Clinicomycological Study of the Spectrum of Pulmonary Aspergillosis at a Tertiary Care Hospital in Central India.

Knowing the spectrum, prevalence, and modes of diagnosis of pulmonary aspergillosis (PA) will be beneficial to clinicians for its early diagnosis and management. This study aims to estimate the prevalence, spectrum, and role of serological tests and radiological findings in the diagnosis of PA. A total of 150 patients were suspected of having PA after obtaining relevant clinical history and radiological imaging. The patients were grouped into each spectrum of PA as invasive PA (IPA), chronic necrotizing PA (CNPA), aspergilloma, allergic bronchopulmonary aspergillosis (ABPA) based on predisposing factors, clinical and radiological findings, and the guidelines of 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 (EORTC/MSG). Samples (bronchoalveolar lavage (BAL), sputum, blood) were collected from these patients and processed in a microbiology lab. BAL and sputum were subjected to microscopy by potassium hydroxide mount, calcofluor white mount, and culture. The serum was separated from blood by centrifugation and subjected to specific serological tests based on the spectrum of PA that the patient was suspected to have. For IPA, serum and BAL galactomannan antigen enzyme-linked immunosorbent assay (ELISA) was performed. For CNPA and aspergilloma, the anti-Aspergillus IgG antibody ELISA was performed. For ABPA, the tests performed were total immunoglobulin E (IgE) ELISA, Aspergillus fumigatus-specific IgE ELISA, and anti-Aspergillus immunoglobulin G (IgG) antibody ELISA. After compiling the clinical, radiological, culture, and serological findings, patients were diagnosed to have a particular spectrum of PA. The prevalence of IPA was 1.4%, CNPA was 4%, ABPA was 3.2%, and aspergilloma was 2.9%. CNPA was the predominant spectrum of PA in our study. Culture positivity for Aspergillus species was seen the highest in aspergilloma patients, followed by IPA, ABPA, and CNPA patients. A. fumigatus was the most common causative agent of PA, except for IPA for which Aspergillus flavus was the most common causative. Aspergillus niger and Aspergillus terreus were less the frequent causes of PA. A combination of radiological, microbiological, and serological tests along with clinical correlation is needed to confirm the diagnosis of PA.

Aspergillus Galactomannan Titer as a Diagnostic Marker of Invasive Pulmonary Aspergillosis in Lung Transplant Recipients: A Single-Center Retrospective Cohort Study.

Invasive pulmonary aspergillosis (IPA) can occur in immunocompromised patients, and an early detection and intensive treatment are crucial. We sought to determine the potential of Aspergillus galactomannan antigen titer (AGT) in serum and bronchoalveolar lavage fluid (BALF) and serum titers of beta-D-glucan (BDG) to predict IPA in lung transplantation recipients, as opposed to pneumonia unrelated to IPA. We retrospectively reviewed the medical records of 192 lung transplant recipients. Overall, 26 recipients had been diagnosed with proven IPA, 40 recipients with probable IPA, and 75 recipients with pneumonia unrelated to IPA. We analyzed AGT levels in IPA and non-IPA pneumonia patients and used ROC curves to determine the diagnostic cutoff value. The Serum AGT cutoff value was 0.560 (index level), with a sensitivity of 50%, specificity of 91%, and AUC of 0.724, and the BALF AGT cutoff value was 0.600, with a sensitivity of 85%, specificity of 85%, and AUC of 0.895. Revised EORTC suggests a diagnostic cutoff value of 1.0 in both serum and BALF AGT when IPA is highly suspicious. In our group, serum AGT of 1.0 showed a sensitivity of 27% and a specificity of 97%, and BALF AGT of 1.0 showed a sensitivity of 60% and a specificity of 95%. The result suggested that a lower cutoff could be beneficial in the lung transplant group. In multivariable analysis, serum and BALF AGT, with a minimal correlation between the two, showed a correlation with a history of diabetes mellitus.

Refractory invasive pulmonary aspergillosis due to Aspergillus flavus detected with the combination of two in-house Aspergillus qPCR.

