The impact of the updated EORTC/MSG criteria on the classification of hematological patients with suspected invasive pulmonary aspergillosis

ObjectivesOur aim was to evaluate the effect of the updated European Organization for Research and Treatment of Cancer (EORTC) and Mycoses Study Group 2019 definitions for invasive pulmonary aspergillosis (IPA) on patient classification and the related all-cause 12-week mortality.MethodsIn this retrospective cohort study from our tertiary care centre, we reclassified patients with haematological malignancy who underwent bronchoalveolar lavage between 2014 and 2019 for suspected IPA using the novel EORTC 2019 criteria. We performed receiver operating characteristic curve analysis to define the optimal cut-off for positive PCR and galactomannan and present survival analyses and their possible association with these diagnostic criteria through post hoc comparisons with log rank and Cox regression.ResultsFrom 323 episodes of suspected IPA in 282 patients, 73 were reclassified: 31 (42.5%) from possible to probable IPA, 5 (6.8%) from EORTC criteria not met to probable IPA, and 37 (50.7%) from EORTC criteria not met to possible IPA. Probable IPA increased therefore 11.1% (64/323, 19.8% to 100/323, 30.9%), mostly due to positive PCR (31/36, 86.1%). There was no difference in mortality between newly defined possible and probable IPA (log rank p = 0.950). Mortality was higher in probable cases with lower cycle thresholds (Ct values) versus higher Ct values (p = 0.004). Receiver operating characteristic curve analysis showed an optimal Ct value cut-off of 36.8 with a sensitivity of 75% (95% CI 64.9%–85.1%) and a specificity of 61.7% (95% CI 53.5–69.9) for 12-week mortality.DiscussionThe new EORTC criteria led to 11.1% more probable IPA diagnoses, mostly due to Aspergillus PCR. Restricting positive PCR to below a certain threshold might improve the discrimination of the new EORTC IPA categories for mortality.     

Invasive pulmonary aspergillosis is associated with cytomegalovirus viremia in critically ill patients - A retrospective cohort study

Background/PurposeCytomegalovirus (CMV) viremia is associated with a higher mortality rate and prolonged intensive care unit (ICU) stay for critically ill patients. CMV infection causes transient but substantial immunosuppression for transplant recipients, increasing risk of fungal infection. The association between CMV viremia and invasive pulmonary aspergillosis (IPA) for critically ill patients is still unknown.MethodsWe retrospectively analyzed patients received bronchoalveolar lavage (BAL), galactomannan test, influenza survey and blood CMV viral load test in ICUs of a university hospital between April 2017 and May 2020. Independent risks for IPA were analyzed by multivariable logistic regression.ResultsA total of 136 patients were included. Twenty-one patients had IPA, 48 patients had CMV viremia and 22 patients had influenza. In a multivariable logistic regression model, patients with CMV viremia or influenza had higher IPA risk (adjusted odds ratio, 3.98 and 8.72; 95% CI, 1.26–12.60 and 2.64–28.82; p value = 0.019 and <0.001, respectively.). Patients with detectable CMV in BAL fluid did not have higher IPA risk (crude odds ratio, 0.95; 95% CI, 0.33–2.79; p value = 0.933). After stratifying patients by CMV viral load, the IPA risk is higher for patients with higher viral loads. There is an additive synergistic effect on IPA risk between CMV viremia and influenza infection.ConclusionFor critically ill patients, CMV viremia is an independent risk factor of IPA. Patients with higher blood CMV viral loads have a higher risk of IPA. CMV viremia and influenza have an additive synergistic effect for IPA risk in critically ill patients.     

Invasive Aspergillosis after Pandemic (H1N1) 2009

We report 2 patients with invasive aspergillosis after infection with pandemic (H1N1) 2009. Influenza viruses are known to cause immunologic defects and impair ciliary clearance. These defects, combined with high-dose corticosteroids prescribed during influenza-associated adult respiratory distress syndrome, may be novel risk factors predisposing otherwise immunocompetent patients to invasive aspergillosis.     

Experimental aspergillosis in guinea pigs: influence of itraconazole on fungaemia and invasive fungal growth

Summary. The guinea pig model of experimental aspergillosis was used to evaluate the efficacy of itraconazole 2.5 and 5 mg kg^-1 in preventing the invasive phase of the disease when animals were already loaded with Aspergillus conidia. Evaluations were made by recording the survival rates, culturing fragments of nine organs, examining seven organs by means of histochemistry and immunohistochemistry (mAb EB-Al to Aspergillus galactomannan) and by serological titration of galactomannan. The data indicate that itraconazole is highly effective in preventing true invasive aspergillosis. Serological evaluations of antigenaemia suggest that low titres may only reflect fungaemia, while titres of 1:8 and above are suggestive of invasive disease.
Zusammenfassung. Das Meerschweinchen-Modell der experimentellen Aspergillose wurde eingesetzt, um die Wirkung von 2,5 mg und 5 mg kg^-1 Itraconazol zur Prävention der invasiven Krankheitsphase zu bewerten, wenn die Versuchstiere bereits mit Aspergillus -Konidien beladen sind. Die Bewertung stützt sich auf die Überlebensrate, auf Pilzkulturen aus neun verschiedenen Organen, auf histochemische und immunhistochemische Untersuchungen von sieben Organen mittels MOB EB-Al-Antikörpern gegen Aspergillus -Galactomannan sowie auf die Serotitration dieses Antigens. Die Ergebnisse belegen die hohe Wirksamkeit des Itraconazols in der Prävention der echt invasiven Aspergillose. Antigen-Titrationen im Serum sprechen dafür, daß geringe Titer lediglich das Fungämie-Stadium widerspiegeln, während Antigentiter ≥ 1:8 eine invasive Aspergillose belegen.     

