Role of serial fluorodeoxyglucose positron emission tomography-computed tomography (18FDG-PET-CT) in assessing treatment response in treatment naïve chronic pulmonary aspergillosis subjects.

BACKGROUND: The role of 2-deoxy-2-18(F) fluoro-D-glucose (FDG) positron emission tomography (PET)-computed tomography (CT) in assessing treatment response in chronic pulmonary aspergillosis (CPA) remains to be determined. OBJECTIVE: To compare changes in FDG-PET/CT parameters in CPA subjects with treatment success or failure. METHODS: We treated consecutive treatment-naïve CPA subjects with six months of oral itraconazole. We performed PET-CT at baseline and six months. A multi-disciplinary team categorized response as treatment success or failure. We recorded the maximum standardised uptake value (SUVmax), SUVpeak, and total glycolytic activity (TLG). After treatment, FDG uptake similar to the background uptake or ≥13 units decline in Z-score was considered a complete metabolic response (CMR). A >25%, >30%, and > 45% decline in SUVmax, SUVpeak, and TLG was labelled as a partial metabolic response (PMR). A >30%, >30%, or >75% increase in the SUVmax, SUVpeak, and TLG represented progressive metabolic disease. RESULTS: We included 94 CPA subjects (63 males) with a mean age of 46.2 years. A follow-up PET-CT was performed on 77 subjects. We recorded treatment success and failure in 43 and 34 subjects. The median SUVmax at baseline was 6.7, which significantly reduced with treatment. CMR was seen in 18.6% of those with treatment success and none with treatment failure. A higher proportion of subjects with treatment success achieved PMR. 19% of the subjects with treatment success had progressive metabolic disease. CONCLUSION: FGD-PET/CT demonstrated metabolic activity in all CPA subjects. Most PET-CT parameters improved with treatment; however, one-fifth of the subjects were misclassified on PET-CT.

Superiority trials in invasive aspergillosis: a harsh reality check with the IA-DUET (HOVON502) trial.

The IA-DUET study aimed to compare azole-echinocandin combination with azole monotherapy for invasive aspergillosis. Recruitment was hindered by patient ineligibility, competing studies, and guidelines favoring combination therapy when azole resistance was unknown. The low IA-attributable mortality suggests future trials may benefit from cluster randomization or composite endpoints to enhance efficiency.

European Study of Cerebral Aspergillosis treated with Isavuconazole (ESCAI): A study by the ESCMID Fungal Infection Study Group.

BACKGROUND: Cerebral aspergillosis (CA) is associated with high mortality. According to the European Conference on Infections in Leukemia and the European Society of Clinical Microbiology and Infectious Diseases guidelines, the recommended first-line treatment for all forms of aspergillosis is voriconazole or isavuconazole. However, little is known about the efficacy and safety of isavuconazole in CA. METHODS: We conducted a European multicenter retrospective study of patients treated with isavuconazole for proven or probable CA between 2014 and 2022 and compared the outcomes with those of weighted control groups from the previously published French national cohort of CA, the Cerebral Aspergillosis Lesional Study (CEREALS). RESULTS: Forty patients from 10 countries were included. The main underlying conditions were hematological malignancies (53%) and solid-organ transplantation (20%). Isavuconazole was administered as a first-line treatment to 10 patients, primarily in combination therapy, resulting in control of CA in 70% of these cases. Thirty patients received isavuconazole after a median of 65 days on another therapy, mostly because of side effects (50%) or therapeutic failure (23%) of the previous treatment. Predominantly given as monotherapy, it achieved control of CA in 73% of the patients. Seventeen patients (43%) underwent neurosurgery. When measured, isavuconazole levels were low in cerebrospinal fluid but adequate in serum and brain tissue. Isavuconazole toxicity led to treatment interruption in 7.5% of the patients. Twelve-week mortality was 18%. Comparison with the CEREALS cohort showed comparable survival in patients receiving isavuconazole or voriconazole as a first-line treatment. CONCLUSIONS: Isavuconazole appears to be a well-tolerated treatment. Mortality of CA treated with isavuconazole is similar to that reported with voriconazole.

Invasive Pulmonary Aspergillosis in Critically Ill Patients with Hantavirus Infection, Austria.