We present a case of probable invasive pulmonary aspergillosis due to Aspergillus flavus, in a female patient treated for an acute myeloid leukemia. Two weeks after an allogenic stem cell transplantation a probable invasive pulmonary aspergillosis was diagnosed based on thoracic imaging combined with positive galactomannan antigen and positive in-house mitochondrial Aspergillus qPCR in serum. Although an antifungal treatment was initiated, Aspergillus qPCR and galactomannan antigen remained positive in serum and worsening of the thoracic lesions was observed. The discordance between the negativity of the in-house ribosomal Aspergillus qPCR (specific to A. fumigatus) and the positivity of the in-house mitochondrial Aspergillus qPCR (targeting A. fumigatus and some other Aspergillus) allowed the suspicion of a thermophilic Aspergillus species that was not A. fumigatus. No strain was obtained in culture but the involvement of A. flavus was confirmed using a specific A. flavus qPCR. This case illustrated the usefulness of our original strategy combining two different in-house Aspergillus qPCRs, in addition to galactomannan assay, to diagnose invasive aspergillosis in hematology patients.

Case report: Vascular graft infection due to Aspergillus species presenting with recurrent vascular occlusion.

BACKGROUND: An aortic graft implantation is an effective therapeutic method for various aortic diseases. However, it is known that sometimes these implanted grafts can be the foci of infections. Here we report a rare case of graft infection that presented multiple embolisms of aortic branches and peripheral organs. CASE PRESENTATION: A 63-year-old Japanese woman with a history of aortic graft implantation presented with occlusions of large arteries in different loci and time points, with elevation of non-specific inflammatory markers. Thoracic contrast-computed tomography (CT) captured vegetation in the descending aortic graft and the [18F]fluorodeoxyglucose positron emission tomography/computed tomography ([18F]FDG PET/CT) showed accumulation of FDG in the same site, suggesting a graft infection. Despite all these suspicious findings, repeated blood culture examinations never detected any microorganisms. A diagnosis of Aspergillus graft infection was made based on an elevated serum ß-D glucan (ßDG) and a positive Aspergillus galactomannan (GM) antigen test. The patient subsequently had surgery with replacement of the descending aortic graft and anti-fungal drugs were instituted with significant improvement noted. CONCLUSION: In the present case, the patient's specific feature in the anatomical vascular construction, past operation, and basal fundamental diseases collaboratively contributed to the pathogenesis of the present infection. It is important to recognize the risk of graft infection and conduct imaging studies when indicative symptoms emerge. The negativity in blood culture studies often makes detection of pathogenic microbes extremely difficult. This case suggests that non-cultural tests such as bDG and GM can be useful for diagnosis and starting appropriate anti-fungal drugs in the early stages.

Incidence and Risk Factors for Inappropriate Use of Non-Culture-Based Fungal Assays: Implication for Diagnostic Stewardship.

BACKGROUND: Non-culture-based fungal assays (NCBFAs) have been used increasingly to help diagnose invasive fungal diseases. However, little is known about inappropriate use of NCBFAs. We aimed to investigate inappropriate use of NCBFAs in a tertiary academic hospital. METHODS: This retrospective cohort study included patients who underwent testing with beta-D glucan (BDG) between January and March 2018 or with galactomannan antigen (GMA) or cryptococcal antigen (CRAG) between January and June 2018. Testing was deemed appropriate if the clinical presentation was compatible with a fungal infection and there was a predisposing host factor at the time of ordering. We compared patients with appropriate and inappropriate use of NCBFAs using multivariate logistic regression analysis. RESULTS: Four hundred seventy patients (BDG, 394; GMA, 138; CRAG, 164) met inclusion criteria and were evaluated. About 80% of NCBFAs were deemed inappropriate. Ordering by transplant medicine physicians, repetitions of the test, the absence of predisposing factors for fungal infections, and the absence of recommendations from infectious diseases consultants were associated with an increased risk of inappropriate NCBFA use. CONCLUSIONS: We found that a large proportion of NCBFAs were deemed inappropriate. There is an opportunity for diagnostic stewardship to reduce avoidable fungal testing among patients at low risk for fungal infection.

Disseminated histoplasmosis diagnosed by cross-reactivity with the Aspergillus galactomannan antigen in an HIV-positive patient.

