Pulmonary administration of voriconazole involves advantages, including optimization of lung penetration and reduction of adverse effects and interactions. However, there is scarce evidence about its use and there are no commercial presentations for nebulization. We aim to characterize a compounded voriconazole solution for nebulization and describe its use in our center.
This is a retrospective observational study including patients who received nebulized voriconazole to treat fungal lung diseases (infection or colonization). Voriconazole solution was prepared from commercial vials for intravenous administration.
The pH and osmolarity of voriconazole solutions were adequate for nebulization. Ten patients were included, nine adults and a child. The dosage was 40 mg in adults and 10 mg in the pediatric patient, diluted to a final concentration of 10 mg/ml, administered every 12-24 hours. The median duration of treatment was 139 (range: 26-911) days. There were no reported adverse effects and the drug was not detected in plasma when nebulized only.
Voriconazole nebulization is well tolerated and it is not absorbed into the systemic circulation; further research is needed to assess its efficacy.

Pulmonary mucormycosis (PM) is a life-threatening invasive mold infection. Diagnosis of mucormycosis is challenging and often delayed, resulting in higher mortality.
Are the disease presentation of PM and contribution of diagnosis tools influenced by the patient\'s underlying condition?
All PM cases from six French teaching hospitals between 2008 and 2019 were retrospectively reviewed. Cases were defined according to updated European Organization for Research and Treatment of Cancer/Mycoses Study Group criteria with the addition of diabetes and trauma as host factors and positive serum or tissue PCR as mycologic evidence. Thoracic CT scans were reviewed centrally.
A total of 114 cases of PM were recorded, including 40% with disseminated forms. Main underlying conditions were hematologic malignancy (49%), allogeneic hematopoietic stem cell transplantation (21%), and solid organ transplantation (17%). When disseminated, main dissemination sites were the liver (48%), spleen (48%), brain (44%), and kidneys (37%). Radiologic presentation included consolidation (58%), pleural effusion (52%), reversed halo sign (26%), halo sign (24%), vascular abnormalities (26%), and cavity (23%). Serum quantitative polymerase chain reaction (qPCR) was positive in 42 (79%) of 53 patients and BAL in 46 (50%) of 96 patients. Results of transthoracic lung biopsy were diagnostic in 8 (73%) of 11 patients with noncontributive BAL. Overall 90-day mortality was 59%. Patients with neutropenia more frequently displayed an angioinvasive presentation, including reversed halo sign and disseminated disease (P < .05). Serum qPCR was more contributive in patients with neutropenia (91% vs 62%; P = .02), and BAL was more contributive in patients without neutropenia (69% vs 41%; P = .02). Serum qPCR was more frequently positive in patients with a > 3 cm main lesion (91% vs 62%; P = .02). Overall, positive qPCR was associated with an early diagnosis (P = .03) and treatment onset (P = .01).
Neutropenia and radiologic findings influence disease presentation and contribution of diagnostic tools during PM. Serum qPCR is more contributive in patients with neutropenia and BAL examination in patients without neutropenia. Results of lung biopsies are highly contributive in cases of noncontributive BAL.

