BACKGROUND: The treatment success rates in patients with tuberculosis are known to be lower in the private sector compared to the public sector. To improve treatment outcomes in the private sector we developed a public-private collaboration model for strengthening health education and case holding activities with public health nursing in the private sector. METHODS: We performed a prospective cohort study in new smear positive pulmonary tuberculosis patients treated at private hospitals, selected by non-randomization, with an intervention consisting of health education and case holding activities by specially trained public health nurses (intervention group) results were compared with cases treated without the intervention (conventional group). Physicians were asked to treat both groups routinely. The treatment outcomes of patients under treatment by the National Tuberculosis Programme were also analyzed for comparison. RESULTS: There were 172 cases each in the intervention and conventional groups. The mean age was 48.9+/-19.0 and 48.2+/-19.7 in the respective groups (p=0.66). The PHN interacted with the cases in the intervention group by initial face to face interview and telephone calls an average of 7.1+/-9.2 times during the initial six months. The intervention group showed a significantly higher treatment success rate, 91.6%, (Rate Ratio [RR]; 1.23, 95% Confidence Interval [CI]; 1.12~1.36), lower default, 3.6%, (RR; 0.31, 95% CI; 0.13~0.75) and transfer-out rate, 3.0%, (RR; 0.32, 95% CI; 0.12~0.86) than the conventional group where they were: 75.0%, 11.6%, 9.3%, respectively. The success rate was even higher than the rate (80.5%) of 1,027 cases treated in health centers (RR; 1.11, 95% CI; 1.05~1.17). Of the completed cases in the intervention group, 82.2% regarded the role of the public health nurse as very helpful. CONCLUSION: The treatment success rate, of tuberculosis patients in the private sector, was significantly improved by an intervention using a public-private collaboration model.
Cohort Studies ; Cooperative Behavior ; Health Education ; Hospitals, Private ; Humans ; Private Sector ; Prospective Studies ; Public Health Nursing ; Public Sector ; Telephone ; Tuberculosis ; Tuberculosis, Pulmonary

Although mycobacterial culture and the subsequent drug-susceptibility test (DST) for anti-tuberculosis (TB) drugs take several months to complete using solid media, there are no reports on the turnaround times of these tests under clinical conditions. The aim of this study was to determine the interval between initiation of anti-TB treatment and receipt of DST requested at an outpatient clinic. We prospectively enrolled patients with culture-positive pulmonary TB at Seoul National University Hospital from September 2002 to December 2004. Patients were followed up monthly. Mycobacterial cultures were done using Ogawa media at Seoul National University Hospital. DST were performed at the Korean Institute of Tuberculosis. Of the 104 patients enrolled, 54 were male. The median age was 41 yr. The median interval from initiation of anti-TB treatment to receipt of mycobacterial culture results by clinicians was 37 days (range, 0-89 days). The median interval from initiation of treatment to confirmation of DST by requesting clinicians was 80.5 days (range, 28-145 days). Clinicians only received the results of DST more than two months after initiation of treatment when they followed up patients monthly and mycobacterial culture was performed using solid media.
Tuberculosis, Pulmonary/*drug therapy ; Time Factors ; Prospective Studies ; Middle Aged ; *Microbial Sensitivity Tests ; Male ; Humans ; Female ; Antitubercular Agents/pharmacology/*therapeutic use ; Aged ; Adult ; Adolescent

