Treatment Principles for the Management of Mold Infections

Kontoyiannis, Dimitrios P.; Lewis, Russell E.

doi:10.1101/cshperspect.a019737

Cited by 22 publications

(25 citation statements)

References 73 publications

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“…In our analysis, MIC values and selected antifungals did not impact patient outcome. When recovering a mould from a clinical specimen in a symptomatic patient, guidelines recommend first‐line treatment with an azole . Considering susceptibility patterns and non‐availability of epidemiologic cut‐off values (ECVs), appropriate decision of antifungal treatment and evaluation of response remain challenging in Rasamsonia spp.…”

Section: Discussionmentioning

confidence: 99%

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Risk factors and mortality in invasive Rasamsonia spp. infection: Analysis of cases in the FungiScope^® registry and from the literature

Stemler

Salmanton‐García

Seidel

et al. 2019

Mycoses

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Summary Background The new Rasamsonia spp. complex can develop invasive infection in immunosuppression or chronic pulmonary disease. It has potential to be misidentified as other genera due to morphological similarities. Nowadays, there is a gap of knowledge on this fungi. Objectives To provide knowledge base of risk factors and therapeutic decisions in invasive Rasamsonia spp. complex infection. Patients/Methods Cases of invasive infection due to Rasamsonia spp. (formerly Geosmithia/Penicillium spp.) from FungiScope® registry and all reported cases from a literature were included. Results We identified 23 invasive infections due to Rasamsonia spp., six (26.1%) in the FungiScope® registry. Main risk factors were chronic granulomatous disease (n = 12, 52.2%), immunosuppressive treatment (n = 10, 43.5%), haematopoietic stem cell transplantation (n = 7, 30.4%), graft‐versus‐host disease and major surgery (n = 4, 17.4%, each). Predominantly affected organs were the lungs (n = 21, 91.3%), disease disseminated in seven cases (30.4%). Fungal misidentification occurred in 47.8% (n = 11), and sequencing was used in 69.6% of the patients (n = 16) to diagnose. Breakthrough infection occurred in 13 patients (56.5%). All patients received antifungal treatment, mostly posaconazole (n = 11), caspofungin (n = 10) or voriconazole (n = 9). Combination therapy was administered in 13 patients (56.5%). Susceptibility testing showed high minimum inhibitory concentrations for azoles and amphotericin B, but not for echinocandins. No preferable treatment influencing favourable outcome was identified. Overall mortality was 39% (n = 9). Conclusion Rasamsonia spp. are emerging fungi causing life‐threatening infections, especially in immunocompromised and critically ill patients. Mortality is high. Treatment is challenging and clinicians dealing with this patient population should become aware of this infection constituting a medical emergency.

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Section: Discussionmentioning

confidence: 99%

“…suggestive of other fungi, especially Paecilomyces spp., challenges timely diagnosis and treatment. Hence, these infections might be an azole 34. Considering susceptibility patterns and non-availability of epidemiologic cut-off values (ECVs), appropriate decision of antifungal treatment and evaluation of response remain challenging in Rasamsonia spp.…”

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confidence: 99%

Risk factors and mortality in invasive Rasamsonia spp. infection: Analysis of cases in the FungiScope^® registry and from the literature

Stemler

Salmanton‐García

Seidel

et al. 2019

Mycoses

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“…Global warming is inducing rapid movement of fungal pathogens and may increase the prevalence of fungal disease in human, as fungi adapt to survive in warmer temperatures . Knowledge of the local epidemiology of invasive fungal infections is essential for effective infection control programs and antifungal stewardship . The epidemiology of fungal infections in Sweden is largely unknown, except for candidemia .…”

Section: Introductionmentioning

confidence: 99%

“…6 Knowledge of the local epidemiology of invasive fungal infections is essential for effective infection control programs and antifungal stewardship. 7 The epidemiology of fungal infections in Sweden is largely unknown, except for candidemia. 8 The aim of this study was to estimate the annual burden of fungal infections in Sweden using data mainly from 2016.…”

Section: Introductionmentioning

confidence: 99%

Estimated burden of fungal infections in Sweden

Özenci

Klingspor

Ullberg

et al. 2019

Mycoses

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Summary The aim of this study was to estimate the annual burden of fungal infections in Sweden using data mainly from 2016. Data on specific populations were obtained from Swedish national data registries. Annual incidence and prevalence of fungal disease was calculated based on epidemiological studies. Data on infections due to Cryptococcus sp., Mucorales, Histoplasma capsulatum, Coccidioides immitis and Pneumocystis jirovecii were retrieved from Karolinska University Laboratory and covers only 25% of Swedish population. In 2016, the population of Sweden was 9 995 153 (49.8% female). The overall burden of fungal infections was 1 713 385 (17 142/100 000). Superficial fungal infections affect 1 429 307 people (1429/100 000) based on Global Burden of Disease 14.3% prevalence. Total serious fungal infection burden was 284 174 (2843/100 000) in 2016. Recurrent Candida vulvovaginitis is common; assuming a 6% prevalence in women. Prevalence of allergic bronchopulmonary aspergillosis and severe asthma with fungal sensitisation were estimated to be 20 095 and 26 387, respectively. Similarly, chronic pulmonary aspergillosis was estimated to affect 490 patients after tuberculosis, sarcoidosis and other conditions. Candidemia incidence was estimated to be 500 in 2016 (4.7/100 000) and invasive aspergillosis 295 (3.0/100 000). In Stockholm area, Mucorales were reported in three patients in 2015, while Cryptococcus spp. were reported in two patients. In 2016, there were 297 patients PCR positive for P jirovecii. The present study shows that the overall burden of fungal infections in Sweden is high and affects 17% of the population. The morbidity, mortality and the healthcare‐related costs due to fungal infections warrant further studies.

