Aspergillosis In Non-neutropenic Patients Research Articles

Performance of mNGS in bronchoalveolar lavage fluid for the diagnosis of invasive pulmonary aspergillosis in non-neutropenic patients.

The diagnosis of invasive pulmonary aspergillosis (IPA) diseases in non-neutropenic patients remains challenging. It is essential to develop optimal non-invasive or minimally invasive detection methods for the rapid and reliable diagnosis of IPA. Metagenomic next-generation sequencing (mNGS) in bronchoalveolar lavage fluid (BALF) can be a valuable tool for identifying the microorganism. Our study aims to evaluate the performance of mNGS in BALF in suspected IPA patients and compare it with other detection tests, including serum/BALF galactomannan antigen (GM) and traditional microbiological tests (BALF fungal culture and smear and lung biopsy histopathology). Ninety-four patients with suspicion of IPA were finally enrolled in our study. Thirty-nine patients were diagnosed with IPA, and 55 patients were non-IPA. There was significance between the IPA and non-IPA groups, such as BALF GM (P < 0.001), history of glucocorticoid use (P = 0.004), and pulmonary comorbidities (P = 0.002), as well as no significance of the other demographic data including age, sex, BMI, history of cigarette, blood GM assay, T-SPOT.TB, and NEUT#/LYMPH#. The sensitivity of the BALF mNGS was 92.31%, which was higher than that of the traditional tests or the GM assays. The specificity of BALF mNGS was 92.73%, which was relatively similar to that of the traditional tests. The AUC of BALF mNGS was 0.925, which presented an excellent performance compared with other traditional tests or GM assays. Our study demonstrated the important role of BALF detection by the mNGS platform for pathogen identification in IPA patients with non-neutropenic states, which may provide an optimal way to diagnose suspected IPA disease.

Invasive cerebral aspergillosis in non-neutropenic patients: A case series from Western India.

Invasive cerebral aspergillosis (ICA) is a rare but fatal infection affecting neutropenic immunocompromised patients. Recently cases have been reported in non-neutropenic settings also. We hereby present a series of ICA cases in non-neutropenic patients diagnosed at our tertiary care centre in Western India between March to October 2021. All patients with clinico-radiological suspicion of CNS infections were analysed. Data regarding Clinico-radiological features, diagnosis, treatment and outcome were collected. After ruling out bacterial, viral and mycobacterial causes, appropriate samples were sent for KOH (potassium hydroxide) wet mount, fungal culture, histopathology and serum/CSF galactomannan. A total of four patients were diagnosed with ICA with a mean age of 43.5 years. Three patients had significant comorbidities; Diabetes mellitus, chronic liver disease and COVID-19 pneumonia treated with dexamethasone, respectively. One patient had no known predisposing factor. Radiologically, one patient presented with a frontal brain abscess and two patients had multiple subcortical hyperintensities. Three patients were diagnosed based on CSF galactomannan (Platelia™ Aspergillus antigen, Bio-Rad, France) with OD >1 and one patient had high serum galactomannan (OD >2). CSF culture grew Aspergillus species in two patients. All patients were treated with Voriconazole. One patient recovered, and the remaining three succumbed due to delayed presentation and extensive cerebral involvement. Even in non-neutropenic patients, a high index of suspicion is warranted for cerebral aspergillosis. CSF galactomannan can be considered a reliable marker for diagnosing ICA in non-neutropenic settings. Early diagnosis allows timely antifungal therapy, which could be a key to improving the outcomes.

