In some patients with treatment-refractory pulmonary nontuberculous mycobacterial disease, the addition of inhaled amikacin was associated with microbiologic and/or symptomatic improvement; however, toxicity was common. Prospective evaluation of inhaled amikacin for mycobacterial disease is warranted.
Increasing numbers of cystic fibrosis (CF) and non-CF bronchiectasis patients are affected by pulmonary nontuberculous mycobacteria (NTM) infection worldwide. Two species of NTM account for up to 95% of the pulmonary NTM infections: Mycobacterium avium complex (MAC) and Mycobacterium abscessus complex (MABSC). Diagnosis of pulmonary NTM infection is based on criteria specified in the 2007 American Thoracic Society/Infectious Disease Society of America (ATS/IDSA) guidelines. While many initial positive cultures do not progress to active NTM disease, even a single positive NTM sputum culture obtained from higher risk groups such as classic CF or older women with bronchiectasis and very low body mass index should be closely monitored for progressive disease. Macrolides remain the most effective agents available against MAC and MABSC. Infection with MABSC may be associated with worse clinical outcomes, as more than half of MABSC isolates have inducible macrolide resistance conferred by an active erm(41) gene. Of growing concern in CF is that MABSC is becoming more common than MAC, seems to target younger patients with classic CF, and is more difficult to manage, often requiring prolonged courses of intravenous antibiotics. Recurrence rates of NTM after initial successful treatment remain high, likely due to nonmodifiable risk factors raising the question of whether secondary prophylaxis is feasible. More rapid and readily available methods for detecting inducible macrolide resistance and better in vitro susceptibility testing methods for other drugs that correlate with clinical responses are needed. This is crucial to identify more effective regimens of existing drugs and for development of novel drugs for NTM infection.
COVID-19 is unique in that it is spread through everyday contact with other people. Therefore, social protective measures, beyond medical protective measures, such as social distancing, lockdowns, border closures, and human tracing are initiated to control the spread of COVID-19. Such responses have produced secondary issues such as drastic changes in people's way of life and work, housing instability, economic shock, and privacy issues. This paper examines the four domains of urban and regional issues related to the secondary impact of COVID-19, including (1) social distancing, urban structure, community, and density; (2) housing affordability; (3) lockdowns, border closures, reshoring, and regional economic recovery; and (4) smart city technology, contact tracing, and privacy. The following six recommendations have been proposed. First, institutional and cultural factors are more important than urban features, such as population density. To handle infectious diseases such as COVID-19, it is important to build systems, technology, infrastructure, and urban structures that can strengthen resilience instead of implementing a directionless policy of dispersion. Second, it is necessary to improve accessibility to essential services at the community level, including medical facilities and food supply. Third, continuous effort should be made to boost housing affordability, as it is directly related to people's basic life. Fourth, measures are needed to protect those people who are socioeconomically disadvantaged. There is also the need to restore global trade and economic relations. Fifth, since data technology-based COVID-19 control raises the human tracing and privacy issue, we must ensure the principles of privacy management, such as transparency and voluntary consent, are being met. Finally, since COVID-19 is spread through people, individuals may become anxious and fearful of others without grounds; this may increase prejudice and hatred, including xenophobia. Significant social effort is needed to overcome such ill-defined anxiety and fear and maintain a healthy civil society.
fThe smooth-to-rough colony morphology shift in Mycobacterium abscessus has been implicated in loss of glycopeptidolipid (GPL), increased pathogenicity, and clinical decline in cystic fibrosis (CF) patients. However, the evolutionary phenotypic and genetic changes remain obscure. Serial isolates from nine non-CF patients with persistent M. abscessus infection were characterized by colony morphology, lipid profile via thin-layer chromatography and matrix-assisted laser desorption ionization-time of flight mass spectrometry (MALDI-TOF MS), sequencing of eight genes in the GPL locus, and expression level of fadD23, a key gene involved in the biosynthesis of complex lipids. All 50 isolates were typed as M. abscessus subspecies abscessus and were clonally related within each patient. Rough isolates, all lacking GPL, predominated at later disease stages, some showing variation within rough morphology. While most (77%) rough isolates harbored detrimental mutations in mps1 and mps2, 13% displayed previously unreported mutations in mmpL4a and mmpS4, the latter yielding a putative GPL precursor. Two isolates showed no deleterious mutations in any of the eight genes sequenced. Mixed populations harboring different GPL locus mutations were detected in 5 patients, demonstrating clonal diversification, which was likely overlooked by conventional acid-fast bacillus ( MABSC causes serious chronic pulmonary infections in those with underlying conditions such as bronchiectasis or cystic fibrosis (CF). In the United States and some other parts of the world, it is the second most frequent pulmonary nontuberculous mycobacterial (NTM) infection (28%), after Mycobacterium avium complex, and its prevalence is increasing (6, 7). MABSC causes significant mortality in the CF population. In Scandinavian countries, one-fourth of CF patients who have persistently positive MABSC sputum cultures have received lung transplantation or died (8).Glycopeptidolipid (GPL) is the most abundant glycolipid in the outer cell envelope of MABSC, and its synthesis and transport are controlled by the GPL locus (9). A growing number of studies have linked the rough colony morphology in MABSC to loss of GPL, increased pathogenicity, and clinical decline in CF patients (10)(11)(12)(13)(14)(15)(16). While most studies of persistent MABSC infection focused on CF patients, less is known about MABSC in the non-CF population regarding presence of mixed populations, clonal relatedness, and phenotypic and genotypic changes of strains collected over time.We have very limited understanding of the evolutionary phenotypic and genetic changes occurring in MABSC during persistent human lung infection. We lack the fundamental knowledge needed to identify selective pressures associated with rough morphology and, once identified, how to reverse them. To address these questions, we collected serial clinical isolates of M. abscessus from non-CF patients with persistent pulmonary infection who were followed for 5 years or more and assessed strain relatedness and diversity, colony...
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