• Tuberculosis and Respiratory Diseases
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• v.50 no.6
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• pp.686-692
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• 2001

Background : Outbreaks of multidrug-resistant tuberculosis(MDR-TB) are caused by the low rate of treatment response due to limitation in number of available drugs and high rates of adverse drug side-effects. This study analysed the risk factors for MDR-TB patients, who did not respond to treatment, with an aim to improve the rate of treatment response. Methods : Retrospective study of 111 MDR-TB patients at National Mokpo Tuberculosis Hospital from Jan. 1996 to Dec. 1998 was made. The patients were separated into two groups ; group I comprised of patients who were treated successfully and group II comprised of those were not treated successfully. In order to analyze the risk factors for treatment failure, differences between the two groups were compared and the confidence limit regarding the results were tested using an independent t-test. chi-square test and a Fisher's exact test. Results : The treatment failure rate of MDR-TB patients was 32% (36 patients), and treatment success rate 68%(75 patients). This study found no significant difference between two groups in terms of age, sex, family history, extent of the disease on the chest X-ray, the number of sensitive drugs in the treatment regimen, and the number of sensitive bactericidal drugs in the treatment regimen (p>0.05). However, a past history of pulmonary tuberculosis, cavitary lesions on the chest X-ray, the number of treatments, the number of resistant drugs and the number of drugs used showed a significant difference(p<0.05). Conclusion : The rate of treatment failure in MDR-TB was increased by a past history of pulmonary tuberculosis, cavitary lesions on the chest X-ray, the number of treatments, the number of resistant drugs and the number of drugs used. For improving the treatment response of MDR-TB, every effort should be made to reduce the drug resistance caused by failure of the first treatment.

• Tuberculosis and Respiratory Diseases
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• v.78 no.2
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• pp.78-84
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• 2015

Background: Reports of therapeutic drug monitoring (TDM) for second-line medications to treat multidrug-resistant tuberculosis (MDR-TB) remain limited. Methods: A retrospective cohort from the Virginia state tuberculosis (TB) registry, 2009-2014, was analyzed for TDM usage in MDR-TB. Drug concentrations, measured at time of estimated peak ($C_{max}$), were compared to expected ranges. Results: Of 10 patients with MDR-TB, 8 (80%) had TDM for at least one drug (maximum 6 drugs). Second-line drugs tested were cycloserine in seven patients (mean $C_{2hr}$, $16.6{\pm}10.2{\mu}g/mL$; 4 [57%] below expected range); moxifloxacin in five (mean $C_{2hr}$, $3.2{\pm}1.5{\mu}g/mL$; 1 [20%] below); capreomycin in five (mean $C_{2hr}$, $21.5{\pm}14.0{\mu}g/mL$; 3 [60%] below); para-aminosalicylic acid in five (mean $C_{6hr}$, $65.0{\pm}29.1{\mu}g/mL$; all within or above); linezolid in three (mean $C_{2hr}$, $11.4{\pm}4.1{\mu}g/mL$, 1 [33%] below); amikacin in two (mean $C_{2hr}$, $35.3{\pm}3.7{\mu}g/mL$; 1 [50%] below); ethionamide in one ($C_{2hr}$, $1.49{\mu}g/mL$, within expected). Two patients died: a 38-year-old woman with human immunodeficiency virus/acquired immune deficiency syndrome and TB meningitis without TDM, and a 76-year-old man with fluoroquinolone-resistant (pre-extensively drug-resistant) pulmonary TB and low linezolid and capreomycin concentrations. Conclusion: Individual pharmacokinetic variability was common. A more standardized approach to TDM for MDR-TB may limit over-testing and maximize therapeutic gain.

