Clinical Aspects of Pulmonary Nontuberculous Mycobacteriosis

Nontuberculous mycobacterial (NTM) infections are an emerging problem. Common organisms include Mycobacterium avium, M. intracellulare, and M. kansasii, along with the M. avium intracellulare complex (MAC), which includes both M. avium and M. intracellulare. Typically, NTM infections affect the lungs and subsequently demonstrate a chronic course. Therefore, persistent respiratory symptoms generally indicate of the presence of pulmonary NTM diseases, and chest radiography, along with a sputum examination, are essential for its diagnosis. Because NTM are ubiquitous environmental organisms, a positive culture from a minimum of two separate expectorated sputum samples are required to make a diagnosis. The repertoire of effective drugs for treatment is considerably limited, indicating the need for long-term management with multiple drugs. Establishing a treatment regimen with high therapeutic efficacy and safety is an important issue for the future.     

Nontuberculous mycobacterial lung disease in patients without HIV infection: a retrospective analysis over 3 years

Introduction: Nontuberculous mycobacterial lung infections are relatively common in immunocompromised patients but are now increasingly being diagnosed in immunocompetent individuals. These organisms are not always pathogenic bacteria when isolated from human samples. The identification of which isolates are contaminants or colonizers is based on internationally accepted criteria. The clinical significance of the isolation of nontuberculous mycobacteria (NTM) from respiratory specimens in Italy is unknown. Objective: study was performed to evaluate the local epidemiology of NTM pulmonary infection in Naples in patients with positive respiratory specimens, and also to describe the clinical and radiological features of NTM pulmonary disease in immunocompetent patients with or without pre‐existing lung disease. Methods: Between December 2006 and September 2009, the clinical records and radiological examinations of 39 patients with 55 positive cultures for NTM species by sputum or bronchial wash or lavage were reviewed. Results: According to microbiological, clinical and radiological criteria, our study identified 16 patients with NTM lung infection as a ‘disease’ group and 23 patients in a ‘contamination’ group but without disease. M. intracellulare (n = 7, 41.2%), followed by M. kansasii (n = 5, 29.4%) were the most common NTM found in the ‘disease’ group. We detected a high number of M. gordonae isolates in respiratory samples obtained by fibrobronchoscopy. Conclusions: We evaluated the clinical significance of isolations in our reference centre in Naples. Forty‐one of all patients have ‘disease’, M. intracellulare and M. kansasii are mainly responsible. NTM species were analyzed in relation to their frequency. Assumptions were made about low pathogenic NTM isolations. Please cite this paper as: Del Giudice G, Iadevaia C, Santoro G, Moscariello E, Smeraglia R and Marzo C. Nontuberculous mycobacterial lung disease in patients without HIV infection: a retrospective analysis over 3 years. Clin Respir J 2011; 5:203–210.     

Identification and characterization of nontuberculous mycobacteria isolated from suspected pulmonary tuberculosis patients in eastern china from 2009 to 2019 using an identification array system

ObjectiveNontuberculous mycobacteria (NTM) species are increasingly being isolated and have become a key factor affecting public health by causing pulmonary diseases. Most NTM species do not respond to conventional tuberculosis (TB) drugs. This study aimed to identify NTM isolated from suspected pulmonary TB patients from the Zhejiang province and analyze their distribution in the region.MethodsA total of 1,113 NTM isolates from patients suspected to be suffering from acid-fast bacilli-positive tuberculosis were identified at the species level, using the CapitalBio Mycobacterium identification array and polymerase chain reaction amplification and sequencing of 16S-23S gene internal transcribed spacer (ITS), 16S rRNA, and hsp65.ResultsOf the 23,138 isolates, we identified 1,102 NTM (4.8%), mainly including Mycobacterium intracellulare (54.81%, 604/1,102), M. chelonae-M. abscessus (16.52%, 182/1,102), M. avium (13.16%, 145/1,102), M. kansasii (8.17%, 90/1,102), and M. gordonae (3.27%, 36/1,102).ConclusionThe distribution of NTM species observed in patients with suspected pulmonary tuberculosis provides guidance for the diagnosis and treatment of NTM pulmonary diseases.     

