scholarly journals Antituberculous Drug Resistance in Western Canada (1993 to 1994)

1997 ◽  
Vol 4 (2) ◽  
pp. 71-75 ◽  
Author(s):  
Richard Long ◽  
Anne Fanning ◽  
Robert Cowie ◽  
Vernon Hoeppner ◽  
Mark Fitzgerald ◽  
...  

OBJECTIVES: To estimate the magnitude of antituberculous drug resistance and identify prospectively the risk factors for its development in tuberculosis (TB) patients in western Canada over a one-year period.DESIGN: Comparison of drug-resistant and nondrug-resistant cases of TB.SETTING: Western Canada.PATIENTS: All people with TB reported to the TB registries of Manitoba, British Columbia, Alberta and Saskatchewan between February 1, 1993 and January 31, 1994.MAIN OUTCOME MEASURES: Drug susceptibility testing was performed in all cases of culture-positive tuberculosis. Patients at risk for human immunodeficiency virus (HIV) infection were serotested.RESULTS: Of 534 culture positive cases of TB, 37 (6.9%) were drug resistant. Odds ratios suggested that the risk of drug resistance was significantly higher among those with reactivation than among those with new disease, and among those born outside of Canada than among those born in Canada. Ninety per cent of the foreign-born patients with drug-resistant disease were from Asia. Of the 35 patients with drug resistance whose type of resistance was known, 76% had initial and 24% had acquired drug resistance. The initial resistance rate in Asian-born patients was 14%. Most of the 37 drug-resistant cases were resistant to isoniazid (68%), streptomycin (49%) or both (22%). Twelve (32%) of the 37 cases were resistant to two or more first-line drugs. Of 14 patients who were HIV seropositive only one, a foreign-born patient, was drug resistant.CONCLUSION: Antituberculous drug resistance is low among Canadian-born patients in western Canada, but not uncommon among those born outside Canada. Initial therapy of foreign-born patients should include four first-line drugs.

2009 ◽  
Vol 20 (8) ◽  
pp. 566-570 ◽  
Author(s):  
P Tabarsi ◽  
E Chitsaz ◽  
A Moradi ◽  
P Baghaei ◽  
P Farnia ◽  
...  

The objective of this study was to determine the drug resistance prevalence and its pattern among tuberculosis (TB)–HIV patients in Iran. In this retrospective study, all admitted TB/HIV patients presenting to our tertiary centre during 2005–2007 were considered. After confirmation for TB–HIV, first-line DST was performed for culture-positive patients. The drug resistance patterns and the treatment outcomes were analysed. Of the total 92 TB/HIV patients, 27 were culture negative, and DST were available in 65. Intravenous drug abuse was seen in 59 (90.8%). Thirty-seven (57%) were ‘sensitive’ cases and 28 (43%) were ‘any drug resistance’ cases. Twenty-one (32.3%) were mono-drug, three (4.6%) poly-drug and four (6.1%) were multidrug-resistant TB patients. Previous anti-TB medication was significantly associated with any drug resistance ( P = 0.041; 95% confidence interval =0.086–0.984); however, having any drug resistance did not affect the treatment outcome ( P = 0.56). Streptomycin showed the highest resistance rate (27%) followed by isoniazid (20%), pyrazinamide (9.8%), rifampin (9.2%) and ethambutol (3%). Drug resistance to antitubercular agents in TB–HIV co-infected patients in Iran is high compared with other reports. Drug resistance is higher among those who have had prior anti-TB medication.


2013 ◽  
Vol 98 (2) ◽  
pp. 175-180 ◽  
Author(s):  
Lan Xu ◽  
Xu Jian-Zhong ◽  
Liu Xue-Mei ◽  
Ge Bao-Feng

