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3.
BMC Pulm Med ; 23(1): 218, 2023 Jun 20.
Article in English | MEDLINE | ID: mdl-37340431

ABSTRACT

PURPOSE: Real-world data on antibiotic management of nontuberculous mycobacterial lung disease (NTM-LD) is limited for many countries. This study aimed to evaluate real-world treatment practices of NTM-LD in the Netherlands using medication dispensing data. METHODS: A retrospective longitudinal real-world study was conducted using IQVIA's Dutch pharmaceutical dispensing database. The data are collected monthly and include approximately 70% of all outpatient prescriptions in the Netherlands. Patients initiated on specific NTM-LD treatment regimens between October 2015 and September 2020 were included. The main areas of investigation were initial treatment regimens, persistence on treatment, treatment switching, treatment compliance in terms of medication possession rate (MPR) and restarts of treatment. RESULTS: The database included 465 unique patients initiated on triple- or dual-drug regimens for the treatment of NTM-LD. Treatment switches were common and occurred approximately 1.6 per quarter throughout the treatment period. The average MPR of patients initiated on triple-drug therapy was 90%. The median time on therapy for these patients was 119 days; after six months and one year, 47% and 20% of the patients, respectively, were still on antibiotic therapy. Of 187 patients initiated on triple-drug therapy, 33 (18%) patients restarted antibiotic therapy after the initial treatment had been stopped. CONCLUSION: When on therapy, patients were compliant with the NTM-LD treatment; however, many patients stopped their therapy prematurely, treatment switches often occurred, and part of patients had to restart their therapy after a longer treatment gap. NTM-LD management should be improved through greater guideline adherence and appropriate involvement of expert centers.


Subject(s)
Lung Diseases , Mycobacterium Infections, Nontuberculous , Pneumonia , Humans , Retrospective Studies , Netherlands , Mycobacterium Infections, Nontuberculous/drug therapy , Mycobacterium Infections, Nontuberculous/epidemiology , Mycobacterium Infections, Nontuberculous/microbiology , Anti-Bacterial Agents/therapeutic use , Nontuberculous Mycobacteria , Lung Diseases/drug therapy , Lung Diseases/epidemiology , Lung Diseases/microbiology
4.
Ned Tijdschr Tandheelkd ; 128(3): 145-149, 2021 Mar.
Article in Dutch | MEDLINE | ID: mdl-33734219

ABSTRACT

A 48 year old woman was referred by her general practitioner to an oral and maxillofacial surgeon because of an asymptomatic, slow growing intra-oral tumor since three years. There were no sensory and motor symptoms. A well-defined tumor of 5 cm in diameter was located in the right cheek between the zygomaticus arch and the labial commissure. The skin and the intra-oral mucosa were intact without any change in colour or texture. The MRI showed a solitary mass with benign characteristics. A transoral radical excisional biopsy was performed under general anesthesia. Histopathological examination revealed a rare soft tissue perineurioma tumor.


Subject(s)
Nerve Sheath Neoplasms , Soft Tissue Neoplasms , Biopsy , Cheek , Female , Humans , Middle Aged , Mouth Mucosa , Nerve Sheath Neoplasms/diagnosis , Nerve Sheath Neoplasms/surgery
6.
J Hosp Infect ; 104(2): 214-235, 2020 Feb.
Article in English | MEDLINE | ID: mdl-31715282

ABSTRACT

Mycobacterial infection-related morbidity and mortality in patients following cardiopulmonary bypass surgery is high and there is a growing need for a consensus-based expert opinion to provide international guidance for diagnosing, preventing and treating in these patients. In this document the International Society for Cardiovascular Infectious Diseases (ISCVID) covers aspects of prevention (field of hospital epidemiology), clinical management (infectious disease specialists, cardiac surgeons, ophthalmologists, others), laboratory diagnostics (microbiologists, molecular diagnostics), device management (perfusionists, cardiac surgeons) and public health aspects.


