Pulmonary Nontuberculous Mycobacteria Infection Research Articles

Laboratory Diagnosis of Non-Tuberculous Mycobacterium Infections in Bronchiectasis Patients: Issues and Controversies

Non-tuberculous mycobacteria (NTM) are environmental microbes that can cause pulmonary infection and are especially problematic in bronchiectasis patients with or without cystic fibrosis (CF). Microbiological identification of NTM in these patients is difficult given the high microbial burden in the lungs and the need to differentiate between colonization and transient and true infection. Determining if and when to initiate antimicrobial treatment against this multi-drug-resistant group of organisms is also challenging. To address the changing landscape of care for these patients, the U.S. Cystic Fibrosis Foundation and the European Cystic Fibrosis Society convened an expert committee in 2016 and drafted new guidelines for the management of NTM in CF patients. These recommendations update the 2007 American Thoracic Society and Infectious Disease Society of America guidelines on the diagnosis and treatment of NTM pulmonary infections. Here, we provide data to support the new recommendations and discuss the advancements and ongoing challenges associated with NTM infections.

Surveillance of Extrapulmonary Nontuberculous Mycobacteria Infections, Oregon, USA, 2007-2012.

Limited data are available describing extrapulmonary nontuberculous mycobacteria (NTM) infections in the general population. We describe results from statewide population-based laboratory surveillance in Oregon, USA, during 2007–2012. We defined a case of extrapulmonary NTM infection as >1 isolate from skin/soft tissue, disseminated sites, lymph node, joint, or other sites. The annual incidence of extrapulmonary NTM infection (other than Mycobacterium gordonae) was stable, averaging 1.5 cases/100,000 population. Median age of the 334 patients was 51 years, and 53% of patients were female. Half of cases were caused by M. avium complex, but rapid-growing NTM species accounted for one third of cases. Most extrapulmonary NTM infections are skin/soft tissue. Compared with pulmonary NTM infection, more extrapulmonary infections are caused by rapid-growing NTM species. the designation of NTM as a reportable disease in Oregon in 2014 will result in better detection of changes in the incidence and patterns of disease in the future.

Oxazolidinone Therapy for Recalcitrant Pulmonary Nontuberculous Mycobacterial Infection

SESSION TITLE: Chest Infections SESSION TYPE: Original Investigation Poster PRESENTED ON: Wednesday, November 1, 2017 at 01:30 PM - 02:30 PM PURPOSE: Non-tuberculous mycobacteria (NTM) are emerging pathogens that affect immunocompromised and immunocompetent subjects. The incidence and prevalence of NTM lung disease is increasing and treatment options are lengthy and fraught with toxicities and poor outcome. The decision to start treatment requires individualized assessment and analysis of antimicrobial resistance patterns. Use of linezolid in NTM patients was recently reported for the first time in a multicenter non-randomized study (Winthrop et al, ERJ, 2015). Here we report the use of linezolid and tidezolid in eleven subjects with recalcitrant pulmonary NTM infection. METHODS: The study was a retrospective analysis of the outcome of oxazolidinone therapy in subjects with a diagnosis of NTM. We identified eleven patients during a 3 year study period. Radiology, microbiology, prior NTM therapy, macrolide sensitivity, oxazolidinone regimen and drug toxicities were noted for all subjects. RESULTS: The majority of patients were female (90%) and caucasian. The median age was 65 years (range 26-77). Common comorbidities were asthma, COPD, bronchiectasis, GERD and depression. Six of the eleven subjects had cavitary disease and the remaining had significant bronchiectasis with a nodular or cystic component on radiology. Ten subjects (90%) grew Mycobacterium avium intracellulare. Other subjects grew M abscessus (55%), and M kansasii. Macrolide resistance (erm gene) was confirmed in 6 subjects (55%). Prior to the institution of oxazolidinone therapy, all subjects had been on complex antimicrobial regimens which included amikacin, augmentin, clofazimine, cefoxitin, ethambutol, macrolides, meropenem, moxifloxacin, rifampin and tigecycline. Ten subjects (90%) were treated with oral linezolid. Five patients (45%) had to be transitioned from linezolid to tidezolid due to adverse effects. The most commonly used regimen for linezolid was 600mg once daily (72.7%). This dose was decreased to 300 mg once daily in one patient due to nausea. The most commonly used regimen for tidezolid was 200mg once daily (83%). Average duration of therapy was 10.2 months for linezolid and 6 months for tidezolid. Patients were routinely monitored for symptoms, blood counts and peripheral neuropathy. The most common side effects observed were peripheral neuropathy (three patients), nausea (three patients), thrombocytopenia (one patient) and anemia (one patient). In one case, linezolid was stopped due to drug interaction with an antidepressant. Therapy was discontinued in one patient due to cost considerations. Three patients continue on oxazolidinone therapy without any complications. Vitamin B6 was prescribed for every patient to prevent hematological complications and peripheral neuropathy. CONCLUSIONS: In summary, we have demonstrated that both linezolid and tidezolid can be used for longer durations in the treatment of recalcitrant NTM disease. Adverse events requiring cessation of therapy are common but some of these could be due to other therapies or coexistent comorbidities. Larger studies are required to ascertain efficacy and tolerability. CLINICAL IMPLICATIONS: Oxazolinidone antimicrobials could be considered in the treatment regimen of patients with difficult NTM infection. DISCLOSURE: The following authors have nothing to disclose: Kelsey Luoma, Shivani Singh, Doreen Addrizzo-Harris No Product/Research Disclosure Information

