Serum Galactomannan Detection Research Articles

Metagenomic next-generation sequencing for the diagnosis of invasive pulmonary aspergillosis in type 2 diabetes mellitus patients

Invasive pulmonary aspergillosis (IPA) in patients with diabetes mellitus has high incidence, especially in Type 2 diabetes mellitus (T2DM). The aim of this study was to evaluate the diagnostic efficacy of metagenomic next-generation sequencing (mNGS) for IPA in patients with T2DM. A total of 66 patients with T2DM were included, including 21 IPA and 45 non-IPA patients, from January 2022 to December 2022. The demographic characteristics, comorbidities, laboratory test results, antibiotic treatment response, and 30-day mortality rate of patients were analyzed. The diagnostic accuracy of mNGS and conventional methods was compared, including sensitivity, specificity, positive predictive value and negative predictive value. The sensitivity and specificity of mNGS were 66.7% and 100.0%, respectively, which were significantly higher than those of fluorescence staining (42.1% and 100%), serum 1,3-β-D-glucan detection (38.1% and 90.9%), serum galactomannan detection (14.3% and 94.9%) and BALF galactomannan detection (47.3% and 70.7%). Although the sensitivity of BALF culture (75.0%) was higher than that of mNGS (66.7%), the turnover time of mNGS was significantly shorter than that of traditional culture (1.6 days vs. 5.0 days). The sensitivity of mNGS combined with BALF culture reached 100.0%. In addition, mNGS has a stronger ability to detect co-pathogens with IPA. 47.6% of T2DM patients with IPA were adjusted the initial antimicrobial therapy according to the mNGS results. This is the first study to focus on the diagnostic performance of mNGS in IPA infection in T2DM patients. MNGS can be used as a supplement to conventional methods for the diagnosis of IPA in patients with T2DM.

Cerebral aspergillosis in the era of new antifungals: The CEREALS national cohort study Nationwide CEREbral Aspergillosis Lesional study (CEREALS)

Cerebral aspergillosis (CA) is a life-threatening disease for which diagnosis and management remain challenging. Detailed analyses from large cohorts are lacking. We included 119 cases of proven (n=54) or probable (n=65) CA diagnosed between 2006 and 2018 at 20 French hospitals. Data were collected at baseline and during follow-up. Cerebral imaging was reviewed centrally by two neuroradiologists. The most frequent underlying conditions were hematological malignancy (40%) and solid organ transplantation (29%). Galactomannan was detected in the serum of 64% of patients. In 75% of cases, at least one of galactomannan, Aspergillus PCR, and β-d-glucan was positive in the cerebrospinal fluid. Six-week mortality was 45%. Two distinct patterns of disease were identified according to presumed route of dissemination. Presumed haematogenous dissemination (n=88) was associated with a higher frequency of impaired consciousness (64%), shorter time to diagnosis, the presence of multiple abscesses (70%), microangiopathy (52%), detection of serum galactomannan (69%) and Aspergillus PCR (68%), and higher six-week mortality (54%). By contrast, contiguous dissemination from the paranasal sinuses (n=31) was associated with a higher frequency of cranial nerve palsy (65%), evidence of meningitis on cerebral imaging (83%), macrovascular lesions (61%), delayed diagnosis, and lower six-week mortality (30%). In multivariate analysis and in a risk prediction model, haematogenous dissemination, hematological malignancy and the detection of serum galactomannan were associated with higher six-week mortality. Distinguishing between hematogenous and contiguous dissemination patterns appears to be critical in the workup for CA, as they are associated with significant differences in clinical presentation and outcome.