We investigated a cohort of 370 patients in Austria with hantavirus infections (7.8% ICU admission rate) and detected 2 cases (cumulative incidence 7%) of invasive pulmonary aspergillosis; 1 patient died. Hantavirus-associated pulmonary aspergillosis may complicate the course of critically ill patients who have hemorrhagic fever with renal syndrome.

Invasive aspergillosis in liver transplant recipients in the current era.

Invasive aspergillosis (IA) is a rare but fatal disease among liver transplant recipients (LiTRs). We performed a multicenter 1:2 case-control study comparing LiTRs diagnosed with proven/probable IA and controls with no invasive fungal infection. We included 62 IA cases and 124 matched controls. Disseminated infection occurred only in 8 cases (13%). Twelve-week all-cause mortality of IA was 37%. In multivariate analyses, systemic antibiotic usage (adjusted odds ratio [aOR], 4.74; P = .03) and history of pneumonia (aOR, 48.7; P = .01) were identified as independent risk factors associated with the occurrence of IA. Moreover, reoperation (aOR, 5.99; P = .01), systemic antibiotic usage (aOR, 5.03; P = .04), and antimold prophylaxis (aOR, 11.9; P = .02) were identified as independent risk factors associated with the occurrence of early IA. Among IA cases, Aspergillus colonization (adjusted hazard ratio [aHR], 86.9; P < .001), intensive care unit stay (aHR, 3.67; P = .02), disseminated IA (aHR, 8.98; P < .001), and dialysis (aHR, 2.93; P = .001) were identified as independent risk factors associated with 12-week all-cause mortality, while recent receipt of tacrolimus (aHR, 0.11; P = .001) was protective. Mortality among LiTRs with IA remains high in the current era. The identified risk factors and protective factors may be useful for establishing robust targeted antimold prophylactic and appropriate treatment strategies against IA.

Reverse-transcriptase real-time PCR in the diagnostic strategy for invasive infections caused by Aspergillus fumigatus.

The aim was to develop an RT-qPCR targeting Aspergillus fumigatus and compare its performance to that of Aspergillus fumigatus qPCR for the diagnosis of invasive aspergillosis (IA). Samples from patients of the Lyon University hospitals for whom a suspicion of IA led to the realization of an Aspergillus fumigatus qPCR molecular diagnostic test over a 2-year period were included. The patients were classified according to the European Organization for Research and Treatment of Cancer/Mycoses Study Group (EORTC-MSGERC) criteria for suspected IA; RT-qPCR and qPCR assays were performed on all included samples. The sensitivities and specificities of RT-qPCR and qPCR were calculated and compared using the results of the EORTC-MSGERC classification as reference. The cycle threshold (Ct) results were compared according to IA classification and sample type. Among the 193 samples analyzed, 91 were classified as IA excluded, 46 as possible IA, 53 as probable IA, and 3 as proven IA. For all sample types, RT-qPCR was significantly more sensitive than qPCR for all IA classifications with an additional 17/102 samples detected (P-value < 0.01). For plasma samples, sensitivity was significantly higher and specificity significantly lower using RT-qPCR for all IA classifications (P-value < 0.001). The mean Ct obtained with RT-qPCR were significantly lower than those obtained with qPCR for all IA classifications and all sample types (P-value < 0.001 and P-value < 0.0001, respectively). RT-qPCR presents a higher sensitivity than qPCR for the diagnosis of IA due to Aspergillus fumigatus, particularly in samples with an intrinsically low fungal load.IMPORTANCEAspergillus fumigatus belongs to the critical priority group of the World Health Organization fungal priority pathogens list. Invasive aspergillosis (IA) is a life-threatening infection with poor prognosis and challenging diagnosis. PCR has been integrated into the 2020 European Organization for Research and Treatment of Cancer/Mycoses Study Group consensus definitions for IA diagnosis. However, due to frequent low fungal burdens, its sensitivity needs to be improved. This work presents an innovative method for detecting total nucleic acids, corresponding to both ribosomal RNA and DNA, that enables IA diagnosis with greater sensitivity than conventional techniques, especially in non-invasive samples such as blood, enhancing the monitoring of this infection in high-risk patients.

Performance of the Aspergillus galactomannan lateral flow assay with a digital reader for the diagnosis of invasive aspergillosis: a multicenter study.

