Nontuberculous mycobacteria (NTM) are ubiquitous organisms; their isolation from clinical specimens does not always indicate clinical disease. The incidence of NTM lung diseases has been increasing worldwide. Although the geographic diversity of NTM species is well known, Mycobacterium avium complex (MAC), M. abscessus complex (MABC), and M. kansasii are the most commonly encountered and important etiologic organisms. Two distinct types of NTM lung diseases have been reported, namely fibrocavitary and nodular bronchiectatic forms. For laboratory diagnosis of NTM lung diseases, both liquid and solid media cultures and species-level identification are strongly recommended to enhance growth detection and determine the clinical relevance of isolates. Treatment for NTM lung diseases consists of a multidrug regimen and a long course of therapy, lasting more than 12 months after negative sputum conversion. For MAC lung disease, several new macrolide-based regimens are now recommended. For nodular bronchiectatic forms of MAC lung diseases, an intermittent three-time-weekly regimen produces outcomes similar to those of daily therapy. Treatment of MABC lung disease is very difficult, requiring long-term use of parenteral agents in combination with new macrolides. Treatment outcomes are much better for M. massiliense lung disease than for M. abscessus lung disease. Thus, precise identification of species in MABC infection is needed for the prediction of antibiotic response. Likewise, increased efforts to improve treatment outcomes and develop new agents for NTM lung disease are needed.
Anti-Bacterial Agents/therapeutic use ; Drug Therapy, Combination ; Humans ; Lung Diseases/*diagnosis/drug therapy/epidemiology ; Mycobacterium Infections, Nontuberculous/*diagnosis/drug therapy/epidemiology ; Mycobacterium avium Complex/isolation & purification ; Sputum/microbiology

No abstract available.
Aged ; Bronchiectasis/*diagnosis/microbiology ; Humans ; Male ; Mycobacterium/classification/*genetics/isolation & purification ; Mycobacterium Infections/*diagnosis/microbiology ; Phylogeny ; Polymerase Chain Reaction ; RNA, Ribosomal, 16S/chemistry/genetics/metabolism ; Republic of Korea ; Sequence Analysis, DNA

INTRODUCTIONGranulomatous cervicofacial lymphadenitis (GCL) is not uncommon in children. Nontuberculous mycobacteria (NTM) seem to be the predominant cause. We sought to study the clinical and microbiological profile of patients with GCL, and identify features that may impact outcome.

METHODSChildren aged < 16 years who presented to KK Women's and Children's Hospital, Singapore, between January 1998 and December 2006, and who had GCL were identified from laboratory records. Clinical and laboratory data was collected and analysed for risk factors for patients with positive lymph node cultures, and for patients with and without recurrence after treatment.

RESULTSIn all, 60 children were identified, with a median age of 56 (interquartile range [IQR] 34-101) months. Median duration of symptoms before presentation was 5 (IQR 4-8) weeks. The majority presented with single (73.3%) or unilateral (96.7%) lymphadenopathy, located in the submandibular, preauricular/parotid or infra-/post-auricular region (76.7%). Out of 51 patients, 26 (51.0%) had a tuberculin skin test reading of ≥ 10 mm. Out of 52 patients, 10 (19.2%) had positive mycobacterial cultures, which included seven isolates of NTM. Out of 34 cases, tuberculous polymerase chain reaction was positive in 11 (32.4%). With regard to recurrence after initial treatment, age < 5 years at presentation was found to be a predictor for recurrence (p = 0.008), while initial complete excision of affected nodes predicted no recurrence (p = 0.003).

CONCLUSIONIn our study, younger age was noted to be associated with a higher chance of recurrence, while complete excision of the involved node at initial presentation predicted non-recurrence.

