Journal of Antimicrobial Chemotherapy jac.oxfordjournals.org Contact us for more information: t: +44 (0) 1865 355 190 e: [email protected]www.oxfordjournals.org/corporate Journal of Antimicrobial Chemotherapy is the leading European journal in antimicrobial research. Our readership includes representatives of academia, industry and health services, and includes those who are influential in formulary decisions. The journal features original articles on the laboratory aspects and clinical use of antimicrobials including antibacterial, antiviral, antifungal, and antiprotozoal agents. It is published on behalf of The British Society for Antimicrobial Chemotherapy and all members receive a copy as part of their subscription. Advertising & Sales Contacts Naomi Reeves Advertising Sales Manager t: +44 (0)1865 355396 e: [email protected]Caroline Bracken Supplements Development Manager t:+44 (0)1865 353794 e: [email protected]For reprints, ePrints or tailored products: e: [email protected]www.oxfordjournals.org/corporate 2013 Media Kit Impact Factor: 5.068 Ranking: 7/70 Si: Infectious Diseases 18/112 Si: Microbiology Journal Citation Reports® (Science Citation Index, ISI) Target Audience: Microbiologists Frequency: 12 Peer Reviewed: Yes Editor-In-Chief: Dr Alan P. Johnson Society Affiliation: The British Society for Antimicrobial Chemotherapy Average Monthly Page Views: 332,800 Average Monthly Unique IPs: 101,310 Average Available Ad Impressions: 584,890* *Combined monthly leaderboard and skyscraper positions No. Of eTOC Subscribers: 4,053 Useful Information Print Circulation: 720 Geographic Breakdown: UK 35% - Europe 29% - North America 16% - Rest of World 20% JAC www.jac.oxfordjournals.org Volume 67, Number 9, September 2012 ISSN 0305-7453 (print) ISSN 1460-2091 (online) Journal of Antimicrobial Chemotherapy 1 LATEST IMPACT FACTOR 5.068
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Journal of Antimicrobial Chemotherapyjac.oxfordjournals.org
Contact us for more information:t: +44 (0) 1865 355 190e: [email protected]/corporate
Journal of Antimicrobial Chemotherapy is the leading European journal in antimicrobial research. Our readership includes representatives of academia, industry and health services, and includes those who are influential in formulary decisions.
The journal features original articles on the laboratory aspects and clinical use of antimicrobials including antibacterial, antiviral, antifungal, and antiprotozoal agents.
It is published on behalf of The British Society for Antimicrobial Chemotherapy and all members receive a copy as part of their subscription.
Frequency: 12Peer Reviewed: Yes Editor-In-Chief: Dr Alan P. Johnson Society Affiliation: The British Society for Antimicrobial Chemotherapy
Average Monthly Page Views: 332,800Average Monthly Unique IPs: 101,310Average Available Ad Impressions: 584,890**Combined monthly leaderboard and skyscraper positionsNo. Of eTOC Subscribers: 4,053
Useful Information
Print Circulation: 720Geographic Breakdown: UK 35% - Europe 29% - North America 16% - Rest of World 20%
JAC
www.jac.oxfordjournals.org
Volume 67, Number 9, September 2012 ISSN 0305-7453 (print) ISSN 1460-2091 (online)
Received 11 January 2012; returned 5 March 2012; revised 14 April 2012; accepted 16 April 2012
Objectives: Kanamycin is an important second-line drug used to treat multidrug-resistant (MDR) tuberculosis(TB). Molecular analysis of the rrs gene seems to be not enough to identify every case of kanamycin resistance.In the present study we evaluated the incidence of eis mutations in kanamycin-resistant Mycobacteriumtuberculosis isolates.
Methods: We analysed 70 MDR M. tuberculosis clinical isolates. All isolates were screened for rrs and eis muta-tions using single-strand conformation polymorphism and sequencing. Phenotypic drug susceptibility testingwas performed using Bactec MGIT 960 and the absolute concentration method on Lowenstein–Jensenmedium.
Results: eis mutations were found in 10 isolates. The most prevalent mutations were the A1401G substitutionin the rrs gene and the C14T substitution in the eis promoter region.
Conclusions: Our study shows that the eis promoter region is a useful molecular marker of kanamycin resist-ance in the Moscow region. Complex analysis of rrs and eis mutations will significantly reduce the time to diag-nose kanamycin resistance in TB patients, compared with phenotypic drug resistance testing.
IntroductionAccording to the WHO report, in 2010 there were an estimated8.8 million incident cases of tuberculosis (TB) globally. InRussia, the epidemiological situation is complicated by a highprevalence of multidrug-resistant (MDR) TB, showing resistanceto at least isoniazid and rifampicin. Furthermore, extensively drug-resistant (XDR) strains of Mycobacterium tuberculosis, defined asMDR with additional resistance to any of the fluoroquinolonesand any of the second-line injectable drugs (kanamycin, amikacinor capreomycin), emerge as a serious challenge to TB manage-ment and control.1 MDR-TB and XDR-TB require more expensive,long-term and less effective treatment courses than pan-susceptible TB.2 As the choice of chemotherapeutic agents islimited, rapid and accurate drug susceptibility testing (DST), espe-cially for second-line injectable drugs, is crucial.
Second-line injectable drugs include the aminoglycosideskanamycin and amikacin, and a polypeptide antibiotic—capreomycin. Kanamycin and capreomycin are the mostcommonly used second-line injectable drugs in Russia. Themechanism of action of the second-line injectable drugs consistsof binding to the 16S rRNA in the 30S ribosomal subunit, thusarresting protein synthesis in the bacterial cell. Mutations in the
16S rRNA gene, rrs, cause high-level resistance to kanamycinand cross-resistance to amikacin and sometimes capreomycin.3
In a recent paper, Zaunbrecher et al.4 reported the impact ofmutations in the eis promoter region onM. tuberculosis kanamycinsusceptibility. eis encodes an aminoglycoside acetyltransferasespecific to kanamycin. Mutations in the eis promoter region leadto an increased synthesis of the enzyme and inactivation of thedrug.
The aim of the present study was to define the role of eismutations in the development of kanamycin resistance inpatients from antituberculosis clinics in Moscow. Few studieshave investigated this to date and, to our knowledge, none inRussia.
Material and methods
Bacterial isolatesFor the present study we chose 70 M. tuberculosis clinical isolates. Iso-lates were obtained from sputum provided by patients previouslytreated at the Moscow Scientific and Clinical Antituberculosis Centerand two specialized antituberculosis clinics in Moscow. All isolates wereidentified as MDR on the basis of bacteriological [culture in Mycobacteria
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