Mycobacterium xenopi, Mycobacterium fortuitum, Mycobacterium kansasii, and other nontuberculous mycobacteria in an area of endemicity for AIDS.

Between 1981 and 1990, cultures of specimens from 86 patients at State University of New York-Health Sciences Center at Brooklyn were positive for nontuberculous mycobacteria other than Mycobacterium avium/Mycobacterium intracellulare complex or Mycobacterium gordonae. The most common species isolated were Mycobacterium xenopi (33), Mycobacterium fortuitum (28), Mycobacterium kansasii (7), and Mycobacterium chelonae (6). Thirty-five patients (41%) had clinical and/or serological evidence of human immunodeficiency virus (HIV) infection. Patients from whom M. xenopi and M. kansasii were isolated were significantly more likely to be infected with HIV than were the remaining patients in this series. Most of the mycobacterial isolates were cultured from respiratory secretions. However, extrapulmonary infections with M. fortuitum, M. xenopi, M. kansasii, Mycobacterium terrae, and Mycobacterium scrofulaceum did occur among the HIV-infected patients.     

Mycobacterium kansasii and M. scrofulaceum isolates from HIV-negative South African gold miners: incidence, clinical significance and radiology.

SETTING: A South African gold mining hospital. OBJECTIVE: To investigate the clinical significance of non-tuberculous mycobacteria (NTM) isolates, and estimate NTM disease incidence in human immunodeficiency virus (HIV) negative miners. DESIGN: Retrospective case series describing clinical and radiological features associated with NTM sputum isolates from HIV-negative miners between January 1993 and July 1996, and a comparison group with Mycobacterium tuberculosis infection. RESULTS: Of miners with NTM isolates, 90% had been HIV-tested and 81% were HIV-negative. M. kansasii and M. scrofulaceum accounted for 202 (68%) and 41 (14%) isolates respectively. More than 80% of miners with M. kansasii or M. scrofulaceum were smear positive, and new cavitation was present in 78% and 74% respectively. Treatment failure occurred in 3% of M. kansasii and 12% of M. scrofulaceum patients. A normal pre-morbid radiograph was significantly less common in NTM than M. tuberculosis patients (odds ratio 0.26 and 0.10 for M. kansasii and M. scrofulaceum, respectively). NTM disease incidence, defined as NTM isolate plus new cavitation, was estimated at 66 and 12 per 100000 person-years for M. kansasii and M. scrofulaceum, respectively. CONCLUSIONS: M. kansasii and M. scrofulaceum disease are common in HIV-negative South African gold miners. Most isolates are associated with new cavitation against a background of silicosis or old TB scarring.     

The epidemiology of nontuberculous mycobacterial diseases in the United States. Results from a national survey

During the 2-yr period 1981-83, demographic, clinical, and laboratory information was collected for 5,469 patients from whom nontuberculous mycobacteria (NTM) had been isolated. Among the potential NTM pathogens, isolates of Mycobacterium avium complex were most frequent, followed by M. kansasii, M. fortuitum, M. scrofulaceum, and M. chelonae. Almost 90% of the isolates were obtained from respiratory specimens. Prevalence rates for NTM disease, as calculated by a diagnostic algorithm, were highest for M. avium complex (1.3/10(5)), M. fortuitum-M. chelonae (0.2/10(5)). The data suggest a changing epidemiologic picture of NTM disease due perhaps to the decreasing incidence of tuberculosis, the increasing prevalence of chronic lung disease, and increased culturing of diagnostic specimens, as well as possibly a change in the ecology of these organisms.     

Incidence and clinical significance of non-tuberculous mycobacteria isolated from clinical specimens during a 2-y nationwide survey

A 2-y nationwide survey of patients in Denmark with non-tuberculous mycobacteria (NTM) cultures was undertaken. Patients were identified by means of records held at the International Reference Laboratory of Mycobacteriology, Statens Serum Institut, Denmark. The objectives were to identify isolated NTM to species level, to describe the incidence of the various species and to evaluate the clinical significance of pulmonary NTM isolates other than M. avium complex (MAC) and M. gordonae. Identification was performed by means of hybridization or sequencing of 16S rDNA. The clinical significance of pulmonary NTM isolates was evaluated by means of questionnaires concerning patients (was sent to the clinicians!) patients who had NTM isolated for the first time using bacteriologic, radiographic and clinical criteria. A total of 1110 specimens (2.1%) from 525 patients grew NTM. After MAC (n = 198) and M. gordonae (n = 168), most patients had M. abscessus (n = 21), M. malmoense (n = 20) and M. xenopi (n = 17) isolated. Of the pulmonary patients, 50.6% met bacteriologic criteria, 75.3% radiographic criteria and 53.4% clinical criteria for significant infection. Almost half of the pulmonary patients met all the criteria for significant NTM infection that could be evaluated. Clinically significant infection was associated with underlying disease in most patients.     

