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2012, Cystic Fibrosis - Renewed Hopes Through Research
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NTM produce insidious infections that require several months of combined antibiotic therapy, difficult eradication and frequent relapses with progressive lung function deterioration (Esther et al., 2010). They represent an important social and health problem (Olivier et al., 2003), with not well defined and unsolved aspects, such as mode of infection, pathogenic role, standardized treatment or prophylaxis. In this chapter we will review the main epidemiological, clinical, diagnostic, therapeutic and prophylactic aspects of NTM infections in CF patients. www.intechopen.com Cystic Fibrosis-Renewed Hopes Through Research 208 2. Epidemiology and pathogenesis 2.1 General aspects The term NTM refers to Mycobacterium spp. different to M. tuberculosis complex and M. leprae. These microorganisms are widely distributed in the environment (water, soil, dust, animals and food). Almost all NTM are less virulent and contagious than M. tuberculosis (Runyon, 1959; Brown-Elliot et al., 2002). There are more than 100 described species, of which only 15-20 produce infections in humans. NTM are resistant to chlorination and ozonation (Prim et al., 2004) and to multiple antiseptics and antibiotics. They are opportunistic microorganisms capable of causing disease in a different range of locations (skin and soft tissues, lymph nodes and lung) as well as disseminated diseases. The extent and severity of infection depends on the anatomic and immune integrity of the host. These bacteria can adhere to biomedical materials (catheters, prosthesis, filters or membranes of inhalation systems) forming a biofilm that may complicate the pharmacological treatment of such infections (Williams et al., 2009).
Thorax, 1990
Fifty four patients with cystic fibrosis, aged 3-67 years, were studied prospectively for pulmonary mycobacterial infection. Sputum smears and cultures were carried out and intradermal skin tests performed. Mycobacteria were cultured from six patients in association with clinical deterioration; four patients had positive direct smears. Mycobacterium tuberculosis, M aviumintracellulare, M kansasit, and M gordonae were isolated. There were no deaths and all improved with chemotherapy. A third of the other 48 patients had positive skin test responses (> 6 mm) to purified protein derivative (PPD)
Clinical Infectious Diseases, 2001
Background: Non-tuberculous mycobacteria (NTM) are ubiquitous environmental organisms. Patients with pre-existing lung damage are susceptible to NTM, but their prevalence in bronchiectasis is unknown. Distinguishing between lung colonisation and disease can be difficult. Methods: A prospective study of 100 patients with bronchiectasis was undertaken to evaluate the prevalence of NTM in sputum, and a retrospective analysis of clinical, microbiological, lung function and radiology data of our clinic patients with NTM sputum isolates over 11 years was performed. Results: The prevalence of NTM in this population of patients with bronchiectasis was 2%. Patients in the retrospective study were divided into three groups: bronchiectasis + multiple NTM isolates (n = 25), bronchiectasis + single isolates (n = 23), and non-bronchiectasis + multiple isolates (n = 22). Mycobacterium avium complex (MAC) species predominated in patients with bronchiectasis compared with non-bronchiectasis lung disease (72% v 9%, p,0.0001). Single isolates were also frequently MAC (45.5%). Multiple isolates in bronchiectasis were more often smear positive on first sample than single isolates (p,0.0001). NTM were identified on routine screening samples or because of suggestive radiology. No particular bronchiectasis aetiology was associated with an NTM. Pseudomonas aeruginosa and Staphylococcus aureus were frequently co-cultured. Six (25%) of multiple NTM patients had cavities of which five were due to MAC. Half the patients with multiple isolates were treated, mostly due to progressive radiology. Conclusions: NTM are uncommon in non-cystic fibrosis bronchiectasis. Routine screening identifies otherwise unsuspected patients. MAC is the most frequent NTM isolated.
Journal of Clinical Microbiology, 2014
Worldwide, nontuberculous mycobacteria (NTM) have become emergent pathogens of pulmonary infections in cystic fibrosis (CF) patients, with an estimated prevalence ranging from 5 to 20%. This work investigated the presence of NTM in sputum samples of 129 CF patients (2 to 18 years old) submitted to longitudinal clinical supervision at a regional reference center in Rio de Janeiro, Brazil. From June 2009 to March 2012, 36 NTM isolates recovered from 10 (7.75%) out of 129 children were obtained. Molecular identification of NTM was performed by using PCR restriction analysis targeting the hsp65 gene (PRA-hsp65) and sequencing of the rpoB gene, and susceptibility tests were performed that followed Clinical and Laboratory Standards Institute recommendations. For evaluating the genotypic diversity, pulsed-field gel electrophoresis (PFGE) and/or enterobacterial repetitive intergenic consensus sequence PCR (ERIC-PCR) was performed. The species identified were Mycobacterium abscessus subsp. bolletii (n ؍ 24), M. abscessus subsp. abscessus (n ؍ 6), Mycobacterium fortuitum (n ؍ 3), Mycobacterium marseillense (n ؍ 2), and Mycobacterium timonense (n ؍ 1). Most of the isolates presented resistance to five or more of the antimicrobials tested. Typing profiles were mainly patient specific. The PFGE profiles indicated the presence of two clonal groups for M. abscessus subsp. abscessus and five clonal groups for M. abscesssus subsp. bolletii, with just one clone detected in two patients. Given the observed multidrug resistance patterns and the possibility of transmission between patients, we suggest the implementation of continuous and routine investigation of NTM infection or colonization in CF patients, including countries with a high burden of tuberculosis disease.