• Tuberculosis and Respiratory Diseases
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• v.77 no.4
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• pp.161-166
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• 2014

Since tuberculosis (TB) remains a major global health concern and the incidence of multi-drug resistant (MDR)-TB is increasing globally, new modalities for the detection of TB and drug resistant TB are needed to improve TB control. The Xpert MTB/RIF test can be a valuable new tool for early detection of TB and rifampicin resistance, with a high sensitivity and specificity. Late-generation fluoroquinolones, levofloxacin, and moxifloxacin, which are the principal drugs for the treatment of MDR-TB, show equally high efficacy and safety. Systemic steroids may reduce the overall TB mortality attributable to all forms of TB across all organ systems, although inhaled corticosteroids can increase the risk of TB development. Although fixed dose combinations were expected to reduce the risk of drug resistance and increase drug compliance, a recent meta-analysis found that they might actually increase the risk of relapse and treatment failure. Regarding treatment duration, patients with cavitation and culture positivity at 2 months of TB treatment may require more than 6 months of standard treatment. New anti-TB drugs, such as linezolid, bedaquiline, and delamanid, could improve the outcomes in drug-resistant TB. Nontuberculous mycobacterial lung disease has typical clinical and immunological phenotypes. Mycobacterial genotyping may predict disease progression, and whole genome sequencing may reveal the transmission of Mycobacterium abscessus. In refractory Mycobacterium avium complex lung disease, a moxifloxacin-containing regimen was expected to improve the treatment outcome.

• Tuberculosis and Respiratory Diseases
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• v.69 no.2
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• pp.95-102
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• 2010

Background: The increasing rate of drug-resistant tuberculosis (TB) is a threat to the public health and TB control. In Korea, about 75~80% of TB patients are treated in private hospitals and the rate has been continuously increasing since 2000. Methods: On a retrospective basis, we enrolled 170 newly diagnosed with or retreated for multidrug-resistant TB (MDR-TB) in 2004 from 21 private hospitals. We extracted the following demographics and treatment history from patient medical records: initial treatment outcomes, cumulative survival rates, treatment outcomes, and prognostic factors. Results: Of the 170 patients, the majority were male (64.1%), the mean age was 44.5 years old, and mean body-mass-index was $20.2kg/m^2$. None of the patients tested positive for HIV. Eleven (6.5%) were confirmed to have extensively drug-resistant TB (XDR-TB) at treatment initiation. Treatment success rates were not different between XDR-TB (36.4%, 4/11) and non-XDR MDR-TB (51.6%, 82/159). Default rate was high, 21.8% (37/170). Far advanced disease on X-ray was a significant negative predictor of treatment success; advanced disease and low BMI were risk factors for all-cause mortality. Conclusion: In private hospitals in Korea, the proportion of XDR-TB in MDR-TB was comparable to previous data. The treatment success rate of MDR-/XDR-TB remains poor and the failure rate was quite high. Adequate TB control policies should be strengthened to prevent the further development and spread of MDR-/XDR-TB in Korea.

• Tuberculosis and Respiratory Diseases
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• v.64 no.3
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• pp.187-193
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• 2008

Background: Multidrug-resistant tuberculosis (MDR-TB) and extensively drug resistant tuberculosis (XDR-TB) are serious threats to worldwide tuberculosis control, but the national burden and the trends of infectious spread are largely unknown. Methods: We retrospectively reviewed the results of drug sensitivity tests and medical records of patients that were diagnosed with culture-confirmed pulmonary tuberculosis and were admitted to the National Masan Tuberculosis Hospital between 2001 and 2005. Results: From 2001 to 2005, the proportion of MDR-TB among new cases was 9.2%, 13.8%, 16.9%, 23% and 27.0% in 2001, 2002, 2003, 2004 and 2005, respectively, and the proportion of MDR-TB among previously treated cases was 58.5%, 60.2%, 62.7%, 61.7% and 71.3% in 2001, 2002, 2003, 2004 and 2005, respectively. A significant increasing trend could be discerned for MDR-TB among both new and previously treated cases (p<0.001, p=0.002 for trend, respectively). The proportion of XDR-TB among new cases was 0%, 2.3%, 3.1%, 2.5% and 6.3% in 2001, 2002, 2003, 2004 and 2005, respectively, and the proportion of XDR-TB among previously treated cases was 9.1%, 15.7%, 17.3%, 19.9% and 19.1% in 2001, 2002, 2003, 2004 and 2005, respectively. A significant increasing trend could be discerned for XDR-TB among both new and previously treated cases (p=0.005, p<0.001 for trend, respectively). Conclusion: Both MDR-B and XDR-TB were gradually increased among both new and previously treated cases. Integrated national surveillance, including the public and private sectors, will be needed to estimate the exact status of antituberculous drug resistance.

