To determine baseline levels of anti-tuberculosis drug resistance in Orel Oblast.
Drug susceptibility testing (DST) records from 1 July 1999 to 30 June 2000 for patients with sputum acid-fast bacilli smear-positive pulmonary tuberculosis were reviewed. Treatment and incarceration status were obtained from the tuberculosis register. Patients with 1 month or less of prior treatment were defined as new cases; those previously treated for more than 1 month were defined as retreatment cases.
Of 246 smear-positive isolates, 212 (86%) had DST performed. Of these, 190 (90%) were from new and 22 (10%) from retreatment cases; 171 (81%) were from community and 41 (19%) were from prison patients. Any drug resistance was more common among prison than community patients (44% vs. 30%, P = 0.05). MDR-TB was found in 14 (6.6%) of 212 isolates, and was more prevalent in prison compared with community patients (12% vs. 5%, P = 0.05). Retreatment cases were more likely than new cases to have MDR-TB (prevalence ratio [PR] = 8.5, 95%CI = 3.3-22.3), although the PR was higher for prison than for community retreatment cases (10.0 vs. 5.8).
New cases with MDR-TB were less prevalent in Orel Oblast compared with other survey sites in Russia. Any drug resistance and MDR-TB were associated with prior treatment, especially in the prison population. Continued monitoring of trends in drug resistance following DOTS implementation is needed.
To estimate the magnitude of antituberculous drug resistance and identify the risk factors for its development in tuberculosis patients in Manitoba over a 10-year period. As well, to examine the clinical course of the patients whose initial or subsequent isolates of Mycobacterium tuberculosis were resistant to one or more drugs.
Comparison of drug-resistant and non-drug-resistant cases of tuberculosis.
All people with tuberculosis reported to the Central Tuberculosis Registry of Manitoba between Jan. 1, 1980, and Dec. 31, 1989.
Of 1478 cases of active tuberculosis 1086 were culture positive, and drug susceptibility testing was performed in these cases. The clinical course, including outcome of treatment, of all drug-resistant cases was described.
Of 1086 culture-positive cases of tuberculosis 77 (7.1%) were drug resistant. Odds ratios suggested that the risk of drug resistance was significantly higher among the immigrants than among the other Canadians. Compared with the other Canadians the risk of drug resistance was 9.9 times greater among the immigrants in whom tuberculosis developed within the first year after arrival in Canada and 5.4 times greater among the immigrants in whom it developed 2 to 5 years after arrival in Canada. Of the 71 patients with drug-resistant disease whose type of resistance was known 62% had never taken antituberculous drugs before and 38% had. Most (91%) of the 77 cases of drug-resistant disease were resistant to first-line drugs, especially isoniazid and streptomycin. Thirty-two (42%) of the 77 cases were resistant to two or more first-line drugs. Of patients with drug-resistant disease a subgroup of 10 had disease that became resistant to several drugs over the 10-year period. The outcome of treatment in these individuals was poor, and they presented a particular public health problem.
Resistance to one or more first-line antituberculous drugs continues to complicate the treatment of tuberculosis and may facilitate the spread of the disease.
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Eight newly synthesized compounds--fluorenyliden derivatives have been studied for their antibacterial activity as to M. tuberculosis H37Rv and different kinds of atypical bacteria. The expressed antimicrobial activity in vitro of 5-[(fluorenyliden-3-hydrason)-aminomethyl]-thioglycolic acid (IR-95.6), lithium salt (fluorenyliden-5-aminomethyl)-thioglycolic acid (LI-15), lithium salt (fluorenyliden-9-hydraside)-thioglycolic acid (LI-75), with respect to M. tuberculosis H37Rv and considerable bacteriostatic action of all the studied substances as to M. fortuitum 23 have been established.