PURPOSE: The objective of this multicenter study was to compare the diagnostic performance of lateral flow assay (LFA) and enzyme-linked immunosorbent assay (ELISA) to detect the Dynamiker Aspergillus Galactomannan levels in serum and bronchoalveolar lavage fluid (BALF) samples for I. METHODS: We registered 310 clinically suspected Aspergillus infection patients from December 2021 to February 2023 and classified them into subgroups as the "IA group" and "non-IA group" based on the latest EORTC/MSG guidelines. The immunoassays were analyzed by LFA and ELISA respectively. RESULTS: Galactomannan was examined using LFA, and serum and BALF samples demonstrated sensitivities of 82.57% and 89.47%, specificities of 90.76% and 92.00%, PPVs of 89.11% and 96.23%, and NPVs of 85.04% and 79.31%, respectively. Galactomannan was observed using two assays in serum and BALF samples and showed PPAs of 95.11% and 93.33%, NPAs of 89.19% and 96.30%, and TPAs of 92.47% and 94.25%, respectively. The ROC curve demonstrated that LFA had optimum diagnostic value when the index value (I value) = 0.5, the sensitivity was 84.94%, and the specificity was 90.97%. CONCLUSION: Compared to the ELISA method, the LFA has shown excellent performance for the diagnosis of IA in serum and BALF sample and can be used as an assay for the early diagnosis of patients with IA. The dynamic change in galactomannan levels may be useful for assessing treatment response.

Evaluation of the JF5-based Aspergillus galactomannoprotein lateral flow device for diagnosing invasive aspergillosis in cancer patients.

PURPOSE: Cancer patients are at heightened risk for invasive aspergillosis (IA), a condition associated with elevated mortality risk. The JF5-based Aspergillus Galactomannoprotein Lateral Flow Device (AspLFD) offers rapid point-of-care testing (POCT) for IA. This study evaluated the diagnostic performance of AspLFD in cancer populations. METHODS: This retrospective study examined cancer patient bronchoalveolar lavage fluid (BALF) and serum samples collected between September 2021 and January 2023. Both AspLFD and galactomannan (GM) assays were conducted, and the results were analysed by two independent researchers. RESULTS: This study included 242 samples from 218 cancer patients, with 58 BALF and 184 serum samples. The overall agreement between AspLFD and GM assay results was 92.1%, with a kappa value of 0.552. AspLFD diagnosed proven/probable IA with a sensitivity and specificity of 91.7% and 95.3%, respectively, whereas GM exhibited sensitivity and specificity values of 83.3% and 93.7%, respectively. There were no statistical differences in the sensitivity and specificity between the two methods (P > 0.05). For serum analyses, AspLFD and GM exhibited similar sensitivity (66.7% vs. 66.7%, P > 0.05) and specificity (98.6% vs. 96.6%, P > 0.05) values. However, the sensitivity of the AspLFD was superior to the GM assay (100% vs. 88.9%) in BALF analyses but the difference was not statistically significant (P > 0.05), with no difference in specificity (83.7% vs. 83.7%, P > 0.05). In the solid-tumour cohort, both the AspLFD and GM assay exhibited high sensitivity (100% for both) and specificity (94.2% vs. 92.8%, P > 0.05). CONCLUSION: The AspLFD demonstrated good performance in diagnosing IA in cancer patients, especially those with solid tumours. The AspLFD is thus an alternative POCT, particularly when GM evaluations are not readily available.

Diagnosis of invasive aspergillosis in haemato-oncology patients in a routine diagnostic setting.

