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The list of clinically important nontuberculous mycobacteria (NTM) is growing as new species continue to be identified and older ones are found to be pathogenic. Molecular techniques such as real-time PCR and gene amplification and restriction length polymorphism are promising tools for rapid identification of NTM. Optimal therapy for a documented Mycobacterium gordonae infection remains undefined. The majority of isolates tested have been resistant in vitro to isoniazid and pyrazinamide, whereas many are susceptible to ethambutol, rifampin, clarithromycin, linezolid, and the fluoroquinolones. Unlike other nontuberculous mycobacteria, M. simiae produces niacin and thus may be confused with M. tuberculosis. M. simiae can colonize the respiratory tract, and the lung is the most commonly reported site of infection. The majority of reported infections have occurred in persons living near rivers or stagnant bodies of water. A recent open-label randomized trial conducted in Ghana compared two regimens for early, limited M. ulcerans infections. In this study, 73 of 76 patients who received streptomycin and rifampin for 8 weeks and 68 of 75 patients who received 4 weeks of streptomycin and rifampin followed by 4 weeks of rifampin and clarithromycin had healed lesions at 1 year after the start of treatment. Infections with M. xenopi have shown variable responses to drug therapy. Recommendations for initial therapy include isoniazid, a rifamycin, ethambutol, and clarithromycin with or without an initial course of streptomycin. Pyrazinamide and ciprofloxacin have been included in some successful regimens.

In this study, mycobacteria, which were previously identified as Mycobacterium tuberculosis complex (MTC), and mycobacteria other than tuberculosis (MOTT) with cord factor and the p‐nitro‐alpha‐acetyl‐amino‐beta‐hydroxypropiophenone (NAP) test were reanalysed using the polymerase chain reaction—restriction fragment length polymorphism (PCR‐RFLP) analysis method in order to confirm the identification, and at the same time, species accepted as MOTT were identified. Although the results of the NAP test were obtained within 3‐5 days, the PCR‐RFLP results were obtained in 1 day. Ten species identified as MTC with the NAP test and cord factor were confirmed with the PCR‐RFLP method. Fourteen species accepted as MOTT were identified as Mycobacterium species with the evaluation of the bands observed after the restriction of PCR product with the PCR‐RFLP method. These were as follows: three species Mycobacterium intracellulare type I, two species Mycobacterium phlei, two species Mycobacterium kansasii, one species Mycobacterium fortuitum type I, one species Mycobacterium gordonae type I, one species Mycobacterium abscessus type I, one species Mycobacterium scrofulaceum, one species Mycobacterium szulgai type I, one species Mycobacterium avium type II, and one species Mycobacterium terrae. Hence, the results of both the cord factor and the NAP test were confirmed with the molecular method, and at the same time, mycobacteria species identification was made by determining the fastest, easiest, and the most accurate result‐giving method. Because PCR‐RFLP is a very rapid method that provides exact identification of mycobacteria species, it can be performed in routine procedures.

Non-tuberculous mycobacteria (NTM) are important pathogens in lung transplant recipients. This study describes the spectrum of NTM respiratory tract infections and examines the association of NTM infections with lung transplant complications.Data from 208 recipients transplanted from November 1990 to November 2005 were analyzed. Follow-up data were available to November 2010. Lung infection was defined by bronchoalveolar lavage, sputum, or blood cultures in the appropriate clinical setting. All identified NTM respiratory tract infections were tabulated. The cohort of patients with NTM lung infections (NTM+) were compared to the cohort without infection (NTM-). Univariate and multivariate analysis was performed to determine characteristics associated with NTM infection. Survival analyses for overall survival and development of bronchiolitis obliterans syndrome (BOS) were also performed.In total, 52 isolates of NTM lung infection were identified in 30 patients. The isolates included Mycobacterium abscessus (46%), Mycobacterium avium complex (MAC) (36%), Mycobacterium gordonae (9%), Mycobacterium chelonae (7%), and Mycobacterium fortuitum (2%), with multiple NTM isolates seen on 3 different occasions. The overall incidence was 14%, whereas cumulative incidences at 1, 3, and 5 years after lung transplantation were 11%, 15%, and 20%, respectively. Comparisons between the NTM+ and NTM- cohorts revealed that NTM+ patients were more likely to be African-American and have cytomegalovirus mismatch. Although no difference was seen in survival, the NTM+ cohort was more likely to develop BOS (80% vs. 58%, P = 0.02). NTM+ infection, however, was not independently associated with development of BOS by multivariate analysis.With nearly 20 years of follow-up, 14% of lung recipients develop NTM respiratory tract infections, with M. abscessus and MAC more commonly identified. M. gordonae was considered responsible for nearly 10% of NTM infections. Although survival of patients with NTM infections is similar, a striking difference in BOS rates is present in the NTM+ and NTM- groups.

