Glycopeptidolipid Genotype Correlates With the Severity of Mycobacterium abscessus Lung Disease

2020 ◽  
Vol 221 (Supplement_2) ◽  
pp. S257-S262 ◽  
Author(s):  
Bing Li ◽  
Meiping Ye ◽  
Lan Zhao ◽  
Qi Guo ◽  
Jianhui Chen ◽  
...  
Keyword(s):  
Lung Disease ◽  
Retrospective Analysis ◽  
Clinical Data ◽  
Clinical Characteristics ◽  
Mycobacterium Abscessus ◽  
Clinical Isolates ◽  
Colony Morphology ◽  
Wild Type ◽  
Mutant Type ◽  
The Relationship

Abstract Background Smooth and rough colony morphotypes of Mycobacterium abscessus are associated with virulence, but some isolates form both smooth and rough colonies, impeding successful morphotype identification. Reportedly, smooth/rough morphotypes are also related to the glycopeptidolipid (GPL) genotype. However, the accuracy of GPL genotyping to discriminate morphotypes and the relationship between GPL genotype and clinical characteristics of M abscessus lung disease have not been verified. Methods A retrospective analysis of colony morphology, GPL genotype, and clinical data from 182 patients with M abscessus lung disease was conducted. Results Of 194 clinical isolates, 126 (65.0%), 15 (7.7%), and 53 (27.3%) exhibited rough, smooth, and mixed colony morphotypes, respectively. Glycopeptidolipid genotyping indicated that 86.7% (13 of 15) of smooth isolates belonged to the GPL-wild type (WT) group, whereas 98.4% (124 of 126) of rough isolates belonged to the GPL-mutant type (MUT) group. Therefore, GPL genotyping accurately distinguished between smooth and rough morphotypes. Mixed colony morphotypes were also divided into GPL-WT (18.9%) and GPL-MUT (81.1%) groups. Further analysis revealed that patients infected with the GPL-MUT group presented with significantly worse baseline clinical characteristics and exacerbated episodes of lung disease. Conclusions Glycopeptidolipid genotyping accurately distinguishes smooth and rough colony morphotypes. Patients infected with the GPL-MUT genotype exhibit worse clinical characteristics and are at a higher risk of exacerbated lung disease.

scholarly journals Mab_3083c Is a Homologue of RNase J and Plays a Role in Colony Morphotype, Aggregation, and Sliding Motility of Mycobacterium abscessus

2021 ◽  
Vol 9 (4) ◽  
pp. 676
Author(s):  
Ting-Yu Liu ◽  
Sheng-Hui Tsai ◽  
Jenn-Wei Chen ◽  
Yu-Ching Wang ◽  
Shiau-Ting Hu ◽  
...  
Keyword(s):  
Type Strain ◽  
Wild Type Strain ◽  
Opportunistic Pathogen ◽  
Mycobacterium Abscessus ◽  
Colony Morphology ◽  
Clinical Strain ◽  
Immunocompromised Patients ◽  
Clinical Infection ◽  
Wild Type ◽  
Sliding Motility

Mycobacterium abscessus is an opportunistic pathogen causing human diseases, especially in immunocompromised patients. M. abscessus strains with a rough morphotype are more virulent than those with a smooth morphotype. Morphotype switch may occur during a clinical infection. To investigate the genes involved in colony morphotype switching, we performed transposon mutagenesis in a rough clinical strain of M. abscessus. A morphotype switching mutant (smooth) named mab_3083c::Tn was obtained. This mutant was found to have a lower aggregative ability and a higher sliding motility than the wild type strain. However, its glycopeptidolipid (GPL) content remained the same as those of the wild type. Complementation of the mutant with a functional mab_3083c gene reverted its morphotype back to rough, indicating that mab_3083c is associated with colony morphology of M. abscessus. Bioinformatic analyses showed that mab_3083c has a 75.4% identity in amino acid sequence with the well-characterized ribonuclease J (RNase J) of M. smegmatis (RNase JMsmeg). Complementation of the mutant with the RNase J gene of M. smegmatis also switched its colony morphology from smooth back to rough. These results suggest that Mab_3083c is a homologue of RNase J and involved in regulating M. abscessus colony morphotype switching.