Invasive Aspergillosis (IA) is a potentially lethal infection in high-risk haemato-oncology patients. Since traditional diagnostic methods have many inherent challenges, Polymerase Chain Reaction (PCR) has been used to diagnose IA. This prospective study evaluated a commercial AsperGenius multiplex real-time PCR for its clinical utility in diagnosing IA compared with galactomannan (GM) testing serum samples from haemato-oncology patients with clinically suspected IA. A total of 107 patients were recruited between April 2022 and March 2023. Serum samples (n = 113) collected from those patients for the routine diagnosis by GM Enzyme Linked Immuno-Sorbent Assay (ELISA) were subjected to PCR. The patients were categorised into probable, possible, and no IA based on revised (2020) and previous (2008) European Organization for Research and Treatment of Cancer and the National Institute of Allergy and Infectious Diseases Mycoses Study Group (EORTC-MSG) criteria. The performance characteristics of PCR and GM were calculated against the EORTC criteria by combining probable and possible cases as diseased groups. Among the 107 recruited patients, 93 were categorised into probable/possible IA (diseased group) and 14 into no IA group. The PCR was positive in 53 samples from 49 patients. The sensitivity and specificity of single positive PCR and GM were 51.61% [95% confidence interval, 41-62], 92.86% (66.1-99.8) and 26.88% (18.2-37.1), 92.86% (66.1-99.8), respectively. The combination-based strategy (GM and/or PCR positive) exhibited a moderate sensitivity of 62.37% (51-72.2) and a specificity of 85.71% (57.2-98.2). To conclude, the combined strategy of serum GM and/or PCR positivity, along with radiological findings that fulfilled the EORTC/MSG criteria, has improved the diagnosis of probable IA among high-risk haematological patients with clinically suspected IA.

Invasive aspergillosis is a serious and often deadly fungal infection. Diagnosing it early is crucial, especially for patients with weakened immune systems. This study identified that combining polymerase chain reaction, galactomannan antigen testing, and imaging scans improves the accuracy of diagnosis.

Aspergillus fumigatus-a systematic review to inform the World Health Organization priority list of fungal pathogens.

Recognizing the growing global burden of fungal infections, the World Health Organization established a process to develop a priority list of fungal pathogens (FPPL). In this systematic review, we aimed to evaluate the epidemiology and impact of invasive infections caused by Aspergillus fumigatus to inform the first FPPL. The pre-specified criteria of mortality, inpatient care, complications and sequelae, antifungal susceptibility, risk factors, preventability, annual incidence, global distribution, and emergence were used to search for relevant articles between 1 January 2016 and 10 June 2021. Overall, 49 studies were eligible for inclusion. Azole antifungal susceptibility varied according to geographical regions. Voriconazole susceptibility rates of 22.2% were reported from the Netherlands, whereas in Brazil, Korea, India, China, and the UK, voriconazole susceptibility rates were 76%, 94.7%, 96.9%, 98.6%, and 99.7%, respectively. Cross-resistance was common with 85%, 92.8%, and 100% of voriconazole-resistant A. fumigatus isolates also resistant to itraconazole, posaconazole, and isavuconazole, respectively. The incidence of invasive aspergillosis (IA) in patients with acute leukemia was estimated at 5.84/100 patients. Six-week mortality rates in IA cases ranged from 31% to 36%. Azole resistance and hematological malignancy were poor prognostic factors. Twelve-week mortality rates were significantly higher in voriconazole-resistant than in voriconazole-susceptible IA cases (12/22 [54.5%] vs. 27/88 [30.7%]; P = .035), and hematology patients with IA had significantly higher mortality rates compared with solid-malignancy cases who had IA (65/217 [30%] vs. 14/78 [18%]; P = .04). Carefully designed surveillance studies linking laboratory and clinical data are required to better inform future FPPL.

Report of three azole-resistant Aspergillus fumigatus cases with TR34/L98H mutation in hematological patients in Barcelona, Spain.

OBJECTIVES: We aimed to report the emergence of azole-resistant invasive aspergillosis in hematologic patients admitted to a tertiary hospital in Spain during the last 4 months. METHODS: Prospective, descriptive study was performed to describe and follow all consecutive proven and probable invasive aspergillosis resistant to azoles from hematological cohort during the last 4 months. All patients had fungal cultures and antifungal susceptibility or real-time PCR detection for Aspergillus species and real-time PCR detection for azole-resistant mutation. RESULTS: Four cases of invasive aspergillosis were diagnosed in 4 months. Three of them had azole-resistant aspergillosis. Microbiological diagnosis was achieved in three cases by means of fungal culture isolation and subsequent antifungal susceptibility whereas one case was diagnosed by PCR-based aspergillus and azole resistance detection. All the azole-resistant aspergillosis presented TR34/L98H mutation. Patients with azole-resistant aspergillosis had different hematologic diseases: multiple myeloma, lymphoblastic acute leukemia, and angioimmunoblastic T lymphoma. Regarding risk factors, one had prolonged neutropenia, two had corticosteroids, and two had viral co-infection. Two of the patients developed aspergillosis under treatment with azoles. CONCLUSION: We have observed a heightened risk of azole-resistant aspergillosis caused by A. fumigatus harboring the TR34/L98H mutation in patients with hematologic malignancies. The emergence of azole-resistant aspergillosis raises concerns for the community, highlighting the urgent need for increased surveillance and the importance of susceptibility testing and new drugs development.