Micobacterias no tuberculosas. ¿Una amenaza emergente?

Introduction and objective

Non-tuberculous mycobacteria (NTM) isolates are becoming more common. The main objective of our study was to establish the number and diversity of NTM species in our region and their distribution according to the source sample, age and gender of the patients, and to analyse clinically significant isolates.

Clinical features of infection caused by non-tuberculous mycobacteria: 7 years’ experience

Introduction

Non-tuberculous mycobacteria (NTM) are ubiquitous organisms associated with various infections. The aim of the study was to determine the most relevant clinical characteristics of NTM during the 7-year period.

Methodology

A retrospective study of NTM infections was conducted between January 2009 and December 2016. The American Thoracic Society/Infectious Disease Society of America criteria were used to define cases of pulmonary or an extrapulmonary site.

Results

A total of 85 patients were included in the study. Pulmonary cases predominated 83/85 (98%), while extrapulmonary NTM were present in 2/95 (2%) patients. Overall, ten different NTM species were isolated. The most common organisms were slow-growing mycobacteria (SGM) presented in 70/85 (82.35%) patients. Isolated SGM strains were Mycobacterium avium complex (MAC) in 25/85 (29.41%) patients, M. xenopi in 20/85 (23.53%) patients, M. kansasii in 15/85 (17.65%) patients and M. peregrinum and M. gordonae in 5/85 (5.88%) patients each. Isolated rapid-growing mycobacteria (RGM) strains were M. abscessus in 8/85 (9.41%) patients, M. fortuitum in 4/85 (4.71%) patients and M. chelonae in 3/85 (3.53%) patients. Almost all patients (98%; 83/85) had comorbidities. Among 75 (88.24%) patients who completed follow-up, 59 (69.41%), 10 (11.76%) and 6 (7%), were cured, experienced relapse and died, respectively.

Conclusion

In the present study, pulmonary NTM infections were more frequent compared to extrapulmonary disease forms. SGM were most common isolates with MAC pulmonary disease the most frequently found. Comorbidities have an important role in NTM occurrence. Further investigation should focus on an NTM drug susceptibility testing.

     

The role of the third acid-fast bacillus smear in tuberculosis screening for infection control purposes: A controversial topic revisited

INTRODUCTION:

Recent studies have suggested that two negative acid-fast bacillus (AFB) smears may be as effective as three when screening patients with suspected Mycobacterium tuberculosis for respiratory isolation purposes. However, current recommendations in Canada, the United States and Europe still support a three-smear approach.

METHODS:

The microbiology database of a tertiary care hospital was searched for sputum, tracheal aspirates and bronchoalveolar lavage samples from 2003 to 2007 that had been sent for mycobacterial testing. The first patient specimen to become AFB smear positive was noted. As well, the time required to collect the third specimen in hospitalized patients who remained smear negative was used to estimate the savings in isolation costs associated with a two-smear approach.

RESULTS:

There were 8347 respiratory specimens from 5168 patients in the five-year period. Of these patients, 2.2% (116 of 5168) were AFB smear positive, of whom 55.2% (64 of 116) were culture positive for Mycobacterium tuberculosis. Overall 89% (57 of 64) of patients were identified as being AFB smear positive by the first smear, 7.8% (five of 64) were identified by the second smear and 3.2% (two of 64) were identified by further smears. Smear-negative patients spent a combined 710 days in isolation awaiting collection of the third sample at a cost of approximately $142,000 over five years.

CONCLUSION:

A two-smear approach for discontinuation of respiratory isolation precautions is safe and has the potential to reduce hospital expenditures.     

Isolation prevalence of pulmonary nontuberculous mycobacteria in Ontario in 2007

BACKGROUND:

The reported prevalence of pulmonary nontuberculous mycobacteria (NTM) infections is increasing.

OBJECTIVE:

To determine the ‘isolation prevalence’ of NTM in 2007 and compare it with previously published research that examined the increasing rates of isolation of NTM from clinical pulmonary specimens between 1997 and 2003.