Subject(s)
Cross Infection , Mycobacterium Infections, Nontuberculous , Mycobacterium , Anti-Bacterial Agents/therapeutic use , Cardiac Surgical Procedures/adverse effects , Cardiac Surgical Procedures/methods , Cardiology , Cardiopulmonary Bypass , Communicable Diseases , Cross Infection/diagnosis , Cross Infection/drug therapy , Cross Infection/microbiology , Cross Infection/prevention & control , Equipment Contamination , Humans , Mycobacterium/isolation & purification , Mycobacterium Infections, Nontuberculous/diagnosis , Mycobacterium Infections, Nontuberculous/drug therapy , Mycobacterium Infections, Nontuberculous/prevention & control , Risk Factors , Societies, Medical , United Kingdom
7.
Int J Tuberc Lung Dis ; 23(2): 236-238, 2019 02 01.
Article in English | MEDLINE | ID: mdl-30808457

ABSTRACT

A paediatric case of multidrug-resistant tuberculosis in which endo-oesophageal ultrasound-guided fine-needle aspiration using an endobronchial ultrasound-guided bronchoscope was used to collect a sample for microbial analyses is presented. In our experience, ultrasound-guided sampling techniques, both endo-oesophageal and endobronchial, can be safely used for the diagnosis of paediatric intrathoracic tuberculous lymphadenopathy in children aged 3 years. Interventional pulmonologists with experience in using these techniques should be part of the multidisciplinary team treating these patients.


Subject(s)
Endoscopic Ultrasound-Guided Fine Needle Aspiration/methods , Tuberculosis, Multidrug-Resistant/diagnosis , Bronchoscopes , Child , Endoscopic Ultrasound-Guided Fine Needle Aspiration/instrumentation , Humans , Male
9.
Clin Microbiol Infect ; 24(6): 599-603, 2018 Jun.
Article in English | MEDLINE | ID: mdl-29174730

ABSTRACT

BACKGROUND: The implementation of MALDI-TOF MS for microorganism identification has changed the routine of the microbiology laboratories as we knew it. Most microorganisms can now be reliably identified within minutes using this inexpensive, user-friendly methodology. However, its application in the identification of mycobacteria isolates has been hampered by the structure of their cell wall. Improvements in the sample processing method and in the available database have proved key factors for the rapid and reliable identification of non-tuberculous mycobacteria isolates using MALDI-TOF MS. AIMS: The main objective is to provide information about the proceedings for the identification of non-tuberculous isolates using MALDI-TOF MS and to review different sample processing methods, available databases, and the interpretation of the results. SOURCES: Results from relevant studies on the use of the available MALDI-TOF MS instruments, the implementation of innovative sample processing methods, or the implementation of improved databases are discussed. CONTENT: Insight about the methodology required for reliable identification of non-tuberculous mycobacteria and its implementation in the microbiology laboratory routine is provided. IMPLICATIONS: Microbiology laboratories where MALDI-TOF MS is available can benefit from its capacity to identify most clinically interesting non-tuberculous mycobacteria in a rapid, reliable, and inexpensive manner.


Subject(s)
Nontuberculous Mycobacteria/isolation & purification , Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization/methods , Bacteriological Techniques , Humans , Mycobacterium Infections, Nontuberculous/diagnosis , Workflow
10.
Clin Microbiol Infect ; 23(3): 167-172, 2017 Mar.
Article in English | MEDLINE | ID: mdl-27664776

ABSTRACT

The rpoB gene codes for the RNA polymerase ß subunit, which is the target of rifampicin, an essential drug in the treatment of tuberculosis and other mycobacterial infections. This gene is present in all bacteria, but its length and nucleotide sequence vary between bacterial species, including mycobacteria. Mutations in the rpoB gene alter the structure of this protein and cause drug resistance. To describe the resistance-associated mutations, the scientific and medical communities have been using, since 1993, a numbering system based on the Escherichia coli sequence annotation. Using E. coli reference for describing mutations in mycobacteria leads to misunderstandings, particularly with the increasing use of whole genome sequencing, which brought an alternative numbering system based on the Mycobacterium tuberculosis rpoB sequence. We propose using a consensus numbering system for the reporting of resistance mutations based on the reference genomes from the species interrogated (such as strain H37Rv for M. tuberculosis). This manuscript provides the necessary figures and tables allowing researchers, microbiologists and clinicians to easily convert other annotation systems into one common language.