The non-tuberculous mycobacteriosis

The Japanese Society for Tuberculosis officially announced that public name of "atypical mycobacteriosis" was changed to the Nontuberculous Mycobacteriosis, on April 2003. We sent out questionnaires on number of nontuberculous mycobacteriosis (NTM) to 2051 respiralogists. The number of newly diagnosed NTM patients from Apr. 2001 to Sep. 2001 were 1522 cases, those were 29.2% of all mycobacteriosis containing TB. The M. avium-intracellulare (MAC) disease took up 82.8% of all NTM, and M. kansasii disease took 8.1%. The rare species were M. gordonae, M. abscessus, M. fortuitum, M. chelonae, M. szulgai, M. scrofulaceum and M. xenopi. The former investigations noted that in the northan half of Japan, M. avium disease predominated M. intracellulare disease in MAC, and M. intracellulare disease overwhelmed in the southern half of Japan. Our newest examination revealed that in the northan half, M. avium is predominant but, in the southern half, the rate of two species is almost the same. Dr. Kobashi and his group surveyed the effect of combined chemotherapy following the guidelines on treatment for MAC disease. They revealed that the clinical effect of the combined chemotherapy (RFP, EB, SM and CAM) was better than that of the other regimens. However the efficacy of this therapy was unsatisfactory compared with the effect for pulmonary TB.     

Diagnosis and treatment of atypical mycobacterial infections of the respiratory tract

INTRODUCTION: Non tuberculous mycobacteria (NTM), unlike tuberculous mycobacteria, are not strictly human pathogens. The diagnosis of infection and the choice of treatment remain difficult. BACKGROUND: Evidence of a NTM in a pulmonary sample is not synonymous with infection. The diagnosis depends on the association of clinical, radiological and microbiological factors. If a NTM is isolated from a respiratory sample, the probability of infection depends on the species. The main NTMs responsible for pulmonary infection in France are Mycobacterium avium intracellulare, Mycobacterium xenopi, Mycobacterium kansasi and Mycobacterium abscessus. Their management is difficult and poorly understood. Treatment is well established for M. avium intracellulare and M. kansasii, with combinations of clarithromycin-rifampicin-ethambutol and isoniazid-rifampicin-ethambutol respectively. For M. xenopi, the optimal treatment is not known and a combination of clarithromycin-rifampicin-ethambutol, with moxifloxacin as an alternative, is currently recommended. In general, treatment is prolonged and often associated with problems of tolerance. VIEWPOINT AND CONCLUSION: The management of NTM infection, taking into account of the increase in patients "at risk", is an important issue. Further studies are needed to improve the criteria for infection and to find the optimal therapeutic combinations.     

Antimycobacterial susceptibility against nontuberculous mycobacteria using brothmic NTM

PURPOSE: Recently the incidence of pulmonary nontuberculous mycobacteria infection has increased among patients not only implicated with AIDS, but also without predisposing conditions. However, an effective antimicrobial therapy for the disease has not been established yet, because of the absence of highly active therapeutic drugs. We compared the in vitro antimicrobial activities of five antituberculous drugs, clarithromycin and fluoroquinolones against 92 clinical isolates belonging to three species of slowly growing nontuberculous mycobacteria. MATERIAL AND METHODS: M. avium (31 strains), M. intracellulare (44 strains), and M. kansasii (17 strains), all of which were isolated from sputum specimens of previously untreated patients with pulmonary nontuberculous mycobacteria infection, were used. The eight agents tested were streptomycin, ethambutol, kanamycin, isoniazid, rifampicin, clarithromycin, levofloxacin and gatifloxacin. The drug susceptibility of these strains in terms of MIC (minimum inhibitory concentration) was determined by BrothMIC NTM. RESULTS: The MICs of rifampicin, clarithromycin, levofloxacin and gatifloxacin for all three species were low and gatifloxacin was more active than levofloxacin between two fluoroquinolones. Regarding clarithromycin, 100% of the strains were susceptible to 2 micrograms/ml or less and none of the strains were resistant on this level. In contrast, the MICs of ethambutol and isoniazid for M. avium and M. intracellulare were high and less active in vitro than the other antimicrobial agents. CONCLUSION: These MIC studies suggest that rifampicin, clarithromycin, levofloxacin, and gatifloxacin have excellent in vitro antimicrobial activities against M. avium, M. intracellulare and M. kansasii and especially clarithromycin may be very useful as a drug therapy for previously untreated patients. In the treatment of pulmonary nontuberculous mycobacterium infection, further studies are needed to evaluate the clinical effects of these drugs and to observe the drug resistance, on the basis of the results of the drug susceptibility test by BrothMIC NTM.     

