title: Quinolone-resistant Salmonella typhi in Viet Nam: molecular basis of resistance and clinical response to treatment.
abstract: Nalidixic acid-resistant Salmonella typhi (NARST) was first isolated in Viet Nam in 1993. Analysis of the quinolone resistance-determining region of gyrA in 20 NARST isolates by polymerase chain reaction and single-stranded conformational polymorphism yielded two novel patterns: pattern II corresponding to a point mutation at nucleotide 87 Asp-->Gly (n = 17), and pattern III corresponding to a point mutation at nucleotide 83 Ser-->Phe (n = 3). In trials of short-course ofloxacin therapy for uncomplicated typhoid, 117 (78%) of 150 patients were infected with multidrug-resistant S. typhi, 18 (15%) of which were NARST. The median time to fever clearance was 156 hours (range, 30-366 hours) for patients infected with NARST and 84 hours (range, 12-378 hours) for those infected with nalidixic acid-susceptible strains (P < .001). Six (33.3%) of 18 NARST infections required retreatment, whereas 1 (0.8%) of 132 infections due to susceptible strains required retreatment (relative risk = 44; 95% confidence interval = 5.6-345; P < .0001). We recommend that short courses of quinolones not be used in patients infected with NARST.
authors.affiliation: Wellcome Trust Clinical Research Unit, Cho Quan Hospital, Ho Chi Minh City, Viet Nam.
authors.forename: J
authors.initials: J
authors.lastname: Wain
authors.forename: N T
authors.initials: NT
authors.lastname: Hoa
authors.forename: N T
authors.initials: NT
authors.lastname: Chinh
authors.forename: H
authors.initials: H
authors.lastname: Vinh
authors.forename: M J
authors.initials: MJ
authors.lastname: Everett
authors.forename: T S
authors.initials: TS
authors.lastname: Diep
authors.forename: N P
authors.initials: NP
authors.lastname: Day
authors.forename: T
authors.initials: T
authors.lastname: Solomon
authors.forename: N J
authors.initials: NJ
authors.lastname: White
authors.forename: L J
authors.initials: LJ
authors.lastname: Piddock
authors.forename: C M
authors.initials: CM
authors.lastname: Parry
mesh_terms: D042462:4-Quinolones; D000890:Anti-Infective Agents / Q000494:pharmacology*; D002648:Child; D027081:DNA Gyrase; D004250:DNA Topoisomerases, Type II / Q000235:genetics*; D004352:Drug Resistance, Microbial / Q000235:genetics; D018432:Drug Resistance, Multiple / Q000235:genetics*; D005260:Female; D006801:Humans; D008297:Male; D008826:Microbial Sensitivity Tests; D011446:Prospective Studies; D012485:Salmonella typhi / Q000145:classification / Q000187:drug effects* / Q000235:genetics; D017422:Sequence Analysis, DNA; D014435:Typhoid Fever / Q000188:drug therapy* / Q000382:microbiology; D014744:Vietnam / Q000453:epidemiology
chemical_list: D042462:4-Quinolones; D000890:Anti-Infective Agents; D027081:DNA Gyrase; D004250:DNA Topoisomerases, Type II