Subject(s)
Antibiotics, Antitubercular/pharmacology , Bacterial Proteins/genetics , DNA-Directed RNA Polymerases/genetics , Genotype , Genotyping Techniques/standards , Microbial Sensitivity Tests/standards , Mutant Proteins/genetics , Rifampin/pharmacology , Consensus , Escherichia coli , Escherichia coli Proteins/genetics , Humans , Mutation , Mycobacterium/drug effects , Mycobacterium tuberculosis , Terminology as Topic
11.
Int J Tuberc Lung Dis ; 20(7): 934-40, 2016 07.
Article in English | MEDLINE | ID: mdl-27287647

ABSTRACT

SETTING: The value of microbiological criteria in diagnosing non-tuberculous mycobacteria pulmonary disease (NTM-PD) and monitoring its epidemiology is unknown. OBJECTIVES: To correlate the rate of NTM-PD based on microbiological criteria (American Thoracic Society/Infectious Diseases Society of America [ATS/IDSA] or stricter microbiological criteria) compared with the full ATS/IDSA criteria, to assess the positive predictive value (PPV) of different microbiological criteria in predicting NTM-PD, and to evaluate the clinical relevance of different NTM species. DESIGN: Retrospective study of all patients with pulmonary NTM isolates in Croatia during an 8-year period. NTM species were divided into low, intermediate and high clinical relevance groups for additional analyses. RESULTS: Good correlation between both microbiological and full ATS/IDSA criteria was observed. The PPV of stricter and ATS/IDSA microbiological criteria was respectively 93.3% and 59.8%. The usefulness of microbiological criteria varied between groups. ATS/IDSA microbiological criteria had a PPV of 89.8% in the high relevance group, while in the intermediate relevance group, the PPV of stricter and ATS/IDSA microbiological criteria was respectively 94.3% and 63.4%. CONCLUSIONS: Microbiological criteria are useful in detecting NTM-PD, allowing laboratory-based monitoring. Stricter criteria should be used for species of low clinical relevance, and less stringent criteria for species of high relevance in the local setting.


Subject(s)
Bacteriological Techniques , Mycobacterium Infections, Nontuberculous/microbiology , Nontuberculous Mycobacteria/isolation & purification , Respiratory Tract Infections/microbiology , Adolescent , Adult , Aged , Child , Child, Preschool , Croatia/epidemiology , Female , Humans , Incidence , Infant , Infant, Newborn , Male , Middle Aged , Mycobacterium Infections, Nontuberculous/diagnosis , Mycobacterium Infections, Nontuberculous/epidemiology , Nontuberculous Mycobacteria/classification , Predictive Value of Tests , Prevalence , Reproducibility of Results , Respiratory Tract Infections/diagnosis , Respiratory Tract Infections/epidemiology , Retrospective Studies , Young Adult
12.
New Microbes New Infect ; 9: 63-5, 2016 Jan.
Article in English | MEDLINE | ID: mdl-26909156

ABSTRACT

A case of cavitary pulmonary disease caused by Mycobacterium heckeshornense in Uruguay is described. This is the first case reported in the Latin America and Caribbean region, showing that this species is a worldwide opportunistic human pathogen.

13.
J Breath Res ; 10(1): 016002, 2016 Jan 29.
Article in English | MEDLINE | ID: mdl-26824272

ABSTRACT

Volatile organic compound (VOC) analysis in exhaled breath is proposed as a non-invasive method to detect respiratory infections in cystic fibrosis patients. Since polymicrobial infections are common, we assessed whether we could distinguish Pseudomonas aeruginosa and Aspergillus fumigatus mono- and co-cultures using the VOC emissions. We took headspace samples of P. aeruginosa, A. fumigatus and co-cultures at 16, 24 and 48 h after inoculation, in which VOCs were identified by thermal desorption combined with gas chromatography - mass spectrometry. Using multivariate analysis by Partial Least Squares Discriminant Analysis we found distinct VOC biomarker combinations for mono- and co-cultures at each sampling time point, showing that there is an interaction between the two pathogens, with P. aeruginosa dominating the co-culture at 48 h. Furthermore, time-independent VOC biomarker combinations were also obtained to predict correct identification of P. aeruginosa and A. fumigatus in mono-culture and in co-culture. This study shows that the VOC combinations in P. aeruginosa and A. fumigatus co-microbial environment are different from those released by these pathogens in mono-culture. Using advanced data analysis techniques such as PLS-DA, time-independent pathogen specific biomarker combinations can be generated that may help to detect mixed respiratory infections in exhaled breath of cystic fibrosis patients.