• Journal of Yeungnam Medical Science
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• v.41 no.2
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• pp.113-119
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• 2024

Background: Missing isoniazid (INH) resistance during tuberculosis (TB) diagnosis can worsen the outcomes of INH-resistant TB. The BD MAX MDR-TB assay (BD MAX) facilitates the rapid detection of TB and INH and rifampin (RIF) resistance; however, data related to its performance in clinical setting remain limited. Moreover, its effect on treatment outcomes has not yet been studied. Methods: We compared the performance of BD MAX for the detection of INH/RIF resistances to that of the line probe assay (LPA) in patients with pulmonary TB (PTB), using the results of a phenotypic drug sensitivity test as a reference standard. The treatment outcomes of patients who used BD MAX were compared with those of patients who did not. Results: Of the 83 patients included in the study, the BD MAX was used for an initial PTB diagnosis in 39 patients. The sensitivity of BD MAX for detecting PTB was 79.5%. The sensitivity and specificity of BD MAX for INH resistance were both 100%, whereas these were 50.0% and 95.8%, respectively, for RIF resistance. The sensitivity and specificity of BD MAX were comparable to those of LPA. The BD MAX group had a shorter time interval from specimen request to the initiation of anti-TB drugs (2.0 days vs. 5.5 days, p=0.001). Conclusion: BD MAX showed comparable performance to conventional tests for detecting PTB and INH/RIF resistances. The implementation of BD MAX as a diagnostic tool for PTB resulted in a shorter turnaround time for the initiation of PTB treatment.

• Tuberculosis and Respiratory Diseases
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• v.48 no.6
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• pp.853-869
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• 2000

Background : Following several decades of decline, the incidence of tuberculosis has recent1y begun to increase in many countries of this the control of this disease has been impeded by the emergence of multi-drug resistant tuberculosis (MDR-TB). The development of rapid diagnostic methods and effective new drugs are needed to control MDR-TB. One of the new drugs for MDR-TB is rifabutin (RBU) which has been known to be effective in some patients with MDR-TB. A few reports showed that some types of mutations of the rpoB gene, which were known to be present in 96-98% of rifampicin-resistant M. tuberculosis, were associated with the rifampicin-resistant but RBU-susceptible phenotype. This study was performed to investigate the correlation between RBU susceptibility and the patterns of rpoB gene mutations in Korean MDR-TB. Methods : Sixty-five clinical isolates of multi-drug resistant Mycobacterium tuberculosis, gathered from patients who visited the Asan Medical Center from July 1997 to June 1999, were investigated. Clinical responses to rifabutin-containing regimen were evaluated. An RBU susceptibility test and sequencing analysis of rpoB gene were performed, and the results were analyzed to confirm which mutations correlated with RBU-susceptible MDR-TB. Results : Fifty-three of 56 (95%) clinical isolates of MDR-TB had 60 mutations of the rpoB gene. The most frequent mutations were found at codon 531 (43%), and two mutations were combined in seven clinical isolates. Five of 53 (10%) clinical isolates showed the RBU-susceptible phenotype, and in them the characteristic patterns of point mutations were found at codon 509, 516, and 526. Conclusion : The frequency and pattern of mutations of the rpoB gene of Korean MDR-TB isolates were similar to those in western countries, where the prevalence of tuberculosis is low, but some show RBU-susceptible phenotypes. RBU-susceptible MDR-TB isolates showed the characteristic pattern of mutations of the rpoB gene which could be used to rapidly diagnose RBU susceptibility.

• Tuberculosis and Respiratory Diseases
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• v.66 no.3
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• pp.198-204
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• 2009

Background: First-line drugs, if sensitive, are the most potent drugs in the treatment of multidrug-resistant tuberculosis (MDR-TB). This study examined the frequency and risk factors associated with acquired drug resistance to first-line drugs during a standardized treatment using first-line drugs in patients with MDR-TB. Methods: This study included patients who were diagnosed with MDR-TB at the National Masan Tuberculosis Hospital between January 2004 and May 2008, treated with standardized first-line drugs, and for whom the preand post-treatment results of the drug susceptibility test were available. Their medical records were reviewed retrospectively. Results: Of 41 MDR-TB patients, 14 (34.1%) acquired additional resistance to ethambutol (EMB) or pyrazinamide (PZA). Of 11 patients initially resistant to isoniazid (INH) and rifampicin (RFP), 3 (27.3%) acquired additional resistance to both EMB and PZA, and 3 (27.3%) to PZA. Of 18 patients initially resistant to INH, RFP and EMB, 6 (33.3%) acquired additional resistance to PZA. Of 6 patients initially resistant to INH, RFP and PZA, 2 (33.3%) acquired additional resistance to EMB. Ten of the 41 MDR-TB patients (24.4%) changed from resistant to susceptible. No statistically significant risk factors associated with acquired resistance could be found. Conclusion: First-line drugs should be used cautiously in the treatment of MDR-TB in Korea considering the potential acquisition of drug resistance.