Adolescent ; Child ; Child, Preschool ; Female ; Humans ; Infant ; Lymphadenitis ; diagnosis ; epidemiology ; microbiology ; Lymphatic Diseases ; diagnosis ; microbiology ; Male ; Mycobacterium ; Mycobacterium Infections ; diagnosis ; epidemiology ; microbiology ; Recurrence ; Retrospective Studies ; Singapore ; Treatment Outcome ; Tuberculin Test

Mycobacterium neoaurum is rapidly growing mycobacteria that can cause human infections. It commonly causes bloodstream infections in immunocompromised hosts, and unlike other mycobacteria species, it rarely causes pulmonary infections. We confirmed the first pulmonary infection case in Korea caused by M. neoaurum using full-length 16S rRNA gene sequencing.
Adult ; Female ; Humans ; Lung Diseases/*diagnosis/microbiology ; Mycobacterium/genetics/*isolation & purification ; Mycobacterium Infections/*diagnosis/microbiology ; Nontuberculous Mycobacteria/genetics/isolation & purification ; RNA, Ribosomal, 16S/genetics ; Republic of Korea ; Sequence Analysis, RNA

Lung disease caused by nontuberculous mycobacteria (NTM) represents an increasing proportion of all mycobacterial diseases. We investigated recent occurrences of NTM and evaluated the clinical significance of NTM isolates from 752 respiratory specimens collected from patients at National Health Insurance Service Ilsan Hospital between January 2007 and May 2011. Specimens were incubated on solid and liquid media (BACTEC MGIT 960, BD, USA) for 6-8 weeks, and PCR and reverse blot hybridization were performed (REBA Myco-ID, Molecules & Diagnostics, Korea). Clinical features of the patients were reviewed through medical records. The most frequently isolated organism was Mycobacterium avium (46.7%), followed by M. intracellulare (14.8%), M. fortuitum (7.2%), and M. abscessus (6.6%). The most common mycobacteria among definitive cases of NTM lung disease were M. avium (42/351, 12.0%), M. intracellulare (19/111, 17.1%), M. abscessus (11/50, 22.0%), M. massiliense (4/13, 30.8%), and M. fortuitum (4/54, 7.4%). Clinically significant cases of NTM lung disease increased from 4 patients in 2007 to 32 in 2011. The mean patient age was 64 yr (range: 35-88 yr), and 58 (64%) patients were women. Patients suffered from cough, productive sputum, and hemoptysis. In summary, the most common mycobacteria causing NTM lung disease were M. avium and M. intracellulare; however, cases of M. massiliense and M. abscessus infection are on the rise in Korea.
Adult ; Aged ; Aged, 80 and over ; Bronchoalveolar Lavage Fluid/microbiology ; DNA, Bacterial/analysis ; Female ; Hospitals, General/standards/*trends ; Humans ; Lung Diseases/diagnosis/*microbiology ; Male ; Middle Aged ; Mycobacterium Infections, Nontuberculous/diagnosis/*microbiology ; Nontuberculous Mycobacteria/genetics/*physiology ; Nucleic Acid Hybridization ; Polymerase Chain Reaction ; Reagent Kits, Diagnostic ; Republic of Korea ; Sputum/microbiology

BACKGROUND: Bacteria of the Mycobacterium abscessus group are the second most common pathogens responsible for lung disease caused by nontuberculous mycobacteria in Korea. There is still a lack of studies investigating the genetic mechanisms involved in M. abscessus resistance to antibiotics other than clarithromycin. This study investigated the characteristics of drug resistance exhibited by M. abscessus clinical isolates from Korea. METHODS: We performed drug susceptibility testing for a total of 404 M. abscessus clinical strains. Subspecies were differentiated by molecular biological methods and examined for mutations in drug resistance-related genes. RESULTS: Of the 404 strains examined, 202 (50.00%), 199 (49.26%), and 3 (0.74%) strains were identified as M. abscessus, M. massiliense, and M. bolletii, respectively. Of the 152 clarithromycin-resistant strains, 6 possessed rrl mutations, while 4 of the 30 amikacin-resistant strains contained rrs mutations, and 5 of the 114 quinolone-resistant strains had gyr mutations. All mutant strains had high minimal inhibitory concentration values for the antibiotics. CONCLUSIONS: Our results showed the distribution of the strains with mutations in drug resistance-related genes was low in the M. abscessus group. Furthermore, we performed drug susceptibility testing and sequence analyses to determine the characteristics of these genes in the M. abscessus group.
Anti-Bacterial Agents/pharmacology ; Bacterial Proteins/genetics ; Clarithromycin/pharmacology ; DNA Gyrase/genetics ; *Drug Resistance, Bacterial ; Humans ; Methyltransferases/genetics ; Microbial Sensitivity Tests ; Mutation ; Mycobacterium/drug effects/*isolation & purification ; Mycobacterium Infections, Nontuberculous/diagnosis/*microbiology ; Republic of Korea ; Sequence Analysis, DNA

