Background
Candida parapsilosis complex consists of three species, the prevalence and geographical distribution of which might vary. Increasing rates of fluconazole resistance among C. parapsilosis ...complex were reported from various centres.
Objectives
Aim of this study was to identify invasive C. parapsilosis complex strains up to species level, explore rates and molecular mechanisms of azole resistance and analyse temporal changes at a single centre.
Methods
Isolates from blood cultures from 1997 to 2017 were included. Species were identified using RFLP of the SADH gene and confirmed with ITS sequencing when needed. In vitro susceptibility to fluconazole, voriconazole and posaconazole was tested and evaluated using EUCAST guidelines. Sequences of ERG11 and MRR1 genes were analysed for fluconazole non‐susceptible isolates.
Results
A total of 283 isolates from 181 patients were tested for azole susceptibility. All were C. parapsilosis sensu stricto, except one C. orthopsilosis. All three azoles were effective against 213 of the isolates from 135 patients, including one C. orthopsilosis. Fluconazole resistance was 13.3% (24/181 patients). While the first fluconazole‐resistant isolates were detected in 2004, increase was evident after 2011. In ERG11, Y132F mutation was the most common among fluconazole non‐susceptible isolates (71.7%), followed by G458S (10.9%) and D421N (4.3%). In MRR1, R405K (56.5%) and G927C (8.7%) were detected. However, association of these mutations to azole resistance is yet to be investigated.
Conclusions
Rising azole resistance rates in C. parapsilosis sensu stricto isolates particularly after 2011 were of concern. The well‐known Y132F mutation was the predominant mechanism of azole resistance while accompanied with other genetic mutations.
Summary
Background
Fungaemia due to rare yeasts has been recognised as an emerging, clinically relevant, but less investigated condition. Intrinsic resistance or reduced susceptibility of these ...species to echinocandins or fluconazole remains as a challenge in empirical treatment.
Objectives
To describe the clinical characteristics, administered antifungal agents, outcomes of patients with rare yeasts other than Candida (RY‐OTC) fungaemia and determine the antifungal susceptibility profiles of the isolates.
Patients and methods
RY‐OTC fungaemia between January‐2001 and December‐2018 were retrospectively evaluated. Antifungal susceptibility tests were performed according to CLSI M27‐A3.
Results
We identified 19 patients with fungaemia due to 20 RY‐OTC (8 Trichosporon asahii, 4 Cryptococcus neoformans, 4 Saprochaete capitata, 3 Rhodotorula mucilaginosa, 1 Trichosporon mucoides) with an incidence of 2.2% among 859 fungaemia episodes. Haematological malignancy was the most common (42%) underlying disorder. In 6 patients, RY‐OTC fungaemia developed as breakthrough infection while receiving echinocandins, amphotericin B or fluconazole. Amphotericin B, fluconazole or voriconazole were the drugs of choice for the initial treatment of breakthrough fungaemia. Among patients without previous exposure to antifungals, the most common empirical treatment was an echinocandin (50%), followed by fluconazole (42%) and amphotericin B (8%). Overall mortality was 47%. Worse outcome was most common among patients receiving echinocandins (83% vs 25%, P < .05). Voriconazole and posaconazole showed the highest in vitro activity against all the isolates tested. Amphotericin B MICs were relatively higher and the degree of activity of fluconazole and itraconazole was variable.
Conclusions
Early recognition of RY‐OTC and knowledge about their susceptibility patterns remain crucial in initial treatment pending susceptibility data of isolates.
Background
COVID‐19‐associated pulmonary aspergillosis (CAPA) has been reported as an important cause of mortality in critically ill patients with an incidence rate ranging from 5% to 35% during the ...first and second pandemic waves.
Objectives
We aimed to evaluate the incidence, risk factors for CAPA by a screening protocol and outcome in the critically ill patients during the third wave of the pandemic.
Patients/Methods
This prospective cohort study was conducted in two intensive care units (ICU) designated for patients with COVID‐19 in a tertiary care university hospital between 18 November 2020 and 24 April 2021. SARS‐CoV‐2 PCR‐positive adult patients admitted to the ICU with respiratory failure were included in the study. Serum and respiratory samples were collected periodically from ICU admission up to CAPA diagnosis, patient discharge or death. ECMM/ISHAM consensus criteria were used to diagnose and classify CAPA cases.