• Tuberculosis and Respiratory Diseases
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• v.72 no.1
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• pp.44-49
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• 2012

Background: Multidrug-resistant tuberculosis (MDR-TB) is an increasing public health problem and poses a serious threat to global TB control. Fluoroquinolone (FQ) and aminoglycoside (AG) are essential anti-TB drugs for MDR-TB treatment. REBA MTB-FQ$^{(R)}$ and REBA MTB-KM$^{(R)}$ (M&D, Wonju, Korea) were evaluated for rapid detection of FQ and kanamycin (KM) resistance in MDR-TB clinical isolates. Methods: M. tuberculosis (n=67) were isolated and cultured from the sputum samples of MDR-TB patients for extracting DNA of the bacilli. Mutations in genes, gyrA and rrs, that have been known to be associated with resistance to FQ and KM were analyzed using both REBA MTB-FQ$^{(R)}$ and REBA MTB-KM$^{(R)}$, respectively. The isolates were also utilized for a conventional phenotypic drug susceptibility test (DST) as the gold standard of FQ and KM resistance. The molecular and phenotypic DST results were compared. Results: Sensitivity and specificity of REBA MTB-FQ$^{(R)}$ were 77 and 100%, respectively. Positive predictive value and negative predictive value of the assay were 100 and 95%, respectively, for FQ resistance. Sensitivity, specificity, positive predictive value and negative predictive value of REBA MTB-KM$^{(R)}$ for detecting KM resistance were 66%, 94%, 70%, and 95%, respectively. Conclusion: REBA MTB-FQ$^{(R)}$ and REBA MTB-KM$^{(R)}$ evaluated in this study showed excellent specificities as 100 and 94%, respectively. However, sensitivities of the assays were low. It is essential to increase sensitivity of the rapid drug resistance assays for appropriate MDR-TB treatment, suggesting further investigation to detect new or other mutation sites of the associated genes in M. tuberculosis is required.

• Tuberculosis and Respiratory Diseases
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• v.60 no.2
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• pp.171-179
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• 2006

Background : Despite the emerging danger of MDR-TB to human beings, there have only been a limited number of drugs developed to treat MDR-TB since 1970. This study investigated the cross-resistance rate between rifampicin (RFP) and rifabutin (RBU) in order to determine the efficacy of rifabutin in treating MDR-TB. In addition, the results of rifabutin were correlated with the rpoB mutations, which are believed to be markers for MDR-TB and RFP resistance. Methods : The MICs of RBU were tested against 126 clinical isolates of MDR-TB submitted to the clinical laboratory of National Masan TB Hospital in 2004. Five different concentrations ($10-160{\mu}g/ml$) were used for the MICs. The detection of the rpoB mutations was performed using a RFP resistance detection kit with a line probe assay(LiPA), which contains the oligonucleotide probes for 5 wide type and 3 specific mutations (513CCA, 516GTC, and 531TTG) The rpoB mutation was determined by direct sequencing. Results : The rate of cross-resistance between RFP and RBU was 70.5%(74/105) at $20{\mu}g/ml$ RBU(ed note: How much RFP?) Most mutations (86.3%) occurred in the 524~534 codons. The His526Gln, His526Leu, Leu533Pro, Gln513Glu, and Leu511Pro mutations(Ed note: Is this correct?) were associated with the susceptibilty to RBU. Conclusion : Based on the cross-resistance rate between RFP and RBU, RBU may be used effectively in some MDR-TB patients. Therefore, a conventional drug susceptibility test for RBU and a determination of the critical concentration are needed. However, rpoB gene mutation test may be have limited clinical applications in detecting RBU resistance.