Non-tuberculous mycobacteria disease as a cause of hospitalization in HIV-infected subjects.

OBJECTIVES: The present study characterized and determined the prevalence of mycobacterial diseases (tuberculosis (TB) and non-tuberculous mycobacteria (NTM)) as a cause of hospitalization among HIV-infected subjects consecutively admitted to a large metropolitan hospital during 2001/2002. METHODS: Hospital discharge diagnoses were established for 521 HIV-positive patients. RESULTS: Respiratory disease accounted for 49% of the admissions. Community acquired pneumonia (CAP) was the main cause of respiratory disease (52%) followed by Pneumocystis carinii (PCP, 24%), non-tuberculous mycobacteria (NTM, 11%) and Mycobacterium tuberculosis (TB, 9%). Mycobacterium tuberculosis disease was established using bacteriological, clinical and radiographic criteria. NTM disease was defined following the American Thoracic Society criteria. NTM was disseminated in the majority of cases (19 Mycobacterium avium complex (MAC), one Mycobacterium kansasii). Nine patients had respiratory disease (seven MAC, one Mycobacterium fortuitum, one Mycobacterium kansasii) and one had gastrointestinal disease caused by MAC. Mortality was 10% for NTM disseminated cases; none of the TB patients died over the course of the study. The length of hospitalization for NTM patients was longer (15+/-13 days) than for other respiratory cases (10+/-10, p=0.04). CONCLUSIONS: NTM disease along with its related mortality is a significant pathology as a cause of hospitalization among HIV-infected individuals.     

Pulmonary infection with nontuberculous mycobacteria

Nontuberculous mycobacterial infections (NTM) are being increasingly recognized as a cause of chronic pulmonary disease. We recently reviewed the clinical, radiologic, and bacteriologic presentation of 89 adult patients ill enough to have been hospitalized between 1981 and 1985 with the diagnosis of NTM. Preexisting lung disease was present in 82% and alcohol abuse in 40%. Although M. avium complex was identified in 51% of the patients, M. xenopi, which is usually reported to occur infrequently, accounted for 38% of our cases and M. kansasii for only 9%. Treatment was limited by a high incidence of associated disease, in vitro drug resistance, drug toxicity, and a mortality rate of 32% within 18 months of admission. Nevertheless, bacteriologic conversion occurred in 29% of those treated. M. xenopi appears to be an important pathogen in southern Ontario. It differs from the other NTM by having a different pattern of in vitro drug resistance but not by its clinical or radiologic presentation.     

Sentinel-site surveillance of Mycobacterium avium complex pulmonary disease.

The incidence of Mycobacterium avium complex (MAC) pulmonary disease in HIV-negative patients was studied prospectively from January 1, 2000 to December 31, 2002 through 32 sentinel sites distributed all over France. Among the 275 patients who yielded MAC isolates from respiratory clinical specimens, 101 (36.7%) met the bacteriological, radiographical and clinical criteria established by the American Thoracic Society for nontuberculous mycobacterial respiratory disease. Of these 101 patients, 81 had underlying lung disease, mainly previous tuberculosis, bronchectasis or chronic obstructive pulmonary disease. Among the 20 patients with no underlying lung disease, 12 had a predisposing factor such as leukaemia or immunosuppressive treatment and eight had no predisposing factor. All patients with MAC respiratory disease had clinical symptoms, commonly cough and fatigue, and 52 (51.5%) were sputum smear positive for acid-fast bacillus. The ratio of patients with Mycobacterium avium complex pulmonary disease to patients with pulmonary tuberculosis in France was estimated to be 3% and the incidence of Mycobacterium avium complex pulmonary disease in France was 0.2 per 100,000 inhabitants.     

Nontuberculous mycobacteria in non-HIV patients: epidemiology, treatment and response.