Abstract Spinal tuberculosis is the most common manifestation of extrapulmonary tuberculosis. However, there have been few reports on the topic of drug-resistant spinal tuberculosis. The aim of this study was to investigate the efficacy and safety of treatment with a combination of surgery and individual chemotherapy guided by drug susceptibility testing for drug-resistant spinal tuberculosis. We retrospectively analyzed 19 patients with drug-resistant spinal tuberculosis. After surgery, individual chemotherapy was tailored for each patient according to his or her drug resistance profile and previous history of chemotherapy. The patients were followed up clinically and radiologically for an average period of 36 months. Among 19 drug-resistant spinal tuberculosis cases, 16 were multidrug-resistant tuberculosis (MDR-TB), and 3 were non–MDR-TB. The patients with MDR-TB and non–MDR-TB had undergone previous chemotherapy for an average of 12.50 ± 2.00 months (0–55 months) and 5.50 ± 1.20 months (0–60 months), respectively. A total of 16 patients underwent open operations, and the other 3 had percutaneous drainage and local chemotherapy. Patients received individual chemotherapy for an average of 24 months postoperatively. All patients had been cured at the final follow-up. Drug-resistant spinal tuberculosis is mainly acquired through previous irregular chemotherapy and the spread of drug-resistant strains. Treatment with a combination of surgery and individual chemotherapy is feasible in the treatment of severe complications and the prevention of acquired drug resistance.


2014 ◽  
Vol 59 (1) ◽  
pp. 414-420 ◽  
Author(s):  
Kanchan Ajbani ◽  
Shou-Yean Grace Lin ◽  
Camilla Rodrigues ◽  
Duylinh Nguyen ◽  
Francine Arroyo ◽  
...  

ABSTRACTReliable molecular diagnostics, which detect specific mutations associated with drug resistance, are promising technologies for the rapid identification and monitoring of drug resistance inMycobacterium tuberculosisisolates. Pyrosequencing (PSQ) has the ability to detect mutations associated with first- and second-line anti-tuberculosis (TB) drugs, with the additional advantage of being rapidly adaptable for the identification of new mutations. The aim of this project was to evaluate the performance of PSQ in predicting phenotypic drug resistance in multidrug- and extensively drug-resistant tuberculosis (M/XDR-TB) clinical isolates from India, South Africa, Moldova, and the Philippines. A total of 187 archived isolates were run through a PSQ assay in order to identifyM. tuberculosis(via the IS6110marker), and to detect mutations associated with M/XDR-TB within small stretches of nucleotides in selected loci. The molecular targets includedkatG, theinhApromoter and theahpC-oxyRintergenic region for isoniazid (INH) resistance; therpoBcore region for rifampin (RIF) resistance;gyrAfor fluoroquinolone (FQ) resistance; andrrsfor amikacin (AMK), capreomycin (CAP), and kanamycin (KAN) resistance. PSQ data were compared to phenotypic mycobacterial growth indicator tube (MGIT) 960 drug susceptibility testing results for performance analysis. The PSQ assay illustrated good sensitivity for the detection of resistance to INH (94%), RIF (96%), FQ (93%), AMK (84%), CAP (88%), and KAN (68%). The specificities of the assay were 96% for INH, 100% for RIF, FQ, AMK, and KAN, and 97% for CAP. PSQ is a highly efficient diagnostic tool that reveals specific nucleotide changes associated with resistance to the first- and second-line anti-TB drug medications. This methodology has the potential to be linked to mutation-specific clinical interpretation algorithms for rapid treatment decisions.


1999 ◽  
Vol 6 (2) ◽  
pp. 155-160 ◽  
Author(s):  
Ahmed Hersi ◽  
Kevin Elwood ◽  
Robert Cowie ◽  
Dennis Kunimoto ◽  
Richard Long