BACKGROUND & OBJECTIVES: There is a paucity of information on extrapulmonary tuberculosis as much of the attention is focussed on pulmonary tuberculosis. This prospective study aimed at identification and characterisation of mycobacterial isolates from extra pulmonary sites and the evaluation of the drug susceptibility patterns of Mycobacterium tuberculosis isolates from extrapulmonary sites using the conventional method and the E-test. METHODS: A total of 350 specimens from patients of extrapulmonary tuberculosis with varied presentation, were studied. Speciation and characterisation of isolates were done on the basis of growth and biochemical characteristics. Drug susceptibility testing for M. tuberculosis isolates was done by proportion method for isoniazid, rifampicin, ethambutol and pyrazinamide, whereas resistance ratio method was used for streptomycin. E-test (AB Biodisk, Sweden) was carried out to compare susceptibility patterns of the M. tuberculosis isolates for isoniazid and rifampicin with the conventional method. RESULTS: Thirty two of 350 (9.14%) patients clinically suspected to have extrapulmonary tuberculosis were culture positive for mycobacteria. On characterisation, 20 of the 32 isolates were identified as M. tuberculosis and 12 as non-tubercular mycobacteria (NTM) with 5 of the 12 being Mycobacterium avium complex. Among M. tuberculosis isolates both initial and acquired resistance was highest for streptomycin followed by isoniazid, rifampicin and ethambutol. No strain showed resistance to pyrazinamide. Two strains were found to be multidrug resistant. Drug susceptibility patterns by conventional method corroborate with the E-test results. INTERPRETATION & CONCLUSION: This study shows that the characterisation and species identification of mycobacterial isolates along with drug susceptibility testing help in better understanding of extrapulmonary tuberculosis. E-test had the advantage of being rapid and simple without need for additional equipment.
The spread of multidrug-resistant (MDR) and extensively drug-resistant (XDR) Mycobacterium tuberculosis compromises effective control of tuberculosis (TB) in Siberia. Early identification of drug-resistant isolates is, therefore, crucial for effective treatment of this disease. The aim of this study was to conduct drug susceptibility testing and identify mutations in drug resistance genes in clinical isolates of M. tuberculosis from some TB patients presenting for treatment in Siberia.
Thirty randomly selected clinical isolates of M. tuberculosis were obtained from the Novosibirsk Research Institute of Tuberculosis, Russia. Isolates were screened for drug resistance and characterized by variable number of tandem repeats (VNTR)-typing using 15 standard and four additional loci. Deligotyping on multiple large sequences was performed using 10 loci.
Twenty-nine of the isolates were assigned XDR status. Twenty-eight isolates belonged to the M. tuberculosis Beijing family, from which 11 isolates were considered the M11 type (39%), two the M2 type (7%), and one the M33 type (3%). Seventeen isolates (60.7%) from this family exhibited unique genetic patterns. The remaining two isolates belonged to the Latino-American Mediterranean family. Gene sequences (rpoB, katG, rrs, rpsL, tlyA, gidB, gyrA, gyrB) were analyzed to identify mutations that confer resistance to rifampicin, isoniazid, amikacin, kanamycin, capreomycin, and ofloxacin. The most common mutations among the XDR isolates were S531L in RpoB, S315T in KatG, various codon 94 mutations in gyrA, A90V in GyrA, K43R in RpsL, and 1401 A ? G in rrs; these confer resistance to rifampicin, isoniazid, ofloxacin, streptomycin and kanamycin/capreomycin, respectively. There was high congruence between the two typing methods (VNTR typing and deligotyping) and RD105, RD149, RD152, RD181, and RD207 regions of difference were absent from the 28 Beijing family isolates.
Deligotyping can be used for rapid and reliable screening of M. tuberculosis isolates, followed by more in-depth genotyping. Identification of Beijing family isolates with extensive drug resistance confirms that such strains have epidemiological importance in Siberia. Rapid detection of mutations that lead to drug resistance should facilitate selection of effective drug therapies, and the development of early prevention strategies to combat this infection.
The first line anti-tuberculosis drug pyrazinamide (PZA) is important when treating PZA susceptible multidrug-resistant tuberculosis (MDR-TB). Several drug resistance surveys have however reported PZA resistance among a significant proportion of multidrug-resistant (MDR) cases and this undoubtedly highlights the need for accurate and reliable detection of PZA resistance. Unfortunately, the testing of PZA susceptibility is associated with technical difficulties and even though the introduction of pncA sequencing has helped to address this issue, misclassification may still occur. In this study, we determined the prevalence and characteristics of PZA resistance in Swedish MDR-TB strains.
153 MDR-TB strains isolated in Sweden between 2003 and 2015 were analyzed for PZA resistance by considering both phenotypic and genotypic data.
