BACKGROUND: Mycobacterium abscessus group lung infection is characterized by low cure rates. Improvement in quality of life may be a reasonable treatment goal.
OBJECTIVE: The objective of this study was to evaluate change in quality of life in response to therapy, predictors of improvement in quality of life, and association of quality of life with traditional outcome measures.
METHODS: Forty-seven patients were treated for Mycobacterium abscessus group lung infection (including one with Mycobacterium chelonae) and were followed prospectively for 2 years between December 2009 and May 2012. St. George\'s Respiratory Questionnaire (SGRQ) was administered, chest computed tomography (CT) imaging was carried out, and culture data were collected at multiple time points. Predictors of improvement in the SGRQ total score greater than or equal to a minimal clinically important difference (MCID) at 12 months were evaluated.
RESULTS: Patients were 85% female and 94% white, with a mean age of 65 years. Nine (20%) had a genetic diagnosis of cystic fibrosis (none F508del homozygous). Coinfection with Mycobacterium avium complex occurred in 28% and Pseudomonas in 26%. Chest CT imaging universally indicated bronchiectasis and nodules; 51% had lung cavities. Treatment included a mean of 17 months of antibiotics, and lung resection in 34%. Seventeen patients with M. avium complex (36%) and one with Mycobacterium kansasii were treated for coinfection. The mean SGRQ total score (SD) at baseline was 35 (20). At all follow-up time points, the mean SGRQ total score (SD) was significantly lower (better) than at baseline: 27 (17) at 3 months, P < 0.01; 27 (19) at 6 months, P < 0.01; 27 (20) at 12 months, P < 0.01; and 30 (22) at 24 months, P = 0.02. At 12 and 24 months, respectively, 60% and 56% had improvement greater than or equal to the MCID in SGRQ total score. Improvement greater than or equal to the MCID at 12 months was positively associated with a history of respiratory exacerbation, isolate susceptible to imipenem-cilastatin, and lung resection surgery, and negatively associated with nodules >4 mm in diameter on chest CT imaging, but these associations were not statistically significant in multivariable analysis. At 24 months, 16 patients (48%) with complete data were culture negative for 1 year and had discontinued M. abscessus group treatment.
CONCLUSIONS: Quality of life was a sensitive indicator of treatment response and has the potential to be a useful parameter to guide treatment.

OBJECTIVE: To study clinical manifestation and pathology change of different time points of rabbit keratitis caused by non-tuberculous mycobacteria (NTM).
METHODS: Forty-eight eyes from 48 rabbits were randomly divided into three groups:under-flap infection group (UFI group), under-flap infection group with corticosteroid (UFIC group) and surface infection group (SI group). The cornea infiltration area of all rabbits was observed. Bacterial quantitative culture and histopathological examination were performed.
RESULTS: In the earliest stage (5 days), the cornea was cloudy and edematous. In the middle stage (7 - 14 days), cornea stromal infiltration became its major clinical sign. In the last stage (21 days), corneal neovascularization and fibrosis were developed. The mean stromal infiltration area in UFIC group was greater than those of UFI group and SI group (F = 9.362, 8.341, P < 0.05). The number of NTM in UFIC group was higher than those of UFI group and SI group (F = 411.272, P < 0.05). In histopathological examination, there were infiltrates with polymorphonuclear leukocytes (PMN) in the corneal stroma in the early stage and acid-fast bacilli was found. A plenty of lymphocytes in the cornea was found in the middle stage of NTM keratitis. In the latter stage, the fibroblast cells proliferation and corneal ulcer were cured. During the course of this infection, the number of CD4+, CD8+ T lymphocyte increased significantly, and then decreased gradually following the regress of the infection. In the stage (5 - 21 days), CD4+ T lymphocyte decreased significantly in UFIC group compared with other two groups (F = 21.907, 196.521, 12.552, 11.100, P < 0.01).
CONCLUSIONS: The clinical characteristic of rabbit keratitis is the multifocal dense superficial stromal infiltrates. CD4+ T lymphocyte may play an important role in NTM keratitis.