The first total synthesis of the branched oligosaccharide OSE-1 of Mycobacterium gordonae (strain 990) is reported. An intramolecular aglycon delivery approach was used for constructing the desymmetrized 1,1'-α,α-linked trehalose moiety. A [3+2] glycosylation of the trisaccharide donor and trehalose acceptor furnished the right hand side pentasaccharide. Regioselective O3 glycosylation of L-rhamnosyl 2,3-diol allowed expedient synthesis of the left hand side tetrasaccharide. The nonasaccharide was assembled in a highly convergent fashion through a [4+5] glycosylation.

Mycobacteria are associated with a number of well-characterized diseases, yet we know little about their stress biology in natural ecosystems. This study focuses on the isolation and characterization of strains from Yellowstone National Park (YNP) and Glacier National Park (GNP; USA), the majority of those identified were Mycobacterium parascrofulaceum, Mycobacterium avium (YNP) or Mycobacterium gordonae (GNP). Generally, their windows for growth spanned a temperature range of > 60 °C; selected isolates grew at super-saturated concentrations of hydrophobic stressors and at levels of osmotic stress and chaotropic activity (up to 13.4 kJ kg(-1) ) similar to, or exceeding, those for the xerophilic fungus Aspergillus wentii and solvent-tolerant bacterium Pseudomonas putida. For example, mycobacteria grew down to 0.800 water activity indicating that they are, with the sole exception of halophiles, more xerotolerant than other bacteria (or any Archaea). Furthermore, the fatty-acid composition of Mycobacterium cells grown over a range of salt concentrations changed less than that of other bacteria, indicating a high level of resilience, regardless of the stress load. Cells of M. parascrofulaceum, M. smegmatis and M. avium resisted the acute, potentially lethal challenges from extremes of pH ( 13), and saturated MgCl2 solutions (5 M; 212 kJ kg(-1) chaotropicity). Collectively, these findings challenge the paradigm that bacteria have solute tolerances inferior to those of eukaryotes.

Background The incidence of infection with non-tuberculous mycobacteria (NTM) after lung transplant is insufficiently defined. Data on the impact of NTM infection on lung transplant survival are conflicting. Methods To quantify the incidence and outcomes of colonization and disease with NTM in patients after lung transplantation, the medical records, chest imaging, and microbiology data of 237 consecutive lung transplant recipients between 1990 and 2005 were reviewed. American Thoracic Society (ATS)/Infectious Diseases Society of America and Centers for Disease Control criteria were used to define pulmonary NTM disease and NTM surgical-site infections (SSI), respectively. Incidence rates for NTM colonization and disease were calculated. Comparisons of median survival were done using the log-rank test. Results NTM were isolated from 53 of 237 patients (22.4%) after lung transplantation over a median of 25.2 months of follow-up. The incidence rate of NTM isolation was 9.0/100 person-years (95% confidence interval [CI), 6.8-11.8), and the incidence rate of NTM disease was 1.1/100 person-years (95% CI 0.49-2.2). The most common NTM isolated was Mycobacterium avium complex (69.8%), followed by Mycobacterium abscessus (9.4%), and Mycobacterium gordonae (7.5%). Among these 53 patients, only 2 patients met ATS criteria for pulmonary disease and received treatment for M. avium. One patient had recurrent colonization after treatment, the other one was cured. Four of the 53 patients developed SSI, 3 caused by M. abscessus and 1 caused by Mycobacterium chelonae. Three of these patients had persistent infection requiring chronic suppressive therapy and one died from progressive disseminated disease. A total of 47 (89%) patients who met microbiologic but not radiographic criteria for pulmonary infection were not treated and were found to have only transient colonization. Median survival after transplantation was not different between patients with transient colonization who did not receive treatment and those who never had NTM isolated. Conclusion Episodic isolation of NTM from lung transplant recipients is common. Most isolates occur among asymptomatic patients and are transient. Rapidly growing NTM can cause significant SSI, which may be difficult to cure. NTM disease rate is higher among lung transplant recipients than in the general population. In this cohort, NTM isolation was not associated with increased post-transplantation mortality.