Demolition of a hospital building by controlled explosion: the impact on filamentous fungal load in internal and external air

The demolition of a maternity building at our institution provided us with the opportunity to study the load of filamentous fungi in the air. External (nearby streets) and internal (within the hospital buildings) air was sampled with an automatic volumetric machine (MAS-100 Air Samplair) at least daily during the week before the demolition, at 10, 30, 60, 90,120, 180, 240, 420, 540 and 660 min post-demolition, daily during the week after the demolition and weekly during weeks 2, 3 and 4 after demolition. Samples were duplicated to analyse reproducibility. Three hundred and forty samples were obtained: 115 external air, 69 'non-protected' internal air and 156 protected internal air [high efficiency particulate air (HEPA) filtered air under positive pressure]. A significant increase in the colony count of filamentous fungi occurred after the demolition. Median colony counts of external air on demolition day were significantly higher than from internal air (70.2 cfu/m(3) vs 35.8 cfu/m(3)) (P < 0.001). Mechanical demolition on day +4 also produced a significant difference between external and internal air (74.5 cfu/m(3) vs 41.7 cfu/m(3)). The counts returned to baseline levels on day +11. Most areas with a protected air supply yielded no colonies before demolition day and remained negative on demolition day. The reproducibility of the count method was good (intra-assay variance: 2.4 cfu/m(3)). No episodes of invasive filamentous mycosis were detected during the three months following the demolition. Demolition work was associated with a significant increase in the fungal colony counts of hospital external and non-protected internal air. Effective protective measures may be taken to avoid the emergence of clinical infections.     

Invasive aspergillosis: results of an 8-year study

We analysed retrospectively 90 cases of invasive aspergillosis (IA) which occurred at the University Hospital and the Thoraxklinik gGmbH Heidelberg between 1991 and 1998. 71 cases were histologically proven, 19 were probable diseases. There were 49 male and 41 female patients, with a mean age of 51.5 years (range 16 days to 80 years). Underlying diseases were: hematological malignancies in 52% (n = 47; 24 with acute leukemia), solid organ transplantation (n = 11; 9 liver, 1 kidney, 1 heart), solid cancer (n = 10), others (n = 21), and in one case no underlying disease was diagnosed. Only 54 cases (60%) were correctly diagnosed as IA during lifetime of the patients. In 59 cases (65%) only the lung was affected, 25 patients suffered from disseminated IA, in 6 patients only extrapulmonary lesions were present. 11 patients underwent lung surgery, 63 patients received antimycotic drugs (44 amphotericin B, 15 fluconazole, 4 itraconazole), 21 were not treated antimycotically. 68 patients (71%) died, from these 30 (36%) due to IA during remission of the underlying disease. The laboratory methods showed the following sensitivities, respectively: microscopy by calcofluor white staining 17%, culture 69%, Aspergillus-PCR from respiratory tract samples and biopsies 95%, galactomannan antigen detection by latex agglutination 28%, by enzyme immunoassay 59%, Aspergillus antibody detection 23%.     

Environmental Aerobiological Studies in Allergic Bronchopulmonary Aspergillosis

An aerobiological pilot study was undertaken to measure airborne concentrations of Aspergillus spores in and around the dwellings of two patients with allergic bronchopulmonary aspergillosis (ABPA). The aim of the investigation was 1) to find a specific source of Aspergillus antigen, and 2) to find out whether disease activity, or exacerbation, paralleled Aspergillus spore prevalence. In the environment of the first patient heavy spore contaminated air was found in a cow-shed, and the adjacent hayloft and scullery. The patient experienced no typical exacerbation during the study period, probably because she now scrupulously avoided this source. The environment of the second patient contained lower spore concentrations in and around the house, and the patient had no typical exacerbation, possibly due to low-intensity exposure. Both patients, however, had increased bronchial obstruction during periods with high Aspergillus spore content in the outside air. The results suggest that avoidance of Aspergillus spore sources and low overall exposure may play a major role in preventing exacerbation of the disease.     

Case report: successful interdisciplinary treatment of cerebrally disseminated invasive pulmonal aspergillosis in a child with acute myeloid leukemia

Invasive pulmonary aspergillosis (IPA) is a life-threatening infection in immunocompromised patients. Mortality rates of cerebrally disseminated IPA approach 100%. We report on a case of a 9-year-old girl with acute myeloid leukemia, who acquired cerebrally disseminated IPA during chemotherapy-induced leukopenia. Longtime survival was achieved by left pneumonectomy and neurosurgical resection of the intracerebral lesion combined with systemic application of itraconazole and liposomal amphotericin B. A review of literature revealed 7 other cases of cerebrally disseminated IPA with survival of more than 12 months.