Over-expression of the pathway specific positive regulator gene is an effective way to activate silent gene cluster. In the curret study, the SARP family regulatory gene, vasR2, was over-expressed in strain Verrucosispora sp. NS0172 and the cryptic gene cluster responsible for the biosynthesis of pentaketide ansamycin was partially activated. Two tetraketides (1 and 2) and a triketide (3) ansamycins, together with five known compounds (4-8), were isolated and elucidated from strain NS0172OEvasR2. Their NMR data were completely assigned by analysis of their HR-ESI-MS and
Micromonosporaceae/metabolism* ; Multigene Family ; Polyketides/metabolism* ; Rifabutin/metabolism*

HSP90 is a molecular chaperone that increases the stability of client proteins. Cancer cells show higher HSP90 expression than normal cells because many client proteins play an important role in the growth and survival of cancer cells. HSP90 inhibitors mainly bind to the ATP binding site of HSP90 and inhibit HSP90 activity, and these inhibitors can be distinguished as ansamycin and non-ansamycin depending on the structure. In addition, the histone deacetylase inhibitors inhibit the activity of HSP90 through acetylation of HSP90. These HSP90 inhibitors have undergone or are undergoing clinical trials for the treatment of cancer. On the other hand, recent studies have reported that various reagents induce cleavage of HSP90, resulting in reduced HSP90 client proteins and growth suppression in cancer cells. Cleavage of HSP90 can be divided into enzymatic cleavage and non-enzymatic cleavage. Therefore, reagents inducing cleavage of HSP90 can be classified as another class of HSP90 inhibitors. We discuss that the cleavage of HSP90 can be another mechanism in the cancer treatment by HSP90 inhibition.
Acetylation ; Adenosine Triphosphate ; Binding Sites ; Drug Therapy ; Hand ; Heat-Shock Proteins ; Histone Deacetylase Inhibitors ; Hot Temperature ; Indicators and Reagents ; Molecular Chaperones ; Rifabutin

BACKGROUND/AIMS: Optimized regimen has not yet been established for failures of multiple Helicobacter pylori (H. pylori) eradication. Hence, we aimed to evaluate the efficacy of rifabutin-based rescue therapy, at least after three eradication failures. METHODS: Twelve patients, who failed in the treatment for H. pylori eradication at least three times, were consecutively enrolled between 2007 and 2015 at Seoul National University Bundang Hospital. The rifabutin-based rescue regimen was consisted of proton pump inhibitor (PPI), rifabutin (150 mg b.i.d.), and amoxicillin (1 g b.i.d.), given for 7 or 14 days. MIC concentration test by the agar dilution method was performed on six patients prior to rifabutin-based rescue therapy. RESULTS: One patient did not take this regimen, and per-protocol (PP) analysis was performed in 11 patients. The overall eradication rate by intention-to-treat and PP analysis with rifabutin-based rescue therapy was 50.0% (6/12 patients) and 54.5% (6/11 patients), respectively. There was no difference of the eradication rate depending on the underlying disease, smoking, alcohol, number of previous eradication failures, and CYP2C19 genotype. All of the six patients were susceptible to rifabutin, but only three of them succeeded in eradicating with H. pylori. Side effects occurred in two patients (18.2%), and compliance was 90.9%. CONCLUSIONS: Even the eradication rate of rifabutin-based rescue therapy was not very good. Rifabutin-based rescue therapy could be considered as a rescue therapy, perhaps as the fourth or the fifth-line treatment option. No correlation of rifabutin sensitivity with eradication success rate of H. pylori suggests that frequent administration of high dose PPI and amoxicillin might be important.
Agar ; Amoxicillin ; Compliance ; Cytochrome P-450 CYP2C19 ; Genotype ; Helicobacter pylori* ; Helicobacter* ; Humans ; Methods ; Proton Pumps ; Rifabutin ; Salvage Therapy ; Seoul ; Smoke ; Smoking