Results
A total of 302 patients were admitted to the two ICUs during the study period, and 213 were included in the study. CAPA was diagnosed in 43 (20.1%) patients (12.2% probable, 7.9% possible). In regression analysis, male sex, higher SOFA scores at ICU admission, invasive mechanical ventilation and longer ICU stay were significantly associated with CAPA development. Overall ICU mortality rate was higher significantly in CAPA group compared to those with no CAPA (67.4% vs 29.4%, p < .001).
Conclusions
One fifth of critically ill patients in COVID‐19 ICUs developed CAPA, and this was associated with a high mortality.
Access to the appropriate tools is crucial for early diagnosis and clinical management of invasive fungal infections. This Review aims to describe the invasive fungal infection diagnostic capacity of ...Europe to better understand the status and the most pressing aspects that need improvement. To our knowledge, this is the first time that the mycological diagnostic capability and access to antifungal treatments of institutions has been evaluated at a pan-European level. Between Nov 1, 2021, and Jan 31, 2022, 388 institutions in Europe self-assessed their invasive fungal infection management capability. Of the 388 participating institutions from 45 countries, 383 (99%) had access to cultures, 375 (97%) to microscopy, 363 (94%) to antigen-detection assays, 329 (85%) to molecular tests (mostly PCR), and 324 (84%) to antibody tests for diagnosis and management. With the exception of microscopy, there were considerable differences in access to techniques among countries according to their gross domestic product. At least one triazole was available in 363 (94%) of the institutions, one echinocandin in 346 (89%), and liposomal amphotericin B in 301 (78%), with country gross domestic product-based differences. Differences were also observed in the access to therapeutic drug monitoring. Although Europe is well prepared to manage invasive fungal infections, some institutions do not have access to certain diagnostic tools and antifungal drugs, despite most being considered essential by WHO. These limitations need to be overcome to ensure that all patients receive the best diagnostic and therapeutic management.
Introduction
There are no precise data about the effect of Aspergillus infection on lung function other than allergic bronchopulmonary aspergillosis (ABPA) in patients with cystic fibrosis (pwCF). ...Here, we aimed to determine clinical phenotypes caused by Aspergillus spp. using laboratory and immunologic parameters and to compare Aspergillus phenotypes in terms of pulmonary function tests (PFT) prospectively.
Methods
Twenty‐three pwCF who had Aspergillus isolation from respiratory cultures in the last year (case group) and 20 pwCF without Aspergillus isolation in sputum (control group) were included. Aspergillus immunoglobulin (Ig)‐G, Aspergillus IgE, Aspergillus polymerase chain reaction (PCR), galactomannan, total IgE from blood samples, and Aspergillus PCR and galactomannan from sputum, and skin prick test reactivity to Aspergillus antigen were used to distinguish different Aspergillus phenotypes. Pulmonary functions and frequency of pulmonary exacerbations were evaluated during a 1‐year follow‐up.
Results
Of 23 pwCF, 11 (47.8%) had Aspergillus colonization, nine (39.1%) had Aspergillus bronchitis, and three (13%) had ABPA. Aspergillus infection was not associated with worse z‐scores of forced expiratory volume in the first second (FEV1) (p = 0.612), forced vital capacity (p = 0.939), and the median FEV 1% decline (0.0%/year vs. −4.7%/year, p = 0.626). The frequency of pulmonary exacerbations in the Aspergillus infected and noninfected groups was similar.
Conclusion
Although Aspergillus spp. Isolation in pwCF was not associated with decreased lung function, a further decline was seen in the ABPA subgroup, and frequent pulmonary exacerbations during the 1‐year follow‐up.
Summary
Invasive pulmonary aspergillosis (IPA) optimal duration of antifungal treatment is not known. In a joint effort, four international scientific societies/groups performed a survey to capture ...current practices in European haematology centres regarding management of IPA. We conducted a cross‐sectional internet‐based questionnaire survey in 2017 to assess practices in sixteen European countries concerning IPA management in haematology patients including tools to evaluate treatment response, duration and discontinuation. The following four groups/societies were involved in the project: European Society of Clinical Microbiology and Infectious Diseases (ESCMID) Fungal Infection Study Group (EFISG), Infectious Diseases Working Party‐European Society for Blood and Bone Marrow Transplantation (IDWP‐EBMT), European Organisation for Research and Treatment‐Infectious Disease group (EORTC‐IDG) and Sorveglianza Epidemiologica Infezioni nelle Emopatie (SEIFEM). A total of 112 physicians from 14/16 countries answered the survey. Galactomannan antigen was available in serum and bronchoalveolar lavage in most centres (106/112 95% and 97/112 87%, respectively), quantitative Aspergillus PCR in 27/112 (24%) centres, β‐D‐glucan in 24/112 (21%) and positron emission tomography in 50/112 (45%). Treatment duration differed between haematological malignancies, with a median duration of 6 weeks IQR 3‐12 for patients with AML, 11 4‐12 for patients with allogenic stem cell transplantation and GvHD and 6 3‐12 for patients with lymphoproliferative disease. Treatment duration significantly differed according to country. Essential IPA biomarkers are not available in all European countries, and treatment duration is highly variable according to country. It will be important to provide guidelines to help with IPA treatment cessation with algorithms according to biomarker availability.