361. Think Fungus! – Clinical profile, Risk factors and Diagnostic Utility of Galactomannan in diagnosis of Invasive Aspergillosis in Non-Neutropenic patients – A Prospective Study from India

Abstract Background Invasive aspergillosis(IA) is known to occur in immunocompromised patients including neutropenic patients. But there has been a trend of increasing cases in non-neutropenic host with the emergence of newer risk factors like DM, cirrhosis etc. The aim of this study was to evaluate the clinical features &amp; risk factors of IA in non-neutropenic patients &amp; to look at the clinical utility of galactomannan in diagnosis of IA. Methods This was a prospective observational study which included the suspected cases of IA, based on the clinical &amp; radiological criteria. Patients with haematological &amp; solid organ malignancy were excluded. In patients with suspected Invasive pulmonary aspergillosis (IPA), serum &amp; BAL, while in patients with suspected CNS IA CSF &amp; serum samples were sent for galactomannan analysis (Platelia ELISA). The clinical features, risk factors, outcomes were analysed. Results We screened 243 patients with suspected IA, of which 49 non-neutropenic patients with IA (16 Proven &amp; 33 Probable cases) were included. The mean age was 47.8 years. Of all IA cases 69.5% (n=34) were IPA, 20.4% (n=10) were CNS aspergillosis &amp; 10.2% (n=5) showed disseminated form of IA. The common symptoms included Fever (71.4%), cough (71.3%), expectoration (44.7%) &amp; dyspnoea (59.1%) in IPA, while in CNS aspergillosis, presented with fever (73.3%), altered sensorium (53%).The predominant risk factor included previous TB, DM, COVID-19. The radiological manifestations in IPA included the typical cavity (40.4%, n=17), Centrilobular nodules with tree in bud appearance in 56.5% (n=23). The CNS aspergillosis was associated with ring enhancing lesion (41.6%, n=5) with leptomeningeal enhancement (50%, n=6), while cerebral abscess was seen in 16.6% (n=2) patients. The positivity of galactomannan were 24.4%, 91.3% &amp; 87.5% in serum, BALF &amp; CSF respectively. Culture positivity &amp; Direct smear positivity was 18.3% &amp; 28.5% respectively. The overall mortality was 20.4%. Complete response in 3 months follow-up period was seen in 69.3% patients. Conclusion The clinical manifestations of IA in non-neutropenic are diverse &amp; nonspecific. Also, culture &amp; direct microscopy lack sensitivity, hence diagnostic markers like Galactomannan can be used for early diagnosis of IA in patients with newer emerging risk factors. Disclosures All Authors: No reported disclosures.

P499 A cross-sectional observational to assess the role of Bronchoalveolar lavage fluid galactomannan in the diagnosis of invasive pulmonary aspergillosis in non-neutropenic patients

Poster session 3, September 23, 2022, 12:30 PM - 1:30 PMObjective: This study was done to assess the role of Bronchoalveolar lavage fluid (BALF) galactomannan (GM) in the diagnosis of invasive pulmonary aspergillosis (IPA) in non-neutropenic patients and to determine the optimal cut-off value of BALF GM for diagnosing IPA in non-neutropenic hosts.MethodsWe conducted a cross-sectional observational study on 96 non-neutropenic patients of age > 18 years with suspected pulmonary infections of fungal etiology. A detailed history of predisposing conditions was obtained and routine laboratory investigations with chest computerized (CT) tomography were performed. Fiberoptic bronchoscopy under local anesthesia and sedation was done using a video bronchoscope. Bronchoalveolar lavage was done from the segment or lobe of interest instilling 60-100 ml of saline withdrawn under low pressure and the sample was tested for a battery of investigations; fungal KOH smear; fungal culture; GM by Platelia Aspergillus enzyme immunoassay; and others required for diagnosis. A protected brush specimen and transbronchial lung biopsy were done wherever feasible. The yield from the BALF GM assay was compared with diagnosis based on definitions given by EORTC/MSG excluding host factors. Patients were classified into three groups namely non-IPA, probable IPA, and proven IPA. For statistical analysis, probable and proven IPA were taken as one group i.e., the IPA group. Mann-Whitney test and Chi-Square test along with Fisher's exact test were performed for inter-group comparison between quantitative and qualitative variables respectively. The receiver operator characteristic curve was used to establish a cut-off point of BALF GM and Serum GM for predicting IPA. Sensitivity, specificity, PPV, and NPV were calculated. The McNemar test was used for the comparison of sensitivity and specificity. Inter-rater kappa agreement was used to find the strength of agreement of BALF GM, BALF culture, and BALF DM.ResultsOut of 96, 1 was diagnosed with proven IPA, 34 were probable IPA cases and 61 were not IPA cases. Chronic kidney disease (CKD) as a risk factor was more common in IPA cases compared to non-IPA cases (25.7% vs. 8.2%, P-value .019). Chest CT showed cavity in a significant number of IPA patients compared to non-IPA cases (60% vs. 29.5%, P-value .003). BALF direct microscopy, culture, and serum GM had sensitivities < 60% but specificities close to 95%. BALF GM showed promising results with a sensitivity of 88.5% and specificity of 85.7% at cutoff value of 0.8.See Figures below.Conclusions: Our study highlights the magnitude of IPA in non-neutropenic hosts with unconventional risk factors like CKD, diabetes, and the need for increased vigilance for diagnosis of IPA in such patients. We suggest a lower cut-off value of BALF GM against 1 as in EORTC/MSG criteria and consider CKD as one of the risk factors for IPA.