As the incidence of nontuberculous mycobacterial infection has been increasing recently in Korea, the importance of drug susceptibility test for clinical isolates of mycobacteria has become larger. In this study we determined the antimicrobial susceptibility patterns of clinical isolates of M. fortuitum and M. abscessus in Korea, and evaluated the efficacy of a modified broth microdilution method using 2,3-diphenyl-5-thienyl-(2)-tetrazolium chloride (STC), in terms of its ability to provide accurate and easy-to-read minimal inhibitory concentration (MIC) endpoints for the susceptibility testing of rapidly growing mycobacteria. Most isolates of M. fortuitum and M. abscessus in Korea are susceptible or intermediately susceptible to amikacin, cefoxitin, ciprofloxacin, and clarithromycin. Many isolates of M. fortuitum are susceptible to doxycycline, sulfamethoxazole, and imipenem, while many M. abscessus isolates are resistant to these drugs. In the present study, the modified broth microdilution method using STC was found to be reliable, easy to read, and inexpensive for M. fortuitum and M. abscessus susceptibility testing. The modified colorimetric MIC testing method using STC was proven to be a useful surrogate for RGM antibiotic susceptibility testing.
Anti-Bacterial Agents/pharmacology ; Cefoxitin/pharmacology ; Chemistry, Pharmaceutical/methods ; Ciprofloxacin/pharmacology ; Clarithromycin/pharmacology ; Colorimetry/methods ; Drug Resistance, Bacterial ; Korea ; *Microbial Sensitivity Tests ; Mycobacterium/*metabolism ; Mycobacterium fortuitum/*metabolism ; Tetrazolium Salts/*pharmacology

Mycobacterium xenopi is a nontuberculous mycobacterium (NTM) that rarely causes pulmonary disease in Asia. Here we describe the first case of M. xenopi pulmonary disease in Korea. A 66-year-old man was admitted to our hospital with a 2-month history of productive cough and hemoptysis. His past medical history included pulmonary tuberculosis 44 years earlier, leading to a right upper lobectomy. Chest X-ray upon admission revealed cavitary consolidation involving the entire right lung. Numerous acid-fast bacilli were seen in his initial sputum, and M. xenopi was subsequently identified in more than five sputum cultures, using molecular methods. Despite treatment with clarithromycin, rifampicin, ethambutol, and streptomycin, the infiltrative shadow revealed on chest X-ray increased in size. The patient's condition worsened, and a right completion pneumonectomy was performed. The patient consequently died of respiratory failure on postoperative day 47, secondary to the development of a late bronchopleural fistula. This case serves as a reminder to clinicians that the incidence of NTM infection is increasing in Korea and that unusual NTM are capable of causing disease in non-immunocompromised patients.
Aged ; Bacterial Proteins/genetics ; Heat-Shock Proteins/genetics ; Humans ; Korea ; Lung Diseases/*diagnosis/*microbiology/radiography ; Male ; Mycobacterium Infections, Atypical/*diagnosis/microbiology/radiography ; Mycobacterium xenopi/classification/genetics/*isolation & purification ; Phylogeny ; Sequence Analysis, DNA

BACKGROUND: Normal cell proliferation and viability is strongly depends on the availability of metabolic energy and the maintenance of the appropriate adenylate-nucleotide pools. Hypothetically, changes in adenylate kinase (AK) expression could therefore be associated with adaptation to altered growth characteristics or inversely altered growth characteristics of proliferating cells could drive the changes in the metabolic profile. This study investigated whether the expression of either AK1 or a Mycobacterium tuberculosis adenylate kinase mutant which has the same catalytic activity of AK1 could affect the growth rate of slow-growing BCG. METHOD: Recombinant BCGs, which were cloned the human muscle-type adenylate kinase synthetic gene (AK1) and adenylate kinase mutation gene (AKmtDM) of Mycobacterium tuberculosis into the Mycobacterium/E.coli expression vectors, were constructed. Recombinant BCGs and wild-type BCG were cultured in 7H9 media and the optical density at 600nm was measured at intervals of 2-3 days. RESULT: There wasn't the growth rate change induced by AK1 or AKmtDM expression in recombinant BCGs. CONCLUSION: The expression of AK1 or Mycobacterium tuberculosis adenylate kinase mutant in BCG does not affect the growth rate of BCG.
Adenylate Kinase* ; Cell Proliferation ; Clone Cells* ; Genes, Synthetic* ; Humans* ; Metabolome ; Mycobacterium bovis* ; Mycobacterium tuberculosis* ; Mycobacterium*

