title: Public health impact of isoniazid-resistant Mycobacterium tuberculosis strains with a mutation at amino-acid position 315 of katG: a decade of experience in The Netherlands.
abstract: A previous limited study demonstrated that Mycobacterium tuberculosis isolates with a mutation at amino-acid position 315 of katG (Delta315) exhibited high-level resistance to isoniazid and were more frequently resistant to streptomycin. In the present study, isoniazid-resistant M. tuberculosis isolates from 8,332 patients in The Netherlands (1993-2002) were screened for the Delta315 mutation. Isoniazid resistance was found in 592 (7%) isolates, of which 323 (55%) carried Delta315. IS6110 restriction fragment length polymorphism analysis showed that Delta315 isolates occurred in clusters, suggesting recent transmission, at the same frequency as isoniazid-susceptible isolates. In contrast, other isoniazid-resistant isolates clustered significantly less frequently. Delta315 isolates were high-level isoniazid-resistant, streptomycin-resistant and multidrug-resistant significantly more often, and may have a greater impact on public health, than other isoniazid-resistant isolates.
authors.affiliation: Department of Medical Microbiology, Academic Medical Center, University of Amsterdam, Amsterdam, the Netherlands. h.r.vandoorn@amc.uva.nl
authors.forename: H R
authors.initials: HR
authors.lastname: van Doorn
authors.forename: P E W
authors.initials: PE
authors.lastname: de Haas
authors.forename: K
authors.initials: K
authors.lastname: Kremer
authors.forename: C M J E
authors.initials: CM
authors.lastname: Vandenbroucke-Grauls
authors.forename: M W
authors.initials: MW
authors.lastname: Borgdorff
authors.forename: D
authors.initials: D
authors.lastname: van Soolingen
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000995:Antitubercular Agents / Q000494:pharmacology*; D001426:Bacterial Proteins / Q000235:genetics*; D002374:Catalase / Q000235:genetics*; D024901:Drug Resistance, Multiple, Bacterial; D006801:Humans; D007538:Isoniazid / Q000494:pharmacology*; D008875:Middle Aged; D009154:Mutation; D009169:Mycobacterium tuberculosis / Q000187:drug effects* / Q000235:genetics; D011634:Public Health
chemical_list: D000995:Antitubercular Agents; D001426:Bacterial Proteins; D002374:Catalase; C480353:katG protein, Mycobacterium tuberculosis; D007538:Isoniazid