50 mg the first week and then 25 mg during intensive chemotherapy until recovery of neutropenia (3 consecutive absolute neutrophil count (ANC) ≥1x109/L or one ANC ≥1.5x109/L). Treatment was resumed during neutropenic episodes following subsequent chemotherapy cycles. Serum galactomannan assay was performed twice weekly during neutropenia. High-resolution chest computed tomography was done when there was a clinical suspicion of IPA. Fluconazole was allowed but antifungal drugs with anti-mold activity were not permitted. The trial is registered at www.clinicaltrials.gov as NCT01615809. RESULTSThirty-two patients were included, 19 were male (59.4%), median age was of 5.5 years (range 3-16). Twenty-nine patients were diagnosed with acute lymphoblastic leukemia (ALL), 3 with acute myeloid leukemia. Among the patients with ALL, 24 had a de novo ALL and 5 a relapsed ALL. A total of 389 administrations of nebulized ABCL were performed, with a median per patient of 13 (range 1-19). All patients tolerated the drug and no patient had to discontinue it due to intolerance or an adverse event. No patient presented a severe adverse event in relation to ABCL. Five patients suffered from mild adverse events (cough, eye discomfort). Nine patients were withdrawn from the study, 2 were referred to another institution to undergo bone marrow transplantation and 7 due to systemic administration of an antifungal agent with anti-mold activity. Three of these patients developed a possible or probable IPA. There were no other cases of IPA. CONCLUSIONSProphylactic nebulizations with ABCL were well tolerated, safe and feasible in children aged 3-18 years diagnosed with acute leukemia. There is a need to perform further studies with a higher number of patients to evaluate the efficacy of this approach. DisclosuresRives:Teva Pharma: Other. Off Label Use: Nebulized Amphotericin-B lipid complex is not approved for prophylaxis of invasive fungal infection in pediatric patients with acute leukemia.

Serum galactomannan versus a combination of galactomannan and polymerase chain reaction-based Aspergillus DNA detection for early therapy of invasive aspergillosis in high-risk hematological patients: a randomized controlled trial.

The benefit of the combination of serum galactomannan (GM) assay and polymerase chain reaction (PCR)-based detection of serum Aspergillus DNA for the early diagnosis and therapy of invasive aspergillosis (IA) in high-risk hematological patients remains unclear. We performed an open-label, controlled, parallel-group randomized trial in 13 Spanish centers. Adult patients with acute myeloid leukemia and myelodysplastic syndrome on induction therapy or allogeneic hematopoietic stem cell transplant recipients were randomized (1:1 ratio) to 1 of 2 arms: "GM-PCR group" (the results of serial serum GM and PCR assays were provided to treating physicians) and "GM group" (only the results of serum GM were informed). Positivity in either assay prompted thoracic computed tomography scan and initiation of antifungal therapy. No antimold prophylaxis was permitted. Overall, 219 patients underwent randomization (105 in the GM-PCR group and 114 in the GM group). The cumulative incidence of "proven" or "probable" IA (primary study outcome) was lower in the GM-PCR group (4.2% vs 13.1%; odds ratio, 0.29 [95% confidence interval, .09-.91]). The median interval from the start of monitoring to the diagnosis of IA was lower in the GM-PCR group (13 vs 20 days; P = .022), as well as the use of empirical antifungal therapy (16.7% vs 29.0%; P = .038). Patients in the GM-PCR group had higher proven or probable IA-free survival (P = .027). A combined monitoring strategy based on serum GM and Aspergillus DNA was associated with an earlier diagnosis and a lower incidence of IA in high-risk hematological patients. Clinical Trials Registration. NCT01742026.

Impact and cost of the serum galactomannan assay at a tertiary care facility.