BACKGROUND: IS6110 DNA fingerprint is a very useful tool for investigating the transmission of tuberculosis. The aim of this study was to identify the epidemiological situations within a given area (one province). METHODS: The 681 Mycbobacterium tuberculosis isolates from patients, who were registered at health centers in Gyeonggi Province from May to December in 2004, were subjected to IS6110 DNA fingerprinting. Patients belonging to clusters were interviewed by health-workers to determine their previous contacts or household TB history. RESULTS: The number of IS6110 copies of the 681 isolates showed diverse fingerprint patterns from 0 to 21 of which the most prevalent copy number was 10 from 120 isolates (17.6%). Thirty-three isolates (4.8%) belonged to the K strain, and 128 isolates (18.8%) belonged to the K family. There were 180 (26.4%) isolates belonged belonging to fifty clusters, of which two clusters were within household transmission. Forty-three (23.9%) out of 180 patients resided in an area under the same health center control. The rate of clusters in those aged 60-70 was higher than in any other age group ( 95% CI of RR : 1.072 ~ 1.988). CONCLUSION: This is the first report of an epidemiological survey based on a whole province using a DNA fingerprinting technique for M. tuberculosis. These results will be helpful in developing a program or policies to prevent the transmission of TB.
Dermatoglyphics ; DNA Fingerprinting* ; DNA* ; Epidemiology ; Family Characteristics ; Gyeonggi-do* ; Humans ; Mycobacterium tuberculosis* ; Mycobacterium* ; Tuberculosis

PURPOSE: Multidrug-resistant tuberculosis (MDR-TB) is an emerging threat to human beings. However, there is little data on the current status of MDR-TB in Korea. This study investigated the current status of MDR-TB in Korea using a survey of all the data from drug susceptibility tests (DST) performed across the country over the last three years. METHOD: The DST results between Jan. 2000 and Dec. 2002 from 7 laboratories, which were in charge of all antituberculous DSTs across the country as of March 2002, were collected and analyzed to determine the actual number of drug-resistant or MDR-TB patients, annual trend, degree and pattern of resistance against anti-TB drugs, etc. RESULTS: Six laboratories used the absolute concentration method for DST and one used the proportional method. 59, 940 tests had been performed over the 3 year study period. The number of DST performed annually was 18,071, 19,950, and 21,919 in 2000-2002, respectively. The number of resistant tuberculosis patients (resistant against at least one anti-TB drug) had increased by 16.9% from 6,338 in 2000 to 7,409 in 2002. The rate of resistant tuberculosis among all DST results was 35.1% in 2000, 34.5% in 2001, and 33.8% in 2002. The number of MDR-TB patients (resistant against at least both isoniazid and rifampin) showed an increasing trend (14.5%) from 3,708 in 2000 to 4,245 in 2002. CONCLUSION: Approximately 4,000 MDR-TB cases are newly identified by DST annually and the number is showing an increasing trend. This study suggests that in order to cope with the current MDR-TB situation, the DST methods will need to be standardized and more aggressive measures will be required.
Humans ; Isoniazid ; Korea* ; Tuberculosis ; Tuberculosis, Multidrug-Resistant*

BACKGROUND: Sputum smear microscopy is rapid, economic, and useful to detect patients with transmittable tuberculosis, albeit laborious. We aimed to evaluate the usefulness of an automated acid-fast bacilli stainer, which had been developed for lowering the labor and maintaining or increasing the staining quality. METHODS: One hundred sputum samples including some known positive smear specimens which were selected from clinical specimens requested for smear and culture for mycobacteria at Pusan National University Hospital, were used for evaluation. Auramine/rhodamine fluorescent acid-fast stainings were performed manually or by using the automated stainer, AT-2000F (Dagatron, Ilsan, Korea). Ziehl-Neelsen stain was also performed simultaneously. RESULTS: Concordance rate between automated and manual fluorescent stains was 98.0% and that between automated fluorescent and manual Ziehl-Neelsen stains was 88.0%. In all discordant cases, the automated stains showed one-grade higher results compared to the respective manual fluorescent or Ziehl-Neelsen stains. With the automatic stainer, all staining procedures were processed automatically except for slide loading and unloading. The process time was reduced by a half, and the slide-to-slide or day-to-day variations of staining quality were reduced compared with the manual fluorescent stain. CONCLUSION: Acid-fast bacilli stain using automated stainer AF-2000F can reduce the processing time, labor, and variations of staining quality, and enhance or maintain the detection of positive smears.
Busan ; Coloring Agents ; Humans ; Microscopy ; Sputum ; Tuberculosis