BACKGROUND: Pulmonary cryptococcosis (PC) is a fungal infection that can have a variable prognosis depending on several factors. The objective of this study was to analyse the characteristics of pulmonary lesions and identify prognostic factors in patients with PC who were human immunodeficiency virus (HIV) -negative and underwent antifungal treatment.
METHODS: The study enrolled patients diagnosed with PC who were negative for HIV. Symptoms, CT characteristics of pulmonary lesions, serum cryptococcal capsular antigen (CrAg) titre, underlying diseases, and duration of antifungal treatment were evaluated over a 2-year follow-up.
RESULTS: A total of 63 patients (40 men and 23 women) with a mean age of 50.4 years were included. Half of the patients (50.8%) were asymptomatic, and the most common symptoms were cough (44.4%), expectoration (27.0%), and fever (17.5%). Pulmonary lesions were mainly present in the peripheral and lower lobes of the lung, with 35 cases classified as nodular-type lesions and 28 cases classified as mass-type lesions. At the first, third, sixth, 12th, and 24th-month follow-ups, the median proportion of residual pulmonary lesions were 59.6%, 29.9%, 12.2%, 9.6%, and 0.0%, respectively. During antifungal treatment, the lesions of 33 patients achieved complete response, while the remaining 30 patients did not. Compared with the non-CR group, the CR group had a lower baseline serum CrAg titre (median, 1:20 vs 1:80, P < 0.01), smaller pulmonary lesion size (median area, 1.6 cm2 vs 6.3 cm2, P < 0.01), lower Hounsfield-units (HU) radiodensity (median, - 60.0 HU vs - 28.5 HU, P < 0.05), more nodular-type lesions (72.7% vs 36.7%, P < 0.01), and fewer air-bronchogram signs (18.2% vs 43.3%, P < 0.05). Multivariate logistic regression analysis showed that a larger lesion size on chest CT scans was associated with a lower likelihood of achieving complete response [OR: 0.89; 95% CI (0.81-0.97); P < 0.05].
CONCLUSIONS: PC was more commonly observed in HIV-negative men, and chest CT scans mostly revealed nodular-type lesions. After antifungal treatment, patients with smaller lesions had a better prognosis.

There has been a rapid increase in the number of human adenovirus type 7 (HAdV-7) and invasive pulmonary fungal infections (IPFIs) co-infection.
In this study, we included patients with confirmed HAdV-7 infection during the period from 2018 to 2019 to explore clinical characteristics of severe HAdV-7 pneumonia combined with IPFIs.
Among the 143 patients, 35 cases were co-infected with IPFIs. Others were assigned to the control group (n Z 108). Patients wereprone to be complicated with respiratory failure, heart failure and hemophagocytic syndromein IPFIs group. Thirty-one species of fungi were detected in the IPFIs group, among whichAspergillus was the most common species. Compared to control group, patients had lowerlevels of WBC, CD3þ T lymphocyte counts and CD19þ B lymphocyte counts in IPFIs group.
Aspergillus is the most common species in IPFIs combined with severe HAdV-7 pneumonia. For children with severe HAdV-7 pneumonia who are younger, have a long course of disease, and have been admitted to the ICU, we should predict the occurrence of IPFIs when there is multi-system dysfunction and the reduction of CD3+ T lymphocyte counts and CD19+ B lymphocyte counts in course of their disease.

With the widespread use of antibacterial drugs and increasing number of immunocompromised patients, pulmonary fungal infections are becoming more common. However, the incidence of pulmonary fungal and bacterial co-infection is rarely reported. In this study, 119 patients definitively diagnosed with pulmonary fungal infections between July 2018 and March 2020 were assessed using metagenomic next-generation sequencing (mNGS) as well as traditional pathogen detection to gauge the incidence of fungal and bacterial co-infection and evaluate the associated risk factors. We found that of the 119 patients with fungal infections, 48 (40.3%) had pulmonary fungal and bacterial co-infection. We identified immunocompromised status and the presence of one or more pulmonary cavities as risk factors associated with fungal and bacterial co-infection. The most commonly isolated fungi species were Aspergillus, Pneumocystis, and Rhizopus. The most commonly isolated bacterial species were Pseudomonas aeruginosa, Acinetobacter baumannii, and Stenotrophomonas maltophilia. Seventy-nine (66.4%) patients had received empirical antibiotic treatment before their pathogenic test results became available, and 41.7% (fungal infection group) and 38.7% (fungal and bacterial co-infection group) of the patients had their antibacterial drug dosage changed accordingly. This mNGS-based study showed that the incidence of fungal and bacterial co-infection is significant. Our research outcomes can, thus, guide the use of antibacterial drugs in the treatment of clinical fungal infections.

