• 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.

• Tuberculosis and Respiratory Diseases
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• v.59 no.3
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• pp.250-256
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• 2005

Background : Fluoroquinolone drugs are an important anti-tuberculous agent for the treatment of multi-drug resistant tuberculosis. However, many drugs belonging to the fluoroquinolones have different cross resistance to each other. Methods : Sixty-three ofloxacin (OFX) resistant and 10 pan-susceptible M. tuberculosis isolates were selected, and compared for their cross resistance using a proportion method on Lowenstein-Jensen media, containing ofloxacin (OFX), ciprofloxacin (CIP), levofloxacin (LVX), moxifloxacin (MXF), gatifloxacin (GAT) and sparfloxacin (SPX), at concentrations ranging from 0.5 to $3{\mu}g/ml$. DNA extracted from the isolates was directly sequenced after amplifying from the gyrA and gyrB genes. Results : The 63 OFX resistant M. tuberculosis isolates showed complete cross resistance to CIP, but only 90.5, 44.4, 36.5 and 46.0% to LVX, MXF, GAT, and to SPX, respectively. Fifty-one of the isolates (81.0%) had point mutations in codons 88, 90, 91 and 94 in gyrA, which are known to be correlated with OFX resistance. The Gly88Ala, Ala90Valand Asp94Ala mutations in gyrA showed a tendency to be susceptible to MXF, GAT and SPX. Only 4 isolates had mutations in the gyrB gene, which did not affect the OFX resistance. Conclusion : About 60% of the OFX resistant M. tuberculosis isolates were susceptible to GAT, SPX and MXF. These fluoroquinolones may be useful in the treatment of TB patients showing OFX resistance.

• Membrane Journal
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• v.33 no.6
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• pp.398-408
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• 2023

This work developed a hood and filter for antibacterial protective clothing for medical powered air purifying respirators (PAPR) that can be used in medical settings and quarantine against infectious diseases such as Zika virus, Middle East respiratory syndrome (MERS), and coronavirus disease-19 (COVID-19). The hood material of the protective clothing was made of polypropylene spunlace nonwoven fabric (SFS) was used for withstand wind pressure and external physcial pressure. Forthermore, in order to reduce the user's risk of infection, phytoncide-based materials were used on the outer-surface of the hood to achieve a 99.9% antibacterial effect, and the inner-surface were treated with hydro-philic materials to improve absorbency by 25%. In addition to evaluating the artificial blood penetration resistance, dry mi-croorganism penetration resistance, wet bacteria penetration resistance, and bacteriophage penetration resistance required for medical protective clothing hoods, it received a passing evaluation of levels 2-6. Meanwhile, as a result of evaluating the performance of the antibacterial treated spunlace high efficiency particulate air (HEPA) filter, excellent antibacterial properties, dust removal rate, and differential pressure effect were confirmed. All performance evaluations were conducted by an accredited certification body in accordance with the medical PAPR certification standards.

• Tuberculosis and Respiratory Diseases
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• v.80 no.2
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• pp.187-193
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• 2017

Background: Third-generation tyrosine kinase inhibitors of the epidermal growth factor receptor (EGFR-TKIs) have proved efficacious in treating non-small cell lung cancer (NSCLC) patients with acquired resistance resulting from the T790M mutation. However, since almost 50% patients with the acquired resistance do not harbor the T790M mutation, retreatment with first- or second-generation EGFR-TKIs may be a more viable therapeutic option. Here, we identified positive response predictors to retreatment, in patients who switched to a different EGFR-TKI, following initial treatment failure. Methods: This study retrospectively reviewed the medical records of 42 NSCLC patients with EGFR mutations, whose cancers had progressed following initial treatment with gefitinib or erlotinib, and who had switched to a different first-generation EGFR-TKI during subsequent retreatment. To identify high response rate predictors in the changed EGFR-TKI retreatment, we analyzed the relationship between clinical and demographic parameters, and positive clinical outcomes, following retreatment with EGFR-TKI. Results: Overall, 30 (71.4%) patients received gefitinib and 12 (28.6%) patients received erlotinib as their first EGFR-TKI treatment. Following retreatment with a different EGFR-TKI, the overall response and disease control rates were 21.4% and 64.3%, respectively. There was no significant association between their overall responses. The median progression-free survival (PFS) after retreatment was 2.0 months. However, PFS was significantly longer in patients whose time to progression was ${\geq}10months$ following initial EGFR-TKI treatment, who had a mutation of exon 19, or whose treatment interval was <90 days. Conclusion: In patients with acquired resistance to initial EGFR-TKI therapy, switched EGFR-TKI retreatment may be a salvage therapy for individuals possessing positive retreatment response predictors.

