Antifungal drug resistance is a significant clinical problem for the management of invasive aspergillosis. Clinicians need accurate information as rapidly as possible in order to minimise the impact of resistance on their patients, however traditional culture tehniques are usually slow and often fail. Pyrosequencing offers us the chance to rapidly detect resistance, is highly accurate and is not limited to specific genes associated with resistance. The authors review current diagnostic methods and highlight the potential of pyrosequencng to aid in a diagnosis complete with resistance profile to improve clinical outcomes.
Paradoxal Trends in Azole-Resistant Aspergillus fumigatus in a National Multicenter Surveillance Program, the Netherlands, 2013-2018. Lestrade et. al., 2020.
The authors investigated the prevalence of azole resistance of Aspergillus fumigatus isolates in the Netherlands by screening clinical A. fumigatus isolates for azole resistance during 2013–2018. They analyzed azole-resistant isolates phenotypically by in vitro susceptibility testing and for the presence of resistance mutations in the Cyp51A gene. Over the 6-year period, 508 (11%) of 4,496 culture-positive patients harbored an azole-resistant isolate. Resistance frequency increased from 7.6% (95% CI 5.9%–9.8%) in 2013 (58/760 patients) to 14.7% (95% CI 12.3%–17.4%) in 2018 (112/764 patients) (p = 0.0001). TR34/L98H (69%) and TR46/Y121F/T289A (17%) accounted for 86% of Cyp51A mutations. However, the mean voriconazole MIC of TR34/L98H isolates decreased from 8 mg/L (2013) to 2 mg/L (2018), and the voriconazole-resistance frequency was 34% lower in 2018 than in 2013 (p = 0.0001). Their survey showed changing azole phenotypes in TR34/L98H isolates, which hampers the use of current PCR-based resistance tests.
The domestic pig as human-relevant large animal model to study adaptive anti-fungal immune responses against airborne Aspergillus fumigatus. Schmidt, 2020.
Pulmonary mucosal immune response is critical for preventing opportunistic Aspergillus fumigatus infections. Although fungus-specific CD4+ T cells in blood are described to reflect the actual host-pathogen interaction status, little is known about Aspergillus-specific pulmonary T-cell responses. Here, we exploit the domestic pig as human-relevant large animal model and introduce antigen-specific T-cell enrichment in pigs to address Aspergillus-specific T cells in the lung compared to peripheral blood.
How to: interpret MICs of antifungal compounds according to the revised clinical breakpoints v. 10.0 European committee on antimicrobial susceptibility testing (EUCAST). Arendrup, 2020.
EUCAST has revised the definition of the susceptibility category I from ‘Intermediate’ to ‘Susceptible, Increased exposure’. This implies that I can be used where the drug concentration at the site of infection is high, either because of dose escalation or through other means to ensure efficacy. Consequently, I is no longer used as a buffer zone to prevent technical factors from causing misclassifications and discrepancies in interpretations. Instead, an Area of Technical Uncertainty (ATU) has been introduced for MICs that cannot be categorized without additional information as a warning to the laboratory that decision on how to act has to be made. To implement these changes, the EUCAST-AFST (Subcommittee on Antifungal Susceptibility Testing) reviewed all, and revised some, clinical antifungal breakpoints.
Oral administration of voriconazole with surgical fungal plaque debridement for the treatment of sinonasal aspergillosis with cribriform plate lysis in three dogs. Bray et. al., 2020
Findings in these 3 dogs indicated that surgical fungal plaque debridement followed by oral treatment with voriconazole may be an effective treatment option for dogs with sinonasal aspergillosis and cribriform plate lysis. Further evaluation of this treatment regimen with repeated CT examinations and longer follow-up times is warranted.
Reviews
Review of influenza-associated pulmonary aspergillosis in ICU patients and proposal for a case definition: an expert opinion.Verweij et. al., 2020.
Invasive pulmonary aspergillosis is increasingly reported in patients with influenza admitted to the intensive care unit (ICU). Classification of patients with influenza-associated pulmonary aspergillosis (IAPA) using the current definitions for invasive fungal diseases has proven difficult, and the authors aim was to develop case definitions for IAPA that can facilitate clinical studies. Conclusion: A consensus case definition of IAPA is proposed, which will facilitate research into the epidemiology, diagnosis and management of this emerging acute and severe Aspergillus disease, and may be of use to study CAPA..
Annually, over 150 million severe cases of fungal infections occur worldwide, resulting in approximately 1.7 million deaths per year. Alarmingly, these numbers are continuously on the rise with a number of social and medical developments during the past decades that have abetted the spread of fungal infections. Additionally, the long-term therapeutic application and prophylactic use of antifungal drugs in high-risk patients have promoted the emergence of (multi)drug-resistant fungi, including the extremely virulent strain Candida auris. Hence, fungal infections are already a global threat that is becoming increasingly severe. In this article, we underline the importance of more and effective research to counteract fungal infections and their consequences.
Clinical Relevance and Characteristics of Aspergillus calidoustus and Other Aspergillus Species of Section Usti. Glampedakis et. al., 2020.
The Aspergilli of section Usti (group ustus) are represented by over 20 species, of which Aspergillus calidoustus is the most relevant human pathogen. Invasive aspergillosis (IA) caused by these fungi is rare but could represent an emerging issue among the expanding population of patients with long-term immunosuppression receiving antifungal prophylaxis. Clinicians should be aware of this unusual type of IA, which often exhibits distinct clinical features, such as an insidious and prolonged course and a high occurrence of extra-pulmonary manifestations, such as skin/soft tissue or brain lesions. Moreover, these Aspergillus spp. pose a therapeutic challenge because of their decreased susceptibility to azole drugs. In this review, we outline the microbiological and clinical characteristics of IA due to Aspergillus spp. of section Usti and discuss the therapeutic options.
Patients and carers
Maybe you or a loved one has just received a diagnosis of aspergillosis and you’re not sure where to start. Or maybe you need to share information about your condition with your doctor, carer, housing association or benefits assessor. Our patients and carers website can provide you with everything you need to know about aspergillosis.
This month we have talked a lot about the considerations for people who are classified as highly vulnerable to COVID-19 severe symptoms as they are being asked to stop shielding now that many countries are slowly lifting the lockdown..
Further information on this, and other COVID-19 information is available on aspergillosis.org
Other meetings and support
We host a weekly video phone call (Software: Zoom) with around 4-8 patients and a member of National Aspergillosis Centre (NAC) staff twice each week. You can use a computer or mobile device to join the video at Aspergillosis Community Support. This meeting runs from 10:00-11:00 BST every Tuesday & Thursday and is also presented in our private Facebook group (see below).
There is an additional meeting on the first Friday of every month which normally takes place at NAC but for the period of time when we are unable to hold face-to-face meetings we are meeting on Zoom, using the same registration details.To receive a text reminder when each monthly meeting is approaching send us your mobile phone number (NB this doesn't operate in the US) to admin@aspergillus.org.uk
- Our Aspergillosis Support Facebook Group has over 2300 members and is a safe place to meet and talk to other people with aspergillosis
- We also have a Facebook group for carers, friends and family of someone who is affected by the disease - join here
- To find our regional and international groups, search for 'aspergillosis' in Facebook.
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More and more conferences are switching to exclusively online presentation as COVID-19 continues to restrict travel and social contact throughout the world.
Asilomar has moved to 2022.
ECFG has moved to 2023
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(MFIG)
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(free online microscopy course)
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Fungal Infection Trust, PO Box 482, Macclesfield, Cheshire SK10 9AR