Recently, the prevalence trend of pulmonary fungal infection (PFI) has rapidly increased. Changes in the risk factors for, distributions of underlying diseases associated with and clinical characteristics of some individual PFIs have been reported in the past decade. However, data regarding PFIs remain uncertain. This study reports the epidemiological characteristics and trends of PFIs over time in recent years. We applied an automated natural language processing (NLP) system to extract clinically relevant information from the electronic health records (EHRs) of PFI patients at the First Affiliated Hospital of Guangzhou Medical University. Then, a trend analysis was performed. From January 1, 2013, to December 31, 2019, 40,504 inpatients and 219,414 outpatients with respiratory diseases were screened, in which 1368 inpatients and 1313 outpatients with PFI were identified. These patients were from throughout the country, but most patients were from southern China. Upward trends in PFIs were observed in both hospitalized patients and outpatients (P<0.05). The stratification by age showed that the incidence of hospitalized patients aged 14-30 years exhibited the most obvious upward trend, increasing from 9.5 per 1000 patients in 2013 to 88.3 per 1000 patients in 2019. Aspergillosis (56.69%) was the most common PFI, but notably, the incidence rates of Talaromyces marneffei, which used to be considered uncommon, exhibited the most rapid increases. In younger PFI patients, the incidence and trend of PFIs have increased. Infection by previously uncommon pathogens has also gradually increased. Increased attention should be paid to young PFI patients and uncommon PFI pathogen infections.

OBJECTIVE: To compare the chest CT patterns of acute graft-versus-host disease (aGVHD) and infections within 100 days after allogeneic hematopoietic stem cell transplantation (allo-HSCT) in pediatric recipients to help hematologist make definitive diagnosis as early as possible.
METHODS: A total of 143 pediatric recipients from January 2015 to June 2019 who were diagnosed pulmonary aGVHD or infections within 100 days after allo-HSCT were enrolled in this study. Two observers evaluated the extent and distribution (unilateral, bilateral) of the CT patterns. The patterns were then classified as ground-glass opacity (GGO) (localized, patchy, diffuse), consolidation (localized, patchy, diffuse), reticulation (localized, patchy, diffuse), nodules (localized, multiple), bronchiectasis, pleural effusion, air trapping, tree-in-bud sign, and pneumomediastinum. The onset time and radiological patterns of the two cohorts were statistically compared.
RESULTS: The mean onset time of aGVHD (n = 85) and infections group (viral n = 29, bacterial n = 22, fungal n = 7, total n = 58) was 36.89 ± 24.34 (range, 10-99 days) and 23.48 ± 20.65 days (range, 4-94 days) with a significant difference (P = .001). The top three underlying diseases were acute lymphoblastic leukemia (ALL) (n = 49, 57.6%); acute myeloid leukemia (AML) (n = 24, 28.2%); and aplastic anemia (AA) (7.1%) in aGVHD group and hemophagocytic syndrome (HPS) (n = 33, 56.9%); AA (n = 9, 15.5%); and ALL (n = 6, 10.3) in infection group. GGO (41.2%) in aGVHD prevailed on CT, whereas GGO (53.4%) and consolidations (43.1%) were more prevalent in infections. The distribution of GGO showed more diffuse in aGVHD (P = .031) and symmetric while patchier GGO prefers infections (P < .001). No differences were found in the reticulation. Nodules were more common in infections (P = .004) while pleural effusion was more common in aGVHD group (P < .035).
CONCLUSIONS: Imaging patterns of aGVHD on CT differ substantially from that of infections. Physicians and radiologists should be aware of such radiological differences in order to give accurate treatment. Notably, definite diagnosis should be made in combination with clinical manifestations, signs, and laboratory tests.

OBJECTIVE: To describe the epidemiology, management and outcome of individuals with mucormycosis; and to evaluate the risk factors associated with mortality.
METHODS: We conducted a prospective observational study involving consecutive individuals with proven mucormycosis across 12 centres from India. The demographic profile, microbiology, predisposing factors, management and 90-day mortality were recorded; risk factors for mortality were analysed.
RESULTS: We included 465 patients. Rhino-orbital mucormycosis was the most common (315/465, 67.7%) presentation followed by pulmonary (62/465, 13.3%), cutaneous (49/465, 10.5%), and others. The predisposing factors included diabetes mellitus (342/465, 73.5%), malignancy (42/465, 9.0%), transplant (36/465, 7.7%), and others. Rhizopus species (231/290, 79.7%) were the most common followed by Apophysomyces variabilis (23/290, 7.9%), and several rare Mucorales. Surgical treatment was performed in 62.2% (289/465) of the participants. Amphotericin B was the primary therapy in 81.9% (381/465), and posaconazole was used as combination therapy in 53 (11.4%) individuals. Antifungal therapy was inappropriate in 7.6% (30/394) of the individuals. The 90-day mortality rate was 52% (242/465). On multivariate analysis, disseminated and rhino-orbital (with cerebral extension) mucormycosis, shorter duration of symptoms, shorter duration of antifungal therapy, and treatment with amphotericin B deoxycholate (versus liposomal) were independent risk factors of mortality. A combined medical and surgical management was associated with a better survival.
CONCLUSIONS: Diabetes mellitus was the dominant predisposing factor in all forms of mucormycosis. Combined surgical and medical management was associated with better outcomes. Several gaps surfaced in the management of mucormycosis. The rarer Mucorales identified in the study warrant further evaluation.

