Two new isomeric modified tripeptides, aspergillamides C and D (compounds 1 and 2), together with fifteen known compounds (compounds 3-17), were obtained from the marine sponge-derived fungus Aspergillus terreus SCSIO 41008. The structures of the new compounds, including absolute configurations, were determined by extensive analyses of spectroscopic data (NMR, MS, UV, and IR) and comparisons between the calculated and experimental electronic circular dichroism (ECD) spectra. Butyrolactone I (compound 11) exhibited strong inhibitory effects against Mycobacterium tuberculosis protein tyrosine phosphatase B (MptpB) with the IC being 5.11 ± 0.53 μmol·L, and acted as a noncompetitive inhibitor based on kinetic analysis.
4-Butyrolactone ; analogs & derivatives ; chemistry ; isolation & purification ; pharmacology ; Animals ; Aspergillus ; chemistry ; Chemistry Techniques, Analytical ; Dipeptides ; chemistry ; isolation & purification ; pharmacology ; Enzyme Inhibitors ; chemistry ; isolation & purification ; pharmacology ; Indoles ; chemistry ; isolation & purification ; pharmacology ; Molecular Structure ; Mycobacterium tuberculosis ; drug effects ; Peptides ; chemistry ; isolation & purification ; pharmacology ; Polyketides ; chemistry ; isolation & purification ; pharmacology ; Porifera ; microbiology ; Protein Tyrosine Phosphatases ; chemistry

Objective: To understand the etiological characteristics and drug susceptibility of Mycobacterium thermoresistibile and Mycobacterium elephantis isolated from a cow with mastitis and provide evidence for the prevention and control of infectious mastitis in cows. Methods: The milk sample was collected from a cow with mastitis, which was pretreated with 4% NaOH and inoculated with L-J medium for Mycobacterium isolation. The positive cultures were initially identified by acid-fast staining and multi-loci PCR, then Mycobacterium species was identified by the multiple loci sequence analysis (MLSA) with 16S rRNA, hsp65, ITS and SodA genes. The drug sensitivity of the isolates to 27 antibiotics was tested by alamar blue assay. Results: Two anti-acid stain positive strains were isolated from the milk of a cow with mastitis, which were identified as non-tuberculosis mycobacterium by multi-loci PCR, and multi-loci nucleic acid sequence analysis indicated that one strain was Mycobacterium thermoresistibile and another one was Mycobacterium elephantis. The results of the drug susceptibility test showed that the two strains were resistant to most antibiotics, including rifampicin and isoniazid, but they were sensitive to amikacin, moxifloxacin, levofloxacin, ethambutol, streptomycin, tobramycin, ciprofloxacin and linezolid. Conclusions:Mycobacterium thermoresistibile and Mycobacterium elephantis were isolated in a cow with mastitis and the drug susceptibility spectrum of the pathogens were unique. The results of the study can be used as reference for the prevention and control the infection in cows.
Animals ; Anti-Bacterial Agents/pharmacology* ; Antitubercular Agents/pharmacology* ; Cattle ; Drug Resistance, Bacterial ; Female ; Humans ; Mastitis, Bovine/microbiology* ; Microbial Sensitivity Tests ; Milk/microbiology* ; Mycobacterium/isolation & purification* ; Mycobacterium Infections/veterinary* ; Mycobacterium tuberculosis/drug effects* ; Nontuberculous Mycobacteria/isolation & purification* ; Polymerase Chain Reaction ; RNA, Ribosomal, 16S/genetics*