Persimmon-derived tannin has bacteriostatic and anti-inflammatory activity in a murine model of Mycobacterium avium complex (MAC) disease.

Nontuberculous mycobacteria (NTM), including Mycobacterium avium complex (MAC), cause opportunistic chronic pulmonary infections. Notably, MAC susceptibility is regulated by various factors, including the host immune system. Persimmon (Ebenaceae Diospyros kaki Thunb.) tannin is a condensed tannin composed of a polymer of catechin groups. It is well known that condensed tannins have high antioxidant activity and bacteriostatic properties. However, it is hypothesized that condensed tannins might need to be digested and/or fermented into smaller molecules in vivo prior to being absorbed into the body to perform beneficial functions. In this study, we evaluated the effects of soluble persimmon-derived tannins on opportunistic MAC disease. Soluble tannins were hydrolyzed and evaluated by the oxygen radical absorbance capacity (ORAC) method. The ORAC value of soluble tannin hydrolysate was approximately five times greater than that of soluble tannin powder. In addition, soluble tannin hydrolysate exhibited high bacteriostatic activity against MAC in vitro. Furthermore, in an in vivo study, MAC infected mice fed a soluble tannin-containing diet showed significantly higher anti-bacterial activity against MAC and less pulmonary granuloma formation compared with those fed a control diet. Tumor necrosis factor α and inducible nitric oxide synthase levels were significantly lower in lungs of the soluble tannin diet group compared with the control diet group. Moreover, proinflammatory cytokines induced by MAC stimulation of bone marrow-derived macrophages were significantly decreased by addition of soluble tannin hydrolysate. These data suggest that soluble tannin from persimmons might attenuate the pathogenesis of pulmonary NTM infection.

Safety and Effectiveness of Clofazimine for Primary and Refractory Nontuberculous Mycobacterial Infection

Clofazimine is an antimicrobial agent that has activity invitro against mycobacteria. Increasingly, it has been used for the treatment of nontuberculous mycobacteria (NTM), despite limited data supporting its use in this setting. The objective of this study was to evaluate the safety, tolerability, and clinical outcomes associated with clofazimine in patients with NTM infection. This observational-cohort study assessed clofazimine as used for pediatric and adult cystic fibrosis (CF) and non-CF patients with pulmonary and extrapulmonary NTM infection as part of a multidrug regimen from 2006 to 2014. Treatment regimens and adverse drug reactions (ADRs) were captured. A total of 112 patients were included (median age, 62 years); 24 patients (21%) had CF. Eighty-seven (78%) had refractory disease with failure of previous therapy. Fifty-four patients (48%) had Mycobacterium abscessus complex, 41 (37%) had Mycobacterium avium complex, and 16 (14%) had two NTM species. The median duration of clofazimine use was 383days (range, 3-2,419days). Sixteen patients (14%) stopped clofazimine due to an ADR after a median of 101days (95%CI, 63-119). Forty-one of 82 patients (50%) with pulmonary disease converted to negative NTM cultures within 12months. Clofazimine was a safe, reasonably tolerated, and active oral drug for NTM infection in our heterogeneous population of pediatric and adult CF and non-CF patients. It should be considered as an alternative drug for treatment of NTM disease.