Background: Whole blood interferon-γ assay QuantiFERON-TB2G (QFT-2G), which is a new specific method for diagnosing tuberculosis (TB), has been developed and used in the clinical field. The aim of the present study was to assess the usefulness of QFT-2G as an indicator, both for diagnosing childhood TB and for assessing therapeutic effectiveness. Methods: The subjects were 61 children introduced to the TB outpatient department for the first time between June 2004 and March 2006. QFT-2G, the tuberculin test and chest computed tomography (CT) were performed for all patients. Results: Ten patients having typical characteristics of primary tuberculosis (PTB) on chest CT, and diagnosed as having tubercle bacillus infections, all had positive reaction on QFT-2G. Of seven patients who had no abnormalities on diagnostic imaging but who reacted positively on QFT-2G, one developed TB later, and no TB was detected over the period of observation in 44 patients with negative QFT-2G at their first consultation. Moreover, four patients with non-tuberculous acid-fast bacilli in which Mycobacterium avium or Mycobacterium gordonae was detected had negative reaction on QFT-2G. In addition, all 10 patients with positive reactions on QFT-2G in whom the subsequent course of the disease was observed had decrease on QFT after treatment. Conclusions: QFT-2G is a powerful tool with a wide application both in diagnosis and in assessment of treatment effectiveness in PTB.

While nontuberculous mycobacterial peritonitis is uncommon among peritoneal dialysis (PD) patients, these infections have serious consequences. They present a significant diagnostic and therapeutic challenge for clinicians. Diagnosis can be delayed due to the slow growth rate of some mycobacterial species. These organisms can also be overlooked when adequate culture media are not used in the microbiological evaluation process. The choice of antimicrobial therapy depends upon isolation and speciation of the infecting Mycobacterium species, and prompt catheter removal is essential. Because serious intra-abdominal complications may follow infection, identifying patient risk factors for nontuberculous mycobacterial peritonitis and initiating prompt diagnosis and treatment are essential. We report three cases of peritonitis associated with Mycobacterium chelonae and Mycobacterium gordonae, each with a unique presentation, and discuss the appropriate diagnosis and treatment strategies for the management of PD-associated mycobacterial infections.

The use of more intensive immunosuppressive regimens and the increasing number of patients that are exposed to immunosuppressive strategies in transplantation medicine have changed the spectrum of infections that is encountered by the clinician. We describe a 62-year-old female renal transplant recipient receiving immunosuppressive therapy who developed complaints of weight loss, diarrhoea, cough, and fever. Increased C-reactive protein and pancytopenia were found. The presence of Mycobacterium gordonae, a non-tuberculous mycobacterium, was eventually demonstrated in bronchoalveolar lavage fluid, bone marrow, spleen, and liver. Determination of the pathogen was accelerated using a Line Probe Assay, a reverse hybridisation technique using an RNA fragment specific for different mycobacterium species. Treatment was initiated using a combination of clarithromycin, ethambutol, and rifampicin. The initial response to treatment was good, but splenectomy and change of immunosuppressive and antimycobacterial therapy were necessary for long-term control of the infection. Problems in the diagnosis and treatment of this uncommon pathogen are discussed.