METHODS:

Isolation prevalence was investigated retrospectively by reviewing a cohort of all positive pulmonary NTM culture results from the Tuberculosis and Mycobacteriology Laboratory, Public Health Laboratory (Toronto, Ontario) in 2007, which identifies at least 95% of NTM isolates in Ontario. Isolation prevalence was calculated as the number of persons with a pulmonary isolate in a calendar year divided by the contemporary population and expressed per 100,000 population. Changes in isolation prevalence from previous years were assessed for statistical significance using generalized linear models with a negative binomial distribution.

RESULTS:

In 2007, 4160 pulmonary isolates of NTM were collected from 2463 patients. The isolation prevalence of all species (excluding Mycobacterium gordonae) was 19 per 100,000 population in 2007 – an increase from previous observations reported for Ontario – corresponding to an average annual increase of 8.5% from 1997 to 2007 (P<0.0001). Average annual increases in isolation prevalence of Mycobacterium avium complex (8.8%, P<0.0001) and Mycobacterium xenopi (7.3%, P=0.0005) were largely responsible for the overall increase, while prevalence rates of rapidly growing mycobacteria remained relatively stable.

CONCLUSION:

The isolation prevalence of pulmonary NTM continues to increase significantly in Ontario, supporting the belief that pulmonary NTM disease is increasingly common.     

Recovery rate of NTM from AFB smear-positive sputum specimens at a medical centre in South Korea.

OBJECTIVE: To investigate the recovery rate of non-tuberculous mycobacteria (NTM) from acid-fast bacilli (AFB) smear-positive sputum specimens at a tertiary care medical centre in South Korea with a high pulmonary tuberculosis (PTB) burden. DESIGN: Retrospective analysis of data from AFB smear- and culture-positive sputum specimens collected between January 1998 and December 2001. RESULTS: Over 4 years, 1328 sputum specimens collected from 616 patients were AFB smear- and culture-positive. NTM were recovered from 9.1% (121/1328) of the smear-positive sputum specimens, and from 8.1% (50/616) of patients with smear-positive sputum. NTM were isolated at least twice in 94% (47/50) of the patients from whom NTM was recovered. The most common organism found was Mycobacterium avium complex, followed by M. abscessus. CONCLUSION: These results suggest that a substantial proportion of patients at a tertiary care medical centre in South Korea with AFB smear-positive sputum specimens may have NTM lung disease rather than PTB.     

Identification and Characteristics of Co-isolation of Multiple Nontuberculous Mycobacteria

Objective Although multiple nontuberculous mycobacteria (NTM) species can be isolated from the same patient, little has been reported on co-isolation. We clarified the trends and characteristics of the co-isolation of multiple NTM species. Methods To collect data on multiple NTM isolation, we first extracted all patients who visited our hospital from 2006 through 2015 with a diagnosis of NTM lung diseases other than Mycobacterium avium complex (MAC) and then reviewed their medical records to evaluate the co-isolation of multiple NTM species. Results Of 213 patients with non-MAC lung disease, the most common NTM species was M. gordonae (32%), followed by M. kansasii (20%) and M. abscessus (14%). Non-MAC NTM lung disease tended to be associated with middle age with a low body mass index and male predominance. Multiple NTM species were isolated from 55 (26%) of the 213 patients. The clinical characteristics associated with multiple NTM species isolation included female predominance, never smokers and the absence of cavity lesions in the lungs. The highest co-isolation rate was observed in patients with M. gordonae isolation (30%), followed by M. furtuitum isolation (26%) and M. abscessus isolation (20%). Only MAC was isolated when co-isolated with M. abscessus. Among M. szulgai, M. peregrinum and M. terrae isolation, no other NTM species were detected. Conclusion Co-isolation of multiple NTM species was not uncommon, with 26% of patients with non-MAC NTM lung diseases showing co-isolation with multiple NTM species. Each NTM species had distinct characteristics in terms of co-isolation.     

A comparison between the efficiency of the Xpert MTB/RIF assay and nested PCR in identifying Mycobacterium tuberculosis during routine clinical practice

Objectives

Polymerase chain reaction (PCR) for the detection of Mycobacterium tuberculosis (MTB) is more sensitive, specific, and rapid than the conventional methods of acid-fast bacilli (AFB) smear and culture. The aim of this study was to determine if the Xpert MTB/rifampicin (RIF) assay had additional advantages over nested PCR for the detection of MTB in a geographical area with intermediate tuberculosis (TB) incidence.