Cough physiology in elderly women with nontuberculous mycobacterial lung infections.

Elderly white, thin, nonsmoking women appear to be more susceptible to lung infections with Mycobacterium avium complex and other nontuberculous mycobacteria (NTM). It has been postulated that such disease in women is related to suppression of their cough. We hypothesized that patients with pulmonary NTM (pNTM) infections may have altered cough physiology compared with unaffected control subjects. We used capsaicin-induced cough to assess the cough reflex in pNTM subjects. Eight elderly white women with stable chronic pNTM infections and six unaffected age-matched control subjects were recruited. There was no significant difference between groups in capsaicin-elicited cough motor response, airflow pattern, or cough frequency. The urge-to-cough (UTC) score at the lowest capsaicin concentration was significantly lower in pNTM than control subjects (P < 0.05). There were no significant differences in the UTC score between pNTM and control subjects at >50 μM capsaicin. These results suggest lower UTC sensitivity to the lowest concentration of capsaicin in pNTM than control subjects. In other words, the pNTM subjects do not sense a UTC when the stimulus is relatively small.NEW & NOTEWORTHY This study investigates the cough motor response and cough sensitivity in patients with nontuberculous mycobacteria (NTM) infection. In elderly white female pulmonary NTM subjects, we demonstrated a capacity to produce coughs similar to that of age-matched control subjects but decreased cough sensitivity in response to a low dose of capsaicin compared with control subjects. These findings are important to understand the pathophysiological mechanisms resulting in NTM disease in elderly white women and/or the syndrome developing in elderly white female NTM patients.

Nontuberculous Mycobacterium during Pregnancy: A Case Report

Background: The purpose of the present case report was to describe an exacerbation of maternal respiratory condition during pregnancy and its association with severe fetal growth restriction. Case: A 29-year old woman, gravida 1, para 0, at 22 weeks’ gestation was admitted to due to poorly controlled asthma and nontuberculous mycobacterium pulmonary infection, namely mycobacterium kansasii. With anti-tuberculous therapy, systemic steroids, in addition to supportive care, gradual clinical improvement was noticed. An uncomplicated cesarean section was performed at 37 weeks’ gestation due to minimal interval growth in a severely growth restricted fetus. Conclusion: Early symmetrical fetal growth restriction should be anticipated with underlying, uncontrolled respiratory pathology, necessitating close monitoring in order to facilitate the optimal timing of delivery.

Factors which influence treatment initiation for pulmonary non-tuberculous mycobacterium infection in HIV negative patients; a multicentre observational study

BackgroundClinical, radiological and microbiological criteria inform diagnosis of pulmonary Non-Tuberculous Mycobacteria (NTM) disease and treatment decisions. This multicentre, review aims to characterise NTM disease meeting ATS/IDSA criteria and define factors associated with initiation of treatment. MethodsSputum samples growing NTM from 5 London hospitals between 2010 and 2014 were identified. Data for HIV-negative individuals meeting ATS/IDSA guidelines for pulmonary NTM disease were extracted. Associations between clinical variables and treatment decision were investigated using Chi-squared, Fishers-exact or Mann Whitney tests. Factors associated with treatment in univariate analysis (p < 0.150) were included in a multivariate logistic regression model. ResultsNTM were identified from 817 individuals' sputum samples. 108 met ATS/IDSA criteria. 42/108 (39%) were initiated on treatment. Median age was 68 (56–78) in the cohort.On multivariate analysis, factors significantly associated with treatment of pulmonary NTM infection were: Cavitation on HRCT (OR: 6.49; 95% CI: 2.36–17.81), presenting with night sweats (OR 4.18; 95% CI: 1.08–16.13), and presenting with weight loss (OR 3.02; 95% CI: 1.15–7.93).Of those treated, 18(43%) have completed treatment, 9(21%) remain on treatment, 10(24%) stopped due to side effects, 5(12%) died during treatment. Mortality was 31% (n = 13) in treated versus 21% (n = 14) in the non-treated cohort. Subgroup analysis of individual NTM species did not observe any differences in treatment initiation or outcomes between groups. DiscussionDecision to treat pulmonary NTM infection requires clinical judgement when interpreting clinical guidelines. Factors independently associated with decision to treat in this HIV-negative cohort include cavitation on HRCT and presenting with night sweats or weight loss.