P144 The uncommon meets the common: Invasive Aspergillosis and tuberculosis co-infection in non-neutropenic patients— arare association

Poster session 2, September 22, 2022, 12:30 PM - 1:30 PMBackground and ObjectiveInvasive aspergillosis (IA) is known to occur in immunocompromised patients including neutropenic patients. But, recently increasing cases have been reported in patients with non-classical risk factors and non-neutropenic patients like diabetes mellitus, chronic lung disease, HIV infection, critically ill patients, etc. According to ISHAM these non-classical risk factors should be included in EORTC/MSG host criteria for diagnosis of invasive aspergillosis.India has a high tuberculosis (TB) burden, and this is always considered as the first differential for any patient with fever, cough, hemoptysis, and weight loss. Post-tubercular chronic pulmonary aspergillosis common reported condition. However, co-infection of active TB and invasive aspergillosis is less reported. This co-infection could be one of the contributors of high morbidity and mortality in cases with tuberculosis.We hereby present a series of five cases of TB concomitant with invasive aspergillosis in non-neutropenic patients.MethodsThis is a prospective observational study, all patients admitted with molecular diagnosis (GeneXpert) of tuberculosis and with at least one non-classical risk factor for invasive aspergillosis were subjected to further evaluation. Diagnosis of invasive aspergillosis was considered in patients who had at least one clinical and one mycological EORTC criteria. Galactomannan level in different samples was measured via PlateliaTM ELISA. The efficacy of different antifungals and outcomes were analyzed.ResultsTotal 57 patients with TB underwent for evaluation of invasive aspergillosis. Among them, five patients were diagnosed to have concomitant TB and invasive aspergillosis, of which three cases of CNS TB and CNS aspergillosis and two had concomitant pulmonary infections. The average age was 31 ± 12 years with a female preponderance (4/5). Two patients were HIV positive, while among non-HIV patients, one had CD4 cytopenia (CD4-171). One patient had no known predisposing factor. Radiologically, most common pulmonary lesions were patchy consolidation with centrilobular nodules with tree in bud appearance, while CNS lesions showed multiple ring-enhancing lesions. All the patients had CBNAAT positive, two from BAL sample, 1 from CSF, and 1 from the lymph node. Rifampicin was sensitive in all, except one who had rifampicin resistance indeterminate. Of these patients, four were probable invasive aspergillosis satisfying the host, mycological and clinical factors as per the EORTC/MSGERC 2021 guidelines. The treatment of coinfection is challenging due to the interaction of rifampicin with voriconazole, which is the drug of choice for invasive aspergillosis. Here, 3 patients were treated with Inj amphotericin B, while the other 2 patients were started on voriconazole with rifampicin sparing regimen for TB. Of the 5 patients, 4 patients survived with excellent response to the treatment, with one fatality.ConclusionThe possibility of concurrent TB and invasive aspergillosis in non-neutropenic hosts should be considered to avoid devastating outcomes. The lack of clinical suspicion may result in misdiagnosis, and most importantly, the chronicity of the infection makes it indistinguishable from TB. Moreover, the co-administration of antifungal and anti-TB medications presents significant therapeutic challenges necessitating thorough evaluation and monitoring.

