Lung infections with Mycobacterium abscessus, a species of multidrug resistant nontuberculous mycobacteria, are emerging as an important global threat to individuals with cystic fibrosis (CF) where they accelerate inflammatory lung damage leading to increased morbidity and mortality. Previously, M. abscessus was thought to be independently acquired by susceptible individuals from the environment. However, using whole genome analysis of a global collection of clinical isolates, we show that the majority of M. abscessus infections are acquired through transmission, potentially via fomites and aerosols, of recently emerged dominant circulating clones that have spread globally. We demonstrate that these clones are associated with worse clinical outcomes, show increased virulence in cell-based and mouse infection models, and thus represent an urgent international infection challenge.Nontuberculous mycobacteria (NTM; referring to mycobacterial species other than M. tuberculosis complex and M. leprae) are ubiquitous environmental organisms that can cause chronic pulmonary infections in susceptible individuals [1,2], particularly those with preexisting inflammatory lung diseases such as cystic fibrosis (CF) [3]. The major NTM infecting CF individuals around the world is Mycobacterium abscessus; a rapidly growing, intrinsically multidrug-resistant species, which can be impossible to treat despite prolonged combination antibiotic therapy [1,[3][4][5], leads to accelerated decline in lung function [6,7], and remains a contraindication to lung transplantation in many centers [3,8,9].Until recently, NTM infections were thought to be independently acquired by individuals through exposure to soil or water [10][11][12]. As expected, previous analyses from the 1990s and 2000s [13][14][15][16] showed that CF patients were infected with unique, genetically diverse strains of M. abscessus, presumably from environmental sources. We used whole genome sequencing at a single UK CF center and identified two clusters of patients (11 individuals in total) infected with identical or near-identical M. abscessus isolates, which social network analysis suggested were acquired within hospital via indirect transmission between patients Phylogenetic analysis of these sequences (using one isolate per patient), supplemented by published genomes from US, France, Brazil, Malaysia, China, and South Korea (Table S1), was performed and analysed in the context of the geographical provenance of isolates ( Figure 1; Figure S1). Within each subspecies, we found multiple examples of deep branches (indicating large genetic differences) between isolates from different individuals, consistent with independent acquisition of unrelated environmental bacteria. However, we also identified multiple clades of near-identical isolates from geographically diverse locations (Figure 1), suggesting widespread transmission of circulating clones within the global CF patient community.To investigate further the relatedness of isolates from different individuals, we a...
BackgroundNosocomial infection of health-care workers (HCWs) during outbreaks of respiratory infections (e.g. Influenza A H1N1 (2009)) is a significant concern for public health policy makers. World Health Organization (WHO)-defined ‘aerosol generating procedures’ (AGPs) are thought to increase the risk of aerosol transmission to HCWs, but there are presently insufficient data to quantify risk accurately or establish a hierarchy of risk-prone procedures.Methodology/Principal FindingsThis study measured the amount of H1N1 (2009) RNA in aerosols in the vicinity of H1N1 positive patients undergoing AGPs to help quantify the potential risk of transmission to HCWs. There were 99 sampling occasions (windows) producing a total of 198 May stages for analysis in the size ranges 0.86–7.3 µm. Considering stages 2 (4–7.3 µm) and 3 (0.86–4 µm) as comprising one sample, viral RNA was detected in 14 (14.1%) air samples from 10 (25.6%) patients. Twenty three air samples were collected while potential AGPs were being performed of which 6 (26.1%) contained viral RNA; in contrast, 76 May samples were collected when no WHO 2009 defined AGP was being performed of which 8 (10.5%) contained viral RNA (unadjusted OR = 2.84 (95% CI 1.11–7.24) adjusted OR = 4.31 (0.83–22.5)).Conclusions/SignificanceWith our small sample size we found that AGPs do not significantly increase the probability of sampling an H1N1 (2009) positive aerosol (OR (95% CI) = 4.31 (0.83–22.5). Although the probability of detecting positive H1N1 (2009) positive aerosols when performing various AGPs on intensive care patients above the baseline rate (i.e. in the absence of AGPs) did not reach significance, there was a trend towards hierarchy of AGPs, placing bronchoscopy and respiratory and airway suctioning above baseline (background) values. Further, larger studies are required but these preliminary findings may be of benefit to infection control teams.
Background: Chronic Pseudomonas aeruginosa infection is a major cause of morbidity and mortality for individuals with cystic fibrosis (CF). P aeruginosa cross infection outbreaks have recently been reported at CF holiday camps and specialist centres. The mechanism of cross infection is unknown. A study was performed to look for the presence of epidemic strains of P aeruginosa in the environment of a CF centre during a cross infection outbreak and to examine their potential modes of spread between patients. Methods: Microbiological sampling of the environment of the CF facility was performed, including room air sampling. Individual P aeruginosa strains were identified by bacterial fingerprinting. The typing patterns were compared with those of epidemic strains responsible for cross infection among the patients. Results: Epidemic P aeruginosa strains were isolated from room air when patients performed spirometric tests, nebulisation, and airway clearance, but were not present in other areas of the inanimate environment of the CF centre. Conclusions: Aerosol dissemination may be the most important factor in patient-to-patient spread of epidemic strains of P aeruginosa during recent cross infection outbreaks at adult CF centres.
In order to investigate the role of bacteria, including Mycoplasma pneumoniae and especially Chlamydia pneumoniae in acute purulent exacerbations of chronic obstructive pulmonary disease (COPD), we examined sputum specimens and acute and convalescent sera taken 26 d apart from 49 outpatients experiencing an acute purulent exacerbation of COPD. The sera were tested for antibodies to C. pneumoniae with the microimmunofluorescence test, and for antibodies to M. pneumoniae with the indirect fluorescence antibody test. Routine microbiologic culture of sputum yielded potentially pathogenic microorganisms in 12 of the 49 patients (24%). Three patients (6%) showed serologic evidence of recent M. pneumoniae infection. Seven patients showed high IgG titers of >/= 1:1,024 to C. pneumoniae, and an additional four had a fourfold increase in IgG titer, suggesting reinfection with C. pneumoniae. Sputum from two of these 11 patients also grew Streptococcus pneumoniae, and one grew Moraxella catarrhalis. Patients with and without serologic evidence of current C. pneumoniae infection showed no significant differences in clinical features or pulmonary function. The high incidence of infection with C. pneumoniae (the sole causal agent in 16% of cases, and the causal agent with other agents in 6%) provides insight into the importance of this organism among agents leading to exacerbations of COPD in Turkey.
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