Invasive aspergillosis carries a high mortality with a rising prevalence in immunocompromised hosts. Diagnosis of invasive aspergillosis is challenging and delays in treatment are associated with poor outcomes. The galactomannan assay (GM), a non-culture-based surrogate marker of fungal infection, is widely used in diagnosis. It is unknown whether this assay impacts clinical decision making. We evaluated whether GM testing results in earlier initiation of antifungal therapy and is cost effective. We carried out a retrospective review of the electronic medical records of all patients undergoing GM at a 907-bed tertiary-care general hospital from July 11, 2011, to June 12, 2012. Records of patients with a positive GM were individually reviewed to determine the timing of the assay result, presence and timing of relevant culture data, whether BAL GM was performed, radiology data consistent with invasive aspergillosis, and the timing of initiation of antifungal therapy. For each case, it was determined whether GM results impacted the decision to initiate antifungal therapy. Forty-six nonduplicate GM samples were positive (>0.5) of 1419 performed. Results were considered to be false positives in 18 cases by care teams. In 21 cases, antifungal therapy was initiated before the assay result based on clinical suspicion, culture data, and/or radiology. The serum GM was performed 164 times at a cost of $21,789 for a single positive result effecting modification of patient care. Serum GM testing at a tertiary-care institution is commonly used but infrequently impacts clinical decision making with major financial burden.

Serum Galactomannan-Based Early Detection of Invasive Aspergillosis in Hematology Patients Receiving Effective Antimold Prophylaxis

There is a practical need to investigate the performance of the serum galactomannan (GM) assay in hematology patients with a potentially low pretest risk of invasive aspergillosis following effective antimold prophylaxis. We present a 4-year study with 262 unselected consecutive high-risk episodes, prospectively managed with posaconazole primary prophylaxis and a uniform diagnostic algorithm, including biweekly serum GM quantification for early detection of invasive aspergillosis. A total of 2972 serum GM tests were performed (median, 11 per episode [range, 3-30]); the vast majority were negative (96.7% of tests and 83.6% of episodes). The incidence of breakthrough invasive aspergillosis was 1.9% (5/262), all with true-positive GM test results. Our study identified 30 false-positive GM evaluable episodes (85.7%; 13.8% of all evaluable episodes), validating with real-life data the low positive predictive value of the assay in this setting (12%). In 26 of these 30 episodes (86.7%), the false-positive result(s) occurred in tests performed as preemptive surveillance only. Conversely, in evaluable cases with positive GM tests and a clinical suspicion of invasive fungal disease, the performance of diagnostic-driven GM tests improved, with a positive predictive value of 89.6%. The low pretest risk of invasive aspergillosis in the context of effective antimold prophylaxis renders serum GM surveillance of asymptomatic patients unreliable, as all results would be either negative or false positive. The test remains useful to diagnose patients with a clinical suspicion of invasive fungal disease, calling for a more efficient copositioning of effective prophylaxis and GM testing in this clinical setting.

Threshold of galactomannan antigenemia positivity for early diagnosis of invasive aspergillosis in neutropenic children

Invasive aspergillosis (IA) is an important cause of morbidity and mortality in immunocompromised patients. Pediatric data on the accuracy and optimal cutoff of galactomannan antigen detection to diagnose IA is sparse and controversial. We evaluated the utility and optimal serum galactomannan assay (GA) cutoff in children. Children with febrile neutropenia due to malignancy, hematopoietic stem cell transplant, aplastic anemia, or congenital neutropenia, were prospectively included from 2007 to 2011. All new episodes of febrile neutropenia were recorded. In case of a previous diagnosis of IA, subsequent episodes were excluded. One to four GA were tested by enzyme immunoassay during each episode. Bronchoalveolar lavage and other relevant samples for mycological diagnosis, and computed tomography of chest/sinus were performed wherever appropriate. IA was classified as "proven", "probable", and "possible" as per the 2008 European Organisation for Research and Treatment of Cancer and Mycoses Study Group Guidelines. The optimal cutoff value was determined using receiver operating characteristic curves in episode-wise analysis. There were 145 patients with 211 febrile episodes included: hematopoietic stem cell transplant (n=15), oncological (n=113), and hematological disorders (n=17). Forty-five children (31.0%) developed IA (5 proven, 15 probable, and 25 possible). Cutoff value of single GA≥0.7 for proven/probable/possible IA offered the best combination of sensitivity (82.2%)/specificity (82.5%), and 94.4% negative predictive value. Two consecutive positive GA≥0.7 had a sensitivity/specificity of 75.0%/91.0%. Index GA≥1.9 was associated with significantly higher mortality in children with IA and overall. Serum GA is sensitive to diagnose IA in pediatric patients with excellent negative predictive value at an optimal cutoff of ≥0.7. Considering two consecutive values ≥0.7 increases specificity to 91.0%.