Diagnostic value of galactomannan in serum and bronchoalveolar lavage fluid for invasive pulmonary aspergillosis in non-neutropenic patients

Objective: To evaluate the diagnostic performance of galactomannan (GM) detection in serum and bronchoalveolar lavage fluid (BALF) for invasive pulmonary aspergillosis (IPA) in non-neutropenic patients. Methods: A total of 291 non-neutropenic patients in the Second Xiangya Hospital of Central South University were included. According to the 2019 EORTC/MSG guidelines, all cases were divided into an IPA group (n = 24) and a non-IPA group (n = 267). Receiver operating characteristic (ROC) curves were drawn to compare the diagnostic efficiency of GM detection in BALF and serum. Results: According to the receiver operating characteristic curves of BALF and serum GM, the areas under the curve were 0.961 and 0.699, respectively. The optimal BALF GM detection was found when the cutoff value was set to 0.87, whereas the sensitivity and specificity were 91.7% and 92.5%, respectively. Conclusions: BALF GM detection is more sensitive than serum GM detection for diagnosing IPA, and the optimal cutoff value for BALF GM is 0.87.

Applicability of the Platelia EIA® Aspergillus test for the diagnosis of aspergilosis in penguins.

Even today, an effective diagnostic test for aspergillosis in penguins is unknown, being the gold standard post-mortem examinations. The fungal antigen galactomannan (GM) has been used as a biomarker of disease in humans and is detected by the Platelia Aspergillus EIA (BioRad)®, a commercial kit based on the sandwich ELISA technique. It is standardized for use in neutropenic patients, however studies have demonstrated its usefulness also possible for birds. The aim of our study was to evaluate the effectiveness of Platelia Aspergillus EIA® test (BioRad-US) in the diagnosis of aspergillosis in Magellanic penguins, determining sensitivity, specificity, and positive and negative predictive values for different cut-off points. Were included in the study, blood serum samples (n = 29) Magellanic penguins in captivity that died by aspergillosis. Detection of GM was performed following manufacturer's instructions and the GM index was obtained by dividing the average value of OD of the duplicate of the clinical sample by duplicate OD of the average value of the cut-off sample provided by the kit. Through information database results were obtained for the presence of anti-Aspergillus fumigatus antibodies detected by agar gel immunodiffusion (AGID) for all serum samples. Results were analyzed using chi-square test and Kruskal-Wallis from SPSS 20.0, IBM®. ROC curve was obtained and from this, rates of sensitivity, specificity, positive and negative predictive values were also calculated based on four different cutoff points (0.5, 1.0, 1.5 and 2.0). The serum GM index did not differ between animals of the case and control group (pkw =0.097). In determining the ROC curve for serum GM detection the value of area under the curve was 0.635. From the values ​​determined by the coordinate of the curve, four different cut points (0.5, 1.0, 1.5 and 2.0) were analyzed, resulting in sensitivity rates ranging from 86.2 to 34.5% % and specificity between 87% and 26.1%. By comparing the serum GM index in group case as the presence or absence of antibodies detected by AGID was found p=0.503. The detection of GM the Platelia Aspergillus EIA® test seems is not be useful for the diagnosis of aspergillosis in naturally infected penguins.

Galactomannan detection in bronchoalveolar lavage fluid corrected by urea dilution for the diagnosis of invasive pulmonary aspergillosis among nonneutropenic patients.

To investigate the diagnostic performance of galactomannan (GM) detection in bronchoalveolar lavage fluid (BALF) corrected by urea dilution and modification of the AspICU clinical algorithm. GM detection in serum and BALF samples was performed in nonneutropenic patients on the day of clinically suspected invasive pulmonary aspergillosis (IPA) between January 2016 and June 2018, and urea was measured in the plasma and BALF. The BALF GM concentration was corrected by urea dilution, and receiver operating characteristic (ROC) curves were generated to determine the optimal cut-off value. A total of 184 patients who were suspected of IPA, were enrolled in this prospective study together with 30 patients with lung cancer as a control group. Seventy-eight patients were diagnosed with IPA, including 37 who were verified by pathology. The urea plasma-to-urea BALF ratio in the IPA group [4.18 (IQR, 3.52-4.91)] was greater than that in the non-IPA group [3.42 (IQR, 3.12-3.76), P<0.001]. The ROC curve showed that defining the cut-off value as 2.94 optical density index (ODI) for the corrected BALF GM resulted in a sensitivity and specificity of 85.91% and 94.07%, respectively, and was more accurate than the use of the uncorrected values (P<0.05). The corrected BALF GM was valuable for diagnosing IPA in nonneutropenic patients. The modified AspICU clinical algorithm based on this measurement represents a reliable diagnostic instrument in clinical settings.