We evaluate the performance of Xpert MTB/RIF for the diagnosis of extrapulmonary tuberculosis (EPTB) in China. The performance of Xpert was evaluated compared to the composite reference standard (CRS), drug susceptibility testing (DST), and imaging examination. The overall sensitivity and specificity of Xpert were 64.1% (195/304) and 100% (24/24), respectively, using CRS as the gold standard. The sensitivity was significantly higher than that of culture for pus (P<0.05). The proportion of EPTB-positive cases diagnosed by imaging was two times more than that diagnosed using Xpert; however, 6 out of 19 cases may have been overdiagnosed by imaging. Compared to phenotypic DST, the sensitivity and specificity of Xpert were 80% (12/15) and 100% (75/75), respectively. Considering its high sensitivity and specificity, Xpert MTB/RIF may be used as a rapid initial test for EPTB diagnosis, and may also support a quicker decision on the treatment regimen. The combination of imaging and Xpert testing could provide high efficiency and accurate diagnosis of suspected EPTB.
Bacterial Proteins ; genetics ; metabolism ; China ; DNA-Directed RNA Polymerases ; genetics ; metabolism ; Diagnostic Tests, Routine ; instrumentation ; methods ; Drug Resistance, Bacterial ; Humans ; Microbial Sensitivity Tests ; Mycobacterium tuberculosis ; drug effects ; genetics ; isolation & purification ; metabolism ; Retrospective Studies ; Rifampin ; pharmacology ; Sensitivity and Specificity ; Sputum ; Tuberculosis ; Tuberculosis, Pulmonary ; diagnosis ; microbiology

OBJECTIVETo compare the performance of MTBDRplus V2 and Xpert MTB/RIF for detecting smear negative pulmonary tuberculosis (PTB).

METHODSClinical PTB suspects were enrolled consecutively in Anhui Chest Hospital and Xi'an Chest Hospital from January to December in 2014. The sputum samples of smear negative PTB suspects were collected and decontaminated. The sediment was used to conduct MTBDRplus V2, Xpert MTB/RIF and drug susceptibility test (DST). All the samples with discrepant drug susceptibility result between molecular methods and phenotypic method were confirmed by DNA sequencing.

RESULTSA total of 1973 cases were enrolled in this study. The detection rates of Mycobacterium tuberculosis complex (MTBC) by MTBDRplus V2 and Xpert MTB/RIF were 27.67% and 27.98%, respectively. When setting MGIT culture result as a gold standard, the sensitivity and specificity of MTBDRplus V2 were 86.74% and 93.84%, and the sensitivity and specificity of Xpert MTB/RIF were 86.55% and 93.43%, respectively. For the detection of the resistance to rifampin, the sensitivity and specificity of MTBDRplus V2 were 94.34% and 96.62%, and the sensitivity and specificity of Xpert MTB/RIF were 88.68% and 95.96%, respectively. For the detection of the resistance to isoniazid, the sensitivity and specificity of MTBDRplus V2 were 77.38% and 98.02%, respectively.

CONCLUSIONMTBDRplus V2 and Xpert MTB/RIF can be used to detect MTBC in smear negative samples with satisfactory performance.

Antitubercular Agents ; pharmacology ; Bacteriological Techniques ; methods ; Drug Resistance, Bacterial ; Humans ; Isoniazid ; pharmacology ; Mycobacterium tuberculosis ; drug effects ; isolation & purification ; Sensitivity and Specificity ; Tuberculosis, Pulmonary ; diagnosis ; microbiology

BACKGROUND/AIMS: We evaluated the trend in the rates of drug-resistant tuberculosis (TB) over time, as well as the difference in the drug-resistance pattern between pulmonary tuberculosis (PTB) and extrapulmonary tuberculosis (EPTB) at a private referral center in South Korea. METHODS: All patients with culture-confirmed TB from 2006 to 2013 were included. RESULTS: In total, 1,745 patients were included: 1,431 (82.0%) were new cases, and 314 (18.0%) were cases treated previously; 1,610 (92.3%) were diagnosed with PTB, and 135 (7.7%) were diagnosed with EPTB. Multidrug-resistant (MDR) and extensively drug-resistant (XDR) TB were detected in 5.8% and 2.0% of new cases and in 20.1% and 8.6% of previously treated cases, respectively. The MDR TB rate during the study period decreased remarkably, whereas the MDR and XDR TB rates decreased significantly in previously treated cases. No difference in the drug-resistance rate was detected between PTB and EPTB. CONCLUSIONS: The TB drug-resistance rate, particularly that of MDR TB, remained high at a private referral hospital, and the drug-resistance rate did not decrease significantly from 2006 to 2013. This finding underscores the need for a national survey regarding the prevalence of drug-resistant TB to obtain the most accurate and current drug-resistance status in South Korea, including the private sector.
Adult ; Aged ; Antitubercular Agents/*therapeutic use ; *Drug Resistance, Multiple, Bacterial ; Extensively Drug-Resistant Tuberculosis/drug therapy/microbiology ; Female ; Hospitals, Private ; Humans ; Male ; Microbial Sensitivity Tests ; Middle Aged ; Mycobacterium tuberculosis/*drug effects/isolation & purification ; Prevalence ; Republic of Korea/epidemiology ; Retrospective Studies ; *Tertiary Care Centers ; Time Factors ; Treatment Outcome ; Tuberculosis, Multidrug-Resistant/diagnosis/*drug therapy/epidemiology/*microbiology ; Tuberculosis, Pulmonary/diagnosis/*drug therapy/epidemiology/*microbiology