Metagenomic next-generation sequencing for the diagnosis of pulmonary aspergillosis in non-neutropenic patients: a retrospective study.

This study aimed to obtain further in-depth information on the value of metagenomic next-generation sequencing (mNGS) for diagnosing pulmonary aspergillosis in non-neutropenic patients. We did a retrospective study, in which 33 non-neutropenic patients were included, of which 12 were patients with pulmonary aspergillosis and 21 were diagnosed with non-pulmonary aspergillosis. Fungi and all other co-pathogens in bronchoalveolar lavage fluid (BALF) (27 cases), blood (6 cases), and/or pleural fluid (1 case) samples were analyzed using mNGS. One of the patients submitted both BALF and blood samples. We analyzed the clinical characteristics, laboratory tests, and radiologic features of pulmonary aspergillosis patients and compared the diagnostic accuracy, including sensitivity, specificity, positive predictive value, and negative predictive value of mNGS with conventional etiological methods and serum (1,3)-β-D-glucan. We also explored the efficacy of mNGS in detecting mixed infections and co-pathogens. We further reviewed modifications of antimicrobial therapy for patients with pulmonary aspergillosis according to the mNGS results. Finally, we compared the detection of Aspergillus in BALF and blood samples from three patients using mNGS. In non-neutropenic patients, immunocompromised conditions of non-pulmonary aspergillosis were far less prevalent than in patients with pulmonary aspergillosis. More patients with pulmonary aspergillosis received long-term systemic corticosteroids (50% vs. 14.3%, p < 0.05). Additionally, mNGS managed to reach a sensitivity of 91.7% for diagnosing pulmonary aspergillosis, which was significantly higher than that of conventional etiological methods (33.3%) and serum (1,3)-β-D-glucan (33.3%). In addition, mNGS showed superior performance in discovering co-pathogens (84.6%) of pulmonary aspergillosis; bacteria, bacteria-fungi, and bacteria-PJP-virus were most commonly observed in non-neutropenic patients. Moreover, mNGS results can help guide effective treatments. According to the mNGS results, antimicrobial therapy was altered in 91.7% of patients with pulmonary aspergillosis. The diagnosis of Aspergillus detected in blood samples, which can be used as a supplement to BALF samples, seemed to show a higher specificity than that in BALF samples. mNGS is a useful and effective method for the diagnosis of pulmonary aspergillosis in non-neutropenic patients, detection of co-pathogens, and adjustment of antimicrobial treatment.

NLRP3, NLRC4 and NLRC5 Gene Polymorphisms Associate with Susceptibility of Pulmonary Aspergillosis in Non-Neutropenic Patients.

Background: Non-neutropenic pulmonary aspergillosis is one of the most common and serious fungal infections. Previous studies have shown that single nucleotide polymorphisms (SNPs) of pattern recognition receptors genes are associated with susceptibility to aspergillosis. NOD-like receptors (NLRs) play an important role in the immunological response against fungal infection. In this study, we investigated the relationship between polymorphisms of three NLRs and susceptibility to pulmonary aspergillosis disease in non-neutropenic patients. Methods: We included 73 patients with proven pulmonary aspergillosis and 103 healthy controls. A total of sixteen SNPs in the NLRP3, NLRC4, and NLRC5 genes were detected by PCR-direct sequencing. Then, we evaluated the association between these polymorphisms and susceptibility to aspergillosis. Results: Fifteen SNPs were consistent with Hardy–Weinberg equilibrium except for NLRP3 rs7525979. A total of eight SNPs (NLRP3 rs3806265, NLRC4 rs212704 and NLRC5 rs1684579, rs12598522, rs3995817, rs3995818, rs34531240, rs28438857) were observed an association with susceptibility of pulmonary aspergillosis. The CC homozygote of NLRP3 rs3806265, TT homozygote of NLRC5 rs1684579 and T allele of NLRC5 rs12598522 were associated with a higher risk of aspergillosis while TT homozygote of NLRC4 rs212704 was associated with a lower risk of aspergillosis. Especially in the invasive pulmonary aspergillosis subgroup, the TT homozygote of NLRC5 rs1684579 and rs3995817, the CC homozygote of NLRC5 rs34531240 and rs28438857, GG homozygote of NLRC5 rs3995818, the C allele and CC homozygote of NLRP3 rs3806265 were associated with higher susceptibility. Conclusions: This study showed an association between polymorphisms of NLRP3, NLRC4, and NLRC5 and susceptibility to pulmonary aspergillosis for the first time. Further investigations in larger populations are needed, and functional studies are also required to investigate the function of these NLRs in aspergillosis, as well as other fungal infection diseases.