Subject(s)
Aspergillus fumigatus/metabolism , Pseudomonas aeruginosa/metabolism , Volatile Organic Compounds/analysis , Biomarkers/metabolism , Coculture Techniques , Exhalation , Gas Chromatography-Mass Spectrometry , Humans , Specimen Handling
14.
Int J Tuberc Lung Dis ; 19(7): 828-33, 2015 Jul.
Article in English | MEDLINE | ID: mdl-26056110

ABSTRACT

BACKGROUND: The performance of molecular drug susceptibility testing in countries with a low prevalence of drug resistance, such as the Netherlands, has not been adequately studied. OBJECTIVE: To evaluate the diagnostic accuracy of the GenoType(®) MTBDRplus and MTBDRsl assays to detect resistance to first- and second-line anti-tuberculosis drugs in the context of a nationwide screening programme in the Netherlands. RESULTS: The MTBDRplus assay had a sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) of 100%, 99%, 80% and 100% for detecting rifampicin resistance. The sensitivity, specificity, PPV and NPV of either a katG or inhA mutation for detecting isoniazid resistance were 88%, 100%, 100% and 99%. The MTBDRsl assay had a sensitivity, specificity, PPV and NPV of 100%, 99%, 83%, and 100% for detecting moxifloxacin resistance; 62%, 71%, 58% and 74%, respectively, for detecting ethambutol resistance; 86%, 99%, 86% and 99% for detecting amikacin resistance; and 50%, 96%, 71% and 91% for detecting capreomycin resistance. CONCLUSION: The MTBDRplus and MTBDRsl assays may aid in decision making in tuberculosis treatment in low-level drug resistance settings and should preferably be used to exclude resistance.


Subject(s)
Antitubercular Agents/classification , Antitubercular Agents/therapeutic use , Drug Resistance, Multiple, Bacterial/genetics , Extensively Drug-Resistant Tuberculosis/drug therapy , Extensively Drug-Resistant Tuberculosis/genetics , Mycobacterium tuberculosis/isolation & purification , Adult , Female , Genotype , Humans , Logistic Models , Male , Microbial Sensitivity Tests , Middle Aged , Multivariate Analysis , Netherlands , Retrospective Studies , Sensitivity and Specificity , Young Adult
15.
Int J Tuberc Lung Dis ; 18(5): 594-600, 2014 May.
Article in English | MEDLINE | ID: mdl-24903798

ABSTRACT

BACKGROUND: The quality of variable number of tandem repeats (VNTR) typing of Mycobacterium tuberculosis was first investigated in 2009 in 37 laboratories worldwide. The results revealed an inter- and intra-laboratory reproducibility of respectively 60% and 72%. These data spurred an improvement in laboratory-specific assays and global standardisation of VNTR typing. OBJECTIVE: To measure the effects of the technical improvements and increased standardisation, a test panel consisting of 30 M. tuberculosis complex DNA samples was distributed for VNTR typing in 41 participating laboratories from 36 countries. RESULTS: The inter- and intra-laboratory reproducibility increased overall to respectively 78% and 88%. The 33 laboratories that participated in both the first and second proficiency studies improved their inter- and intra-laboratory reproducibility from 62% and 72% to respectively 79% and 88%. The largest improvement in reproducibility was detected in 10 laboratories that use an in-house polymerase chain reaction technique and perform amplicon sizing using gel electrophoresis. Detailed error analysis revealed a reduction in the number of systematic errors, sample exchange events and non-amplifiable loci. CONCLUSION: This second worldwide proficiency study indicates a substantial increase in the reproducibility of VNTR typing of M. tuberculosis. This will contribute to a more meaningful interpretation of molecular epidemiological and phylogenetic studies on the M. tuberculosis complex.


Subject(s)
Bacterial Typing Techniques/standards , DNA, Bacterial/genetics , Laboratory Proficiency Testing/standards , Minisatellite Repeats , Mycobacterium tuberculosis/genetics , Electrophoresis, Agar Gel/standards , Humans , Mycobacterium tuberculosis/classification , Observer Variation , Polymerase Chain Reaction/standards , Predictive Value of Tests , Quality Indicators, Health Care/standards , Reproducibility of Results
16.
Clin Microbiol Infect ; 20(10): 1015-20, 2014 Oct.
Article in English | MEDLINE | ID: mdl-24890253