Nontuberculous Mycobacteria Infection and Prognosis after Surgery of Lung Cancer: A Retrospective Study.

To investigate the association between pulmonary nontuberculous mycobacteria infection (PNTMI) and prognosis after pulmonary resection for non small cell lung cancer (NSCLC), we retrospectively analyzed 391 consecutive patients with NSCLC who underwent surgery. Subjects were grouped based on with/without PNTMI defined by two criteria (12 and 23 PNTMI subjects). Kaplan-Meier analysis showed no significant difference between the two groups regarding overall survival (p = 0.800 and p = 0.912 by two criteria). PNTMI was not identified as a significant factor associated with prognosis by either univariate or multivariate analysis (hazard ratio [HR] = 0.950 and HR = 0.948, respectively).

Health-related quality of life in patients with pulmonary non-tuberculous mycobacteria infection.

The health-related quality of life (HRQoL) in patients with pulmonary non-tuberculous mycobacteria (pNTM) infection has not yet been quantified. To evaluate the reliability and validity of the COPD Assessment Test (CAT) and St George's Respiratory Questionnaire (SGRQ) in quantifying the HRQoL of patients with pNTM. We performed a cross-sectional study of 52 patients with pNTM. All the subjects completed the CAT, SGRQ and Short Form-36 Health Survey (SF-36) questionnaires and underwent pulmonary function testing (PFT). A test-retest was performed and Cronbach α was calculated to assess reliability. Correlations of the CAT and SGRQ with SF-36 and PFT were performed to assess validity. The mean age of the patients was 67 years; 96% (50/52) were female. Both individual and total CAT and SGRQ scores showed good correlation between the test on Day 1 and the repeat test on Day 5. Cronbach's α (0.77-0.92) indicated satisfactory internal consistency. All scores were moderately or strongly correlated with the SF-36 Physical Component Summary score. The SGRQ and CAT questionnaires showed statistically significant validity in assessing HRQoL in patients with pNTM.

Pulmonary Mycobacterium avium-intracellulare is the main driver of the rise in non-tuberculous mycobacteria incidence in England, Wales and Northern Ireland, 2007-2012.

BackgroundThe incidence of non-tuberculous mycobacteria (NTM) isolation from humans is increasing worldwide. In England, Wales and Northern Ireland (EW&NI) the reported rate of NTM more than doubled between 1996 and 2006. Although NTM infection has traditionally been associated with immunosuppressed individuals or those with severe underlying lung damage, pulmonary NTM infection and disease may occur in people with no overt immune deficiency.Here we report the incidence of NTM isolation in EW&NI between 2007 and 2012 from both pulmonary and extra-pulmonary samples obtained at a population level.MethodsAll individuals with culture positive NTM isolates between 2007 and 2012 reported to Public Health England by the five mycobacterial reference laboratories serving EW&NI were included.ResultsBetween 2007 and 2012, 21,118 individuals had NTM culture positive isolates. Over the study period the incidence rose from 5.6/100,000 in 2007 to 7.6/100,000 in 2012 (p < 0.001). Of those with a known specimen type, 90 % were pulmonary, in whom incidence increased from 4.0/100,000 to 6.1/100,000 (p < 0.001). In extra-pulmonary specimens this fell from 0.6/100,000 to 0.4/100,000 (p < 0.001).The most frequently cultured organisms from individuals with pulmonary isolates were within the M. avium-intracellulare complex family (MAC). The incidence of pulmonary MAC increased from 1.3/100,000 to 2.2/100,000 (p < 0.001). The majority of these individuals were over 60 years old.ConclusionUsing a population-based approach, we find that the incidence of NTM has continued to rise since the last national analysis. Overall, this represents an almost ten-fold increase since 1995. Pulmonary MAC in older individuals is responsible for the majority of this change.We are limited to reporting NTM isolates and not clinical disease caused by these organisms. To determine whether the burden of NTM disease is genuinely increasing, a standardised approach to the collection of linked national microbiological and clinical data is required.