Compare the efficacy of antifungal agents as primary therapy for invasive aspergillosis: a network meta-analysis.

BACKGROUND: Several antifungal agents are available for primary therapy in patients with invasive aspergillosis (IA). Although a few studies have compared the effectiveness of different antifungal agents in treating IA, there has yet to be a definitive agreement on the best choice. Herein, we perform a network meta-analysis comparing the efficacy of different antifungal agents in IA. METHODS: We searched PubMed, Embase, and the Cochrane Central Register of Controlled Clinical Trials databases to find studies (both randomized controlled trials [RCTs] and observational) that reported on treatment outcomes with antifungal agents for patients with IA. The study quality was assessed using the revised tool for risk of bias and the Newcastle Ottawa scale, respectively. We performed a network meta-analysis (NMA) to summarize the evidence on antifungal agents' efficacy (favourable response and mortality). RESULTS: We found 12 studies (2428 patients) investigating 11 antifungal agents in the primary therapy of IA. There were 5 RCTs and 7 observational studies. When treated with monotherapy, isavuconazole was associated with the best probability of favourable response (SUCRA, 77.9%; mean rank, 3.2) and the best reduction mortality against IA (SUCRA, 69.1%; mean rank, 4.1), followed by voriconazole and posaconazole. When treated with combination therapy, Liposomal amphotericin B plus caspofungin was the therapy associated with the best probability of favourable response (SUCRA, 84.1%; mean rank, 2.6) and the best reduction mortality (SUCRA, 88.2%; mean rank, 2.2) against IA. CONCLUSION: These findings suggest that isavuconazole, voriconazole, and posaconazole may be the best antifungal agents as the primary therapy for IA. Liposomal amphotericin B plus caspofungin could be an alternative option.

Invasive pulmonary aspergillosis following human metapneumovirus infection in solid-organ transplant recipients: Another virus to add to the list.

There is increasing recognition that respiratory viral infections such as influenza, respiratory syncytial virus, parainfluenza virus, adenovirus, and SARS-CoV-2 can promote the development of invasive fungal pulmonary coinfections, particularly invasive aspergillosis, both in immunocompetent and immunocompromised patients. To date, there are no case reports exploring the role of human metapneumovirus as a risk factor for fungal coinfection. Below, we describe the case of a 63-year-old woman who received a kidney transplant and developed invasive pulmonary aspergillosis after a human metapneumovirus infection and discuss the possible phenomena that could favor this association.

Outcomes of severe aspergillosis in patients undergoing extracorporeal membrane oxygenation: A systematic review.

BACKGROUND: Invasive aspergillosis (IA) can lead to life-threatening respiratory failure necessitating extracorporeal membrane oxygenation (ECMO) support. However, data on ECMO experience in the management of IA patients are scarce. OBJECTIVES: The purpose of this systematic review was to evaluate the potential benefits and risks of ECMO as a supportive intervention for critically ill patients with IA. METHODS: We conducted a systematic review of the literature using the search terms ECMO, extracorporeal membrane oxygenation, Aspergillus and Aspergillosis in two databases (Medline and Scopus). Clinical data were extracted by two independent investigators. Clinical parameters, such as mode of ECMO support, duration of treatment and clinical outcomes, were assessed. RESULTS: Overall, 32 patients were included in the analysis. The age ranged from 5 to 69 years, 59% were male, and 38% were female. The majority of patients suffered from ARDS (82%). 82% received VV-ECMO, and 18% received VA-ECMO. Aspergillus fumigatus was the most frequent cause of IA, coinfections were frequently observed (51%). The overall mortality was 78%. Complications during ECMO support were observed in 21 of the 39 cases (53.8%). CONCLUSIONS: IA poses significant management challenges for critically ill ICU patients, even with ECMO support. Although ECMO appears to improve survival of patients at high risk of AI, potential risks such as bacterial superinfection and altered pharmacokinetics of antifungal drugs must be carefully considered.

Is there still a place for serum galactomannan in the diagnosis of invasive aspergillosis in children at high risk and under antifungal prophylaxis?