ABSTRACT

There is an urgent need for rapid and accurate diagnosis of pyrazinamide-resistant multidrug-resistant tuberculosis (MDR-TB). No diagnostic algorithm has been validated in this population. We hypothesized that pncA sequencing added to rpoB mutation analysis can accurately identify patients with pyrazinamide-resistant MDR-TB. We identified from the Dutch national database (2007-11) patients with a positive Mycobacterium tuberculosis culture containing a mutation in the rpoB gene. In these cases, we prospectively sequenced the pncA gene. Results from the rpoB and pncA mutation analysis (pncA added to rpoB) were compared with phenotypic susceptibility testing results to rifampicin, isoniazid and pyrazinamide (reference standard) using the Mycobacterial Growth Indicator Tube 960 system. We included 83 clinical M. tuberculosis isolates containing rpoB mutations in the primary analysis. Rifampicin resistance was seen in 72 isolates (87%), isoniazid resistance in 73 isolates (88%) and MDR-TB in 65 isolates (78%). Phenotypic reference testing identified pyrazinamide-resistant MDR-TB in 31 isolates (48%). Sensitivity of pncA sequencing added to rpoB mutation analysis for detecting pyrazinamide-resistant MDR-TB was 96.8%, the specificity was 94.2%, the positive predictive value was 90.9%, the negative predictive value was 98.0%, the positive likelihood was 16.8 and the negative likelihood was 0.03. In conclusion, pyrazinamide-resistant MDR-TB can be accurately detected using pncA sequencing added to rpoB mutation analysis. We propose to include pncA sequencing in every isolate with an rpoB mutation, allowing for stratification of MDR-TB treatment according to pyrazinamide susceptibility.


Subject(s)
Algorithms , Antitubercular Agents/pharmacology , Molecular Diagnostic Techniques/methods , Mycobacterium tuberculosis/drug effects , Pyrazinamide/pharmacology , Tuberculosis, Multidrug-Resistant/diagnosis , Adult , Amidohydrolases/genetics , Bacterial Proteins/genetics , DNA Mutational Analysis/methods , DNA-Directed RNA Polymerases , Female , Humans , Male , Microbial Sensitivity Tests/methods , Mutation , Mycobacterium tuberculosis/genetics , Mycobacterium tuberculosis/metabolism , Prospective Studies , Retrospective Studies , Young Adult
17.
Euro Surveill ; 19(11)2014 Mar 20.
Article in English | MEDLINE | ID: mdl-24679719

ABSTRACT

The European Centre for Disease Prevention and Control (ECDC) initiated a project on the molecular surveillance of multi- and extensively drug-resistant tuberculosis (MDR-/XDR-TB) transmission in the European Union (EU) in the period from 2009 to 2011. In total, 2,092 variable number of tandem repeat (VNTR) patterns of MDR-/XDR-TB Mycobacterium tuberculosis isolates were collected, originating from 24 different countries in the period 2003 to 2011. Of the collected VNTR patterns, 45% (n=941) could be assigned to one of the 79 European multiple-country molecular fingerprint clusters and 50% of those (n=470) belonged to one extremely large cluster caused by Beijing strains of one genotype. We conclude that international transmission of MDR-/XDR-TB plays an important role in the EU, especially in the eastern part, and is significantly related to the spread of one strain or clone of the Beijing genotype. Implementation of international cluster investigation in EU countries should reveal underlying factors of transmission, and show how TB control can be improved regarding case finding, contact tracing, infection control and treatment in order to prevent further spread of MDR-/XDR-TB in the EU.


Subject(s)
Extensively Drug-Resistant Tuberculosis/transmission , Mycobacterium tuberculosis/classification , Mycobacterium tuberculosis/isolation & purification , Sentinel Surveillance , Antitubercular Agents/pharmacology , Cluster Analysis , Europe , European Union , Extensively Drug-Resistant Tuberculosis/diagnosis , Extensively Drug-Resistant Tuberculosis/microbiology , Genotype , Humans , Microbial Sensitivity Tests , Minisatellite Repeats/drug effects , Molecular Typing , Mycobacterium tuberculosis/drug effects , Mycobacterium tuberculosis/genetics , Phylogeny , Polymorphism, Genetic
18.
Clin Microbiol Infect ; 20(7): O418-20, 2014 Jul.
Article in English | MEDLINE | ID: mdl-24188165

ABSTRACT

We investigated the effect of Mycobacterium tuberculosis culture supernatant added to sputum cultures collected during the first 8 weeks of anti-tuberculosis treatment. With ongoing treatment duration, time to culture positivity decreased significantly in supernatant-enriched cultures, possibly due to stimulation of dormant or slowly metabolizing M. tuberculosis cells.