Invasive histoplasmosis is the most common AIDS-defining event in endemic regions such as South America. In non-endemic regions, less familiar to the diagnosis, invasive histoplasmosis can be mistakenly diagnosed as miliary tuberculosis leading to a high mortality rate. Here we present the case of an invasive histoplasmosis mistakenly diagnosed as tuberculosis. The diagnosis of histoplasmosis was considered later on, in light of patient's clinical deterioration and positive Aspergillus galactomannan antigens. This case highlights the importance of considering other opportunistic infections when facing a culture-negative miliary tuberculosis without clinical improvement despite anti-tuberculosis therapy. It also draws our attention to the tools available in non-endemic regions that can be helpful in the diagnosis of invasive histoplasmosis.

Prognostic Scores and Azole-Resistant Aspergillus fumigatus in Invasive Aspergillosis from an Indian Respiratory Medicine ICU (ICU Patients with IA Suspicion).

Objective: To assess the effectiveness of three general prognostic models (APACHE II, SAPS II, and SOFA) with serum galactomannan antigen in a clinically suspected invasive aspergillosis (IA) subpopulation admitted to a respiratory medicine ICU and to identify azole-resistant Aspergillus fumigatus (ARAF) cases. Methodology and Results: A total of 235 clinically suspected IA patients were prospectively enrolled and observed 30-day mortality was 29.7%. The three general models showed poor discrimination assessed by area under receiver operating characteristic (ROC) curves (AUCs, <0.7) and good calibration (p = 0.92, 0.14, and 0.13 for APACHE II, SAPS II, and SOFA, respectively), evaluated using Hosmer-Lemeshow goodness-of-fit tests. However, discrimination was significantly better with galactomannan values (AUC, 0.924). In-vitro antifungal testing revealed higher minimum inhibitory concentration (MIC) for 12/34 isolates (35.3%) whereas azole resistance was noted in 40% of Aspergillus fumigatus isolates (6/15) with two hotspot cyp51A mutations, G54R and P216L. Conclusions: Patients diagnosed with putative and probable IA (71.4% and 34.6%, respectively), had high mortality. The general prognostic model APACHE II seemed fairly accurate for this subpopulation. However, the use of local GM cut-offs calculated for mortality, may help the intensivists in prompt initiation or change of therapy for better outcome of patients. In addition, the high MICs highlight the need of antifungal surveillance to know the local resistance rate which might aid in patient treatment.

Performance of the sona Aspergillus Galactomannan Lateral Flow Assay in a Cancer Patient Population.

The diagnosis of invasive aspergillosis can be challenging in cancer patients. Herein, the analytical and clinical performance of the sona Aspergillus galactomannan lateral flow assay (GM LFA) was evaluated and its performance compared to that of the Bio-Rad galactomannan enzyme immunoassay (GM EIA). Serum and bronchoalveolar lavage (BAL) fluid samples received for GM EIA testing between March and August 2019 were included. Positive and negative percent agreement (PPA and NPA) were calculated for the GM LFA compared to the GM EIA. Discrepant analysis was performed by review of the patient's medical records assessing for any evidence of a fungal infection. Five hundred thirty-three samples (85 BAL samples and 448 serum samples) from 379 patients were included in the study. The overall PPA and NPA were 100% (95% confidence interval [CI], 72.2 to 100%) and 97.5% (95% CI, 95.5 to 98.4%), respectively. Fourteen of 24 samples were positive by LFA only. The sensitivity of the GM LFA for proven and probable invasive aspergillosis (IA) was 100% (95% CI, 51.0 to 100%) and 87.5% (95% CI, 55.9 to 99.4%), with a specificity of 95.5% (95% CI, 92.3 to 97.2%) and 96.2% (95% CI, 93.4 to 97.7%), respectively. The sensitivity of the GM EIA for proven and probable IA was 25% (95% CI, 1.28 to 69.9%) and 62.5% (95% CI, 30.6 to 86.3%), with a specificity of 98.2% (95% CI, 96.2 to 99.1%) and 99.2% (95% CI, 97.7 to 99.8%), respectively. The Aspergillus GM LFA outperformed the Aspergillus GM EIA for the detection of the galactomannan antigen in our patient population. The simplicity and rapid time to results makes the Aspergillus GM LFA easy to implement in a wide range of laboratory settings.

New clinical algorithm including fungal biomarkers to better diagnose probable invasive pulmonary aspergillosis in ICU.