BACKGROUND: The performance of serum galactomannan (GM) for the diagnosis of invasive aspergillosis (IA) has been studied mainly in adults. Paediatric data are scarce and based on small and heterogeneous cohorts. OBJECTIVE: To evaluate the performance of serum GM for the diagnosis of IA in a paediatric oncologic population at high risk of IA and to clarify the impact of antifungal prophylaxis on this test. METHODS: We performed a retrospective study from January 2014 to December 2020 in the paediatric oncologic haematologic department of the University Hospital of Bordeaux. The diagnosis of IA was made using the recommendations of the EORTC and the MSGERC. RESULTS: Among the 329 periods at high risk of IA in 222 patients, the prevalence of IA was 1.8% (3 proven and 3 probable IA). In the total population, the sensitivity, and the positive predictive value (PPV) were respectively 50% and 17.6%. Under antifungal prophylaxis, the sensitivity and PPV dropped, respectively, to 33.3% and 14.3%. In this group, the post-test probability of IA was 2% for a negative serum GM and only 14%. CONCLUSION: In this large cohort of children at high risk of IA, the incidence of IA is low and the diagnostic performance of GM is poor, especially in the case of mould-active prophylaxis. Screening should be targeted rather than systematic and should be reserved for patients at highest risk for IA without mould-active prophylaxis. Combination with other tests such as Aspergillus PCR would increase the accuracy of GM in screening setting.

Performance of the clarus Aspergillus galactomannan enzyme immunoassay prototype for the diagnosis of invasive pulmonary aspergillosis in serum.

BACKGROUND: Serum galactomannan (GM) testing is essential for diagnosing invasive aspergillosis (IA), particularly in immunocompromised individuals. The global lack of on-site GM testing capacities necessitates cost-effective alternatives, such as .the clarus Aspergillus GM enzyme immunoassay prototype (clarus AGM prototype). METHODS: This single-centre, cross-sectional study compared the diagnostic performance of the clarus AGM prototype (IMMY, Norman, Oklahoma) with the serological gold standard (=Platelia AGM assay; Bio-Rad, Marnes-la-Cocquette, France). IA was classified according to modified 2020 EORTC/MSG consensus and 2024 FUNDICU criteria. In total, 300 prospectively (May-Dec 2023) and retrospectively (2012-2015) collected samples were included. RESULTS: Among 300 samples from 232 patients, 49 (16%) were classified as proven (n = 1) or probable IA (n = 48). In non-IA cases (n = 250), one patient was classified as possible IA. With the manufacturer recommended cut-off of ≥0.2, sensitivity and specificity of the clarus AGM prototype were 27% (13/49; 95% confidence interval [CI]: 15%-41%) and 99% (248/250; 95% CI: 97%-100%), respectively, while sensitivity and specificity were 78% and 79% when using the optimised Youden's cut-off of 0.0045 ODI. ROC curve analysis demonstrated an area under the curve (AUC) of 0.829 (95% CI: 0.760-0.898) for the clarus AGM prototype in distinguishing between proven/probable IA and non-IA. The AUC for the Platelia AGM was 0.951 (95% CI: 0.909-994). Spearman's correlation analysis showed a weak correlation between the two assays (0.382; p < .001). CONCLUSIONS: The weak correlation between the clarus AGM prototype and Platelia AGM highlights the need for further investigation into the clinical performance of the clarus AGM prototype, giving the different antigen epitopes addressed.

Optimizing Antifungal Treatment Strategies to Prevent Invasive Pulmonary Aspergillosis Infection-Related Deaths in Intensive Care Unit Patients: The Need for Standardization of Research Definitions.

The clinical spectrum of invasive pulmonary aspergillosis (IPA) has expanded in recent decades. A large group of patients admitted to intensive care units (ICU) is indeed susceptible to the development of IPA. Although timely diagnosis and antifungal therapy of IPA in this expanding population is crucial to prevent IPA-related deaths, the magnitude of the favorable prognostic impact of antifungal therapy is difficult to measure precisely. In our opinion, the development of standardized research definitions could have favorable implications for further improving our ability both to measure the favorable effect of antifungal treatment and to prevent IPA-related death in ICU patients.