Mycobacterium avium complex (MAC) is an opportunistic bacterium that primarily infects acquired immune deficiency syndrome (AIDS) patients with low CD4+ T cell counts; however, peritonitis caused by MAC in AIDS patients is rare. Here, we report the first case of peritonitis caused by MAC in AIDS patients in Korea. A 41-year-old female with poor adherence to antiretroviral therapy was admitted to hospital with nonspecific symptoms; an abdominal computed tomography (CT) scan revealed substantial ascites, splenomegaly, and lymphadenopathy. Based on the CT scan and ascitic fluid cultures, MAC peritonitis was diagnosed. In addition to antiretroviral therapy, clarithromycin, rifabutin, and ethambutol were administered to treat the MAC infection, and the patient's symptoms improved.
Acquired Immunodeficiency Syndrome* ; Adult ; Ascites ; Ascitic Fluid ; Cell Count ; Clarithromycin ; Ethambutol ; Female ; HIV ; Humans ; Korea ; Lymphatic Diseases ; Mycobacterium avium Complex* ; Mycobacterium avium* ; Mycobacterium* ; Peritonitis ; Rifabutin ; Splenomegaly ; Tomography, X-Ray Computed

Since the discovery of Helicobacter pylori in 1983 by Warren and Marshall, it has been recognized as one of the most significant risk factors for gastric cancer and has been associated with various gastrointestinal disorders such as peptic ulcer disease. In Korea, the triple therapy of proton pump inhibitor, clarithromycin, and amoxicillin has been recommended as a primary regimen since 1998. However, the eradication rate of conventional first line therapy of H. pylori infection has been decreasing progressively, primarily due to increased resistance to antibiotics. A recent meta-analysis showed that the overall eradication rates were 74.6% by intention-to-treat analysis and 82.0% by per-protocol analysis. Therefore, the need for alternative first line eradication regimens has been rising. Sequential therapy, concomitant therapy, and various combinations of new antibiotics such as quinolone and rifabutin have been introduced as new options, but they have yet to be proven as standard first line therapy. Further nation-wide surveillance regarding the antibiotic resistance rates and well-designed prospective randomized controlled multicenter trials on the empirical first line therapy are necessary to establish the appropriate treatment for H. pylori in Korea.
Amoxicillin ; Anti-Bacterial Agents ; Clarithromycin ; Drug Resistance ; Drug Resistance, Microbial ; Helicobacter pylori* ; Helicobacter* ; Korea* ; Multicenter Studies as Topic ; Peptic Ulcer ; Prospective Studies ; Proton Pumps ; Rifabutin ; Risk Factors ; Stomach Neoplasms

The eradication rate of Helicobacter pylori has been decreasing progressively, primarily due to increased resistance to antibiotics. The widely used standard clarithromycin-based triple therapy regimen is no longer achieving eradication rate of 80% in intent-to-treat analysis in many countries. Due to the primary and secondary resistance to metronidazole, the key antibiotic for second line regimen, eradication rate of standard metronidazole based quadruple therapy is also decreasing. It is rational to check antibiotic resistance for selecting regimens in third-line rescue eradication therapy, but it requires time and resource. Limited studies regarding the efficacy of a dual regimen consisting of high dose proton pump inhibitor and amoxicillin showed controversial results. Efficacy of rescue regimens containing fluoroquinolones, such as levofloxacin and moxifloxacin, were reported to be insufficient due to increasing incidence of primary and secondary resistance. Eradication result of third-line rescue regimens with sitafloxacin, a novel quinolone of which the antibacterial activity towards H. pylori is more than 100-fold that of ciprofloxacin in vitro, is promising. Although prevalence of serious side effect such as myelotoxicity with rifabutin-based rescue regimen is reported to be lower than expected, wider use of rifabutin is still concerned regarding the emergence of resistant mycobacterial species. Rifaximin based rescue regimen is safer and cheaper than rifabuitin based regimen. However, further investigation for better eradication rates by enhancing higher drug concentration in the gastric mucus layer needs to be evaluated.
Amoxicillin ; Anti-Bacterial Agents ; Ciprofloxacin ; Drug Resistance, Microbial ; Fluoroquinolones ; Helicobacter pylori* ; Incidence ; Levofloxacin ; Metronidazole ; Mucus ; Prevalence ; Proton Pumps ; Rifabutin

No abstract available.
Antibiotics, Antitubercular/*adverse effects ; Female ; Humans ; Kidney Transplantation/*adverse effects ; Middle Aged ; Neutropenia/blood/*chemically induced/diagnosis ; Opportunistic Infections/microbiology/*prevention & control ; Recurrence ; Rifabutin/*adverse effects ; Severity of Illness Index ; Time Factors ; Tuberculosis/microbiology/*prevention & control