Differential Impairment of Interferon-γ Responses in Two Cases of Pulmonary Nontuberculous Mycobacterial Disease.

Nontuberculous mycobacteria (NTMs) are weakly virulent intracellular pathogens that are common in food and water supplies. The persistent culture of these organisms in the setting of clinical infection warrants investigation of immune function. In cases of isolated pulmonary NTM (PNTM) disease, underlying immune defects have not been clearly identified. We present two patients with isolated PNTM infection who demonstrated differentially impaired IFN-γ production across a range of stimuli. These cases show that cellular IFN-γ responses may be defective in a proportion of patient suffering PNTM disease and that when assessing responses, the stimulant used in the testing is important to delineate defective cell populations. Impaired IFN-γ responses to IL-12 + BCG seem to be a poor prognostic indicator in PNTM disease and in these cases were not improved by adjuvant IFN-γ.

Current Therapy for Nontuberculous Mycobacterial Pulmonary Disease

Pulmonary infections due to nontuberculous mycobacteria (NTM) occur commonly, are increasing in frequency, and pose many challenges to clinicians. Typically, NTM infections occur in the presence of structural lung disease such as chronic obstructive pulmonary disease (COPD), cystic fibrosis (CF), or bronchiectasis. Pharmacological therapy is the mainstay of treatment but should not be initiated until it is clear that the identification of NTM in bronchial secretions fulfills the criteria for active infection. Pathogenic NTM vary in their response to pharmacological therapy. Successful antimicrobial therapy must include the prolonged use of multiple agents simultaneously. Monotherapy is to be avoided. Mycobacterium avium complex (MAC) is the most common cause of NTM pulmonary infection, and clinical experience with this organism is extrapolated to guide the management of other NTM infections. MAC is best treated with a combination of a macrolide, a rifamycin, and ethambutol. Mycobacterium kansasii infections closely mimic active tuberculosis. In previously untreated patients, therapy with isoniazid, rifampin, and ethambutol is recommended. Mycobacterium abscessus is the most common rapidly-growing NTM pulmonary pathogen. It is very difficult to treat successfully with antimicrobial therapy, and the optimal drug treatment remains undefined. Surgical therapy has a limited but defined role in those with localized disease due to NTM, a significant complication such as life-threatening hemoptysis, or medically unresponsive disease. Surgical resection should be considered in appropriate patients especially in those with M. abscessus infections. The referral of patients to clinicians with experience in treating NTM pulmonary infections is recommended to ensure appropriate monitoring of therapeutic response and pharmacologic toxicity. Many clinical questions concerning NTM pulmonary infections remain incompletely answered. It is hoped that the increased recognition of the burden inflicted by these infections is paralleled by advances in patient-centered research.

Pulmonary Nontuberculous Mycobacterial Infection. A Multisystem, Multigenic Disease.

The clinical features of patients infected with pulmonary nontuberculous mycobacteria (PNTM) are well described, but the genetic components of infection susceptibility are not. To examine genetic variants in patients with PNTM, their unaffected family members, and a control group. Whole-exome sequencing was done on 69 white patients with PNTM and 18 of their white unaffected family members. We performed a candidate gene analysis using immune, cystic fibrosis transmembrance conductance regulator (CFTR), cilia, and connective tissue gene sets. The numbers of patients, family members, and control subjects with variants in each category were compared, as was the average number of variants per person. A significantly higher number of patients with PNTM than the other subjects had low-frequency, protein-affecting variants in immune, CFTR, cilia, and connective tissue categories (35, 26, 90, and 90%, respectively). Patients with PNTM also had significantly more cilia and connective tissue variants per person than did control subjects (2.47 and 2.55 compared with 1.38 and 1.40, respectively; P = 1.4 × 10(-6) and P = 2.7 × 10(-8), respectively). Patients with PNTM had an average of 5.26 variants across all categories (1.98 in control subjects; P = 2.8 × 10(-17)), and they were more likely than control subjects to have variants in multiple categories. We observed similar results for family members without PNTM infection, with the exception of the immune category. Patients with PNTM have more low-frequency, protein-affecting variants in immune, CFTR, cilia, and connective tissue genes than their unaffected family members and control subjects. We propose that PNTM infection is a multigenic disease in which combinations of variants across gene categories, plus environmental exposures, increase susceptibility to the infection.

