Development and clinical implications of a novel CRISPR-based diagnostic test for pulmonary Aspergillus fumigatus infection

ABSTRACTAspergillus fumigatusis the most frequent fungus found in the sputum of cystic fibrosis (CF) subjects. Itraconazole is prescribed for allergic bronchopulmonary aspergillosis (ABPA) orAspergillusbronchitis in CF subjects. We hypothesized thatA. fumigatusisolates in the sputum of CF subjects with previous exposure to itraconazole was associated with higher prevalence of azole resistance. From June 2010 to April 2011, sputum samples from adult CF subjects at Cochin University Hospital (France) were examined systematically for the detection ofA. fumigatus. MICs ofA. fumigatusisolates against azoles were screened using Etest, and reduced susceptibility to azoles was confirmed using the CLSI broth microdilution method.A. fumigatuswas isolated from the sputum of 131/249 (52.6%) adult CF subjects, and 47/131 (35.9%) subjects had received previous treatment with itraconazole. ReducedA. fumigatussusceptibility to itraconazole (MIC, ≥2 mg/liter) was confirmed in 6/131 (4.6%) subjects. All 6 isolates also had reduced susceptibility to posaconazole (MIC, ≥0.5 mg/liter), and 3/6 isolates had reduced susceptibility to voriconazole (MIC, ≥2 mg/liter). Mutations in thecyp51Agene were detected at positions previously implicated to cause resistance in 5 isolates. Azole-resistantA. fumigatusisolates were found in 5/25 (20%) subjects exposed to itraconazole within the previous 3 years. High rates of azole-resistantA. fumigatusisolates were present in adult CF subjects and were associated with recent itraconazole exposure. Although the clinical implications of these findings will require further studies, the cautious use of itraconazole in adult CF subjects can be recommended.

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Azole Resistance in Aspergillus fumigatus: Mechanisms, Route of Resistance Selection, and Clinical Implications

Handbook of Antimicrobial Resistance ◽

10.1007/978-1-4939-0667-3_22-1 ◽

2015 ◽

pp. 1-17 ◽

Cited By ~ 2

Author(s):

Seyedmojtaba Seyedmousavi ◽

Paul E. Verweij

Keyword(s):

Aspergillus Fumigatus ◽

Clinical Implications ◽

Azole Resistance ◽

Resistance Selection

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Proteomic analysis of Aspergillus fumigatus – clinical implications

Expert Review of Proteomics ◽

10.1080/14789450.2016.1203783 ◽

2016 ◽

Vol 13 (7) ◽

pp. 635-649 ◽

Cited By ~ 6

Author(s):

Nicola M. Moloney ◽

Rebecca A. Owens ◽

Sean Doyle

Keyword(s):

Aspergillus Fumigatus ◽

Proteomic Analysis ◽

Clinical Implications

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Antifungal Resistance: Specific Focus on Multidrug Resistance in Candida auris and Secondary Azole Resistance in Aspergillus fumigatus

Journal of Fungi ◽

10.3390/jof4040129 ◽

2018 ◽

Vol 4 (4) ◽

pp. 129 ◽

Cited By ~ 16

Author(s):

Sevtap Arikan-Akdagli ◽

Mahmoud Ghannoum ◽

Jacques Meis

Keyword(s):

Aspergillus Fumigatus ◽

Molecular Mechanisms ◽

Multidrug Resistant ◽

Fungal Species ◽

Antifungal Resistance ◽

Current Status ◽

Clinical Implications ◽

Azole Resistance ◽

Candida Auris

Antifungal resistance is a topic of concern, particularly for specific fungal species and drugs. Among these are the multidrug-resistant Candida auris and azole-resistant Aspergillus fumigatus. While the knowledge on molecular mechanisms of resistance is now accumulating, further data are also available for the clinical implications and the extent of correlation of in vitro resistance to clinical outcomes. This review article summarizes the epidemiology of C. auris infections, animal models focusing on the activity of novel antifungal compounds in C. auris infections, virulence factors, and the mechanisms of antifungal resistance for this multi-resistant Candida species. Regarding A. fumigatus, the significance of azoles in the treatment of A. fumigatus infections, reference methods available for the detection of resistance in vitro, molecular mechanisms of secondary azole resistance, routes of acquisition, and clinical implications of in vitro resistance are covered to provide guidance for the current status of azole resistance in A. fumigatus.