Galactomannan detection for invasive aspergillosis in immunocompromised patients.

Invasive aspergillosis is the most common life-threatening opportunistic invasive mycosis in immunocompromised patients. A test for invasive aspergillosis should neither be too invasive nor too great a burden for the already weakened patient. The serum galactomannan enzyme-linked immunosorbent assay (ELISA) seems to have the potential to meet both requirements. To obtain summary estimates of the diagnostic accuracy of galactomannan detection in serum for the diagnosis of invasive aspergillosis. We searched MEDLINE, EMBASE and Web of Science with both MeSH terms and text words for both aspergillosis and the sandwich ELISA. We checked the reference lists of included studies and review articles for additional studies. We conducted the searches in February 2014. We included cross-sectional studies, case-control designs and consecutive series of patients assessing the diagnostic accuracy of galactomannan detection for the diagnosis of invasive aspergillosis in patients with neutropenia or patients whose neutrophils are functionally compromised. The reference standard was composed of the criteria given by the European Organization for Research and Treatment of Cancer (EORTC) and the Mycoses Study Group (MSG). Two review authors independently assessed quality and extracted data. We carried out meta-analysis using the bivariate method. We investigated sources of heterogeneity by adding potential sources of heterogeneity to the model as covariates. We included 54 studies in the review (50 in the meta-analyses), containing 5660 patients, of whom 586 had proven or probable invasive aspergillosis. When using an optical density index (ODI) of 0.5 as a cut-off value, the sensitivity of the test was 82% (73% to 90%) and the specificity was 81% (72% to 90%). At a cut-off value of 1.0 ODI, the sensitivity was 72% (65% to 80%) and the specificity was 88% (84% to 92%). At a cut-off value of 1.5 ODI, the sensitivity was 61% (47% to 75%) and the specificity was 93% (89% to 97%). None of the potential sources of heterogeneity had a statistically significant effect on either sensitivity or specificity. If we used the test at a cut-off value of 0.5 ODI in a population of 100 patients with a disease prevalence of 9% (overall median prevalence), two patients who have invasive aspergillosis would be missed (sensitivity 82%, 18% false negatives), and 17 patients would be treated unnecessarily or referred unnecessarily for further testing (specificity 81%, 19% false negatives). If we used the test at a cut-off value of 1.5 in the same population, that would mean that four invasive aspergillosis patients would be missed (sensitivity 61%, 39% false negatives), and six patients would be treated or referred for further testing unnecessarily (specificity 93%, 7% false negatives). These numbers should, however, be interpreted with caution because the results were very heterogeneous.

Utilidad de la prueba Aspergillus-LFD para el diagnóstico de aspergilosis: primera experiencia en Chile

The diagnosis of invasive aspergillosis remains a challenge. Detection of galactomannan in serum and bronchoalveolar lavage is a useful tool; however due to methodological and economic reasons, the test frequencies of galactomannan assays vary from daily to weekly, which constitute a risk to the patient. In this study, we aimed to evaluate and correlate the performance of the new kit Aspergillus-LFD with the GM-EIA. Aspergillus-LFD kit represents a fast, economical and simple test; showed a good performance and excellent correlation with GM-EIA kit. Given the above, the Aspergillus-LFD is emerging as an alternative to consider in the early diagnosis of invasive aspergillosis.