In order to evaluate the performance of a molecular Hain line probe assay (Hain LPA) for rapid detection of rifampicin and isoniazid resistance of Mycobacterium tuberculosis in China, 1612 smear positive patients were consecutively enrolled in this study. Smear positive sputum specimens were collected for Hain LPA and conventional drug susceptibility testing (DST). The sensitivity and specificity of Hain LPA were analyzed by using conventional DST as golden reference. The sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) for rifampicin resistance detection were 88.33%, 97.66%, 81.54%, and 98.62%, respectively. The sensitivity, specificity, PPV and NPV for isoniazid resistance detection were 80.25%, 98.07%, 87.25%, and 96.78%, respectively. These findings suggested that Hain LPA can be an effective method worthy of broader use in China.
China ; Genotyping Techniques ; methods ; Humans ; Isoniazid ; pharmacology ; Mycobacterium tuberculosis ; drug effects ; genetics ; isolation & purification ; Rifampin ; pharmacology ; Tuberculosis, Multidrug-Resistant ; diagnosis ; microbiology

70 clinical Mycobacterium tuberculosis strains isolated from AIDS patients in two HIV/AIDS referral hospitals in Beijing were used in this study. M. tuberculosis and non-tuberculosis mycobacterium (NTM) were identified by using multi-locus PCR. M. tuberculosis was genotyped by using 15-locus MIRU-VNTR technique and spoligotyping afterwards. Meanwhile, the drug susceptibilities of the strains to the four first-line anti TB drugs (rifampin, isoniazid, streptomycin, and ethambutol) and the four second-line anti-TB drugs (capreomycin, kanamycin, ofloxacin, and ethionanide) were tested with proportional method. In this study, M. tuberculosis and NTM strains isolated from AIDS patients with TB-like symptoms were identified and genotyping analysis indicated that Beijing genotype was the predominant genotype. In addition, the prevalence of drug-resistant TB, especially the prevalence of XDR-TB, was higher than that in TB patients without HIV infection.
AIDS-Related Opportunistic Infections ; microbiology ; Antitubercular Agents ; pharmacology ; China ; Humans ; Microbial Sensitivity Tests ; Mycobacterium tuberculosis ; classification ; drug effects ; isolation & purification ; Phylogeny ; Tuberculosis ; complications ; microbiology

No abstract available.
Adult ; Antineoplastic Agents/*adverse effects ; Antitubercular Agents/therapeutic use ; Biopsy ; Female ; Gastrointestinal Stromal Tumors/*drug therapy/pathology/surgery ; Humans ; Imatinib Mesylate/*adverse effects ; Lung Diseases, Interstitial/*chemically induced/diagnosis ; Mycobacterium tuberculosis/*isolation & purification ; Protein Kinase Inhibitors/*adverse effects ; Rectal Neoplasms/*drug therapy/pathology/surgery ; Tomography, X-Ray Computed ; Tuberculosis, Pulmonary/diagnosis/drug therapy/*microbiology