OBJECTIVETo analyze the clinical manifestation of interferon gamma receptor 1 deficiency (IFN-γR1 deficiency) and to improve the recognition of this disease in children, decrease diagnostic errors and missed diagnosis.

METHODThe information of one case with IFN-γR1 deficiency (past history of illness, clinical manifestation, laboratory examination and treatment) were analyzed.

RESULTThe patient was a 19-month-old girl with IFN-γR1 deficiency, 1-2 weeks after she was vaccinated with BCG at the age of 18 months, she manifested with lymph nodes at the same site as vaccination site, and repeated rash. Examination found a mass in the right armpit, the size was 3 cm × 3 cm, protruded on the skin, tenacious in nature, poorly mobile. B-mode ultrasound showed right armpit chest heterogeneous hypoechoic mass; abdominal B-mode ultrasound showed pancreatic lymph nodes around the abdominal aorta and mild swelling; chest X-ray showed right axillary lymph nodes, increased double markings. Initial diagnosis was (1) bronchitis, (2) BCG vaccination reaction, (3) Sepsis? . After admission, the patient was given rifampicin + isoniazid + latamoxef + amoxicillin and clavulanate potassium, and then changed to meropenem and Fusidic acid, but treatment showed no improvement. After adding the treatment with anti-inflammatory treatment, i.e., gamma globulin and methylprednisolone, the fever subsided. Conventional treatment with rifampicin + isoniazid 3 months after discharge from hospital were effective, and the axillary lymph nodes were not palpable. Six months after BCG vaccination bone tuberculosis occurred. CT of left hip and left knee showed bilateral hip joint effusion, left distal femur and left proximal tibia bone destruction. Gene detection showed the presence of homozygous IFNγ-R1 gene mutation of c.114_135del(p.E38fsX54). Her parents are consanguinity, both were carriers. In the literature, 99 cases with IFN-γR1 deficiency were reported, 95% of the cases had disseminated tuberculosis, and in 60 cases the dissemination occurred after BCG vaccination.

CONCLUSIONIFN-γR1 is an extremely rare disease in children. If disseminated tuberculosis infection occured, especially after BCG vaccination, or if there were focal/multifocal bone tuberculosis, immune function with conventional detection is considered normal, then IFN-γR1 deficiency should be considered, and early genetic testing for confirming the diagnosis and selecting the appropriate treatment are needed.

Antitubercular Agents ; therapeutic use ; BCG Vaccine ; adverse effects ; Female ; Humans ; Infant ; Lymph Nodes ; diagnostic imaging ; pathology ; Mutation ; genetics ; Mycobacterium Infections ; diagnosis ; drug therapy ; microbiology ; Receptors, Interferon ; deficiency ; genetics ; Tomography, X-Ray Computed ; Tuberculosis, Osteoarticular ; diagnosis ; drug therapy ; microbiology ; Vaccination ; adverse effects