Utility of Aspergillus-LFD: first experience in Chile

The diagnosis of invasive aspergillosis remains a challenge. Detection of galactomannan in serum and bronchoalveolar lavage is a useful tool; however due to methodological and economic reasons, the test frequencies of galactomannan assays vary from daily to weekly, which constitute a risk to the patient. In this study, we aimed to evaluate and correlate the performance of the new kit Aspergillus-LFD with the GM-EIA. Aspergillus-LFD kit represents a fast, economical and simple test; showed a good performance and excellent correlation with GM-EIA kit. Given the above, the Aspergillus-LFD is emerging as an alternative to consider in the early diagnosis of invasive aspergillosis.

Reproducibility of Positive Results for the Detection of Serum Galactomannan by Platelia™ Aspergillus EIA

Galactomannan (GM) was recently included in consensus guidelines as an indirect mycological criterion for the diagnosis of invasive aspergillosis. Currently, there is an enzyme immunoassay available to detect GM in biological samples, the Platelia™ Aspergillus EIA. In this study, the reproducibility of positive results obtained using this assay was evaluated using serum samples from neutropenic patients. A trend toward lower values was observed, and 55%(27/49) of positive results were negative after retesting. A low reproducibility of positive results for the detection of GM in serum was observed.

Comparison of a novel Aspergillus lateral-flow device and the Platelia® galactomannan assay for the diagnosis of invasive aspergillosis following haematopoietic stem cell transplantation

The detection of galactomannan in serum is a cornerstone for the diagnosis of invasive fungal disease (IFD). Because a delay in treatment initiation is associated with a poor outcome, the results have to be available promptly. However, due to methodological and economic reasons, the test frequencies of the commonly used galactomannan assays vary between daily to weekly, meaning that results may be available too late to be clinically useful. The novel Aspergillus lateral-flow device (Aspergillus-LFD) is a rapid test that may overcome these limitations. We compared the diagnostic performance of the Aspergillus-LFD and the Platelia® Aspergillus EIA (GM-EIA) in serum from 101 patients during and after allogeneic haematopoietic stem cell transplantation (HSCT). Clinical data and sera were collected prospectively and patients classified according to the European Organisation for Research and Treatment of Cancer (EORTC)/Mycoses Study Group (MSG) 2008 guidelines. By the end of hospitalisation, one proven, nine probable and 20 possible cases of IFD were identified. Depending on the number of positive serum samples required for test positivity, the sensitivities, specificities and diagnostic odds ratios in patients with proven and probable IFD were as follows. One positive serum required: Aspergillus-LFD 40.0 %, 86.8 % and 3.03; GM-EIA 40.0 %, 89.0 % and 3.64. Two positive sera required: Aspergillus-LFD 20.0 %, 97.8 % and 11.13; GM-EIA 30.0 %, 98.9 % and 38.57. Although the GM-EIA was positive in a higher percentage of samples, this did not result in an earlier diagnosis. If used as a screening test (one positive serum required for test positivity) or to rule out IFD, the Aspergillus-LFD has shown a comparable diagnostic performance to the GM-EIA. However, if the results have to be confirmed by a second positive serum, the GM-EIA exhibited superior sensitivity. In terms of practicability, the Aspergillus-LFD has demonstrated to be a quick (15 min) and easy-to-use test for single-patient detection of Aspergillus antigens.

Validation d’une méthode Elisa pour la recherche de l’antigène aspergillaire galactomannane en vue de l’accréditation

Diagnosis of invasive aspergillosis for patients with high risk of infection is based on the monitoring of Aspergillus antigenemia assessed by the detection of galactomannan in serum by a sandwich-type ELISA (Biorad(®)). The validation of the method was displayed according to the guide COFRAC SH GTA 04. The internal quality control system settled, involves two quality control samples made of pools of sera (negative and positive). The repeatability of the measurements, as estimated by the coefficients of variation (CV), obtained by two different technicians was found from 9 to 13.7% for the positive control. The CV of the negative control, for which the provider indicates it is not useful in the analytical process, was found from 7.1 to 30%. In our experience it could be an indicator of environmental contamination. The evaluation of the intermediary fidelity was 15.7% for the positive control and 22.5% for the negative one. In the lack of reference material (International Standard) and recommendation from scientific societies, performances obtained will be discussed according to the results reported in the technical form of the supplier and those obtained by 39 laboratories participating in the only available external quality assessment program organized in France by ProBioQual(®) where the CV of reproducibility are 44.7% of unit (mean index 0.131) for the negative control and 18% (mean index 1.089) for the positive one in 2011.