BACKGROUND: The classification of invasive pulmonary aspergillosis (IPA) issued by the European Organization for the Research and Treatment of Cancer/Mycoses Study Group Education and Research Consortium (EORTC/MSGERC) is used for immunocompromised patients. An alternative algorithm adapted to the intensive care unit (ICU) population has been proposed (AspICU), but this algorithm did not include microbial biomarkers such as the galactomannan antigen and the Aspergillus quantitative PCR. The objective of the present pilot study was to evaluate a new algorithm that includes fungal biomarkers (BM-AspICU) for the diagnosis of probable IPA in an ICU population. PATIENTS AND METHODS: Data from 35 patients with pathology-proven IPA according to European Organization for the Research and Treatment of Cancer/Mycosis Study Group (EORTC/MSGERC)-2008 criteria were extracted from the French multicenter database of the Invasive Fungal Infections Surveillance Network (RESSIF). The patients were investigated according to the AspICU algorithm, and the BM-AspICU algorithm in analyzing the clinical, imaging, and biomarker data available in the records, without taking into account the pathology findings. RESULTS: Eight patients had to be excluded because no imaging data were recorded in the database. Among the 27 proven IPAs with complete data, 16 would have been considered as putative IPA with the AspICU algorithm and 24 would have been considered as probable IPA using the new algorithm BM-AspICU. Seven out of the 8 patients with probable BM-AspICU IPA (and not classified with the AspICU algorithm) had no host factors and no Aspergillus-positive broncho-alveolar lavage fluid (BALF) culture. Three patients were non-classifiable with any of the two algorithms, because they did not have any microbial criteria during the course of the infection, and diagnosis of proven aspergillosis was done using autopsy samples. CONCLUSION: Inclusion of biomarkers could be effective to identify probable IPA in the ICU population. A prospective study is needed to validate the routine application of the BM-AspICU algorithm in the ICU population.

Digestive enzymes of fungal origin as a relevant cause of false positive Aspergillus antigen testing in intensive care unit patients.

BACKGROUND: Galactomannan antigen (GM) testing is widely used in the diagnosis of invasive aspergillosis (IA). Digestive enzymes play an important role in enzyme substitution therapy in exocrine pancreatic insufficiency. As digestive enzymes of fungal origin like Nortase contain enzymes from Aspergillus, a false-positive result of the test might be possible because of cross-reacting antigens of the cell wall of the producing fungi. We, therefore, asked whether the administration of fungal enzymes is a relevant cause of false-positive GM antigen test results. METHODS: Patients with a positive GM antigen test between January 2016 and April 2020 were included in the evaluation and divided into two groups: group 1-Nortase-therapy, group 2-no Nortase-therapy. In addition, dissolved Nortase samples were analyzed in vitro for GM and ß-1,3-D-glucan. For statistical analysis, the chi-squared and Mann‒Whitney U tests were used. RESULTS: Sixty-five patients were included in this evaluation (30 patients receiving Nortase and 35 patients not receiving Nortase). The overall false positivity rate of GM testing was 43.1%. Notably, false-positive results were detected significantly more often in the Nortase group (73.3%) than in the control group (17.1%, p < 0.001). While the positive predictive value of GM testing was 0.83 in the control group, there was a dramatic decline to 0.27 in the Nortase group. In vitro analysis proved that the Nortase enzyme preparation was highly positive for the fungal antigens GM and ß-1,3-D-glucan. CONCLUSIONS: Our data demonstrate that the administration of digestive enzymes of fungal origin like Nortase leads to a significantly higher rate of false-positive GM test results compared to that in patients without digestive enzyme treatment.

Epidemiology, laboratory diagnosis and clinical aspects of fungal pulmonary infections in 384 patients hospitalized in pulmonary units in Guilan province, Iran.