• Tuberculosis and Respiratory Diseases
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• v.43 no.1
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• pp.8-13
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• 1996

Background: The 463 codon mutation of katG gene has been reported as an useful marker for the detection of isoniazid(INH) resistant strains of M. tuberculosis. This study aimed to elucidate relationship between 463 mutation in katG gene and INH resistance in M. tuberculosis. Method: DNA was extracted from 28 INH susceptible strains(MIC$\geq\;0.2{\mu}g/ml$ on the L$\ddot{o}$wenstein Jensen media) and used for amplification of 189bp fragment containing 463 codon by PCR. Amplified fragments were digested by restriction enzyme Msp I, analyzed by single strand conformation polymorphism(SSCP) in the MDE gel and sequenced to prove mutation. Result: Only 7(25%) out of 28 were digestible by restriction enzyme Msp I. The SSCP pattern of 21 strains were distinctly different from that of M. tuberculosis H37Rv. Msp I undigestible PCR fragment was substituted at 463 codon from Arg(CGG) to Leu(CTG). Conclusion: This finding clearly indicate no relationship between 463 codon mutation of the katG gene and INH resistance.

• Tuberculosis and Respiratory Diseases
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• v.45 no.6
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• pp.1123-1142
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• 1998

Background : The frequency of MOTT has risen as the prevalence of tuberculosis has been declining. Our country has been also. The most of MOTT was resistant to the major anti-tuberculous drugs. Method : To compare clinical characteristics and frequencies of MDR tuberculosis with MOTT, the author studied 65 patients showing AFB culture positive with sputum. The data were collected from 176 patients who had been admitted at the National Masan Tuberculosis Hospital from May to June, 1997 to April, 1998. Result : The frequency of MDR tuberculosis was 43.1% and that of MOTT was 9.2%. Among 65 isolated mycobacteria, 3 cases were M. intracellulare. 2 cases were M. fortuitum, and 1 case was unidentified MOTT. The most frequent age group in 65 culture positive patients was 4th decade and the mean age was 44. The mean age was 61 in MOTT and 42 in M. tuberculosis and had significant difference(p<0.01). The numbers with past history of treatment were 2.3 in MDR tuberculosis and 1.7 in non-MDR tuberculosis and had significant difference(p<0.05). At the time of admission, the most frequent regimen for the treatment of MDR tuberculosis was 24 months regimen(85.7%) with the 2nd line anti-tuberculosis drugs. For non-MDR tuberculosis, 9 or 12 months regimen (72.9%) with the 1st line anti-tuberculosis drugs and had significant difference (p<0.01). At the time of admission, the symptom of weight loss was shown in 84.7% of M. tuberculosis and 50.0% in MOTT and there was significant difference(p<0.05) between them. All of the MOTT were identified to be resistant against INH and PAS. Drug resistance rates to INH, OFX(p<0.01) and PAS(p<0.05) in MOTT were higher than in MDR. All of three M. intracellulare strains were resistant to INH, RFP, PAS and OFX. All of two M. fortuitum strains were resistant to most anti-tuberculosis drugs. And the other MOTT was resistant to INH, EMB and PAS. Conclusion : MOTT was more common in elderly patients than M. tuberculosis. MOTT cases should be considered to be the probability of multiple drug resistance and treatment failure during the 1st treatment because they showed more resistance to anti-tuberculosis drugs than M. tuberculosis cases. Therefore, there should be more careful investigations for clinical characteristics, natural history of disease, and efficient management for MOTT.