A systematic review of the accuracy of diagnostic test of serum galactomannan antigen detection for invasive aspergillosis

To assess the value of galactomannan (GM) double-direct sandwich enzyme-linked immunosorbent assay (ELISA) in the diagnosis of invasive aspergillosis (IA). A search in MEDLINE, EMbase, OVID, CBMdisc and CHKD from Jan. 1991 to Dec. 2008 was conducted to collect all articles about diagnostic tests of serum GM detection. Then the methodological quality was assessed by QUADAS-items, sources of heterogeneity investigated, pooled effect quantities evaluated, and meta-analysis studies, SROC curves, and subgroup analysis performed. Thirty-six articles with a population of 4959 patients were included. The average prevalence of IA was 10%(532/4959). Our meta-analysis reported a median heterogeneity (I(2) = 48.6%, P < 0.05), with a pooled DOR value of 19.10 (95%CI 12.67 - 28.79), a pooled sensitivity of 0.66 (95%CI 0.61 - 0.70), a pooled specificity of 0.90 (95%CI 0.89 - 0.90), a pooled positive likelihood ratio of 5.48 (95%CI 4.27 - 7.02), a pooled negative likelihood ratio of 0.38 (95%CI 0.29 - 0.50), and an area under curve of SROC 0.88. The rate of underdiagnosis of serum GM detection was 34% (168/490) and the rate of misdiagnosis was 10% (466/4469). With a rise in the cut-off value the sensitivity of GM test decreased and specificity increased. Two consecutive positive tests decreased the sensitivity but increased the specificity. Age had no significant effect on the diagnosis by GM test. Both antifungal prophylaxis and antifungal therapy had no significant effect on sensitivity and specificity of GM test for IA diagnosis. Serum GM detection is an effective diagnostic tool for invasive aspergillosis in high-risk populations.

Aislamiento de Aspergillus lentulus en España en un paciente crítico con enfermedad pulmonar obstructiva crónica

Aspergillus lentulus was first described in the year 2005, and since it cannot be phenotypically distinguished from Aspergillus fumigatus, it is conceivable that earlier descriptions (before 2005) could be attributed to this new species. Currently invasive infections caused by A. lentulus are rare and very few cases have been previously published in neutropenic patients, all of them with fatal outcome. Here we report a critically ill non neutropenic patient with chronic obstructive pulmonary disease (COPD) who was admitted to the medical intensive care unit with an exacerbation of COPD and who had been treated with long term corticosteroids. A. fumigatus was cultured from two bronchial aspirates and in a third bronchial aspirate both A. lentulus and A. fumigatus were isolated. On two consecutive days detection of galactomannan in serum was negative whilst detection of (1-3) beta-D glucan was positive (> 518 pg/ml). Minimal inhibitory concentrations (MIC) for itraconazole, voriconazole, caspofungin and amphotericin B were high for this strain of A. lentulus. Given the high MIC values of A. lentulus to available antifungals, the accurate identification of this new species is warranted. To our knowledge, this is the first report of the isolation of A. lentulus in a non-neutropenic critically ill patient, although we note that since it was isolated only once from respiratory specimens, its implication as an etiologic agent of infection for this patient remains to be established.