Serum galactomannan assay for diagnosis of probable invasive Aspergillosis in acute leukemia and hematopoietic stem cell transplantation

Background:Invasive aspergillosis (IA) is a leading cause of mortality in acute leukemia and hematopoietic stem cell transplantation (HSCT).Aims:To determine the yield of galactomannan (GM) assay for the diagnosis of probable IA, its temporal relationship with the computed tomography (CT) scans and correlation with mortality in AL and HSCT.Patients and Methods:Consecutive neutropenic episodes (n=150) among inpatients aged ≥15 years with AL or recipients of HSCT were prospectively evaluated over 1½ years. All patients underwent weekly serum GM assay and optical density index >0.5 for ≥2 samples was defined as positive. IA was diagnosed according to EORTC 2008 guidelines.Results:Of the 150 episodes enrolled, 43 (28.7%) were diagnosed with IA: possible 25 (16.7%), probable 17 (11.3%) and proven 1 (0.7%). The yield of GM assay in diagnosing probable IA was 17/42 (40.5%). In 88.2% of probable IA episodes, GM was positive before high-resolution CT at a median of 10 days (range 1-16). In the episodes with ≥2 samples tested, fatality was higher in those ≥2 values positive for GM, compared to the rest (31% vs. 13.2%, odd ratio 2.96, 95% CI 1.09-8.00; P=0.04).Conclusions:In AL and HSCT, GM assay could identify patients with probable IA earlier than CT chest and also predicted a higher risk of death.

Serum galactomannan assay for the diagnosis of invasive aspergillosis in children with haematological malignancies

Diagnostic efficacy of Galactomannan (GM) assay for invasive aspergillosis (IA) is variably reported. Data from developing countries are scant. Children with haematological malignancies and fever were enrolled prospectively. Blood sample for GM was drawn on the day of admission; levels were measured with Platellia Aspergillus enzyme immunoassay. Diagnostic criteria were adapted from EORTC-MSG-2002. Proven, probable and possible episodes were considered as the disease group. One hundred febrile episodes in 78 patients were evaluated. The mean age was 6.1 years. Majority (75%) episodes were in patients with acute lymphoblastic leukaemia. One episode each was diagnosed with proven and probable IA, while 23 were diagnosed with possible IA. Best results were obtained with a cut-off value of 1.0, with sensitivity, specificity, positive and negative predictive value of 60%, 93%, 75 and 87 respectively. The sensitivity dropped to 40%, at cut-off value of 1.5 and specificity was 38%, at a cut-off of 0.5. A higher value of GM correlated with pulmonary nodules (P = 0.037) and mortality (P = 0.001). GM assay is adjunctive to clinical/radiological evidence. A negative GM assay may not reassure the physician against the use of amphotericin in patients with febrile neutropenia, as it does not exclude the diagnosis of clinically relevant other fungal infections, particular mucormycosis.

Usefulness of the Serum Galactomannan Assay for Early Response Assessment and Treatment Stratifications of Invasive Aspergillosis

The galactomannan (GM) Enzyme Immunoassay (EIA) is an upcoming tool not only for diagnosis but also monitoring of invasive Aspergillosis (IA). Various studies were performed over the last years to apply such a promising instrument correctly. New findings show the potential of this test to segregate affected patients into treatment responders and non-responders at a time point as early as 7–14 days after initiation of antifungal therapy. Current data suggest that serial GM testing in patients receiving antifungal therapy for IA is essential as GMI kinetics may offer the clinician a substantial support in decision making concerning early therapeutic stratifications. The correct interpretation of GM EIA results with respect to the individual context of the patient is, however, absolutely necessary. The following review shall give an overview about the GM-EIA as a tool for IA monitoring and therapy stratification.