Subject(s)
Antitubercular Agents/therapeutic use , Growth Substances/metabolism , Mycobacterium tuberculosis/growth & development , Mycobacterium tuberculosis/isolation & purification , Sputum/microbiology , Tuberculosis, Pulmonary/drug therapy , Tuberculosis, Pulmonary/microbiology , Culture Media/chemistry , Humans , Mycobacterium tuberculosis/metabolism
19.
Ned Tijdschr Tandheelkd ; 120(9): 452-7, 2013 Sep.
Article in Dutch | MEDLINE | ID: mdl-24159751

ABSTRACT

Sialendoscopy: endoscopic approach to obstructive salivary gland defects Obstructive defects of the parotid and the submandibular gland often present themselves clinically by mealtime-related swelling of the affected salivary gland, the so-called 'mealtime syndrome'. Salivary ductal obstruction of the parotid and submandibular gland is predominantly caused by the presence of a salivary stone, a mucous plug, or by ductal stenosis. Until recently, diagnostic and treatment options for these obstructive salivary gland defects were restricted. Surgical removal of the affected salivary gland was often the treatment of choice. By applying sialendoscopy, a minimally invasive, semi rigid optical technique, it is possible to diagnose and treat obstructions which are found in the salivary ductal system. In many cases, therefore, the surgical removal of the salivary gland becomes unnecessary.


Subject(s)
Endoscopy/methods , Salivary Ducts/pathology , Salivary Gland Diseases/diagnosis , Adult , Constriction, Pathologic/diagnosis , Constriction, Pathologic/therapy , Female , Humans , Middle Aged , Salivary Gland Diseases/therapy , Treatment Outcome
20.
Int J Antimicrob Agents ; 42(3): 256-61, 2013 Sep.
Article in English | MEDLINE | ID: mdl-23837923

ABSTRACT

Concentrations of antimycobacterial drugs are an intermediary link between doses administered and eventual response to the drugs. Few pharmacokinetic (PK) studies have focused on drug treatment for nontuberculous mycobacterial (NTM) disease, although a favourable treatment response occurs in just over 50% of patients despite drug treatment for ≥1 year. A prospective, descriptive PK study was performed to assess the plasma pharmacokinetics of rifampicin, ethambutol, clarithromycin, 14-OH-clarithromycin, azithromycin, isoniazid and moxifloxacin. Intensive PK sampling was performed in 14 patients with clinically relevant NTM lung disease. PK parameters were assessed and were compared with available data from the literature. Exposure to clarithromycin when combined with rifampicin was very low [area under the concentration-time curve over 12 h (AUC(0-12 h), geometric mean 2.6 h·mg/L, range 1.6-3.2 h·mg/L; peak concentration in plasma (C(max)), geometric mean 0.3 mg/L, range 0.1-0.7 mg/L]. The mean parent-to-metabolite ratios for clarithromycin to 14-OH-clarithromycin were 0.4 and 0.3 for AUC(0-12 h) and C(max), instead of the typical ratio of ca. 3, probably reflecting increased metabolism of clarithromycin to its (virtually inactive) 14-OH metabolite. Exposure to rifampicin was relatively high, with all patients having a rifampicin C(max) within the reference range. The majority of ethambutol C(max) values were within the reference range. The current study re-emphasises the relevant PK interaction between clarithromycin and rifampicin. This calls for a re-evaluation of dosing strategies in NTM lung disease, as suboptimal drug exposure may contribute to inadequate response to treatment of NTM disease.


Subject(s)
Antibiotics, Antitubercular/pharmacokinetics , Mycobacterium Infections, Nontuberculous/drug therapy , Nontuberculous Mycobacteria/drug effects , Adult , Aged , Aged, 80 and over , Antibiotics, Antitubercular/blood , Antibiotics, Antitubercular/therapeutic use , Drug Interactions , Female , Humans , Lung/microbiology , Male , Metabolic Clearance Rate , Middle Aged , Mycobacterium Infections, Nontuberculous/epidemiology
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