Summary
Exophiala is a genus of black fungi isolated worldwide from environmental and clinical specimens. Data on antifungal susceptibility of Exophiala isolates are limited and the methodology on ...susceptibility testing is not yet standardised. In this study, we investigated in vitro antifungal susceptibilities of environmental Exophiala isolates. A total of 87 Exophiala isolated from dishwashers or railway ties were included. A CLSI M38‐A2 microdilution method with modifications was used to determine antifungal susceptibility for fluconazole, voriconazole, posaconazole, itraconazole, amphotericin B and terbinafine. Minimum inhibitory concentration (MIC) values were determined visually at 48 hours, 72 hours and 96 hours. MIC‐0 endpoint (complete inhibition of growth) was used for amphotericin B and azoles, except fluconazole, for which MIC‐2 endpoint (~50% inhibition compared to growth control) was used. Both MIC‐0 and MIC‐1 (~80% inhibition compared to growth control) results were analysed for terbinafine to enable comparison with previous studies. Fungal growth was sufficient for determination of MICs at 48 hours for all isolates except two Exophiala dermatitidis strains. At 72 hours, most active antifungal agents according to GM MIC were voriconazole and terbinafine, followed by posaconazole, itraconazole and amphotericin B in rank order of decreasing activity. While amphotericin B displayed adequate in vitro activity despite relatively high MICs, fluconazole showed no meaningful antifungal activity against Exophiala.
The frequency of invasive fungal infections shows a rising trend as well as a high morbidity and mortality. Among the causative agents, a shift toward the non-albicans Candida species including ...Candida glabrata species complex is being observed in several centers. Echinocandin resistance is increasingly published; however, isolates presenting with an in vitro resistance have not yet been reported from Turkey. We, herein, report the first FKS mutant and phenotypically echinocandin-resistant C. glabrata clinical strains from a single center in Turkey. In a 43-year-old female patient, several enterocutaneous fistulae developed after a long term hospitalization period and several complicated surgeries. She eventually required parenteral nutrition via a tunneled central venous catheter (CVC). Following a number of bacteremic and fungemic episodes as well as intensive antimicrobial interventions (including fluconazole, caspofungin and anidulafungin), a CVC-related candidemia caused by C. glabrata was detected. The isolated strain yielded high minimum inhibitory concentration (MIC) values for echinocandins and was categorized as resistant. A resistance-related mutation was detected in FKS2 HS1 (D666V). Blood cultures remained negative after the removal of the CVC and treatment with caspofungin and high-dose fluconazole. Following this first case, two additional C. glabrata strains with high echinocandin MICs were isolated from the urine cultures of two unrelated patients from different wards with different mutations in FKS2 HS1 (S663P and delF659). Our findings indicate that routine antifungal susceptibility testing is crucial and underlines the need for attention for the increasing trend of acquired echinocandin resistance in C. glabrata.
Azole‐resistant strains of Aspergillus have been reported from European and Asian countries at varying frequencies. Based on the limited rates of isolation of Aspergillus from clinical samples in ...routine practice and the limited number of the screening studies carried out so far, the true prevalence of triazole resistance and the rate of multiazole‐resistant strains remain partly unknown. Also, available data are mostly for A. fumigatus (complex), thus the situation for non‐fumigatus Aspergilli is less clear. In general, exposure of Aspergillus to antifungal agents via medical or environmental (agricultural) use of these compounds appears to have the possible major impact on acquisition of triazole resistance. Azole resistance in Aspergillus remains to be further elucidated by continued surveillance studies. Based on the possible association with agricultural azole use, environmental sampling appears significant as well.
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