Diagnostic value of the serum galactomannan assay for invasive aspergillosis: It is less useful in non-haematological patients

The serum galactomannan assay (GMA) has been widely used for the diagnosis of invasive aspergillosis (IA). GMA is mainly used in patients with haematological malignancies or in those who have undergone haematopoietic stem cell transplantation (HSCT). However, there are few data from non-haematological patients. We evaluated whether GMA is useful for the diagnosis of IA in non-haematological patients. Patients who were subjected to serum GMA testing from January 2007 to December 2009 were evaluated retrospectively. Patients with haematological diseases or who underwent HSCT were excluded from our analysis. According to the criteria of the European Organization for Research and Treatment of Cancer/Mycoses Study Group revised in 2008, the patients were categorized as proven, probable, possible, or non-IA. Proven and probable cases were defined as IA in this study. Out of 778 patients, 13 (1.6%) had proven (n =9) or probable (n =4) IA. The sensitivity of the GMA was 23.1% (95% confidence interval (CI) 6.1-54.0%) and the specificity was 76.1% (95% CI 72.9-79.0%). The positive predictive value was 1.6% (95% CI 0.4-5.0%) and the negative predictive value was 98.3% (95% CI 96.8-99.1%). The likelihood ratios of a positive and negative test were 0.96 (95% CI 0.35-2.62) and 1.01 (95% CI 0.75-1.36), respectively. In this study, the sensitivity of the GMA for the diagnosis of IA was very low in non-haematological patients. Although the GMA test is considered useful for the diagnosis of IA in haematological patients, it had low diagnostic value for IA in non-haematological patients.

Fatal subarachnoid hemorrhage caused by Aspergillus arteritis without angiographic abnormalities

No source of bleeding is detected by angiogram in 15-20% of patients with nonaneurysmal subarachnoid hemorrhage (SAH). This negative angiographic finding might suggest a benign prognosis. We describe a case of fatal SAH caused by Aspergillus arteritis without formation of fusiform dilatation or aneurysms. A 76-year-old man with a 2-month history of progressive visual loss due to pachymeningitis around the optic nerves suffered from SAH in the bilateral sylvian fissures. Repetitive serum galactomannan assay and angiography showed no abnormality. Post mortem examination revealed marked proliferation of Aspergillus in the granulomas of the frontal base dura mater. In addition, major trunks and several branches of the bilateral middle cerebral arteries were invaded by Aspergillus hyphae, which destroyed the walls in the absence of dilatation and aneurysms. Invasive aspergillosis of the CNS often forms a mycotic aneurysm. However, four autopsy cases of nonaneurysmal SAH due to invasive aspergillosis have been reported. The present case is the second autopsy case of Aspergillus arteritis without angiographic abnormality, resulting in fatal SAH. Aggressive and continuous antifungal therapy is absolutely necessary in suspected cases of invasive aspergillosis of the CNS, even if angiography is negative and therapeutic markers of aspergillosis are normal.

Cross-reactivity of Aspergillus galactomannan in an HIV-infected patient with histoplasmosis

Non-invasive assays are increasingly being used in patients with suspected fungal infections. Limitations to these tests include limited sensitivity, specificity, and cross reactivity with other fungal pathogens. Herein we report a case of disseminated histoplasmosis producing a false positive serum and bronchoalveolar lavage (BAL) Aspergillus galactomannan assays. This test may have a role in the evaluation of patients with suspected histoplasmosis in settings where Histoplasma antigen testing is not widely available.

Serum galactomannan (GM) assay for invasive aspergillosis (IA) in acute leukemia (AL) and hematopoietic stem cell transplantation (HSCT).