Methods

Between February and December 2013, the Xpert MTB/RIF assay and MTB nested PCR, as well as AFB smear and culture, were simultaneously performed on 198 clinical samples (160 pulmonary and 38 non-pulmonary specimens) collected from 171 patients hospitalized at Hallym University Medical Center for possible TB. The accuracy of the diagnosis of MTB culture-positive TB and the turnaround time of reporting laboratory results were calculated and compared. Rifampin resistance by the Xpert MTB/RIF assay was reviewed with that of conventional drug susceptibility testing (DST).

Results

The sensitivity, specificity, and positive and negative predictive values of the Xpert MTB/RIF assay and MTB nested PCR for diagnosis of MTB culture-positive pulmonary TB were 86.1% vs. 69.4% (P=0.1563), 97.8% vs. 94.1% (P=0.2173), 91.2% vs. 75.8% (P=0.1695), and 96.4% vs. 92.0% (P=0.2032), respectively. The median turnaround times of the Xpert MTB/RIF assay and MTB nested PCR were 0 [0-4] days and 4 [1-11] days, respectively (P<0.001). Two cases of rifampin resistance, as determined by the Xpert MTB/RIF assay, were found to be multi-drug resistant (MDR) pulmonary TB by DST.

Conclusions

The Xpert MTB/RIF assay seemed to be sensitive, specific, and comparable to nested PCR for identifying MTB among clinically suspected TB patients, and the assay can be valuable in giving a timely identification of resistance to rifampin.     

Sequential Therapy for Helicobacter pylori Infection in Korea: Systematic Review and Meta-Analysis

Background/Aims

Sequential therapy (ST) for Helicobacter pylori infection in countries other than Korea has shown higher eradication rates than triple therapy (TT). The aim of this study was to evaluate the efficacy of ST in Korea by performing a meta-analysis.

Methods

We performed a comprehensive literature search on the efficacy of ST as a first-line therapy. The odds ratios (ORs) of eradicating H. pylori infection after ST compared with TT were pooled. Pooled estimates of the eradication rates of ST and TT were also calculated.

Results

A total of six studies provided data on 1,759 adult patients. The ORs for the intention to treat (ITT) and the per-protocol (PP) eradication rate were 1.761 (95% confidence interval [CI], 1.403 to 2.209) and 1.966 (95% CI, 1.489 to 2.595). Pooled estimates of the ITT and PP eradication rate were 79.4% (95% CI, 76.3% to 82.2%) and 86.4% (95% CI, 83.5% to 88.8%), respectively, for the ST group, and 68.2% (95% CI, 62.1% to 73.8%) and 78.9% (95% CI, 68.9% to 81.7%), respectively, for the TT group.

Conclusions

Although ST presented a higher eradication rate than TT in Korea, the pooled eradication rates were lower than expected. Further studies are needed to validate ST as a first-line treatment for H. pylori in Korea.     

Utilización de diferentes técnicas de biología molecular integradas en un algoritmo de identificación de micobacterias no tuberculosas

Introduction

The aim of the present work was to demonstrate the utility of a non-tuberculous mycobacteria (NTM) identification algorithm, which integrates different PCR-based techniques and basic phenotypic features. Moreover, the algorithm for pattern restriction analysis of hsp65 (hsp65 PRA) interpretation has been updated.

Methods

The workflow chosen consisted of the identification by a DNA hybridization probe method, followed by PCR-restriction enzyme analysis of hsp65 (hsp65 PRA) in those isolates that cannot be identified by hybridization probes. If necessary, 16S rRNA gene and hsp65 gene sequencing were used for speciation.

Results

A total of 236 NTM were collected, in which 102 (43.2%) isolates were identified by DNA specific probes and 76 (32.2%) isolates were identified with hsp65 PRA. Partial sequencing of the 16S rRNA gene was used for species identification of the remaining 58 (24.5%) isolates. Fifty-three (22.4%) were identified using this method. Five isolates (2.1%) were submitted for partial sequencing of hsp65 gene and one isolate was identified with this method. Four strains (1.7%) could not be identified at species level. Three new PRA patterns were found. Seven isolates tested positive with the AccuProbe Mycobacterium avium complex identification test but did not test positive with the M. avium or Mycobacterium intracellulare specific probes. Five and two of these isolates were identified as M. intracellulare and Mycobacterium colombiense, respectively.