BACKGROUND AND OBJECTIVES: The respiratory tract is the most common site for developing fungal infections. People who have a weakened immune system are more susceptible to respiratory system involvement with fungi. Fungal infections of the respiratory tract are largely unrecognized and their true burden is elusive. Therefore, the aim of the current study was to evaluate the clinical spectrum, demographic characteristics, risk factors, and etiology of fungal respiratory infections in 384 patients hospitalized in pulmonary units of Razi hospital, Guilan province, Iran. MATERIALS AND METHODS: A total of 384 lung specimens (192 Bronchoalveolar lavages (BAL) and 192 sputa) were obtained from patients who met the inclusion criteria. All samples were analyzed by direct microscopy and culture. Fungal identification was accomplished by internal transcribed spacer (ITS) and beta-tubulin sequencing. Also, in patients suspected to invasive pulmonary aspergillosis BAL specimens were tested for galactomannan (GM) antigen. According to the host factors (clinical symptoms, radiology findings and predisposing factors which were defined as inclusion criteria), and the positive results in direct examination, culture and serology (GM for aspergillosis) the infection was confirmed. RESULTS: Fungal respiratory infection was confirmed in 137 cases (35.67%) including 86 (62.77%) males and 51 (37.23%) females and the highest prevalence of infection was found in the age group of 46-72 years (n=75, 54.74%). Cough (n=129, 94.16%), dyspnea (n=111, 81.02%), purulent sputum (n=85, 62.04%) and weight loss (n=77, 56.2%) were the predominant symptoms. Tuberculosis (n=34, 24.81%), taking chemotherapy regimen (n=30, 21.89%) and diabetes mellitus (n=27, 19.70%) were the predominant underlying conditions. Candida albicans (37.22%) and Candida tropicalis (21.89%) represent the two most commonly isolated species in the current study. Furthermore, according to revised EORTC/MSG (2008) definitions for invasive fungal infections, from 5 cases of pulmonary aspergillosis, 2 (40%) cases of probable invasive pulmonary aspergillosis (IPA) and 3 (60%) cases of possible IPA were diagnosed. CONCLUSION: According to the results of this study, infected infants with congenital CMV infection could identify at early stage by testing Guthrie cards (within 21 days of life). Furthermore, since there is a lack of CMV knowledge in our population, educating and effective counseling by obstetricians/gynecologists to the pregnant women are recommended.

Invasive pulmonary aspergillosis treatment duration in haematology patients in Europe: An EFISG, IDWP-EBMT, EORTC-IDG and SEIFEM survey.

Invasive pulmonary aspergillosis (IPA) optimal duration of antifungal treatment is not known. In a joint effort, four international scientific societies/groups performed a survey to capture current practices in European haematology centres regarding management of IPA. We conducted a cross-sectional internet-based questionnaire survey in 2017 to assess practices in sixteen European countries concerning IPA management in haematology patients including tools to evaluate treatment response, duration and discontinuation. The following four groups/societies were involved in the project: European Society of Clinical Microbiology and Infectious Diseases (ESCMID) Fungal Infection Study Group (EFISG), Infectious Diseases Working Party-European Society for Blood and Bone Marrow Transplantation (IDWP-EBMT), European Organisation for Research and Treatment-Infectious Disease group (EORTC-IDG) and Sorveglianza Epidemiologica Infezioni nelle Emopatie (SEIFEM). A total of 112 physicians from 14/16 countries answered the survey. Galactomannan antigen was available in serum and bronchoalveolar lavage in most centres (106/112 [95%] and 97/112 [87%], respectively), quantitative Aspergillus PCR in 27/112 (24%) centres, ß-D-glucan in 24/112 (21%) and positron emission tomography in 50/112 (45%). Treatment duration differed between haematological malignancies, with a median duration of 6 weeks [IQR 3-12] for patients with AML, 11 [4-12] for patients with allogenic stem cell transplantation and GvHD and 6 [3-12] for patients with lymphoproliferative disease. Treatment duration significantly differed according to country. Essential IPA biomarkers are not available in all European countries, and treatment duration is highly variable according to country. It will be important to provide guidelines to help with IPA treatment cessation with algorithms according to biomarker availability.

Diagnostic Performance and Safety of Bronchoalveolar Lavage in Thrombocytopenic Haematological Patients for Invasive Fungal Infections Diagnosis: A Monocentric, Retrospective Experience.