To evaluate the histopathological features observed in patients with cutaneous infections due to nontuberculous mycobacteria (NTM) and to compare the histopathological patterns observed in immunosuppressed patients and normal hosts. Twenty-eight biopsy specimens corresponding to 27 patients with cutaneous infections due to NTM were reviewed. Eighteen biopsies corresponded to normal hosts (14 Mycobacterium marinum, 2 Mycobacterium chelonae, 1 Mycobacterium terrae and 1 Mycobacterium gordonae) and 10 biopsy specimens were obtained from 9 immunosuppressed patients (3 Mycobacterium chelonae, one of which had two biopsies, 1 Mycobacterium abscessus, 2 Mycobacterium kansasii, 1 Mycobacterium marinum, 1 Mycobacterium avium complex and 1 Mycobacterium simiae). A panel of histopathological features was evaluated by two independent observers in each biopsy specimen. Epidermal changes (acanthosis, pseudoepitheliomatous hyperplasia, exocytosis) were mainly observed in M. marinum infections. In immunosuppressed patients the infiltrate tended to be deeper, involving the subcutaneous tissue (100%) with a more diffuse distribution and constant abscess formation. A marked granulomatous inflammatory reaction was observed in 83% of immunocompetent and in 60% of immunosuppressed patients. In immunosuppressed patients a relationship between the chronic evolution of the disease and granuloma formation was demonstrated. A diffuse infiltrate of histiocytes with occasionally foamy appearance was noted in three biopsy specimens from three patients with AIDS. Acute and chronic panniculitis was detected in 8 biopsy specimens. In one biopsy (M. chelonae) an acute suppurative folliculitis was observed. Different histopathological patterns can be noted in biopsy specimens from cutaneous nontuberculous mycobacterial infections. The evolution of the disease and the immunologic status of the host may explain this spectrum of morphological changes. Tuberculoid, palisading and sarcoid-like granulomas, a diffuse infiltrate of histiocytic foamy cells, acute and chronic panniculitis, non-specific chronic inflammation, cutaneous abscesses, suppurative granulomas and necrotizing folliculitis can be detected. Suppurative granulomas are the most characteristic feature in skin biopsy specimens from cutaneous NTM infections. Some histopathological patterns seem more prevalent in immunosuppressed patients.

Primary biliary cirrhosis (PBC) is a chronic cholestatic liver disease associated with autoimmune disorders. The aetiology is unknown, although it has been suggested that the disease may be related to infectious agents. Previous studies revealed that sera from patients with PBC react against Mycobacterium gordonae. This specific reactivity, characterized by a recognition of two membrane polypeptides of 70-65 and 55 kD, cross-react with the two major mitochondrial autoantigens of PBC. As the most immunogenic components of mycobacteria are the heat shock proteins (hsp), which have been associated with autoimmunity, this study has been undertaken to characterize whether the reacting polypeptides in PBC are hsp from M. gordonae. Cultures of M. gordonae were incubated at 37 degrees C and 46 degrees C before sonication, protein extraction and separation by SDS-PAGE. Exposure of M. gordonae to heat shock treatment resulted in membrane protein overexpression, similar to the 70-65-kD polypeptide recognized by the sera from patients with PBC. Immunoprecipitation assays with a monoclonal antibody directed against the Hsp65 kD of mycobacteria and with sera from patients with PBC revealed similar reacting profiles characterized by the precipitation of the overexpressed 65-kD polypeptide from M. gordonae. Competitive immunoblotting showed that binding of the monoclonal antibody to the Hsp65 kD protein was prevented by preincubation with sera from patients with PBC, but not with sera from healthy subjects. Furthermore, monoclonal antibody to the Hsp65 kD protein recognized the main mitochondrial autoantigens of PBC (PDH-E2 and BCKDH-E2). These data indicate the existence of cross-reacting epitopes contained on M. gordonae Hsp65 kD and the main mitochondrial antigens in patients with PBC.

A 4-year-old girl with cystic fibrosis (CF) presented with unrelenting pyrexia commencing shortly after flushing of the central venous catheter (CVC). Mycobacterium gordonae was subsequently isolated from bronchoalveolar lavage, gastric washings, and lung biopsy. While this case most likely represents central line infection by a non-tuberculous mycobacterial (NTM) species, it is difficult to state this definitively in the absence of positive cultures from the CVC. We suggest that infection with NTM should always be considered in CF patients with indwelling devices and unexplained fever.

A 38-year-old woman presented with small, ulcerated, red or bluish nodules on the right hand, clinically resembling mycobacterial granulomas; these appeared a few months after a bite by a rat, while the patient was collecting frogs in a pond in the Belgian Ardennes. The histopathologic picture was compatible with a diagnosis of mycobacterial infection and rare acid-fast bacilli could be found. Repeated bacteriologic investigations were performed and these led to the identification of a strain displaying characteristics of Mycobacterium gordonae. The skin condition responded well to rifampicin (300 mg/day) within 6 months.