The Clinical Characteristics of Patients With Nonneutropenic Invasive Pulmonary Aspergillosis.

Objective: The goal of this study was to reveal the clinical manifestations of nonneutropenic invasive pulmonary aspergillosis (IPA), which are different from those of neutropenic patients.Methods: The clinical data of patients with nonneutropenic IPA were collected at the Department of Respiratory and Critical Care Medicine, Jinling Hospital, from February 2009 to November 2019. We analyzed the general conditions, clinical manifestations, imaging findings, and laboratory tests of these IPA patients.Results: A total of 116 patients with nonneutropenic IPA (31 proven and 85 probable) were included. They had an average age of 59.8 years. The most common underlying disease was chronic obstructive pulmonary disease (COPD, n = 33). The common clinical symptoms included cough (93.1%, n = 108), expectoration (59.5%, n = 69), fever (57.8%, n = 67), hemoptysis (30.2%, n = 35), and dyspnea (40.5%, n = 47). The common CT imaging manifestations included consolidation (47.4%, n = 55), cavities (47.4%, n = 55), air crescent sign (14.7%, n = 17), and nodules (8.6%, n = 10). Multiple lesions (74.1%, n = 86) were more common than single lesions (17.2%, n = 20) and diffuse lesions (8.6%, n = 10). The positive rate of laboratory tests was 88.2% (30/34) for BALF galactomannan (GM), 55.4% (56/101) for serum GM, 45.3% (48/106) for 1,3-β-D-glucan (BDG), 43.3% (46/106) for sputum culture, and 36.4% (20/55) for BALF culture. Patients who had high serum GM level [GM optical density index (ODI) >1] were more likely to have severe respiratory symptoms and higher serum ferritin. Further investigation showed that there was a positive correlation between serum GM level and serum ferritin level.Conclusion: The clinical symptoms and radiological manifestations of nonneutropenic IPA are diverse and often lead to delayed diagnosis. It is important to become more vigilant of aspergillosis in nonneutropenic patients in order to achieve early diagnosis and treatment and to reduce mortality.

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.

Clinical and Non-Clinical Characteristics of Pulmonary Aspergillosis in Non-Neutropenic Patients

Clinical and Non-Clinical Characteristics of Pulmonary Aspergillosis in Non-Neutropenic Patients

Challenges and Solution of Invasive Aspergillosis in Non-neutropenic Patients: A Review.

Invasive aspergillosis (IA) is a serious opportunistic infection, which has increasingly been recognized as an emerging disease of non-neutropenic patients. In this group of patients, the diagnosis of IA can be challenging owing to the lack of specificity of symptoms, the difficulty in discriminating colonization from infection, and the lower sensitivity of microbiological and radiological tests compared with immunocompromised patients. The aim of this article is to present to clinicians a critical review on the management of IA in non-neutropenic patients.

How to manage aspergillosis in non-neutropenic intensive care unit patients.

Invasive aspergillosis has been mainly reported among immunocompromised patients during prolonged periods of neutropenia. Recently, however, non-neutropenic patients in the ICU population have shown an increasing risk profile for aspergillosis. Associations with chronic obstructive pulmonary disease and corticosteroid therapy have been frequently documented in this cohort. Difficulties in achieving a timely diagnosis of aspergillosis in non-neutropenic patients is related to the non-specificity of symptoms and to lower yields with microbiological tests compared to neutropenic patients. Since high mortality rates are typical of invasive aspergillosis in critically ill patients, a high level of suspicion and prompt initiation of adequate antifungal treatment are mandatory. Epidemiology, risk factors, diagnostic algorithms, and different approaches in antifungal therapy for invasive aspergillosis in non-neutropenic patients are reviewed.