OBJECTIVE: To describe the extent of the problem of multidrug-resistant tuberculosis (MDR-TB) in Alberta and British Columbia from 1989 to 1998.DESIGN: A retrospective, population-based descriptive study of all notified MDR-TB cases in the context of all notified TB cases, all notified culture-positive TB cases and all notified drug-resistant TB cases.SETTING: Provinces of Alberta and British Columbia, and their TB registries.PATIENTS: All people with TB reported to the TB registries of Alberta and British Columbia between January 1, 1989 and June 30, 1998.MAIN OUTCOME MEASURES: Drug susceptibility testing was performed in all cases of culture-positive TB. Demographic, clinical and laboratory data on all cases of MDR-TB were recorded.RESULTS: Of 4606 notified cases of TB, 3553 (77.1%) were culture positive. Of these, 365 (10.3%) were drug resistant; of the drug-resistant cases, 24 (6.6%) were MDR. Most MDR-TB patients were foreign-born; of the four Canadian-born patients, two were infected while travelling abroad. Although foreign-born patients were significantly more likely to harbour drug-resistant strains, 14.3% versus 4.8%, respectively (P<0.001), among those who were harbouring a drug-resistant strain, the proportion of Canadian-born versus foreign-born patients with an MDR strain was the same (6.7% versus 6.6%, respectively). From 1994 to 1998 versus 1989 to 1993, the proportion of all drug-resistant strains that were MDR was greater (9.0% versus 4.3%, respectively), but the difference was not statistically significant. Isolates from 16 of the 24 MDR-TB cases had been archived. Each of these was fingerprinted and found to be unique. Most MDR-TB cases (88%) were respiratory. Of those tested for human immunodeficiency virus (n=17), only one was seropositive. MDR-TB was ‘acquired’ in 67% and ‘primary’ in 33% of cases. Eight (33%) of the MDR-TB cases received curative courses of treatment, six (25%) are still being treated, and the remainder have either died (five, 21%), transferred out (four, 17%) or become ‘chronic’ (one, 4%). No secondary case of MDR-TB has been identified in Alberta and British Columbia.CONCLUSIONS: Most MDR-TB in Alberta and British Columbia is imported. The proportion of all drug-resistant cases that are MDR appears to be increasing, but not because of disease acquired from recent contact with MDR-TB in Canada.


ISRN Oncology ◽  
2013 ◽  
Vol 2013 ◽  
pp. 1-12
Author(s):  
Fei Chu ◽  
Jessica A. Naiditch ◽  
Sandra Clark ◽  
Yi-Yong Qiu ◽  
Xin Zheng ◽  
...  

Resistance to cytotoxic agents has long been known to be a major limitation in the treatment of human cancers. Although many mechanisms of drug resistance have been identified, chemotherapies targeting known mechanisms have failed to lead to effective reversal of drug resistance, suggesting that alternative mechanisms remain undiscovered. Previous work identified midkine (MK) as a novel putative survival molecule responsible for cytoprotective signaling between drug-resistant and drug-sensitive neuroblastoma, osteosarcoma and breast carcinoma cells in vitro. In the present study, we provide further in vitro and in vivo studies supporting the role of MK in neuroblastoma cytoprotection. MK overexpressing wild type neuroblastoma cells exhibit a cytoprotective effect on wild type cells when grown in a co-culture system, similar to that seen with doxorubicin resistant cells. siRNA knockdown of MK expression in doxorubicin resistant neuroblastoma and osteosarcoma cells ameliorates this protective effect. Overexpression of MK in wild type neuroblastoma cells leads to acquired drug resistance to doxorubicin and to the related drug etoposide. Mouse studies injecting various ratios of doxorubicin resistant or MK transfected cells with GFP transfected wild type cells confirm this cytoprotective effect in vivo. These findings provide additional evidence for the existence of intercellular cytoprotective signals mediated by MK which contribute to chemotherapy resistance in neuroblastoma.


2020 ◽  
Author(s):  
yanqiang huang ◽  
Xiao-Hua Li ◽  
Yong-Yi Huang ◽  
Xian-ke Luo ◽  
Yan-Chun Qin ◽  
...  