6538 Background: IA is a major cause of mortality in AL and HSCT. The objectives of this study were to determine the yield of GM assay for the diagnosis of probable IA, its temporal relationship with high-resolution computed tomographic scan (HRCT) scans and correlation with mortality in patients of AL and recipients of HSCT. Methods: Consecutive neutropenic episodes among inpatients aged ≥ 15 years with a diagnosis of AL and recipients of HSCT were prospectively evaluated over 1½ years. All patients received oral itraconazole or thrice weekly IV amphotericin B (AmB) as prophylaxis. Weekly serum GM assay was performed for all subjects. Optical density index (ODI) > 0.5 for two or more samples was defined as positive. Patients with persistent fever for ≥ 96 hours on intravenous antibiotics were evaluated with HRCT chest and received empiric AmB. IA was diagnosed according to EORTC 2008 guidelines and treated with therapeutic doses of voriconazole or AmB. Results: Of the 150 episodes enrolled, AL induction constituted 51.3% (AML 35.3%, ALL 16%), high-dose cytarabine 20%, autologous HSCT 24.7%, allogeneic HSCT 2.7% and cladribine for hairy cell leukemia 1.3% episodes. Forty-three episodes (28.7%) were diagnosed with IA: possible 25 (16.7%), probable 17 (11.3%) and proven 1 (0.7%). The yield of GM assay in diagnosing probable IA was 17/42 (39.5%). False-positivity of a single test was 54.2% but decreased to 11.2% with two results. Assessment of sensitivity was impaired due to the lack of proven cases. The lone proven case had 1/1 sample positive (ODI 2.17). In 88.2% of probable IA episodes GM was positive before HRCT at a median of 10 days (range, 1-16) earlier, while HRCT was positive before GM in the remaining 11.8% episodes at median of 3.5 days (range, 1-7) earlier. Of the 23 fatal episodes (15.3%), 17 had a diagnosis of IA. Considering only those episodes with ≥2 samples tested, fatality was 31.0% in those with at least 2 values positive for GM, compared to 13.2% in the episodes with < 2 GM samples positive (OR 2.96, 95% CI 1.09 – 8.00; p=0.04). Conclusions: In a population of high-risk patients, GM assay could identify patients with probable IA earlier than HRCT chest and also predicted a higher risk of death.

Serum and Bronchoalveolar Lavage Fluid Galactomannan Assays in Patients with Pulmonary Aspergilloma

The sensitivities of the serum and bronchoalveolar lavage galactomannan (GM) assays in 48 patients with pulmonary aspergilloma were 38% (13 of 34; 95% confidence interval [CI], 22%-56%) and 92% (33 of 36; 95% CI, 78%-98%), respectively. The positivity of serum GM assays was significantly higher in patients with hemoptysis than in those without hemoptysis (52% vs 9%; P=.02).

Positive Results of Serum Galactomannan Assays and Pulmonary Computed Tomography Predict the Higher Response Rate of Empirical Antifungal Therapy in Patients Undergoing Allogeneic Hematopoietic Stem Cell Transplantation

Invasive fungal disease (IFD) is a leading cause of infection-related mortality among patients undergoing allogeneic hematopoietic stem cell transplantation (allo-HSCT). Although the mortality of IFD has been decreased with empirical antifungal therapy in this population, overtreatment remains a problem, for the persistent or recurrent fever is nonspecific for an IFD. Hence, we explored retrospectively the value of incorporating serum galactomannan (GM) test and pulmonary high-resolution computed tomography (HRCT) as predictors for higher response rate of empirical treatment. In our study, all of 124 patients after allo-HSCT received empirical antifungal therapy when the persistent or recurrent fever developed after receiving broad-spectrum antibiotics. Meanwhile, the levels of serum GM were monitored twice weekly and pulmonary HRCT was performed serially. It showed that the response rate of empirical antifungal therapy was higher in patients with positive results of serum GM tests and/or chest CT scan than that in all patients (66.1% versus 44.6%, P = .008). Moreover, only 10 of 55 patients with both negative GM tests and pulmonary HRCT responded to empirical treatment, and 7 of these 10 patients did not take antifungal agents for prophylaxis. It suggested that these 2 diagnostic tools could not predict patients without adequate Candida prophylaxis well. Thus, we concluded that serum GM assays and pulmonary CT scan could find out patients who really need empirical antifungal therapy, which resulted in improving the efficiency of the treatment.