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Effects of Selected Rhinologic Disorders on the Perception of Nasal Resonance in Children

Language Speech and Hearing Services in Schools ◽

10.1044/0161-1461.1501.44 ◽

1984 ◽

Vol 15 (1) ◽

pp. 44-50 ◽

Cited By ~ 2

Author(s):

Michael P. Rastatter ◽

Melvin Hyman

Keyword(s):

Allergic Rhinitis ◽

Clinical Implications ◽

Normal Children ◽

Nasal Resonance

A group of sophisticated listeners judged the nasal resonance characteristics of normal children versus children evidencing selected rhinologic disorders under three speaking conditions. Results showed that perceptions of denasality are influenced by both speakers and speaking tasks. That is, children with allergic rhinitis and edemic adenoids were perceived as being denasal when they produced VCV utterances and recited sentences. However, their resonance characteristics were deemed normal for vowel productions. Interestingly, children with severely deviated septums were judged to have normal nasal resonance under all speaking conditions. Clinical implications are discussed.

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Perceptions of Stuttering of Different Age Groups

Perspectives of the ASHA Special Interest Groups ◽

10.1044/2019_pers-sig4-2018-0007 ◽

2019 ◽

Vol 4 (6) ◽

pp. 1311-1315

Author(s):

Sergey M. Kondrashov ◽

John A. Tetnowski

Keyword(s):

Age Groups ◽

School Age Children ◽

Clinical Implications ◽

School Age ◽

Fourth Edition ◽

Self Perception ◽

Behavioral Measures ◽

Self Rating ◽

Comparison Results ◽

Subject Pool

Purpose The purpose of this study was to assess the perceptions of stuttering of school-age children who stutter and those of adults who stutter through the use of the same tools that could be commonly used by clinicians. Method Twenty-three participants across various ages and stuttering severity were administered both the Stuttering Severity Instrument–Fourth Edition (SSI-4; Riley, 2009 ) and the Wright & Ayre Stuttering Self-Rating Profile ( Wright & Ayre, 2000 ). Comparisons were made between severity of behavioral measures of stuttering made by the SSI-4 and by age (child/adult). Results Significant differences were obtained for the age comparison but not for the severity comparison. Results are explained in terms of the correlation between severity equivalents of the SSI-4 and the Wright & Ayre Stuttering Self-Rating Profile scores, with clinical implications justifying multi-aspect assessment. Conclusions Clinical implications indicate that self-perception and impact of stuttering must not be assumed and should be evaluated for individual participants. Research implications include further study with a larger subject pool and various levels of stuttering severity.

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Treatment Considerations for Adolescents Who Exhibit Cognitive/Communication Problems: A Neuroscience Perspective

Perspectives of the ASHA Special Interest Groups ◽

10.1044/2020_persp-20-00071 ◽

2020 ◽

Vol 5 (6) ◽

pp. 1767-1775

Author(s):

Martha S. Burns

Keyword(s):

Social Communication ◽

Transition Period ◽

Clinical Intervention ◽

Review Article ◽

Sensitive Period ◽

Clinical Implications ◽

Evidence Based ◽

Communication Problems ◽

Treatment Considerations ◽

Behavioral Growth

Purpose Adolescence is a period of substantial neurophysiological and behavioral growth, representing a second sensitive period of brain development. It is a psychological and social transition period between childhood and adulthood with many beneficial changes occurring, especially with respect to potential responsiveness to clinical intervention. However, adolescent behavioral complexities introduce clinical challenges as well. The purpose of this review article is to review the current neuroimaging research on neurophysiological changes observed during adolescence and the cognitive and social behavioral counterparts, with specific attention to the clinical implications. The review article will then summarize currently available intervention tools that can be utilized by speech-language pathologists working with this population. It will conclude with available evidence-based social-communication approaches that may be applicable as well as available evidence-based supplemental technological cognitive interventions that may be useful in working with adolescents who exhibit language and communication issues. Conclusion As a transition period between childhood and adulthood, adolescence represents a second sensitive period during which there is opportunity for clinically derived beneficial cognitive and communication growth.

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