Antibody specific to thioredoxin reductase as a new biomarker for serodiagnosis of invasive aspergillosis in non-neutropenic patients

BackgroundInvasive aspergillosis (IA) is an important cause of mortality in critically ill patients, but the diagnosis is difficult as clinical and radiological signs are neither sensitive nor specific. Serum galactomannan (GM) is a useful marker for IA, but exhibits low sensitivity in non-neutropenic patients. In our previous work, strong antibody reactivity to thioredoxin reductase of Aspergillus fumigatus was found in non-neutropenic IA patients. Methods and resultsUsing recombinant thioredoxin reductase GliT (TR), an antigenic protein secreted by A. fumigatus, as the coating antigen, an enzyme-linked immunosorbent assay (ELISA) for detecting anti-TR antibodies was developed. The antibody response to TR in IA animal models and 42 non-neutropenic patients with culture- and/or histology-documented IA was investigated. The results showed that anti-TR antibody was detectable in rabbit serum 7–9days after exposure to the fungus. The sensitivity and specificity of the anti-TR antibody assay in patients were 80.9% and 96%, respectively, while the sensitivity of GM in this group of patients was only 52.3%. The specificity of the assay was confirmed by testing the sera from patients infected with other pathogenic fungal species and bacteria.

Invasive Pulmonary Aspergillosis in Non-Neutropenic Patients: Analysis of a 14-Month Prospective Clinical Experience

Invasive pulmonary aspergillosis (IPA) is one of the major causes of morbidity and mortality in severely immunocompromised patients, but recently several authors have reported the occurrence of IPA in liver cirrhosis, chronic obstructive pulmonary disease (COPD) patients, most of whom, but not all, were receiving steroid treatment, with a very high mortality rate. The detection of galactomannan performed in respiratory specimens is a new valuable test for the diagnosis of probable IPA, even in non-neutropenic high risk patients. Since the frequency and clinical impact of IPA in non-hematologic patients is not well known, it seemed rational to us to attempt a prospective study evaluating all patients hospitalized in a university hospital for whom an infectious Diseases consultation was required. this 14-month survey in our hospital, using recently recommended diagnostic criteria, seems to suggest an emerging role of IPA in these patients who may have a higher mortality rate than their neutropenic peers, and provides preliminary evidence that early diagnosis and prompt initiation of antifungal therapy may improve the ultimate outcome of their IPA.

Survey of aspergillosis in non-neutropenic patients in Swiss teaching hospitals

Invasive aspergillosis (IA) is a live-threatening opportunistic infection that is best described in haematological patients with prolonged neutropenia or graft-versus-host disease. Data on IA in non-neutropenic patients are limited. The aim of this study was to establish the incidence, disease manifestations and outcome of IA in non-neutropenic patients diagnosed in five Swiss university hospitals during a 2-year period. Case identification was based on a comprehensive screening of hospital records. All cases of proven and probable IA were retrospectively analysed. Sixty-seven patients were analysed (median age 60 years; 76% male). Sixty-three per cent of cases were invasive pulmonary aspergillosis (IPA), and 17% of these were disseminated aspergillosis. The incidence of IPA was 1.2/10 000 admissions. Six of ten cases of extrapulmonary IA affected the brain. There were six cases of invasive rhinosinusitis, six cases of chronic pulmonary aspergillosis, and cases three of subacute pulmonary aspergillosis. The most frequent underlying condition of IA was corticosteroid treatment (57%), followed by chronic lung disease (48%), and intensive-care unit stays (43%). In 38% of patients with IPA, the diagnosis was established at autopsy. Old age was the only risk factor for post-mortem diagnosis, whereas previous solid organ transplantation and chronic lung disease were associated with lower odds of post-mortem diagnosis. The mortality rate was 57%.