Fungal infections in lung transplant recipients

Despite numerous advances in lung transplantation, survival is still significantly compromised by a higher rate of infections. This review intends to provide an overview of the most common fungal infections afflicting lung transplant recipients, focusing on the most recent developments in diagnosis, therapy and prophylaxis. Although detection of galactomannan in serum has poor sensitivity for the diagnosis of invasive aspergillosis in lung transplant recipients, detection of galactomannan in the bronchoalveolar lavage of a lung transplant recipient, with a compatible clinical illness, is highly suggestive of invasive disease. New antifungal agents, with a broader spectrum of activity and a more tolerable side effect profile, have become available for the treatment and prophylaxis of fungal infections. Evidence suggests that, at least for voriconazole, monitoring of drug concentrations may be advisable to prevent clinical failure due to underdosing and toxicity due to excessive dosing. Fungal infections remain a significant cause of morbidity and mortality in lung transplant recipients; however, advances have been made in the recent years, which will allow earlier diagnosis and more effective and tolerated treatment.

Intravenous PLASMA-LYTE as a Major Cause of False-Positive Results of Platelia Aspergillus Test for Galactomannan Detection in Serum

Galactomannan (GM) detection by the Platelia Aspergillus (PA) enzyme immunoassay (Bio-Rad, France) is a test widely used for the early diagnosis of invasive aspergillosis (IA) in hematooncological patients. False-positive results for this test were reported by several authors, associated mainly with

Diagnostic value of DNA, (1-3)-β- d-glucan, and galactomannan detection in serum and bronchoalveolar lavage of mice experimentally infected with Aspergillus terreus

The aim of this study was to evaluate the diagnostic value of Aspergillus terreus-specific DNA, (1-3)-β- d-glucan (BDG), and galactomannan (GM) in immunosuppressed mice infected intravenously with A. terreus conidia and sacrificed in groups of 12 each on days 1, 3, 5, 7, and 9. A. terreus-specific DNA, BDG, and GM in serum and bronchoalveolar lavage (BAL) were detected by nested polymerase chain reaction (nPCR), Fungitell kit (Associates of Cape Cod, E. Falmouth, MA), and Aspergillus Platelia kit (Bio-Rad, Marnes-laCoquette, France), respectively. Cultures of lung homogenate of all the animals yielded A. terreus. The BDG positivity, GM positivity, and nPCR positivity in serum specimens were 43%, 78%, and 73%, respectively. Combined detection enhanced the positivity to 95% for A. terreus DNA and GM, 83% for GM and BDG, and 95% for DNA, GM, and BDG. In BAL, the GM positivity and nPCR positivity were 80% and 81%, respectively, whereas combined detection increased the positivity to 98%. Detection of GM and DNA offers a sensitive and specific diagnostic option for invasive aspergillosis.

Defining a case of invasive aspergillosis by serum galactomannan.

The timely diagnosis of invasive aspergillosis (IA) remains difficult. In recent years, increased experience has been gained with the Platelia™ Aspergillus enzyme immunoassay. However, the excellent sensitivity and high positive predictive value that has been reported in earlier studies cannot consistently be reproduced in some of the more recent studies. As expected, this stems from major methodological and clinical heterogeneities between studies. This article reviews these between-study heterogeneities and concludes that the detection of serum galactomannan can be used to define a case of IA in a well-defined population of at-risk patients.

Efficacy of amphotericin B or amphotericin B–intralipid in combination with caspofungin against experimental aspergillosis

Infections caused by Aspergillus species are increasing in importance, especially among immunocompromised hosts. The objective of this study was to evaluate the efficacy of combination treatment consisting of the polyene amphotericin B (AMB) or amphotericin B-intralipid admixture (AMB-IL) and the echinocandin caspofungin (CAS) in experimental murine systemic aspergillosis. Inhibition of synthesis of a major component of the fungal cell wall and an effect on the cell membrane, by combining echinocandin and a polyene, may result in a synergistic interaction in vitro and in vivo against Aspergillus fumigatus. ICR mice were immunosuppressed by intraperitoneal (ip) administration of cyclophosphamide (CY). Three days post-CY administration the mice were inoculated intravenously (iv) with A. fumigatus conidia. Infection and treatment were evaluated during an observation period of 30 days in terms of mortality (survival rate and mean survival time) and morbidity (quantitative determination of fungal burden, histopathology, and detection of serum galactomannan). The data showed that combined CAS and AMB or AMB-IL treatment increased the survival of the mice (up to 69.2%) as compared to those treated with each agent alone (44.4, 40.7 and 50%, respectively), and prolonged their mean survival time to 22.5 days. These combinations also resulted in reduction of fungal burden in organs, and decrease in serum galactomannan. The successful results obtained in the experimental animal model of this study may possibly open the way to more effective management of aspergillosis in humans.