• Tuberculosis and Respiratory Diseases
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• v.45 no.2
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• pp.351-359
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• 1998

Background: The effects of exercise on pulmonary function are complex and have been the subject of many investigations. But, there has been disputes about the effect of exercise on spirometric parameters and there is no study about the effect of exercise on IOS(Impulse Oscillometry)parameters. IOS, a new method of pulmonary function test, is based on the relationship between the pressure and flow oscillation which is produced by applying sinusoidal pressure oscillation to the respiratory system via the mouth. Method: Fifty-nine young adults without respiratory symptoms were divided into three groups according to degree of exercise(hard exercise group: mean exercise time is over three hours per week at least for the last one month, light exercise group : between thirty minutes to three hours, nonexercise group : less than thirty minutes) and undertaken pulmonary function test(simple spirometry and IOS). Results: The effects of exercise on spirometric parameters; percentage of predictive value of forced vital capacity(FVC % pred) was higher in hard exercise group than nonexercise group(hard exercise group: $102.4{\pm}14.8$, nonexercise group: $93.7{\pm}9.9$, p=0.017), but there was no significant difference in percentage of predicted value of forced expiratory volume in one second(FEV 1 % pred) and percentage of predicted value of forced expiratory flow 50% (FEF 50% pred) between groups. The effects of exercise on IOS parameters: Reactance at 5Hz(X5) was significantly lower in hard exercise group than nonexercise group(hard exercise group: $-0.166{\pm}0.123hPa/1/s$, nonexercise group: $-0.093{\pm}0.036hPa/1/s$, p=0.006) but there was no significant difference in central resistance(Rc), peripheral resistance(Rp), resonance frequency(RF) and resistance at 5Hz, 20Hz between groups. Conclusion: Hard exercise increased FVC % pred on spirometric parameters and decreased reactance at 5Hz(X5) on IOS parameters.

• Tuberculosis and Respiratory Diseases
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• v.57 no.5
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• pp.405-410
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• 2004

Background : Moxifloxacin is an 8-methoxyquinolone compound which has been shown to have the best activity of the quinolones against M. tuberculosis but there is no literature showing the rate of cross-resistance between moxifloxacin and the other quinolones such as ofloxacin. Therefore, we tested the activity of moxifloxacin against ofloxacin resistant M. tuberculosis by a study of cross-resistance. Methods : We tested MIC's of moxifloxacin and ofloxacin by proportion method against 34 M. tuberculosis isolates showing resistance against ofloxacin at $2.5{\mu}g/m{\ell}$ concentration and 13 ofloxacin susceptible isolates from specimens submitted to clinical laboratory of National Masan Hospital from March 2003 to March 2004. Results : For ofloxacin susceptible isolates, $MIC_{50}$ and $MIC_{90}$ of ofloxacin were all $1.25{\mu}g/m{\ell}$, and $MIC_{50}$ and $MIC_{90}$ of moxifloxacin were $0.31{\mu}g/m{\ell}$ and $0.63{\mu}g/m{\ell}$ respectively. For ofloxacin resistant isolates, $MIC_{50}$ of ofloxacin was over $10{\mu}g/m{\ell}$ and $MIC_{50}$ of moxifloxacin was $5{\mu}g/m{\ell}$, $MIC_{90}$ of ofloxacin and moxifloxacin were all over $10{\mu}g/m{\ell}$. The rate of cross-resistance between the two was 67.6%(23/34) at $2.5{\mu}g/m{\ell}$ concentration. Conclusions : Moxifloxacin showed activity against 82.4%(28/34) of ofloxacin resistant M. tuberculosis at $10{\mu}g/m{\ell}$, but more studies are needed so that moxifloxacin will be used for patient with multi-drug resistant tuberculosis including oflokacin resistance.