Abstract Background: The resistance rate of clinical Helicobacter pylori (Hp) isolates has increased, however, the mechanism of drug resistance is unclear. In this study, we isolated drug-resistant Hp strains isolated from different areas and different populations of China for genomic analysis.Objectives: The aim of this study was to investigate drug resistance in Hp from Bama County, Guangxi, China.Methods: Minimal inhibitory concentrations (MICs) of clarithromycin, metronidazole and levofloxacin were determined and complete genome sequencing was performed with annotation. The presence of hp1181 and hp1184 genes was detected by RT-PCR. The relationships between hp1181, hp1184 and clarithromycin resistance were confirmed by gene mutation and drug-resistant strains. Results: Three drug-resistant Hp strains were isolated from patients with gastritis in Bama County. The strains showed a high degree of homology with hp26695 through complete genome detection and identification. Differences in genome sequences, gene quantity and gene characteristics were detected amongst the three strains. Prediction and analysis of the function on drug-resistant genes indicated that the RNA expression of hp1181 and hp1184 increased in the three strains that were the same in the artificially induced clarithromycin-resistant bacteria. After gene knockout, the drug sensitivity of the strains increased significantly.Conclusions: The expressions of the genes hp1184 and hp1181 were associated with clarithromycin resistance in the Hp from Bama, Guangxi.


2019 ◽  
Vol 5 (4) ◽  
pp. 00008-2019
Author(s):  
Prashant N. Chhajed ◽  
Preyas J. Vaidya ◽  
Neha P. Mandovra ◽  
Vinod B. Chavhan ◽  
Tejashree T. Lele ◽  
...  

This study aimed to examine the use of endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) in the rapid diagnosis of mediastinal tuberculous lymphadenitis and drug-resistant mediastinal tuberculous lymphadenitis.A diagnosis of TB was confirmed by a positive Xpert MTB/RIF test or Mycobacterium tuberculosis culture. Rifampicin-resistant TB (RR-TB) or multidrug-resistant TB (MDR-TB) was diagnosed upon the detection of rifampicin resistance by Xpert MTB/RIF or resistance to rifampicin and isoniazid by phenotypic drug susceptibility testing (DST).Xpert MTB/RIF was positive in 43 of 56 patients (77%) and TB culture was positive in 31 of 56 patients (55%). Of these 56 patients, 25 (45%) were Xpert MTB/RIF positive and TB culture negative, 13 (23%) were Xpert MTB/RIF negative and TB culture positive, and 18 (32%) were Xpert MTB/RIF positive and TB culture positive. 11 patients (20%) had drug-resistant TB: seven with RR/MDR-TB, one with pre-extensively drug-resistant (XDR) TB, two with XDR-TB and one with isoniazid mono-resistance.An Xpert MTB/RIF assay carried out on EBUS-TBNA specimens provides rapid diagnosis of TB. Xpert MTB/RIF testing appears to have additional and more rapid sensitivity compared with culture alone. Culture-based DST provides an additional exclusive yield and the full resistance profile in addition to or instead of rifampicin resistance.


2021 ◽  
Vol 25 (9) ◽  
pp. 754-760
Author(s):  
P. Kamolwat ◽  
D. Nonghanphithak ◽  
A. Chaiprasert ◽  
S. Smithtikarn ◽  
P. Pungrassami ◽  
...  

BACKGROUND: Whole-genome sequencing (WGS) is a promising tool for the detection of drug-resistant TB (DR-TB). To date, there have been few comparisons of diagnostic performance of WGS and phenotypic drug susceptibility testing (DST) in DR-TB.METHODS: We compared drug resistance-conferring mutations identified by WGS analysis using TB-Profiler and Mykrobe with phenotypic DST profiles based on the Löwenstein-Jensen proportion method using drug-resistant Mycobacterium tuberculosis (n = 537) isolates from across Thailand. Based on available phenotypic DST results, diagnostic performance was analysed for resistance against isoniazid, rifampicin, ethambutol (EMB), streptomycin, ethionamide (ETH), kanamycin, capreomycin (CPM), para-aminosalicylic acid, ofloxacin and levofloxacin.RESULTS: High agreement between the two methods was observed for most drugs (>91%), except EMB (57%, 95% CI 53–61) and ETH (70%, 95% CI 66–74). Also, low specificity was observed for EMB (49%, 95% CI 44–54) and ETH (66%, 95% CI 61–71). Sensitivity was high for most drugs (range 83–98%), except CPM (77%, 95% CI 59–88).CONCLUSION: Low agreement between WGS and phenotypic tests for drug resistance was found for EMB and ETH. The current genomic database is insufficient for the identification of CPM resistance. Challenges remain for routine usage of WGS-based DST, especially for second-line anti-TB drugs.


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