Accuracy of BAL Galactomannan in Diagnosing Invasive Aspergillosis: A Bivariate Metaanalysis and Systematic Review

A serum galactomannan (GM) assay has been approved for diagnosing invasive aspergillosis (IA). However, the role of the BAL-GM assay has not been well established. Therefore, we conducted a metaanalysis to determine the overall accuracy of BAL-GM in the diagnosis of IA. After a systematic review of English-language studies, the sensitivity (SEN), specificity (SPE), and positive and negative likelihood ratios (PLR and NLR, respectively) of BAL-GM for the diagnosis of IA were pooled using a bivariate metaanalysis. Hierarchic summary receiver operating characteristic curves were used to summarize overall test performance. Potential between-study heterogeneity was explored by subgroup analyses. We calculated posttest probability to evaluate clinical usefulness. Twelve reports, including 13 studies, met our inclusion criteria. The summary estimates of the BAL-GM assay for proven or probable IA were as follows: SEN, 0.90 (95% CI, 0.79-0.96); SPE, 0.94 (95% CI, 0.90-0.96); PLR, 14.87 (95% CI, 8.89-24.90); and NLR, 0.10 (95% CI, 0.04-0.24). The four summary estimates of the BAL-GM assay for proven IA were 0.94 (95% CI, 0.86-0.98), 0.79 (95% CI, 0.68-0.86), 4.41 (95% CI, 2.87-6.77), and 0.07 (95% CI, 0.03-0.09), respectively. Significant heterogeneity was present. BAL-GM determination is a sensitive and specific test for the diagnosis of proven and probable IA. The measurement of BAL-GM is thus likely to be a useful tool for diagnosing IA. Further studies focused on the impact of treatment agents are needed.

The accuracy of serum galactomannan assay in diagnosing invasive pulmonary aspergillosis.

Galactomannan (GM) antigen is an aspergillus specific antigen that is released during the growth phase of invasive aspergillosis. We aimed to find the optimum cutoff and accuracy of serum Galactomannan assay in immunocompromised patients. Immunocompromised patients diagnosed with invasive pulmonary aspergillosis (IPA) based on the European Organization for Research and Treatment of Cancer/Invasive Mycosis Study Group (EORTC/MSG) with three levels of certainty proven, probable and possible, referred for GM antigen measurement at Immunology, Asthma and Allergy Research Institute (IAARI) from 2006 to 2009 and if they met the criteria were enrolled in this study. Totally 49 patients with IPA were enrolled in our study. According to EORTC/MSG, patients categorized into three levels of certainty: They were diagnosed as 'proven' invasive pulmonary aspergillosis 16(32.7%), 'probable' 18(36.7%) and 'possible' 15(30.6%). The most common host risk factor was solid tumors 17(34.7%). The accuracy of Galactomannan assay increased from 0.5 to 2 cutoffs. The optimum sensitivity and specificity obtained at the index cutoff of ≥1.5 for diagnosis of "proven" IPA; which were respectively, 69.2% and 72.2%. Other cutoffs had high variance between sensitivity and specificity for diagnosis of IPA. The calculated cutoff gained by receiver operating characteristic (ROC) analysis for detecting proven IPA was 1.5. Intermediate accuracy of serum GM test in conjunct with clinical findings would help early IPA detection among immunocompromised patients.

False-positive serum and bronchoalveolar lavage Aspergillus galactomannan assays caused by different antibiotics

Our objective was to identify false-positive serum and bronchoalveolar lavage (BAL) fluid galactomannan (GM) tests caused by various antibiotics commonly used in general practice. Serum and BAL samples from patients who did not have the diagnostic criteria of invasive aspergillosis and received different antibiotics were prospectively analyzed for GM. Serum and BAL samples were also collected from patients who did not receive antibiotics. At the cut-off index of >or=0.5, false-positive serum results were found in patients who received amoxicillin-clavulanate, piperacillin-tazobactam, cefepime, and cefoperazone-sulbactam (26.7%, 58.3%, 14.3%, and 66.7%, respectively). Fungal colonization in BAL samples had a higher BAL GM than those without fungal colonization. In 71 patients who had a negative BAL culture for fungi, at the cut-off value of >or=1.0, false-positive BAL fluid results were found in patients who received amoxicillin-clavulanate (27.3%), piperacillin-tazobactam (50%), cefepime (16.7%), carbapenem (45.5%), and ceftriaxone (45.5%). False-positive serum and BAL GM assays were also detected in patients who did not receive any antibiotics. In summary, this study demonstrates the false-positive GM levels in serum and BAL caused by beta-lactam antibiotics that are commonly used in general practice. Physicians should be aware of this possible interference.