Invasive pulmonary and central nervous system aspergillosis following slops aspiration in a trauma patient

Cerebral aspergillosis is a rare complication of multiple trauma. In this report, we present a remarkable case of multiple lung and brain lesions caused by aspergillosis after a falling incident. A 54-year-old male was admitted with multiple trauma (brain contusion, aspiration pneumonitis with pulmonary contusion, right humerus fracture and right scapular fracture) due to a 6-m fall and aspiration of slops. In view of aspiration pneumonitis (Figure ​(Figure1,1, day 1), intravenous antibiotic treatment (tazocin, moxifloxacin hydrochloride and metronidazole) was started. Brain computerized tomography (CT) on day 12 indicated a focus of encephalomalacia in the left frontal lobe, which was thought to be the progress of brain contusion (Figure ​(Figure1,1, day 12). On the same day, chest CT showed a pulmonary halo sign on the left upper lung (Figure ​(Figure1,1, day 12), and voriconazole therapy was used because of high suspicion of invasive pulmonary fungal infection. Voriconazole treatment had to be stopped, however, due to severe rash 5 days later. Anti-fungus therapy was continued with caspofungin. On day 19, the brain CT showed signs of fungus infection (Figure ​(Figure1,1, day 19). Twenty-two days after injury, the central venous catheter culture grew aspergillus species and established the diagnosis of invasive aspergillosis in this patient; liposomal amphotericin B was then also added to the patient's treatment. On day 34, enhanced CT imaging of the brain showed progression of multiple lesions of fungus infection (Figure ​(Figure1,1, day 34). Unfortunately, the patient died 40 days after injury. Figure 1 Chest and brain computerized tomography on days 1, 12, 19, 28, and 34. Aspiration pneumonitis with pulmonary contusion was shown on day 1. Black arrows, multiple lesions of fungus infection in both the lung and the brain. White arrows, progression of ... We have described invasive aspergillosis with a rapidly progressive and fatal pulmonary and cerebral course in a previously healthy man. Neuroaspergillosis is an uncommon infection associated with an exceedingly high mortality. The diagnosis of neuroaspergillosis is difficult, often made at the terminal stage of disease or on autopsy [1]. Perhaps due to the greater penetration into the central nervous system (CNS), voriconazole treatment greatly improved clinical outcomes with a survival rate of 30% in high-risk patients [2,3]. According to the guidelines for treating invasive pulmonary aspergillosis, voriconazole is recommended for primary treatment [4]. Unfortunately, this patient was refractory to voriconazole because of severe rash, and then caspofungin was selected for salvage therapy. Owing to the large molecular mass, high protein binding and water solubility of caspofungin, its penetration into the CNS was limited [5]; this invasive pulmonary aspergillosis was then further complicated by dissemination to the CNS on day 19. In conclusion, we report a rare trauma case accompanied with invasive pulmonary and CNS aspergillosis following slops aspiration. This case highlights the diagnostic challenge presented by invasive aspergillosis in non-neutropenic patients and underscores its poor prognosis.

Invasive aspergillosis in non-neutropenic patients

Host defense against invasion of Aspergillus spp. relies on effective phagocytosis by neutrophils and macrophages [1]. Accordingly, surveillance mainly focuses on leukaemia patients receiving myeloablative therapies in which the risk for invasive aspergillosis (IA) starts to rise drastically after 10 days of neutropenia. However, IA is occasionally observed in non-neutropenic patients who have some underlying disease or who receive immunosuppressive therapy that does not impair neutrophil counts [2–5].

Chronic Pulmonary Aspergillosis in Nonneutropenic Patients

The newer azoles have proven to be effective in neutropenic patients with invasive pulmonary aspergillosis. However, other than surgical removal of an aspergilloma, we have no standard treatment for chronic pulmonary aspergillosis (CPA) in nonneutropenic patients. Now, researchers in France have retrospectively analyzed cases of CPA treated with voriconazole between November 2001 and May 2004. …