Emerging Infectious Diseases, 2013
Journal of Pathogens, 2015
Nontuberculous mycobacteria (NTM) are emergent pathogens whose importance in human health has been growing. After being regarded mainly as etiological agents of opportunist infections in HIV patients, they have also been recognized as etiological agents of several infections on immune-competent individuals and healthcare-associated infections. The environmental nature of NTM and their ability to assemble biofilms on different surfaces play a key role in their pathogenesis. Here, we review the clinical manifestations attributed to NTM giving particular importance to the role played by biofilm assembly.
Indian Journal of Otolaryngology and Head & Neck Surgery
Tracheostomy is a commonly performed airway surgery for critically ill patients. Tracheostomy tube is an indwelling prosthesis, providing potential surface for growth of bacteria. Biofilm formation by bacteria as a selfprotective mechanism, has led to worrisome antibacterial resistance and thus higher rate of nosocomial infections. A prospective observational study was conducted with a purpose of knowing most common organisms capable of forming biofilm on tracheostomy tube and their antibiotic sensitivity in our setting. Fifty seven percent of the isolates were found to be capable of biofilm production. Acinetobacter baumannii (45%) was the commonest biofilm producer isolated and the commonest multidrug resistant organism (35.7%), followed by Klebsiella pneumoniae (28.5%). Both biofilm producers and non-biofilm producers were found most susceptible to Amikacin (43%), followed by Gentamicin (30%) and Ciprofloxacin (18.5%). No significant association was found between biofilms and ventilators (p value = 0.558) or pre-existing infection (p value = 0.66) using Chi square test. Potentially biofilm producing bacteria were isolated from tracheostomy tube inner surfaces just after a week of their insertion, in majority of patients. Acinetobacter baumannii and Klebsiella pneumoniae were the commonest biofilm forming organisms and Amikacin, Gentamicin and Ciprofloxacin were most sensitive drugs. Multi drug resistant organisms were also commonly found, stressing the need for sensitivity-based antibiotics. Ventilator usage had no strong association with biofilm formation. Patients with non-infectious conditions also harboured bacteria capable of biofilms in tracheostomy tubes demanding the need for stringent tube hygiene measures and prophylactic antibiotics.
Emerging Infectious Diseases, 2008
This 2-year cross-sectional evaluation of nontuberculous mycobacterial (NTM) infections involved all Israeli medical centers that treat cystic fi brosis patients. The study comprised 186 patients whose sputum was analyzed for NTM. The prevalence of NTM isolates was 22.6%, and 6.5% and 10.8% of the patients fulfi lled the 1997 and 2007 American Thoracic Society criteria for NTM lung disease, respectively. Mycobacterium simiae (40.5%), M. abscessus (31.0%), and M. avium complex (14.3%) were the most prevalent. Presence of Aspergillus spp. in sputum and the number of sputum specimens processed for mycobacteria were the most signifi cant predictors for isolation of NTM (odds ratio [OR] = 5.14, 95% confi dence interval [CI] 1.87-14.11 and OR = 1.47, 95% CI 1.17-1.85, respectively). The incidence of NTM pulmonary infections is increasing among cystic fi brosis patients, refl ecting the increase in longevity of such patients as well as environmental exposure to various species of mycobacteria.
Springer eBooks, 2020
Journal of Cystic Fibrosis, 2015
Background: Nontuberculous mycobacteria (NTM) are emerging infections in the CF population. Aims: To assess NTM infection prevalence and associated features in our CF clinic population. Methods: Patient records, 2002-2011, were reviewed for NTM infection. FEV 1 , pancreatic function, sputum microbiology, and serum cytokines were compared in patients with and without NTM infection. Results: Incidence rate of NTM infection increased from 0 in 2002 to 8.7% in 2011 (p b 0.001). NTM infection prevalence increased 3-fold from 5% (4/79) in 2003 to 14.5% (16/110) in 2011 (p = 0.05). Prevalence of chronic NTM lung disease has decreased somewhat since a peak in 2009, with institution of aggressive triple therapy. Of NTM-infected compared to uninfected patients, 88.2% vs. 60.3% had a known 'severe' CFTR genotype (p = 0.04), 88.2% vs. 58.9% were pancreatic insufficient (p = 0.02); 70.6% vs. 43.8% had chronic Pseudomonas aeruginosa (p = 0.06); 75% vs. 32% had Aspergillus infection (p = 0.007) and 23.5% vs 2.7% had allergic bronchopulmonary aspergillosis (p = 0.01). Patients infected with Mycobacterium abscessus had increased TGF-β, TNF-α, IL-1β, IL-2, IL-4 and IL-5 levels (p b 0.05). There was no difference in cytokine levels for all NTM infected compared to uninfected patients. M. abscessus comprised 46% of all NTM infections. Comparing M. abscessus versus other NTM, duration was 10.5 (1-118) months versus 1 (1-70) month, median (range) (p = 0.004); lung disease occurred in 69% versus 17% (p = 0.0004), with sputum conversion in 4/11 versus 5/6, respectively (NS). Conclusions: NTM incidence and prevalence have increased dramatically in our CF clinic, associated with a severe CF genotype and phenotype. M. abscessus, the most prevalent NTM, caused prolonged infection despite therapy. There has been some decrease in the prevalence of NTM lung disease since 2009.
The international journal of tuberculosis and lung disease : the official journal of the International Union against Tuberculosis and Lung Disease, 2010
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