OBJECTIVE: To review the epidemiology of atypical mycobacterial cutaneous infection in Hong Kong.
METHODS: Retrospective study.
METHODS: Social Hygiene Service (Dermatology Division), the largest dermatological referral centre in Hong Kong.
METHODS: Patients with a diagnosis of atypical mycobacterial cutaneous infection based on clinical features, histopathology, with or without a positive culture during the period 1993 to 2002.
METHODS: Epidemiological data, clinical features, histology, microbiological investigation, and treatment response.
RESULTS: Of 345,394 dermatological cases presented over the 10-year period, 33 (0.0096%) cases (19 male, 14 female) of atypical mycobacterial cutaneous infection were diagnosed. The most common type of infection was caused by Mycobacterium marinum (n=17, 51.5%), followed by Mycobacterium avium-intracellulare (n=3, 9.1%) and Mycobacterium chelonae (n=2, 6.1%). The upper limb, especially the hands and fingers, was the most common (69.7%) site of involvement. Tissue culture was positive in 18 (54.5%) cases. All biopsies showed granulomatous histology. Thirty-two patients received treatment and 31 responded. Twenty-six were treated with oral tetracycline group of antibiotics (minocycline, doxycycline, tetracycline). The duration of treatment ranged from 8 to 54 weeks (mean, 24 weeks). Mild transient adverse effects to treatment were reported in six cases.
CONCLUSIONS: Atypical mycobacterial infection is rare in Hong Kong. Because of the low sensitivity of traditional culture techniques, atypical mycobacterial infection may be underdiagnosed if only culture-confirmed cases are included. Polymerase chain reaction provides a rapid and sensitive method to improve diagnostic accuracy. Tissue culture is crucial to determine antimicrobial susceptibility. In our study, tetracycline group of antibiotics, especially minocycline, was an effective treatment, particularly in cases caused by Mycobacterium marinum.

OBJECTIVE: To evaluate the merit of a new alginate efficacy film test to determine the bactericidal activity of the high-level disinfectant ortho-phthalaldehyde (OPA).
METHODS: The efficacy of OPA was investigated using a new sodium alginate surface film test against Mycobacterium chelonae NCIMB 1474 and Epping, and Pseudomonas aeruginosa NCIMB 10421 under different test conditions.
RESULTS: OPA was highly bactericidal against P. aeruginosa but its mycobactericidal efficacy was seriously reduced and produced >or=5 log reductions only at a concentration of 0.5% (w/v) within 30-60 min without organic load.
CONCLUSIONS: The sodium alginate film efficacy was reproducible between repeats. Inactivation results depended upon the concentration of OPA, contact time, the presence of an organic load and the bacterial genera.

OBJECTIVE: To summarize the experience of treatment on wound infection by non-tuberculous Mycobacterium (NTM) after operations.
METHODS: A hundred and sixty-eight patients with NTM incision infection were retrospectively reviewed in terms of diagnosis, treatment and follow-up in a period of 4.5 years. On the basis of the results of in vitro drug sensitivity test, the main antibiotics used were clarithromycin and amikacin. The course of therapy was 4 - 8 months. An extirpative excision was performed in 104 cases following one month treatment by antibiotics and then followed by antibiotic therapy for 3 - 5 months after excision.
RESULTS: Primary closure was achieved in 98 of the 104 cases. Fifty patients were cured by the use of antibiotics with dressing change. Eight patients were cured by dressing change without antibiotics. Five children with wound infection by NTM after circumcision were cured by antibiotics with local laser therapy. One patient with infection after hernia operation was cured by amikacin blocking of the area surrounding the lesion. There was no relapse after follow-up for four and half years.
CONCLUSIONS: The study demonstrates that sensitive antibiotics combined with surgery extirpative excision is effective for wound infection by NTM.

Lipomannan (LM) and lipoarabinomannan (LAM) are major glycolipids present in the mycobacterial cell wall that are able to modulate the host immune response. In this study, we have undertaken the structural determination of these important modulins in Mycobacterium chelonae, a fast growing pathogenic mycobacterial species. One-dimensional and two-dimensional NMR spectra were used to demonstrate that LM and LAM from M. chelonae, designated CheLM and CheLAM, respectively, possess structures that differ from the ones reported earlier in other mycobacterial species. Analysis by gas chromatography/mass spectrometry of the phosphatidyl-myo-inositol anchor, which is thought to play a role in the biological functions of these lipoglycans, pointed to a high degree of heterogeneity based on numerous combinations of acyl groups on the C-1 and C-2 positions of the glycerol moiety. Characterization of the mannan core of CheLM and CheLAM revealed the presence of novel alpha1,3-mannopyranosyl side chains. This motif, which reacted specifically with the lectin from Galanthus nivalis, was found to be unique among a panel of nine mycobacterial species. Then, CheLM and CheLAM were found to be devoid of both the mannooligosaccharide cap present in Mycobacterium tuberculosis and the inositol phosphate cap present in Mycobacterium smegmatis and other fast growing species. Tumor necrosis factor-alpha and interleukin-8 production were assessed from human macrophages with LAM preparations from different species. Our results suggest that the inositol phosphate capping may represent the major cytokine-inducing component of LAMs. This work not only underlines the diversity of LAM structures among various mycobacterial species but also provides new structures that could be useful to dissect the structure-function relationships of these complex molecules.