[Ruptured mycotic cerebral aneurysm in an adult T-cell leukemia/lymphoma patient undergoing allogeneic stem cell transplantation].

A 63-year-old man with adult T-cell leukemia-lymphoma underwent allogeneic bone marrow transplantation from an HLA-matched unrelated donor. On day 17 after transplantation, chest computed tomography (CT) showed nodules in the lower lobes of both lungs, and invasive pulmonary aspergillosis (IPA) was suspected. Treatment with liposomal amphotericin B was started, and improvement of infectious lesions was confirmed with CT on day 28. The antifungal agent was changed to voriconazole on day 52 because of progressive renal dysfunction. Disorders of consciousness and paralysis of the left upper and lower extremities developed on day 61. Brain CT showed subcortical hemorrhage in the right parietal and occipital lobes, and the patient died on day 62. An autopsy revealed filamentous fungi, suspected to be Aspergillus, in the pulmonary nodules and a ruptured cerebral aneurysm. Although IPA occurs in 10% of transplant recipients, vigilant monitoring for mycotic cerebral aneurysms is required to prevent hematogenous dissemination of Aspergillus, which is associated with a high mortality rate.

Utility of Plasma Microbial Cell-Free DNA Whole-Genome Sequencing for Diagnosis of Invasive Aspergillosis in Patients With Hematologic Malignancy or COVID-19.

BACKGROUND: We evaluated the clinical accuracy and utility of whole-genome sequencing (WGS) of plasma microbial cell-free DNA (cfDNA) as a novel noninvasive method in diagnosing invasive aspergillosis (IA) in patients with hematologic malignancy (HM) or coronavirus disease 2019 (COVID-19). METHODS: Adults with HM or COVID-19 and suspected IA were recruited. IA cases were retrospectively diagnosed according to EORTC/MSG definitions and ECMM/ISHAM criteria for HM and COVID-19 patients, respectively. The results of cfDNA WGS were compared with the conventional diagnosis. RESULTS: Microbial cfDNA WGS was performed 53 times from 41 participants (19 from HM, 16 from COVID-19, and 7 from the control group). In participants with HM, Aspergillus cfDNA was detected in 100% of proven IA and 91.7% of probable IA cases. In participants with COVID-19, 50.0% of probable IA were positive for Aspergillus in cfDNA WGS. Concordance between Aspergillus cfDNA detection and proven/probable IA conventional diagnosis was significantly higher in participants with HM than in those with COVID-19. IA diagnosed using EORTC/MGS definitions showed significantly high concordance between Aspergillus cfDNA detection and proven/probable IA. CONCLUSIONS: Aspergillus cfDNA detection strongly correlated with proven/probable IA diagnosed using EORTC/MSG definitions and could be used as an additional diagnostic tool for IA.

ANTIFON-CLIC®, a new clinical decision support system for the treatment of invasive aspergillosis: is it clinically relevant?

BACKGROUND: Invasive aspergillosis (IA) is increasing especially in new groups of patients. Despite advances in management, morbidity and mortality related to IA remain high. Thus, Clinical Decision Support System (CDSS) dedicated to IA are needed to promote the optimal antifungal for each group of patients. PATIENTS AND METHODS: This was a retrospective multicenter cohort study involving intensive care units and medical units. Adult patients who received caspofungin, isavuconazole, itraconazole, liposomal amphotericin B, posaconazole, or voriconazole, for the treatment of IA were eligible for enrollment. The primary objective was the concordance between the clinician's prescription and the prescription recommended by the CDSS. The secondary objective was the concordance according to different hospitals, departments, and indications. RESULTS: Eighty-eight patients (n=88) from three medical hospitals were included. The overall concordance was 97% (85/88) including 100% (41/41) for center A, 92% (23/25) for center B, and 95% (21/22) for center C. There was no significant difference in concordance among the hospitals (P=0.973), the departments (P=1.000), and the indications (P=0.799). The concordance was 70% (7/10) for isavuconazole due to its use as an empirical treatment and 100% (78/78) for the other antifungals. DISCUSSION: The concordance rate was high whatever the hospital, the department, and the indication. The only discrepancy was attributed to the use of isavuconazole as an empirical treatment which is a therapeutic option not included in the CDSS. CONCLUSIONS: This new CDSS dedicated to IA is meeting the clinical practice. Its implementation in routine will help to support antifungal stewardship.