Recent international guidelines published in 1997 and 1999 have proposed diagnostic and treatment criteria for disease caused by nontuberculous mycobacteria (NTM). In this paper, the epidemiological data, diagnostic criteria, treatment regimens and outcomes from 117 HIV-negative patients who had a positive culture for NTM between 1995-1999 are reviewed. The authors wished to identify factors associated with improved outcome in these patients. A total of 71 patients were believed to have a clinical disease caused by NTM, as defined by international criteria. A total of 72% patients were found to have had pulmonary disease. There was a rise in infections between 1995-1999, with a peak in infections in 1997. The most striking rise was in Mycobacterium avium intracellulare complex infections (1995: 33% infections; 1996: 36% infections; 1997: 41% infections; 1998: 61% infections; 1999: 57% infections). There was a link between deprivation and number of positive NTM isolates (34.4% isolates occurred in the areas of lowest Carstairs deprivation index versus 20.6% isolates from areas of least deprivation). There was a significant association between appropriate therapy, defined by American Thoracic Society and British Thoracic Society guidelines, and successful outcome (74%) in contrast to those who received inappropriate treatment prior to the publication of these guidelines. Nontuberculous mycobacteria infections remain a significant problem in non-HIV patients. Adherence to published guidelines may improve patient outcomes.     

Non-tuberculous mycobacteria: patterns of isolation. A multi-country retrospective survey.

OBJECTIVE: To collect data on non-tuberculous mycobacteria (NTM) isolated from clinical laboratories in different countries to establish: 1) whether the isolation of NTM was increasing, 2) which species were increasing, and 3) whether there was any pattern of geographical distribution. DESIGN: In 1996, the Working Group of the Bacteriology and Immunology Section of the International Union Against Tuberculosis and Lung Disease contacted 50 laboratories in different countries for the necessary information. RESULTS: The number of patients reported with NTM was 36099 from 14 countries. Mycobacterium avium complex, M. gordonae, M. xenopi, M. kansasii and M. fortuitum were the five species most frequently isolated. There was a significant upward trend for M. avium complex and M. xenopi. Pigmented mycobacteria predominated in Belgium, the Czech Republic and the Mediterranean coast of Spain. Non-chromogenic mycobacteria were found to be predominant in the area of the Atlantic coast of Brazil and in Turkey, the United Kingdom, Finland and Denmark. CONCLUSIONS: There was an increase in the number of NTM isolated from clinical samples of patients. Isolation of the most frequent species is constantly changing in most of the geographical areas, and newer species are emerging due to better diagnostic techniques to detect and identify NTM.     

Species identification of neglected nontuberculous mycobacteria in a developing country

In developing countries where tuberculosis is still a health challenge, the prevalence of nontuberculous mycobacterial diseases is expected to rise as medical conditions that compromise the immune system become more widespread. In the current study, we aimed to determine the presence and diversity of nontuberculous mycobacteria (NTM) causing infections in Iranian patients. Sixty-seven clinical NTM isolates were identified using conventional and molecular methods, including PCR-restriction fragment length polymorphism analysis (PRA) and 16S rRNA sequencing. Out of 67 patients with confirmed mycobacterial infection, 29 had an associated immunosuppressive syndrome, including 9 who were HIV-infected. Forty-nine NTM isolates were identified using PRA, and the remaining 18 isolates were identified using 16S rRNA sequencing. We obtained the following results: Mycobacterium fortuitum, 30 isolates; M. kansasii, 12 isolates; M. gordonae, 8 isolates; M. porcinum, 3 isolates; M. conceptionense, 3 isolates; M. phlei, 2 isolates; and M. austroafricanum, M. avium, M. elephantis, M. intracellulare, M. lentiflavum, M. monacense, M. parascrofulaceum, and M. thermoresistibile, 1 isolate each; and 1 potentially novel mycobacterial species. With regard to the complexity of identification, it is recommended that laboratory diagnosis of NTM diseases be centralized by strengthening or setting up quality national and regional infrastructure.     

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.     

Nontuberculous mycobacterial lung disease. Substantiation of a less aggressive approach

A nonsurgical, less aggressive, less toxic chemotherapeutic protocol for the management of nontuberculous mycobacterial (NTB) pulmonary infections has been uniformly applied to patients in our institution between 1972 and 1985. Forty-three nonimmunocompromised patients with active lung disease caused by Mycobacterium avium-intracellulare (MAI) (n = 26), M kansasii (n = 16), and M xenopi (n = 1) were identified retrospectively. Eighteen MAI patients were treated with three or four antituberculosis agents resulting in sputum conversion and clinical improvement in 12 (67 percent). Additionally, 11 out of 16 (69 percent) patients completing therapy or still undergoing therapy for persistent MAI disease, achieved sputum conversion and clinical improvement after prolonged therapy (3.6 +/- 0.5 years [SEM]). When M kansasii was identified as the etiologic agent, all patients were treated with four or fewer antituberculosis agents and 14 out of 16 patients (88 percent) achieved sputum conversion and clinical improvement throughout the follow-up period. We conclude that the use of three or four chemotherapeutic agents in the treatment of NTM lung disease provides an excellent probability of successful outcome even in MAI infections.     