Galactomannan Does Not Precede Major Signs on a Pulmonary Computerized Tomographic Scan Suggestive of Invasive Aspergillosis in Patients with Hematological Malignancies

Detection of serum galactomannan (GM) antigen and presence of the halo sign on a pulmonary computerized tomographic (CT) scan have a high specificity but a low sensitivity to diagnose invasive aspergillosis (IA) in patients at risk for this disease. To our knowledge, the relationship between the time at which pulmonary infiltrates are detected by CT and the time at which GM antigens are detected by enzyme immunoassay (EIA) has not been studied. In a prospective study, tests for detection of GM were performed twice weekly for patients with hematological malignancies who had undergone hematopoetic stem cell transplantation (HSCT) or had received induction and/or consolidation chemotherapy. A pulmonary CT scan was performed once weekly. Infiltrates were defined as either major or minor signs. IA was classified as proven, probable, or possible, in accordance with the definition stated by the European Organization for Research and Treatment of Cancer-Invasive Fungal Infections Cooperative Group and the National Institute of Allergy and Infectious Diseases Mycoses Study Group. We analyzed 161 episodes of infection in 107 patients (65 allogeneic HSCT recipients, 30 autologous HSCT recipients, and 66 induction and/or consolidation chemotherapy recipients). A total of 109 episodes with no IA, 32 episodes with possible IA, and 20 episodes with probable or proven IA were identified. Minor pulmonary signs were detected by CT in 70 episodes (43%), and major pulmonary signs were detected by CT in 11 episodes (7%). Univariate and multivariate analyses revealed no significant association between detection of GM by EIA and detection of abnormal pulmonary signs by CT. A significant association was found between GM levels and receipt of piperacillin-tazobactam. GM test results were not positive before major signs were seen on CT images. Only 7 (10%) of 70 patients with minor pulmonary signs had positive GM test results before detection of the greatest pathologic change by CT. We show that detection of GM by EIA does not precede detection of major lesions by pulmonary CT. In the clinical setting, the decision to administer mold-active treatment should based on detection of new pulmonary infiltrates on CT performed early during infection, rather than on results of EIA for detection of GM.

Experimental systemic murine aspergillosis: treatment with polyene and caspofungin combination and G-CSF

In view of the poor therapy outcomes of invasive aspergillosis, the objective of this study was to evaluate the efficacy of combination treatment consisting of the polyene amphotericin-B-intralipid, the echinocandin caspofungin and granulocyte-colony stimulating factor (G-CSF) in experimental murine systemic aspergillosis. With inhibition of synthesis of 1,3-beta-d-glucan in the fungal cell wall by caspofungin and an effect on the cell membrane by amphotericin-B-intralipid, this treatment may result in a synergic effect against Aspergillus fumigatus. Addition of G-CSF may further contribute to therapy of aspergillosis. ICR mice were immunosuppressed by intraperitoneal administration of cyclophosphamide. Three days later, the mice were inoculated intravenously (iv) with A. fumigatus conidia. Infection and treatment were evaluated during an observation period of 30 days in terms of mortality (survival rate and mean survival time) and morbidity (quantitative determination of fungal burden, histopathology, and detection of serum galactomannan). Combination of caspofungin + G-CSF or addition of G-CSF to the combination of caspofungin + amphotericin-B-intralipid increased the survival rate of infected mice up to 78.9% and prolonged their mean survival time to 25 days. These combinations also resulted in a reduction in fungal burden in organs, and a decrease in serum galactomannan. The successful results obtained in the experimental model may possibly open the way to more effective management of aspergillosis in humans.