BACKGROUND: Ethambutol(EMB) is one of the first-line drugs included in short-course anti-tuberculosis therapy. The point mutations in embB gene have been speculated to be associated EMB resistance. However, detection of embB mutations at these positions have been observed in both EMB-susceptible isolates; thus, it remains controversial whether these mutations are associated with EMB resistance METHODS: The 36 M. tuberculosis isolates were selected from clinical isolates which tested susceptible to EMB and resistant to at least one drug. DNA extracted from the isolates was analyzed by amplifying embB gene. The PCR products were purified and directly sequenced. We reviewed the history of past drug susceptibility test results. RESULTS: Out of 36 EMB-susceptible strains, 3 strains (8.3%) had a mutation in codon 306 or 406 of the embB gene. These three strains had at least isoniazid resistance. They grew at 1.0 mcg/ml of EMB in Lowenstein-Jensen media. The patients of the strains were continuously smear-positive for over 3 years despite taking TB therapy. One strain had been EMB-resistant in past drug susceptibility tests. CONCLUSION: EMB-susceptible strains containing embB mutation may be caused by decreased viability in vitro test not by itself.
Codon ; DNA ; Drug Resistance ; Ethambutol ; Humans ; Isoniazid ; Korea ; Mycobacterium tuberculosis* ; Mycobacterium* ; Point Mutation ; Polymerase Chain Reaction ; Tuberculosis

BACKGROUND: Rifabutin (ansamycin) is a spiro-piperidyl rifamycin, which is highly active against Mycobacterium tuberculosis. It has been found that some clinical isolates of tubercle bacilli that are resistant to rifampicin are susceptible to rifabutin, with some patients with multi-drug resistant pulmonary tuberculosis having shown favorable clinical and bacteriological responses to the rifabutin. This study was conducted to find the proportion of rifabutin- susceptible strains among rifampicin-resistant isolates from Korean MDR-TB patients, and investigate the presence of specific rpoB mutations, which may confer resistance to rifampicin, but not to rifabutin. METHODS: 201 rifampicin-resistant and 50 pan-susceptible M. tuberculosis isolates were randomly selected for this study. The isolates were retested at rifampicin and rifabutin concentrations of 0, 20, 40 and 80 microgram/ml, respectively. The isolates that grew at and/or over a rifabutin concentration of 20 microgram/ml were judged rifabutin-resistant. The rpoB gene was extracted from the isolates, and then amplified for direct sequencing to investigate specific rpoB mutations that conferred rifabutin- susceptibility but rifampicin-resistance. RESULTS: Out of the 201 rifampicin-resistant M. tuberculosis, 41 strains (20.4%) were susceptible to rifabutin using the absolute concentration method on Lowenstein-Jensen media. The rpoB mutation types that showed susceptibility to rifabutin were Leu511Pro, Ser512Arg, Gln513Glu, Asp516Ala, Asp516Gly, Asp516Val, Asp516Tyr, Ser522Leu, His526Asn, His526Leu, His526Cys, Arg529Pro and Leu533Pro. A reverse hybridization technique was able to detect 92.5% of the rifabutin-susceptible isolates, with a specificity of 96.1% among 195 M. tuberculosis isolates with the rpoB mutation. CONCLUSIONS: Around 20% of the rifampicin-resistant isolates in Korea showed susceptibility to rifabutin, which was associated with some specific mutations of rpoB. Rifabutin could be used for the treatment of MDR-TB patients, especially when drug susceptibility testing reveals susceptibility to rifabutin.
Humans ; Korea ; Mycobacterium tuberculosis ; Rifabutin ; Rifampin ; Tuberculosis ; Tuberculosis, Pulmonary