Emergence of Mycobacterium simiae in respiratory specimens

Temporal changes in epidemiology of non-tuberculous mycobacteria (NTM) infections have hardly been explored. Frequency of isolation of different NTM species varies geographically. We aimed to determine whether the distribution of Mycobacteria species isolated from respiratory specimens had changed from 1996 to 2003. We analysed data on 484 patient mycobacterial isolates from 23,483 respiratory specimens submitted to the Laboratory of Microbiology in a tertiary medical centre. The proportion of patients with Mycobacterium tuberculosis isolates decreased from 44.6% in period I (1996-1999) to 20.6% in period II (2000-2003). Among the NTM, the proportion of some species increased significantly (Mycobacterium simiae: 8.4% to 31.6%; Mycobacterium fortuitum 12% to 20%; and Mycobacterium chelonae 4.8% to 11.3%), while others decreased (Mycobacterium avium complex 31.3% to 17.3%; Mycobacterium kansasii 28.9% to 7.5%; and Mycobacterium haemophilum 1.2% to 0%). These findings disclose major temporal changes in the distribution of mycobacterial species in respiratory specimens with an impressive emergence and takeover of M. simiae.     

A study of mycobacterial species causing lymphadenitis

This prospective study evaluated the non-tuberculous mycobacteria (NTM) cases of lymphadenitis. A total of 76 isolates of mycobacteria were obtained from 200 lymph node aspirates suspected of tuberculosis, 74 of which were Mycobacterium tuberculosis, one was Mycobacterium fortuitum and one Mycobacterium kansasii. These results highlight the importance of NTM in HIV-negative patients as a case of lymphadenitis, and indicates the re-emergence of NTM as potential lymph node pathogens in this part of the country. Further studies on a larger scale are needed to delineate the association between NTM infections in HIV positive and negative subjects.     

Evaluation of clinical efficacy of isoniazid and ethambutol in the treatment of nontuberculous mycobacteriosis based on in vitro susceptibility testing

Comparing minimal inhibitory concentrations (MICs) determined in various nontuberculous mycobacteria with those for Mycobacterium tuberculosis strains, which were isolated from patients who were untreated previously by any antituberculosis drugs, clinical efficacy of isoniazid and ethambutol in the treatment of nontuberculous mycobacteriosis was evaluated. The MICs of isoniazid for M. tuberculosis strains were 0.03-0.1 microgram/ml, whereas the MICs for M. xenopi strains were 0.1-0.4 microgram/ml, those for M. szulgai 0.2-0.8, and those for M. kansasii 0.8-1.6 micrograms/ml. The fact that M. xenopi strains are susceptible to isoniazid was reported previously, and in this study, it was shown that M. szulgai and M. kansasii are also considerably susceptible to isoniazid. Isoniazid may be useful in the treatment of infection due to these mycobacteria. The MICs of ethambutol for M. tuberculosis strains ranged from 0.8 to 3.13 micrograms/ml. The percentages of strains of various mycobacteria, which are susceptible to 3.13 micrograms/ml ethambutol, were 100% in M. szulgai, 100% in M. nonchromogenicum, 90% in M. gordonae, 88% in M. marinum, 77% in M. kansasii, 46% in M. malmoense, and 30% in M. scrofulaceum. In contrast, the percentage in M. avium complex strains remained only 19%. It has been suggested that ethambutol is effective in the treatment of diseases caused by M. szulgai, M. marinum and M. kansasii.     

Four cases of Mycobacterium xenopi pulmonary disease

Mycobacterium xenopi is very rare pathogen in Japan. We reported herein four cases of M. xenopi pulmonary disease. These patients were all male and their ages ranged from 53 to 72. They all had past history of pulmonary tuberculosis, including two cases who had been also treated for Mycobacterium kansasii pulmonary disease later. The bacilli could be cultured in Mycobacteria Growth Indicator Tube (MGIT) system from 10 sputum samples, but they could not be cultured on Ogawa egg media except for two samples. All four cases fulfilled the criteria for the diagnosis of nontuberculous mycobacteria pulmonary disease proposed by the Japanese Society for Tuberculosis. Combination chemotherapy including isoniazid, rifampicin, and ethambutol was started in all four cases when mycobacteria were detected under tentative diagnosis of the relapse of tuberculosis or Mycobacterium kansasii disease. Sputum converted to culture negative by the chemotherapy in two cases. In one case, the chemotherapeutic regimen was changed to rifampicin, ethambutol, and clarithromycin after the bacteriological identification of M. xenopi, and the new regimen was found to be effective. In the final case, both of the regimens were finally ineffective.