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“…It is estimated that worldwide, more than 200,000 individuals suffer from life-threatening IA, with mortality rates ranging between 30 to 95% (1). These alarming statistics are a result of the generally poor health status of the patients, limited diagnostic and therapeutic options, and the arsenal of virulence-promoting properties of this ubiquitous mold (2,3). Besides the abilities of the fungus to produce potent mycotoxins and to escape from the host innate immune cells, thermophilic growth and versatile nutrient acquisition are further general physiological attributes which favor growth on decaying matter as well as in the human host (4,5).…”

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confidence: 99%

Identification and Characterization of a Novel Aspergillus fumigatus Rhomboid Family Putative Protease, RbdA, Involved in Hypoxia Sensing and Virulence

et al. 2016

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dAspergillus fumigatus is the most common pathogenic mold infecting humans and a significant cause of morbidity and mortality in immunocompromised patients. In invasive pulmonary aspergillosis, A. fumigatus spores are inhaled into the lungs, undergoing germination and invasive hyphal growth. The fungus occludes and disrupts the blood vessels, leading to hypoxia and eventual tissue necrosis. The ability of this mold to adapt to hypoxia is regulated in part by the sterol regulatory element binding protein (SREBP) SrbA and the DscA to DscD Golgi E3 ligase complex critical for SREBP activation by proteolytic cleavage. Loss of the genes encoding these proteins results in avirulence. To identify novel regulators of hypoxia sensing, we screened the Neurospora crassa gene deletion library under hypoxia and identified a novel rhomboid family protease essential for hypoxic growth. Deletion of the A. fumigatus rhomboid homolog rbdA resulted in an inability to grow under hypoxia, hypersensitivity to CoCl 2 , nikkomycin Z, fluconazole, and ferrozine, abnormal swollen tip morphology, and transcriptional dysregulation-accurately phenocopying deletion of srbA. In vivo, rbdA deletion resulted in increased sensitivity to phagocytic killing, a reduced inflammatory Th1 and Th17 response, and strongly attenuated virulence. Phenotypic rescue of the ⌬rbdA mutant was achieved by expression and nuclear localization of the N terminus of SrbA, including its HLH domain, further indicating that RbdA and SrbA act in the same signaling pathway. In summary, we have identified RbdA, a novel putative rhomboid family protease in A. fumigatus that mediates hypoxia adaptation and fungal virulence and that is likely linked to SrbA cleavage and activation.T he filamentous fungus Aspergillus fumigatus grows as an environmental saprophyte but can infect humans and animals through its dispersed asexual conidia. Upon inhalation by an immunocompromised host, conidia can germinate to form hyphae which infiltrate the surrounding lung tissue, causing often fatal invasive aspergillosis (IA). It is estimated that worldwide, more than 200,000 individuals suffer from life-threatening IA, with mortality rates ranging between 30 to 95% (1). These alarming statistics are a result of the generally poor health status of the patients, limited diagnostic and therapeutic options, and the arsenal of virulence-promoting properties of this ubiquitous mold (2, 3). Besides the abilities of the fungus to produce potent mycotoxins and to escape from the host innate immune cells, thermophilic growth and versatile nutrient acquisition are further general physiological attributes which favor growth on decaying matter as well as in the human host (4, 5). Adaptation to O 2 concentrations below normal atmospheric levels of 21% is an additional challenge that A. fumigatus must cope with during colonization. O 2 levels can drop to 2 to 4% on the surface of healthy alveolar tissue and be further diminished to less than 1% upon inflammation (6). Such levels of hypoxia are normally no th...

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Treatment Principles for the Management of Mold Infections

Cited by 22 publications

References 73 publications

Risk factors and mortality in invasive Rasamsonia spp. infection: Analysis of cases in the FungiScope^® registry and from the literature

Risk factors and mortality in invasive Rasamsonia spp. infection: Analysis of cases in the FungiScope^® registry and from the literature

Estimated burden of fungal infections in Sweden

Identification and Characterization of a Novel Aspergillus fumigatus Rhomboid Family Putative Protease, RbdA, Involved in Hypoxia Sensing and Virulence

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Treatment Principles for the Management of Mold Infections

Cited by 22 publications

References 73 publications

Risk factors and mortality in invasive Rasamsonia spp. infection: Analysis of cases in the FungiScope® registry and from the literature

Risk factors and mortality in invasive Rasamsonia spp. infection: Analysis of cases in the FungiScope® registry and from the literature

Estimated burden of fungal infections in Sweden

Identification and Characterization of a Novel Aspergillus fumigatus Rhomboid Family Putative Protease, RbdA, Involved in Hypoxia Sensing and Virulence

Contact Info

Product

Resources

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Risk factors and mortality in invasive Rasamsonia spp. infection: Analysis of cases in the FungiScope^® registry and from the literature

Risk factors and mortality in invasive Rasamsonia spp. infection: Analysis of cases in the FungiScope^® registry and from the literature