The aims of this study were to assess the risk of tuberculosis (TB) and the status of latent tuberculosis infection (LTBI) in Korean patients with inflammatory bowel disease (IBD) receiving tumor necrosis factor (TNF)-alpha blockers. We reviewed medical records of 525 Korean IBD patients (365 TNF-alpha blocker naive and 160 TNF-alpha blocker exposed) between January 2001 and December 2013. The crude incidence of TB was significantly higher in IBD patients receiving TNF-alpha blockers compared to TNF-alpha-blocker-naive patients (3.1% vs. 0.3%, P=0.011). The mean incidence of TB per 1,000 patient-years was 1.84 for the overall IBD population, 4.89 for TNF-alpha blocker users, and 0.45 for TNF-alpha-blocker-naive patients. The adjusted risk ratio of TB in IBD patients receiving TNF-alpha blocker was 11.7 (95% confidence interval, 1.36-101.3). Pulmonary TB was prevalent in patients treated with TNF-alpha blockers (80.0%, 4/5). LTBI was diagnosed in 17 (10.6%) patients, and none of the 17 LTBI patients experienced reactivation of TB during treatment with TNF-alpha blockers. Treatment with TNF-alpha blockers significantly increased the risk of TB in IBD patients in Korea. De novo pulmonary TB infection was more prevalent than reactivation of LTBI, suggesting an urgent need for specific recommendations regarding TB monitoring during TNF-alpha blocker therapy.
6-Mercaptopurine/adverse effects/analogs & derivatives/therapeutic use ; Adult ; Anti-Inflammatory Agents, Non-Steroidal/adverse effects/therapeutic use ; Antibodies, Monoclonal/adverse effects/therapeutic use ; Cohort Studies ; Colitis, Ulcerative/*drug therapy ; Crohn Disease/*drug therapy ; Female ; Humans ; Latent Tuberculosis/chemically induced/diagnosis/*epidemiology ; Male ; Mycobacterium tuberculosis/isolation & purification ; Republic of Korea ; Retrospective Studies ; Tuberculosis, Pulmonary/chemically induced/diagnosis/*epidemiology ; Tumor Necrosis Factor-alpha/*antagonists & inhibitors

The aims of this study were to assess the risk of tuberculosis (TB) and the status of latent tuberculosis infection (LTBI) in Korean patients with inflammatory bowel disease (IBD) receiving tumor necrosis factor (TNF)-alpha blockers. We reviewed medical records of 525 Korean IBD patients (365 TNF-alpha blocker naive and 160 TNF-alpha blocker exposed) between January 2001 and December 2013. The crude incidence of TB was significantly higher in IBD patients receiving TNF-alpha blockers compared to TNF-alpha-blocker-naive patients (3.1% vs. 0.3%, P=0.011). The mean incidence of TB per 1,000 patient-years was 1.84 for the overall IBD population, 4.89 for TNF-alpha blocker users, and 0.45 for TNF-alpha-blocker-naive patients. The adjusted risk ratio of TB in IBD patients receiving TNF-alpha blocker was 11.7 (95% confidence interval, 1.36-101.3). Pulmonary TB was prevalent in patients treated with TNF-alpha blockers (80.0%, 4/5). LTBI was diagnosed in 17 (10.6%) patients, and none of the 17 LTBI patients experienced reactivation of TB during treatment with TNF-alpha blockers. Treatment with TNF-alpha blockers significantly increased the risk of TB in IBD patients in Korea. De novo pulmonary TB infection was more prevalent than reactivation of LTBI, suggesting an urgent need for specific recommendations regarding TB monitoring during TNF-alpha blocker therapy.
6-Mercaptopurine/adverse effects/analogs & derivatives/therapeutic use ; Adult ; Anti-Inflammatory Agents, Non-Steroidal/adverse effects/therapeutic use ; Antibodies, Monoclonal/adverse effects/therapeutic use ; Cohort Studies ; Colitis, Ulcerative/*drug therapy ; Crohn Disease/*drug therapy ; Female ; Humans ; Latent Tuberculosis/chemically induced/diagnosis/*epidemiology ; Male ; Mycobacterium tuberculosis/isolation & purification ; Republic of Korea ; Retrospective Studies ; Tuberculosis, Pulmonary/chemically induced/diagnosis/*epidemiology ; Tumor Necrosis Factor-alpha/*antagonists & inhibitors