BACKGROUND: Although bronchoalveolar lavage (BAL) measurements of galactomannan antigen (GM) seems to be more sensitive than serum testing to detect invasive fungal infection (IFI), a consensus on the most appropriate diagnostic threshold of the BAL GM test is still unclear. Moreover, there is uncertainty as to whether BAL is a safe procedure in patients with hematological malignancies (HM) and thrombocytopenia. OBJECTIVES: Based on this background, 102 adult patients with HM and associated thrombocytopenia were retrospectively analyzed with the dual aim of 1) determining whether BAL is a safe and feasible procedure; and, 2) identifying the most appropriate threshold for GM positivity in the diagnosis of IFI. PATIENTS/METHODS: each BAL was considered as one case/patient. One hundred twelve BALs were carried out in 102 HM patients: at the time of the BAL, the median platelet count (PLTs) in all patients was 47×109/L (1-476), and 31 patients (27%) had PLTs< 20×109/L. RESULTS: complications from the BAL were infrequent (3.5%) and mild. No bleeding was reported. The BAL GM cut off of >0.8 was associated with the best diagnostic accuracy (sensitivity 72.97% and specificity 80%). Antifungal treatment of patients with BAL GM >0.8 resulted in a clinical-radiological improvement in 35/41 patients (85%). CONCLUSIONS: BAL was a safe procedure also in thrombocytopenic patients, permitting an IFI diagnosis not otherwise identifiable using EORTC/MSG criteria. Our data suggest that a BAL GM value of>0.8 represents the most useful cut-off in terms of sensibility and specificity. Further prospective studies on a more significant number of patients are needed to confirm these results.

Invasive Fungal Disease, Isavuconazole Treatment Failure, and Death in Acute Myeloid Leukemia Patients.

We present 2 fatal cases of invasive fungal disease with isavuconazole treatment failure in immunocompromised patients: one with a TR34-L98H azole-resistant Aspergillus fumigatus isolate and the other a Rhizomucor-A. fumigatus co-infection. Such patients probably require surveillance by galactomannan antigen detection and quantitative PCRs for A. fumigatus and Mucorales fungi.

The early diagnostic value of serum galactomannan antigen test combined with chest computed tomography for invasive pulmonary aspergillosis in pediatric patients after hematopoietic stem cell transplantation.

OBJECTIVE: The purpose of our study was to evaluate the diagnostic value of serum galactomannan antigen (GM) testing combined with chest computed tomography (CT) of invasive pulmonary aspergillosis (IPA) in pediatric patients after hematopoietic stem cell transplantation. METHODS: A retrospective nested case-control study was conducted in the identifying IPA among pediatric patients. RESULTS: A total of 141 eligible pediatric recipients with febrile neutropenia were enrolled in this study. All patients in the cases were diagnosed with proven-probable IPA(PP-IPA), while only 9 patients in the controls. GM testing was positive in 38 pediatric recipients in the cases and nine recipients in the controls with sensitivity of 62.3%, specificity of 81.8%. Among all patients with IPA, 46 patients in the cases and 9 patients in the controls had typical features of CT imaging with sensitivity of 79.3%, specificity of 85.2%. For discrimination of participants' GM testing combined with CT evaluation, the AUC of the diagnostic model was 0.887 with PPV of 0.764, and NPV of 0.872. Sensitivity was 0.793, and specificity was 0.852 in IPA. CONCLUSION: The combination methods with serum GM and CT scan might be used as a valuable marker for early diagnosis of IPA in pediatric patients after HSCT.

Utility of serum galactomannan antigen testing combined with chest computed tomography for early diagnosis of invasive pulmonary aspergillosis in patients with hematological malignancies with febrile neutropenia after antifungal drug treatment.

OBJECTIVE: To investigate the value of serum galactomannan antigen (GM) testing combined with chest computed tomography (CT) as a noninvasive method for early diagnosis of invasive pulmonary aspergillosis (IPA) in patients with hematological malignancies with febrile neutropenia after antifungal drug treatment. METHODS: We retrospectively analyzed the data of 376 patients with febrile neutropenia from January 2015 to August 2017. All patients were given broad-spectrum antibiotics and divided into the control group (effective antibiotic treatment, no antifungal drugs given) and the observational group (ineffective antibiotic treatment, antifungal drugs given). The serum GM testing, chest CT, and microbiological examination findings were compared between the two groups. RESULTS: The false-positive rates of GM testing for IPA in the control and observational groups were 4.04% and 8.65%, respectively, and the false-negative rates in the two groups were 1.10% and 9.62%, respectively. Sixty-five patients in the observational group and 11 in the control group had typical features of CT imaging. CONCLUSION: Clinical weekly screening of serum GM and chest CT may be an effective combined approach to the early diagnosis of IPA in patients with febrile neutropenia, even if they have undergone antifungal treatment.