Nontuberculous mycobacteria in cystic fibrosis and non-cystic fibrosis bronchiectasis.

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.

Identification and characterization of non-tuberculous mycobacteria isolated from tuberculosis suspects in Southern-central China.

The incidence of non-tuberculous mycobacteria (NTM)-related death has increased globally recently. To obtain information of the species and characterization of pathogens involved in NTM pulmonary infection in Southern-central China, we identified 160 non-tuberculous infection cases from 3995 acid-fast bacilli (AFB)-positive tuberculous suspects. We then randomly selected 101 non-tuberculous patients, isolated bacteria from their sputa and genotyped the pathogens using the 16S rRNA gene and 16S-23S rRNA internal transcribed spacer sequences. M. intracellulare (32.67%, 33/101), M. abscessus (32.67%, 33/101) and M. fortuitum (7.92%, 8/101) are identified in these isolates. Surprisingly, non-mycobacteria including Gordonia (8.91%, 9/101), Nocardia (5.94%, 6/101) and Tsukamurella (0.99%, 1/101) are also discovered, and the case of Tsukamurella pulmonis infection is first discovered in Southern-central China. Moreover, species of M. mucogenicum group, M. chubuense, M. kansasii, M. gastri, M. avium, M. porcinum and M. smegmatis are identified. In addition, nine immune compromised cases (8.91%, 9/101), including type two diabetes mellitus and HIV/AIDS are found to be infected with non-tuberculous bacteria. This study revealed the distribution and characteristics of non-tuberculous AFB pathogen infection occurred in Southern-central China, and suggested that physicians should be alert of the emerging of NTM and non-mycobacteria infection in AFB positive cases and take caution when choosing chemotherapy for tuberculosis-like pulmonary infections. Generally, this study may help with the development of new strategy for the diagnosis and treatment of mycobacterial infection.

Risk factors for microbiologic failure among Taiwanese adults with Mycobacterium abscessus complex pulmonary disease.

The Mycobacterium abscessus complex is a common cause of pulmonary nontuberculous mycobacteria infections in Taiwan. We examined the risk factors associated with treatment outcome in Taiwanese adults with pulmonary disease caused by the M. abscessus complex. We retrospectively reviewed the records of all patients from a southern Taiwan medical center from 2006 to 2012 who had respiratory specimens identified as M. abscessus complex and met the American Thoracic Society criteria for pulmonary disease. Of the 106 included patients, females (58.5%) and nonsmokers (79.2%) predominated. The mean age of patients was 64.8 years. Sixty-three patients (59.4%) had pre-existing lung disease. Previous mycobacterial pulmonary disease (34.9%) was the most common underlying disorder. Chest radiography indicated that bronchiectasis was common (47.2%) and that cavitations were less common (14.2%). Fifty-six patients received antibiotic treatment. Clinicians were more likely to prescribe antibiotics if the initial sputum acid-fast staining was positive (p < 0.001). Treatment outcome was analyzed in 26 patients who were treated for more than 3 months; three of these patients (11.5%) had clinical failure and 18 (69.2%) experienced sputum conversion. Patients with cavitary lesions were more likely to experience microbiologic failure (p = 0.02). Nine patients had positive cultures after antibiotic treatment for > 1 year. Previous mycobacterial pulmonary disease (p = 0.011) and cavitary lesion (p = 0.034) are risk factors for persistence of M. abscessus complex. With antimicrobial therapy, previous mycobacterial disease, and cavitary lesion are associated with microbiologic failure in Taiwanese adults with M. abscessus complex pulmonary disease.