• Tuberculosis and Respiratory Diseases
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• v.43 no.1
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• pp.14-21
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• 1996

Objectives: Although outbreak of MDR Tb has been a recent problem in western countries, it has been a longstanding problem in Korea. The poor outcome of MDR Tb is mainly due to poor compliance, high rate of side reaction of secondary drugs, and limitation in number of available drugs. Thus, to improve the outcome of MDR Tb, it is crucial to make individualized adequate prescription based on the knowledge of the patterns of resistance to each drugs in the community as well as the natural history. The purpose of present study is to evaluate the clinical features of Korean MDR Tb patients including patterns of drug resistance and success rate of treatment which was prescribed according to the sensitivity tests. Methods: Retroscpective analysis of 71 Korean patients with MDR Tb was made. All strains isolated from patients showed resistence to at least two first line drugs. Patients profile, previous treatment history, patterns of drug resistance, outcome of treatment was analysed. Initial treatment regimen was selected according to the previous treatment history and was modified according to the sensitivity reports. The regimen was composed to include at least 4 sensitive drugs when possible. Results: The patients showed resistance to 4.1 drugs on average. 90% of them were resistant to INH and RFP. Among 71 patients, 35 patients(49%) had cavitary lesions in CXR. Treatment outcome was analysed in 55 patients. 35 patients(67%) were improved after treatment and 18 patients(33%) showed treatment failure. 5 patients showed primary resistance. Treatment outcome could be evaluated in 4 of them and all showed improvement after treatment. 14 patients(20%) had to change their regimens due to drug side effects. The most frequent side effect was elevation of liver enzymes(6 patients). Others included dizziness, hyperuricemia, tinnitus, skin rash, GI troubles. More than 50% of side effects developed within 3 months. In repeated drug sensitivity test, the concordance rate of resistance to INH was 100% and RFP 98%. EMB, PZA showed 80% concordance rate. But in the other drugs, the concordances were less than 50%. Operation was done in 5 patient - 1 patients as a adjunctive means of chemotherapy -. In that case, negative conversion of sputum AFB was done. Conclusion: 2/3 patients of multidrug-resistant tuberculosis were improved by appropriate prescription and regular medication suggesting that more aggressive management and monitoring is indicated in multidrug-resistant tuberculosis.

• Tuberculosis and Respiratory Diseases
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• v.47 no.2
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• pp.184-194
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• 1999

Backgrounds : The advent of penicillin has led to the marked reduction in the mortality from pneumococcal bacteremia, however, the mortality is still relatively high in this post-antibiotic era. Actually the prevalence of infection due to penicillin-resistant penumococci is increasing worldwide, and it is especially high in Korea due to irrelevant use of antibiotics. So, the high mortality of pneumococcal sepsis might be related to the emergence of penicillin-resistant strains, however, many other antibiotics, which eradicate pneumococci effectively, are available in these days. This has led us to suspect the role of penicillin-resistance in the high mortality rate. In this study, we evaluated the effect of penicillin resistance on the mortality of patients with penumococcal bacte remia. Methods: The study population consisted of 50 adult patients with penumococcal bacteremia who were admitted between Jan, 1990 and July, 1997. Medical records were analyzed retrospectively. Results: Most of the patients (96%) had underlying diseases. The most common local disease associated with pneumococcal bacteremia was pneumonia (42%), which was followed by spontaneous bacterial peritonitis (14%), cholangitis (10%), meningitis (8%), liver abscess (4%), pharyngotonsillitis (4%), sinusitis (2%) and cellulitis (2%). While the overall case-fatality rate in this study was 24%, it was higher when peumococcal bacteremia was associated with pneumonia (42%) or meningitis (50%). The rate of penicillin resistance was 40%, which was increased rapidly from 1991. The rate of penicillin resistance was significantly higher in patients with the history of recent antibiotics use and hospitalization within 3 months respectively. The clinical manifestations, that is, age, severity of underlying diseases, nosocomial infection, associated local diseases, and the presence of shock or acute renal failure were not statistically different between the patients with penicillin-resistant and -sensitive pneumococcal bacteremia. The mortality of patients infected with penicillin-resistant pneumococci was not statistically different from those with penicillin-sensitive pneumococcal bacteremia. Conclusion: Penicillin resistance is not associated with high mortality in adult patients with pneumococcal bacteremia. As the overall mortality is high, active penumococcal vaccination is recommended in patients with high risk of infection.