We report a very rare case of a bronchogenic cyst combined with nontuberculous mycobacterial pulmonary disease in an immunocompetent patient. A 21-year-old male was referred to our institution because of a cough, fever, and worsening of abnormalities on his chest radiograph, despite anti-tuberculosis treatment. Computed tomography of the chest showed a large multi-cystic mass over the right-upper lobe. Pathological examination of the excised lobe showed a bronchogenic cyst combined with a destructive cavitary lesion with granulomatous inflammation. Microbiological culture of sputum and lung tissue yielded Mycobacterium avium. The patient was administered anti-mycobacterial treatment that included clarithromycin.
Anti-Bacterial Agents/therapeutic use ; Biopsy ; Bronchogenic Cyst/*complications/diagnosis/immunology/surgery ; Humans ; *Immunocompetence ; Male ; Mycobacterium avium Complex/*isolation & purification ; Mycobacterium avium-intracellulare Infection/*complications/diagnosis/drug therapy/immunology/microbiology ; Pneumonectomy ; Respiratory Tract Infections/*complications/diagnosis/drug therapy/immunology/microbiology ; Sputum/microbiology ; Tomography, X-Ray Computed ; Treatment Outcome ; Young Adult

Mycobacterium longobardum is a slow-growing, nontuberculous mycobacterium that was first characterized from the M. terrae complex in 2012. We report a case of M. longobardum induced chronic osteomyelitis. A 71-yr-old man presented with inflammation in the left elbow and he underwent a surgery under the suspicion of tuberculous osteomyelitis. The pathologic tissue culture grew M. longobardum which was identified by analysis of the 65-kDa heat shock protein and full-length 16S rRNA genes. The patient was cured with the medication of clarithromycin and ethambutol without further complications. To the best of our knowledge, this is the first report of a M. longobardum infection worldwide.
Aged ; Anti-Bacterial Agents/therapeutic use ; Bacterial Proteins/genetics ; Chaperonin 60/genetics ; Clarithromycin/therapeutic use ; Elbow/pathology ; Ethambutol/therapeutic use ; Humans ; Male ; Mycobacterium Infections, Nontuberculous/*microbiology ; Nontuberculous Mycobacteria/classification/genetics/*isolation & purification ; Osteomyelitis/diagnosis/drug therapy/*microbiology/pathology ; RNA, Ribosomal, 16S/genetics ; Treatment Outcome

We used HPLC and AdvanSure real-time PCR (LG Life Sciences, Korea) to retrospectively analyze non-tuberculous mycobacteria (NTM) in 133 clinical specimens. The specimens were culture-positive for NTM and the HPLC method identified 130 strains of mycobacteria from the cultures (97.7%) at the species level. Among the isolates, 48 Mycobacterium. kansasii (36.1%), 39 M. intracellulare (29.3%), 17 M. avium (12.8%), 16 M. abscessus (12.0%), 6 M. fortuitum (4.5%), 2 M. szulgai (1.5%), 2 M. gordonae (1.5%), and 3 unclassified NTM strains (2.3%) were identified. The real-time PCR assay identified 60 NTM-positive specimens (45.1%), 65 negative specimens (48.9%), and 8 M. tuberculosis (TB)-positive specimens (6.0%). The real-time PCR assay is advantageous because of its rapid identification of NTM. However, in our study, the real-time PCR assay showed relatively low sensitivity (45.1%) when using direct specimens including sputum and bronchoalveolar lavage (BAL) fluid. HPLC is useful as it discriminates NTM at the species level, although it is time-consuming and requires specific equipment and technical expertise. A combination of both methods will be helpful for the rapid and accurate identification of mycobacteria in clinical laboratories.
Aged ; Aged, 80 and over ; Bronchoalveolar Lavage Fluid/microbiology ; *Chromatography, High Pressure Liquid ; DNA, Bacterial/genetics ; Female ; Humans ; Male ; Middle Aged ; Mycobacterium/*genetics/isolation & purification ; Mycobacterium Infections/diagnosis/*microbiology ; *Real-Time Polymerase Chain Reaction ; Sputum/microbiology