Diagnostic delay of pulmonary nontuberculous mycobacterial infection in China

&#x0D; &#x0D; &#x0D; &#x0D; Background: Nontuberculous mycobacteria (NTM) infection is an emerging, but neglected public health concern in China.&#x0D; Findings: To investigate diagnostic delay of NTM diseases in China, we analyzed 91 patients with pulmonary NTM infection in Shandong Province. The median diagnostic delay time of the analyzed patients was 84 days, which was significantly associated with rural inhabitance (135 days vs. 73 days of urban inhabitance, p &lt; 0.01) and lower level of first visiting hospitals/clinics (70 and 82 days of tertiary and secondary hospitals/clinics respectively vs. 120 days of primary hospitals/clinics, p &lt; 0.05). M. farcinogenes was isolated from a 79-year-old male patient, which is the first report of pulmonary infection in humans.&#x0D; Conclusions: Our results indicate a significant diagnostic delay of NTM diseases in China, especially for rural patients with limited access to higher-level healthcare services.&#x0D; &#x0D; &#x0D; &#x0D;

The epidemiology of pulmonary nontuberculous mycobacteria: data from a general hospital in Athens, Greece, 2007-2013.

Background. The epidemiology of pulmonary nontuberculous mycobacteria (NTM) in Greece is largely unknown. Objectives. To determine the incidence and the demographic, microbiological, and clinical characteristics of patients with pulmonary NTM infection and pulmonary NTM disease. Methods. A retrospective review of the demographic, microbiological, and clinical characteristics of patients with NTM culture-positive respiratory specimens from January 2007 to May 2013. Results. A total of 120 patients were identified with at least one respiratory NTM isolate and 56 patients (46%) fulfilled the microbiological ATS/IDSA criteria for NTM disease. Of patients with adequate data, 16% fulfilled the complete ATS/IDSA criteria for NTM disease. The incidence of pulmonary NTM infection and disease was 18.9 and 8.8 per 100.000 inpatients and outpatients, respectively. The spectrum of NTM species was high (13 species) and predominated by M. avium-intracellulare complex (M. avium (13%), M. intracellulare (10%)), M. gordonae (14%), and M. fortuitum (12%). The ratio of isolation of NTM to M. tuberculosis in all hospitalized patients was 0.59. Conclusions. The first data on the epidemiology of pulmonary NTM in Athens, Greece, are presented. NTM infection is common in patients with chronic respiratory disease. However, only a significantly smaller proportion of patients fulfill the criteria for NTM disease.

Systematic review/Meta-analysis Prevalence of nontuberculous mycobacteria in patients with bronchiectasis: a meta-analysis

IntroductionNontuberculous mycobacteria (NTM) have emerged as critical opportunistic pathogens of lung diseases recently. Patients with preexisting bronchiectasis are susceptible to NTM. Nevertheless, patients with preexisting bronchiectasis are susceptible to NTM but the prevalence of NTM pulmonary infection in different species and geographical areas is still not fully understood.Material and methodsThe relevant data of the prevalence of NTM in patients with bronchiectasis were retrieved by searching the main databases such as PubMed, MEDLINE, Cochrane Library, and EMBASE. This meta-analysis was performed using Rev. Man 5.1 and Stata 11.0 software. The collected information of NTM prevalence was chosen as the effect size.ResultsThe results of the meta-analysis showed that the overall prevalence of NTM was 9.3% in patients with bronchiectasis. The further stratification of subgroup analysis indicated that the combined prevalence of NTM was higher in studies whose “sample size” was more than or equal to 100 (p = 0.002), in studies in which “time of study” was after or equal to 2002 (p < 0.001), in studies in which “participants’ geographic location” was Asian (p < 0.001) and in studies whose “method of study” was retrospective (p = 0.002) as well, compared with corresponding groups.ConclusionsOur findings suggested that the prevalence NTM infection is high in patients with bronchiectasis. A larger number of definitive randomized trials are still required to assess this research issue.