Mycobacterium avium complex (MAC) is the most common pathogen in nontuberculous mycobacterial lung diseases, but vertebral osteomyelitis caused by MAC is rare. We experienced a case of vertebral osteomyelitis with epidural abscess in a rheumatoid arthritis patient who received immunosuppressive agents. Initial assessment was tuberculous vertebral osteomyelitis, and then treated with antituberculous drugs. Fifty-six days later, Mycobacterium intracellulare was identified from abscess culture and drugs were altered to clarithromycin, rifabutin, and ethambutol. After 3 months of M. intracellulare treatment, the radiological findings showed increases of epidural abscess. According to the suseptibility, the patient received intravenous amikacin for four weeks, and then, oral ciprofloxacin in addition to clarithromycin, rifabutin, and ethambutol. The patient is being treated with the medication for 13 months and currently showing slow improvements.
Abscess ; Amikacin ; Arthritis, Rheumatoid ; Ciprofloxacin ; Clarithromycin ; Epidural Abscess ; Ethambutol ; Humans ; Immunosuppressive Agents ; Lung Diseases ; Mycobacterium ; Mycobacterium avium Complex ; Nontuberculous Mycobacteria ; Osteomyelitis ; Rifabutin

Standard short-course chemotherapy (SSC) is recommended for new patients with pulmonary tuberculosis (TB). This approach has been regarded as among the most effective tools for preventing the development of resistance to anti-TB drugs. We report on the development of multidrug-resistance during SSC in a patient with drug-susceptible TB. Isoniazid, rifampin, pyrazinamide, and ethambutol were started, and negative culture conversion was obtained. Ethambutol was discontinued after 5 weeks of treatment due to visual dysfunction, and pyrazinamide was discontinued after a 2-month phase of intensive treatment. However, M. tuberculosis was cultivated from sputum collected after 9 weeks of treatment. Drug-susceptibility testing revealed resistance to isoniazid, rifampin, ethambutol, and rifabutin. Given that the patient took medication regularly, this observation suggests the possibility that some patients acquire drug resistance during SCC.
Antitubercular Agents ; Drug Resistance ; Drug Resistance, Multiple ; Ethambutol ; Humans ; Isoniazid ; Pyrazinamide ; Rifabutin ; Rifampin ; Sputum ; Tuberculosis ; Tuberculosis, Pulmonary

The aims of this study were to investigate the changing pattern of Helicobacter pylori antibiotic resistance in Jinju over a 15-year period. H. pylori strains were isolated from 170 adults living in Jinju from 1985-1989, 1990-1994 and 1995-1999, and from 23 adults living in Cheongju from 1995 to 1999. Susceptibility to erythromycin, clarithromycin, azithromycin, amoxicillin, tetracycline, metronidazole, furazolidone, levofloxacin, ciprofloxacin, moxifloxacin, and rifabutin was tested using the serial two-fold agar dilution method. Moxifloxacin resistance significantly increased in Jinju from 1985-1989 (0%) to 1995-1999 (14.9%) (p < 0.0001). Resistance to amoxicillin was increasesed trend to decreased trend from 1985 to 1999 (p = 0.033), whereas metronidazole resistance decreased from 37.5% to 21.3%. Resistance to furazolidone was greater from 1985-1989 (9.4%) than in 1995-1999 (2.1%). In comparing Jinju and Cheongju, minimal inhibitory concentrations (MICs) of tetracycline and levofloxacin among H. pylori isolated from Jinju were lower than for isolates from Cheonju (p < 0.05). The levofloxacin resistance rate was higher in Cheongju than in Jinju (p = 0.02). No macrolide resistance was observed in Cheongju. Overall, we did not observe any remarkable antimicrobial resistance increase of H. pylori strains isolated from Jinju over 15 years. The MIC distributions of antimicrobials and antimicrobial resistant rates were time- and region-specific among different strains. Future anti-H. pylori eradication regimens should be designed based on the changing patterns of antimicrobial resistance according to the resident area.
Adult ; Agar ; Amoxicillin ; Anti-Infective Agents ; Aza Compounds ; Azithromycin ; Ciprofloxacin ; Clarithromycin ; Drug Resistance, Microbial ; Erythromycin ; Furazolidone ; Helicobacter ; Helicobacter pylori ; Humans ; Metronidazole ; Ofloxacin ; Quinolines ; Rifabutin ; Tetracycline