The phenotypic test showed that 58% of the multidrug-resistant isolates were PZA resistant and the correlation between phenotype and genotype was solid, although a small number of isolates deviate from the expected phenotypic-genotypic pattern.
The results indicate that the prevalence of pyrazinamide resistance among Swedish MDR cases is increasing.
One hundred and sixteen drug-resistant (DR) Mycobacterium tuberculosis (MBT) strains and 127 multidrug-resistant (MDR) MBT ones isolated from first detected patients with tuberculosis were studied. Molecular genetic methods were used to study 119 strains (54 MDR, 40 DR, and 25 polyresistant (PR) strains. Among the MDR strains, the high in vitro growth rate and intensity was seen 10 times more frequently than those among the strains with preserved drug resistance. The absolute majority (90.9%) of MDR strains and half the PR strains, which circulated in the Republic of Karelia, belonged to the genetic family Beijing. Rifampicin resistance in most MDR strains from the Beijing family was associated with the 531 TCG->TTG mutation of the rpoB gene, which determined a high resistance to rifampicin and a cross-resistance to rifabutins. The presented data demonstrate the epidemic hazard of MDR strains of the Beijing genotype, which circulate in Karelia.
Currently, no information is available on the effect of resistance/susceptibility to first-line drugs different from isoniazid and rifampicin in determining the outcome of extensively drug-resistant tuberculosis (XDR-TB) patients, and whether being XDR-TB is a more accurate indicator of poor clinical outcome than being resistant to all first-line anti-tuberculosis (TB) drugs. To investigate this issue, a large series of multidrug-resistant TB (MDR-TB) and XDR-TB cases diagnosed in Estonia, Germany, Italy and the Russian Federation during the period 1999-2006 were analysed. Drug-susceptibility testing for first- and second-line anti-TB drugs, quality assurance and treatment delivery was performed according to World Health Organization recommendations in all study sites. Out of 4,583 culture-positive TB cases analysed, 361 (7.9%) were MDR and 64 (1.4%) were XDR. XDR-TB cases had a relative risk (RR) of 1.58 to have an unfavourable outcome compared with MDR-TB cases resistant to all first-line drugs (isoniazid, rifampicin ethambutol, streptomycin and, when tested, pyrazinamide), and an RR of 2.61 compared with "other" MDR-TB cases (those susceptible to at least one first-line anti-TB drug among ethambutol, pyrazinamide and streptomycin, regardless of resistance to the second-line drugs not defining XDR-TB). The emergence of extensively drug-resistant tuberculosis confirms that problems in tuberculosis management are still present in Europe. While waiting for new tools which will facilitate management of extensively drug-resistant tuberculosis, accessibility to quality diagnostic and treatment services should be urgently ensured and adequate public health policies should be rapidly implemented to prevent further development of drug resistance.
Comment In: Eur Respir J. 2008 Nov;32(5):1413-518978145
In Quebec, 6.2% of all tuberculosis (TB) isolates from Canadian-born patients are resistant to pyrazinamide (PZA) alone. The clinical significance of PZA-monoresistant (PZA(MR)) TB is unknown.
Canadian-born patients with PZA(MR) TB diagnosed between 1 January 1990 and 31 December 2000 and reported in a prior study were compared to randomly selected Canadian-born patients with fully susceptible isolates diagnosed within the same time period.
A total of 318 patients were eligible, of whom 40 (12.6%) had missing outcome information. Mean total duration of treatment was respectively 9.0 and 8.9 months for those with PZA(MR) and pan-susceptible strains. Respectively 91% and 89% of PZA(MR) and pan-susceptible patients received at least 6 months of rifampin-containing treatment. Among 67 patients with PZA(MR) TB, 51 (76%) were cured, 3 (4%) relapsed, none failed treatment, and 16 (24%) died within 6 months of diagnosis. Of 211 subjects with fully susceptible isolates, 181 (86%) were cured, 2 (1%) relapsed, 2 (1%) failed treatment, and 30 (14%) died within 6 months of diagnosis. PZA monoresistance was associated with decreased odds of successful clinical outcomes compared with pan-susceptible TB (OR 0.4, 95%CI 0.2-0.8).
Patients with PZA(MR) TB had significantly worse clinical outcomes than patients with fully susceptible strains.