Conclusion

This approach allowed us to identify almost all NTM isolates found in this study, including some recently described species.     

Leishmania infantum DNA detection in Phlebotomus tobbi in a new northern focus of visceral leishmaniasis in Iran

Objective

To identify the vector(s), the parasite and the species composition of sand flies in the district during May-October 2012.

Methods

For reaching our objectives we used polymerase chain reaction of kDNA, ITS1-rDNA, followed by restriction fragment length polymorphism.

Results

Two species of Phlebotomus sergenti and Phlebotomus tobbi were the most prevalent among 8 species identified comprising 51.1% and 32.9% respectively. Among the 160 specimens of female sand flies tested by polymerase chain reaction of kDNA, ITS1-rDNA, followed by restriction fragment length polymorphisms, only 1 out of 80 Phlebotomus tobbi (1.25%) were positive to Leishmania infantum parasites.

Conclusions

Our finding showed that Phlebotomus tobbi may play as a vector to circulate the parasite of Leishmania infantum among reservoir(s) and human.     

Evaluation of amplification targets for the specific detection of Bordetella pertussis using real-time polymerase chain reaction

BACKGROUND:

Bordetella pertussis infections continue to be a major public health challenge in Canada. Polymerase chain reaction (PCR) assays to detect B pertussis are typically based on the multicopy insertion sequence IS481, which offers high sensitivity but lacks species specificity.

METHODS:

A novel B pertussis real-time PCR assay based on the porin gene was tested in parallel with several previously published assays that target genes such as IS481, ptx-promoter, pertactin and a putative thialase. The assays were evaluated using a reference panel of common respiratory bacteria including different Bordetella species and 107 clinical nasopharyngeal specimens. Discrepant results were confirmed by sequencing the PCR products.

RESULTS:

Analytical sensitivity was highest for the assay targeting the IS481 element; however, the assay lacked specificity for B pertussis in the reference panel and in the clinical samples. False-positive results were also observed with assays targeting the ptx-promoter and pertactin genes. A PCR assay based on the thialase gene was highly specific but failed to detect all reference strains of B pertussis. However, a novel assay targeting the porin gene demonstrated high specificity for B pertussis both in the reference panel and in clinical samples and, based on sequence-confirmed results, correctly predicted all B pertussis-positive cases in clinical samples. According to Probit regression analysis, the 95% detection limit of the new assay was 4 colony forming units/reaction.

CONCLUSION:

A novel porin assay for B pertussis demonstrated superior performance and may be useful for improved molecular detection of B pertussis in clinical specimens.     

Susceptibility of clinical Moraxella catarrhalis isolates in British Columbia to six empirically prescribed antibiotic agents

BACKGROUND:

Moraxella catarrhalis is a commensal organism of the respiratory tract that has emerged as an important pathogen for a variety of upper and lower respiratory tract infections including otitis media and acute exacerbations of chronic bronchitis. Susceptibility testing of M catarrhalis is not routinely performed in most diagnostic laboratories; rather, a comment predicting susceptibility based on the literature is attached to the report. The most recent Canadian report on M catarrhalis antimicrobial susceptibility was published in 2003; therefore, a new study at this time was of interest and importance.

OBJECTIVE:

To determine the susceptibility of M catarrhalis isolates from British Columbia to amoxicillin-clavulanate, doxycycline, clarithromycin, cefuroxime, levofloxacin and trimethoprimsulfamethoxazole.

METHODS:

A total of 117 clinical M catarrhalis isolates were isolated and tested from five Interior hospitals and two private laboratory centres in British Columbia between January and December 2012. Antibiotic susceptibility of M catarrhalis isolates was characterized using the Etest (E-strip; bioMérieux, USA) according to Clinical Laboratory Standards Institute guidelines.