scholarly journals Rifabutin Is Active against Mycobacterium abscessus Complex

2017 ◽  
Vol 61 (6) ◽  
Author(s):  
Dinah Binte Aziz ◽  
Jian Liang Low ◽  
Mu-Lu Wu ◽  
Martin Gengenbacher ◽  
Jeanette W. P. Teo ◽  
...  
Keyword(s):  
Lung Disease ◽  
Single Point ◽  
Multidrug Resistant ◽  
Mycobacterium Abscessus ◽  
Clinical Isolates ◽  
Content Type ◽  
Approved Drugs ◽  
Global Threat ◽  
Reference Strains

ABSTRACT Lung infections caused by Mycobacterium abscessus are emerging as a global threat to individuals with cystic fibrosis and to other patient groups. Recent evidence for human-to-human transmission worsens the situation. M. abscessus is an intrinsically multidrug-resistant pathogen showing resistance to even standard antituberculosis drugs, such as rifampin. Here, our objective was to identify existing drugs that may be employed for the treatment of M. abscessus lung disease. A collection of more than 2,700 approved drugs was screened at a single-point concentration against an M. abscessus clinical isolate. Hits were confirmed with fresh solids in dose-response experiments. For the most attractive hit, growth inhibition and bactericidal activities against reference strains of the three M. abscessus subspecies and a collection of clinical isolates were determined. Surprisingly, the rifampin derivative rifabutin had MICs of 3 ± 2 μM (3 μg/ml) against the screening strain, the reference strains M. abscessus subsp. abscessus ATCC 19977, M. abscessus subsp. bolletii CCUG 50184-T, and M. abscessus subsp. massiliense CCUG 48898-T, as well as against a collection of clinical isolates. Furthermore, rifabutin was active against clarithromycin-resistant strains. In conclusion, rifabutin, in contrast to rifampin, is active against the Mycobacterium abscessus complex bacteria in vitro and may be considered for treatment of M. abscessus lung disease.

scholarly journals Clinical Characteristics and Treatment Outcomes of Patients with Acquired Macrolide-Resistant Mycobacterium abscessus Lung Disease

2017 ◽  
Vol 61 (10) ◽  
Author(s):  
Hayoung Choi ◽  
Su-Young Kim ◽  
Dae Hun Kim ◽  
Hee Jae Huh ◽  
Chang-Seok Ki ◽  
...  
Keyword(s):  
Lung Disease ◽  
Treatment Outcomes ◽  
Point Mutations ◽  
Mycobacterium Abscessus ◽  
Macrolide Resistance ◽  
Clinical Isolates ◽  
23S Rrna ◽  
Molecular Characteristics ◽  
Rrna Gene ◽  
Content Type

ABSTRACT Macrolide antibiotics are mainstays in the treatment of lung disease due to the Mycobacterium abscessus complex. Although previous studies have reported development of acquired macrolide resistance in this species, limited data are available on the outcomes of lung disease due to macrolide-resistant Mycobacterium abscessus subsp. abscessus. This study evaluated the clinical features, treatment outcomes, and molecular characteristics of macrolide-resistant isolates of M. abscessus subsp. abscessus. We performed a retrospective review of medical records and genetic analysis of clinical isolates from 13 patients who had acquired macrolide-resistant M. abscessus subsp. abscessus lung disease between November 2006 and March 2016. Eleven (85%) patients had the nodular bronchiectatic form of the disease, and two (15%) patients had the fibrocavitary form. When acquired macrolide resistance was detected, 10 (77%) patients were on antibiotic therapy for M. abscessus subsp. abscessus, and three (23%) patients were on therapy for lung disease due to other nontuberculous mycobacteria. The median treatment duration after detecting resistance was 24.0 months (interquartile range, 16.0 to 43.0 months). Treatment outcomes were poor, and final sputum culture conversion was achieved in only one (8%) patient, after resectional surgery. All 13 clinical isolates demonstrated point mutations at position 2058 (n = 10) or 2059 (n = 3) of the 23S rRNA gene, which resulted in acquired macrolide resistance. This study indicates that treatment outcomes are very poor after the development of acquired macrolide resistance in patients with M. abscessus subsp. abscessus lung disease. Thus, more effective measures are needed to prevent development and effectively treat macrolide-resistant M. abscessus subsp. abscessus lung disease.