Beta-lactamase activity was determined using a nitrocefin disc method on 34 Mycobacterium tuberculosis (M. tuberculosis) strains and 13 nontuberculous mycobacteria strains. In the 34 M. tuberculosis strains, 23 strains showed beta-lactamase activity. In 10 Mycobacterium avium complex strains, no beta-lactamase activity was detected. In the Mycobacterium chelonae strains, all three strains examined showed strong beta-lactamase activity. No correlation was found between beta-lactamase activity and resistance to anti-tuberculous chemotherapeutic agents. Four patients who were persistently positive for multi-drug-resistant M. tuberculosis (MDR-TB) on sputum and positive in beta-lactamase activity, were treated with penicillin/beta-lactamase inhibitor combinations. In two cases, the trials were discontinued because of diarrhea; the trials were continued in the remaining two for four months, but the MDR-TB was positive during the course of the therapy. Effectiveness of the therapy with penicillin/beta-lactamase inhibitor combinations against M. tuberculosis was obscure, although many of M. tuberculosis examined showed beta-lactamase activity.

Multifocal stromal infiltrates or \"satellite lesions\" have been considered a characteristic feature of fungal keratitis. We examined two patients with nontuberculous mycobacterial keratitis who clinically presented with satellite lesions. The keratitis consisted of multifocal stromal infiltrates with indistinct white and fluffy margins. Both patients received topical fortified amikacin therapy with poor response. Lamellar keratectomy or penetrating keratoplasty was performed, respectively, in the two patients because of progressive stromal thinning and enlarging satellite lesions. Histopathologically, the main lesions consisted of dense infiltration of inflammatory cells with numerous acid-fast bacilli, while the satellite lesions were composed chiefly of inflammatory cells with fewer mycobacteria. Besides fungal keratitis, nontuberculous mycobacterial keratitis should also be considered when satellite lesions are present.

OBJECTIVE: To investigate causes and clinical findings of non-tuberculous mycobacterial keratitis, and to study its response to topical antibiotic therapy and surgical extirpative keratectomy.
METHODS: A single centre, retrospective review of 22 patients with non-tuberculous mycobacterial keratitis seen in a 3 year period. Laboratory diagnoses were established with Ziehl-Nielsen acid fast staining and Löwenstein-Jensen cultures.
RESULTS: In 20 patients (91%), there was an antecedent history of foreign body eye trauma (18 patients) or elective surgery (two patients). There were 19 cases of Mycobacterium chelonei, and three of M fortuitum. Clinical signs included epithelial defects, satellite or ring stromal infiltrates, crystalline keratopathy, and hypopyon. For topical antibiotic therapy, 20 patients received amikacin, while one patient received rifampin and another received ciprofloxacin, each in accordance with the results of the in vitro drug sensitivities. An extirpative keratectomy was performed in 15 cases; four of these cases additionally required a temporary conjunctival flap in order to finally eradicate the infection. At the end of the follow up period (median 18 months; range 3 months to 3 years) all eyes were stable and free of infection, with 19 (86%) having final visual acuities of 20/200 or better.
CONCLUSIONS: Early clinical recognition and prompt laboratory diagnosis, together with aggressive topical antibiotic therapy and early keratectomy, may shorten morbidity and improve the clinical outcome of non-tuberculous mycobacterial keratitis.

We retrospectively studied lung and hilar lymph nodes at autopsy in 18 patients with cystic fibrosis (CF) who had antemortem sputum cultures positive for nontuberculous mycobacteria (NTM). Histologic features were compared with those of 18 patients with CF who had negative antemortem cultures. The most frequent species isolated was M. chelonae group (10 patients). Multiple cultures were positive for NTM in six patients. Three patients were clinically considered to be infected, and two received antimycobacteria drugs. Necrotizing pulmonary granulomas associated with granulomatous organizing pneumonia were found at autopsy in two patients, each of whom had multiple positive sputum cultures and clinical evidence of infection. In one of these, mycobacterial infection was considered to be an important factor in her terminal illness. Neither necrotizing granulomas nor granulomatous organizing pneumonia were seen in the lung tissue of patients whose antemortem cultures were negative for mycobacteria. There was no difference in the prevalence of other granuloma-like lesions between those with and those without positive sputum cultures. No mycobacteria-related granulomas occurred in hilar lymph nodes, although histoplasma granulomas involved hilar lymph nodes of three patients. We conclude that granulomatous mycobacterial lung disease is present in a minority of patients (two of six patients in this study) who have multiple positive cultures. Histologic evidence of infection was not found in patients who had only one of multiple sputum cultures positive for NTM.