RESULTS:

All isolates were sensitive to amoxicillin-clavulanate, doxycycline, clarithromycin, levofloxacin and trimethoprimsulfamethoxazole. One isolate was intermediately resistant to cefuroxime, representing a 99.15% sensitivity rate to the cephem agent. Cefuroxime minimum inhibitory concentrations (MICs) inhibiting 50% and 90% of organisms (MIC50 and MIC90) were highest among the antibiotics tested, and the MIC90 (3 μg/mL) of cefuroxime reached the Clinical Laboratory Standards Institute breakpoint of susceptibility.

DISCUSSION:

The antibiotic susceptibility of M catarrhalis isolates evaluated in the present study largely confirms the findings of previous surveillance studies performed in Canada. Cefuroxime MICs are in the high end of the sensitive range and the MIC50 and MIC90 observed in the present study are the highest ever reported in Canada.

CONCLUSION:

Although cefuroxime MICs in M catarrhalis are high, all agents tested showed antimicrobial activity, supporting their continued therapeutic and empirical use.     

Nontuberculosis Mycobacterium Disease is a Risk Factor for Chronic Obstructive Pulmonary Disease: A Nationwide Cohort Study

Background

The aim of this study was to evaluate the association between chronic obstructive pulmonary disease (COPD) and nontuberculosis mycobacterium (NTM) disease.

Methods

We used data from the National Health Insurance Research Database of Taiwan in this study. The NTM cohort contained 3,005 patients, and each case was randomly frequency matched by age, sex, income, occupation, and index year with four people from the general population without NTM infections. Multivariate Cox proportional hazards regression was used to calculate adjusted hazard ratios (aHR) of COPD in the NTM cohort compared with the non-NTM cohort.

Results

The incidence of COPD was 3.08-fold higher (21.75 vs. 6.11 per 1,000 person-years) in the NTM cohort than in the non-NTM cohort. The aHR of COPD comparing the NTM cohort with the non-NTM cohort was 3.57 (95 % CI 2.56–4.97) for women and 2.89 (95 % CI 2.31–3.61) for men. The aHR of COPD was higher in the patients with NTM infection and a comorbidity such as bronchopneumonia, pneumonia, diabetes, asthma, and heart disease. The Mycobacterium avium-intracellulare complex group (MAC) and the non-MAC group were isolated in the NTM cohort. The MAC group had a higher aHR of COPD than the non-NTM cohort (aHR = 3.72, 95 % CI 2.94–4.72). The cumulative incidence of COPD in the NTM cohort was higher than in the non-NTM cohort (P < 0.0001, log rank test).

Conclusions

Physicians should be aware of indolent NTM disease that increases the risk of COPD.     

Nontuberculous mycobacterial and Aspergillus infections among cadaveric lung transplant recipients in Japan

Background

Lung transplantation is an effective treatment modality for respiratory failure. Chronic lung infections, including infections caused by nontuberculous mycobacteria (NTM) and Aspergillus, are difficult to control, and uncontrolled infections are relative contraindications for lung transplantation. However, few reports have documented the incidence and outcome of these infections in lung transplant recipients.

Polymerase chain reaction for the differentiation of Mycobacterium intracellulare and Mycobacterium avium

Polymerase chain reaction (PCR) amplification was performed using DNA purified from 15 mycobacterial type strains and from 21 specimens isolated from patients suspected to have non-tuberculous mycobacterial diseases. Using a primer set of MTB1-MTB2,11 specimens out of 21 were Mycobacterium avium and 8 were M. intracellulare, which were verified by the Gen Probe Rapid Diagnostic System for the M. avium complex (MAC). One of the remaining 2 specimens which did not hybridize with the probe for the MAC was identified as M. kansasii and the other was not specifically identified by the conventional culture method. PCR amplification, using a primer set of TB1-TB3, was also performed for the specific identification of M. tuberculosis complex.     

Prognosis of chronic pulmonary aspergillosis in patients with pulmonary non-tuberculous mycobacterial disease

Background

Pulmonary non-tuberculous mycobacterial disease (PNTM) is a known risk factor for chronic pulmonary aspergillosis (CPA). However, few studies have focused on the prognosis of PNTM-associated CPA. In the present investigation, we aimed to elucidate the clinical course and prognostic factors of CPA in patients with PNTM.