Usefulness of Aspergillus Galactomannan Antigen Testing and the Prediction of an Outbreak during Hospital Reconstruction.

Objective This study retrospectively evaluated fungal dissemination due to hospital reconstruction and explored effective methods of predicting an outbreak. Methods Patients suspected of having invasive aspergillosis were tested for Aspergillus galactomannan antigen before and after reconstruction, and the mean values of three months of testing for positive patients were determined. The characteristics of patients with aspergillosis during this period were also assessed. Results Forty-five patients were positive for Aspergillus antigen (>0.5 cut-off index) from January 2013 to December 2014. Mean Aspergillus antigen values significantly increased following reconstruction (p<0.05). Three patients developed pneumonia due to Aspergillus and were diagnosed with "probable" invasive aspergillosis according to the European Organization for Research and Treatment of Cancer and the National Institute of Allergy and Infectious Diseases Mycoses Study Group (EORTC/MSG) criteria. We also discovered that the anteroom to contain dust was not prefabricated and a negative pressure system to remove dust was not used. After construction of the unit, no new cases of aspergillosis were diagnosed. Conclusion Many Aspergillus spores may be transiently floating during hospital reconstruction. Therefore, monthly surveillance with frequent serum galactomannan antigen testing to predict outbreaks is necessary. Surveillance of all patients in the hematology ward is especially important. Reconsideration of prophylactic antifungals may also be necessary during hospital reconstruction.

Update on Actinomucor elegans, a mucormycete infrequently detected in human specimens: how combined microbiological tools contribute efficiently to a more accurate medical care.

Actinomucor elegans is a fungus belonging to mucormycetes and is still probably underdiagnosed due to misidentification. Based on a recent first case of Actinomucor elegans sinusitis in Europe, in an immunocompromised patient under voriconazole treatment, this paper aims to summarize knowledge about A. elegans mucormycoses. Even if the diagnosis of mucormycosis was made using traditional mycology techniques, precise identification of the fungus could only be achieved using molecular tools. In this observation, the galactomannan dosage was positive until the introduction of treatment and surgical debridement. The patient experienced no relapse after one year. By reviewing the four previous A. elegans reported cases and describing the mycological characteristics of this species, we highlight the need to use a combination of tools to improve the diagnostic strategy in such rare and life-threatening clinical situations.

Fatal Mycotic Aneurysm of the Basilar Artery Caused by Aspergillus fumigatus in a Patient with Pituitary Adenoma and Meningitis.

Fungal infections of the central nervous system (CNS) frequently occur in immunosuppressed patients. Here, we describe the case of an immunocompetent 64-year-old man who presented with diplopia, right-sided hemiparesis, and a mild headache after cleaning and replacing nesting boxes of wild birds during the preceding months. Lumbar puncture revealed pleocytosis, elevated protein, and lactate levels in the cerebrospinal fluid (CSF). Initial imaging showed ischemia in the left thalamus and an enlargement of the sellar region. Antibiotic treatment and corticosteroids led to an initial improvement but was followed by rapid deterioration. Antibiotic treatment was modified and antifungal therapy was added. Eighteen days after admission, the patient died from a subarachnoid hemorrhage resulting from the rupture of a fusiform aneurysm of the basilar artery. Microbiological culture of CSF was negative, but a positive galactomannan assay suggested fungal infection which was corroborated by detection of Aspergillus fumigatus DNA in pan-fungal PCR and sequencing. The presence of septated hyphae in the wall of the basilar artery confirmed the diagnosis of a mycotic aneurysm caused by hyphomycetal infection. In addition, brain autopsy revealed the presence of an invasive adrenocorticotrophic hormone-producing pituitary adenoma with arrosion of the sellar bone. This process and its invasiveness likely facilitated the spread of the fungal pathogen from the sphenoid sinus to the dura mater and finally led to cerebral angioinvasion. Our case demonstrates the challenge to timely diagnose and effectively treat aspergillosis as a cause of CNS infection also in apparently immunocompetent patients. The potential of assays detecting fungal antigens and of PCR to facilitate a timely diagnosis is discussed.