Hydrocephalus in Spinal Muscular Atrophy: A Case Report and Review of the Literature

2020 ◽  
Author(s):  
Jeetendra P. Sah ◽  
Aaron W. Abrams ◽  
Geetha Chari ◽  
Craig Linden ◽  
Yaacov Anziska
Keyword(s):  
Spinal Muscular Atrophy ◽  
Clinical Characteristics ◽  
Clinical Presentation ◽  
Muscular Atrophy ◽  
Communicating Hydrocephalus ◽  
Type I ◽  
Review Of The Literature ◽  
Radiographic Findings ◽  
Comprehensive Review ◽  
The Relationship

AbstractIn this article, we reported a case of spinal muscular atrophy (SMA) type I noted to have tetraventricular hydrocephalus with Blake's pouch cyst at 8 months of age following intrathecal nusinersen therapy. The association of hydrocephalus with SMA is rarely reported in the literature. Development of hydrocephalus after intrathecal nusinersen therapy is also reported in some cases, but a cause–effect relationship is not yet established. The aim of this study was to describe the clinical characteristics of a patient with SMA type I and hydrocephalus, to review similar cases reported in the literature, and to explore the relationship between nusinersen therapy and development of hydrocephalus. The clinical presentation and radiographic findings of the patient are described and a comprehensive review of the literature was conducted. The adverse effect of communicating hydrocephalus related to nusinersen therapy is being reported and the authors suggest carefully monitoring for features of hydrocephalus developing during the course of nusinersen therapy.

Clinical Characteristics and Outcomes of Influenza in Hospitalized Pediatric Patients in King Chulalongkorn Memorial Hospital

2020 ◽  
Vol 103 (11) ◽  
pp. 1220-1229
Keyword(s):  
Lung Disease ◽  
Chronic Lung Disease ◽  
Associated Factors ◽  
Clinical Characteristics ◽  
Care Center ◽  
Tertiary Care ◽  
Memorial Hospital ◽  
Molecular Testing ◽  
Duration Of Hospitalization ◽  
Severity Of The Disease

Objective: To describe clinical characteristics and outcomes of laboratory-confirmed influenza in hospitalized children in a tertiary care center and to identify factors associated with the severity. Materials and Methods: The present study was a retrospective medical chart review study conducted at King Chulalongkorn Memorial Hospital, Bangkok, Thailand. Data were extracted from children aged under 15 years old hospitalized between January 2014 and December 2018. Patients who had laboratory-confirmed influenza by rapid antigen detection or molecular testing were included. Severe influenza was defined as patients who developed influenza complications or duration of hospitalization for more than three days. Multivariate logistic regression was used to identify the associated factors with the severity of the disease. Results: Three hundred fifty-seven influenza patients were included with median age of 43 months (IQR 19 to 81), of which 63.3% were aged under 60 months. There were 174 patients (48.7%) with comorbidities, most common were immunosuppression (18.2%), chronic pulmonary disease (12.2%), and congenital heart disease (11.5%). Fifty-seven out of 183 patients (31.1%) had history of influenza vaccination in the medical records. One hundred sixty-one patients (45.1%) had 212 influenza complications including influenza-related pneumonia (89, 24.9%), secondary bacterial infection (53, 14.8%), and neurologic complications (47, 13.2%), in which 27 cases (7.6%) were transferred to intensive care unit (ICU). Four cases (1.1%) died but not directly related to influenza. Associated factors with complicated influenza were aged less than 24 months [aOR 2.67 (95% CI 1.68 to 4.26)] and presence of chronic lung disease [aOR 4.34 [95% CI 2.01 to 9.35)]. Conclusion: Two-third of the children hospitalized with influenza were younger than 60 months. Nearly half developed complications most associated with the age of less than two years old and patients with chronic lung disease. Low rates of vaccination were demonstrated. Keywords: Influenza, Pediatrics, Complications, Pneumonia, Hospitalization

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