Since mould-active azole prophylaxis has become a standard approach for patients with high-risk haematologic diseases, the epidemiology of invasive fungal infections (IFIs) has shifted towards non-Aspergillus moulds. It was aimed to identify the epidemiology and characteristics of non-Aspergillus invasive mould infections (NAIMIs). Proven/probable NAIMIs developed in patients with haematologic diseases were reviewed from January 2011 to August 2018 at Catholic Hematology hospital, Seoul, Korea. There were 689 patients with proven/probable invasive mould infections; of them, 46 (47 isolates) were diagnosed with NAIMIs. Fungi of the Mucorales order (n = 27, 57.4%) were the most common causative fungi, followed by Fusarium (n = 9, 19.1%). Thirty-four patients (73.9%) had neutropenia upon diagnosis of NAIMIs, and 13 (28.3%) were allogeneic stem cell transplantation recipients. The most common site of NAIMIs was the lung (n = 27, 58.7%), followed by disseminated infections (n = 8, 17.4%). There were 23.9% (n = 11) breakthrough IFIs, and 73.9% (n = 34) had co-existing bacterial or viral infections. The overall mortality at 6 and 12 weeks was 30.4% and 39.1%, respectively. Breakthrough IFIs (adjusted hazards ratio [aHR] = 1.99, 95% CI: 1.3-4.41, P = .031) and surgical treatment (aHR = 0.09, 95% CI: 0.02-0.45, P = .003) were independently associated with 6-week overall mortality. NAIMIs were not rare and occur as a complex form of infection often accompanied by breakthrough/mixed/concurrent IFIs and bacterial or viral infections. More active diagnostic efforts for NAIMIs are needed.

A gap exists in the literature regarding dose-response associations of objectively assessed housing quality measures, particularly dampness and mould, with hospitalisation for acute respiratory infection (ARI) among children.
A prospective, unmatched case-control study was conducted in two paediatric wards and five general practice clinics in Wellington, New Zealand, over winter/spring 2011-2013. Children aged <2 years who were hospitalised for ARI (cases), and either seen in general practice with ARI not requiring admission or for routine immunisation (controls) were included in the study. Objective housing quality was assessed by independent building assessors, with the assessors blinded to outcome status, using the Respiratory Hazard Index (RHI), a 13-item scale of household quality factors, including an 8-item damp-mould subscale. The main outcome was case-control status. Adjusted ORs (aORs) of the association of housing quality measures with case-control status were estimated, along with the population attributable risk of eliminating dampness-mould on hospitalisation for ARI among New Zealand children.
188 cases and 454 controls were studied. Higher levels of RHI were associated with elevated odds of hospitalisation (OR 1.11/unit increase (95% CI 1.01 to 1.21)), which weakened after adjustment for season, housing tenure, socioeconomic status and crowding (aOR 1.04/unit increase (95% CI 0.94 to 1.15)). The damp-mould index had a significant, adjusted dose-response relationship with ARI admission (aOR 1.15/unit increase (95% CI 1.02 to 1.30)). By addressing these harmful housing exposures, the rate of admission for ARI would be reduced by 19% or 1700 fewer admissions annually.
A dose-response relationship exists between housing quality measures, particularly dampness-mould, and young children\'s ARI hospitalisation rates. Initiatives to improve housing quality and to reduce dampness-mould would have a large impact on ARI hospitalisation.