title: Antimicrobial drug resistance of Salmonella enterica serovar typhi in asia and molecular mechanism of reduced susceptibility to the fluoroquinolones.
abstract: This study describes the pattern and extent of drug resistance in 1,774 strains of Salmonella enterica serovar Typhi isolated across Asia between 1993 and 2005 and characterizes the molecular mechanisms underlying the reduced susceptibilities to fluoroquinolones of these strains. For 1,393 serovar Typhi strains collected in southern Vietnam, the proportion of multidrug resistance has remained high since 1993 (50% in 2004) and there was a dramatic increase in nalidixic acid resistance between 1993 (4%) and 2005 (97%). In a cross-sectional sample of 381 serovar Typhi strains from 8 Asian countries, Bangladesh, China, India, Indonesia, Laos, Nepal, Pakistan, and central Vietnam, collected in 2002 to 2004, various rates of multidrug resistance (16 to 37%) and nalidixic acid resistance (5 to 51%) were found. The eight Asian countries involved in this study are home to approximately 80% of the world's typhoid fever cases. These results document the scale of drug resistance across Asia. The Ser83-->Phe substitution in GyrA was the predominant alteration in serovar Typhi strains from Vietnam (117/127 isolates; 92.1%). No mutations in gyrB, parC, or parE were detected in 55 of these strains. In vitro time-kill experiments showed a reduction in the efficacy of ofloxacin against strains harboring a single-amino-acid substitution at codon 83 or 87 of GyrA; this effect was more marked against a strain with a double substitution. The 8-methoxy fluoroquinolone gatifloxacin showed rapid killing of serovar Typhi harboring both the single- and double-amino-acid substitutions.
authors.affiliation: Oxford University Clinical Research Unit, Hospital for Tropical Diseases, 190 Ben Ham Tu, Ho Chi Minh City, Vietnam.
authors.forename: Tran Thuy
authors.initials: TT
authors.lastname: Chau
authors.forename: James Ian
authors.initials: JI
authors.lastname: Campbell
authors.forename: Claudia M
authors.initials: CM
authors.lastname: Galindo
authors.forename: Nguyen
authors.initials: N
authors.lastname: Van Minh Hoang
authors.forename: To Song
authors.initials: TS
authors.lastname: Diep
authors.forename: Tran Thu Thi
authors.initials: TT
authors.lastname: Nga
authors.forename: Nguyen
authors.initials: N
authors.lastname: Van Vinh Chau
authors.forename: Phung Quoc
authors.initials: PQ
authors.lastname: Tuan
authors.forename: Anne Laure
authors.initials: AL
authors.lastname: Page
authors.forename: R Leon
authors.initials: RL
authors.lastname: Ochiai
authors.forename: Constance
authors.initials: C
authors.lastname: Schultsz
authors.forename: John
authors.initials: J
authors.lastname: Wain
authors.forename: Zulfiqar A
authors.initials: ZA
authors.lastname: Bhutta
authors.forename: Christopher M
authors.initials: CM
authors.lastname: Parry
authors.forename: Sujit K
authors.initials: SK
authors.lastname: Bhattacharya
authors.forename: Shanta
authors.initials: S
authors.lastname: Dutta
authors.forename: Magdarina
authors.initials: M
authors.lastname: Agtini
authors.forename: Baiqing
authors.initials: B
authors.lastname: Dong
authors.forename: Yang
authors.initials: Y
authors.lastname: Honghui
authors.forename: Dang Duc
authors.initials: DD
authors.lastname: Anh
authors.forename: Do Gia
authors.initials: DG
authors.lastname: Canh
authors.forename: Aliya
authors.initials: A
authors.lastname: Naheed
authors.forename: M John
authors.initials: MJ
authors.lastname: Albert
authors.forename: Rattanaphone
authors.initials: R
authors.lastname: Phetsouvanh
authors.forename: Paul N
authors.initials: PN
authors.lastname: Newton
authors.forename: Buddha
authors.initials: B
authors.lastname: Basnyat
authors.forename: Amit
authors.initials: A
authors.lastname: Arjyal
authors.forename: Tran Thi Phi
authors.initials: TT
authors.lastname: La
authors.forename: Nguyen Ngoc
authors.initials: NN
authors.lastname: Rang
authors.forename: Le Thi
authors.initials: LT
authors.lastname: Phuong
authors.forename: Phan
authors.initials: P
authors.lastname: Van Be Bay
authors.forename: Lorenz
authors.initials: L
authors.lastname: von Seidlein
authors.forename: Gordon
authors.initials: G
authors.lastname: Dougan
authors.forename: John D
authors.initials: JD
authors.lastname: Clemens
authors.forename: Ha
authors.initials: H
authors.lastname: Vinh
authors.forename: Tran Tinh
authors.initials: TT
authors.lastname: Hien
authors.forename: Nguyen Tran
authors.initials: NT
authors.lastname: Chinh
authors.forename: Camilo J
authors.initials: CJ
authors.lastname: Acosta
authors.forename: Jeremy
authors.initials: J
authors.lastname: Farrar
authors.forename: Christiane
authors.initials: C
authors.lastname: Dolecek
mesh_terms: D000900:Anti-Bacterial Agents / Q000494:pharmacology; D001208:Asia; D001459:Bangladesh; D002681:China; D027081:DNA Gyrase / Q000235:genetics; D004252:DNA Mutational Analysis; D027101:DNA Topoisomerase IV / Q000235:genetics; D004352:Drug Resistance, Microbial / Q000235:genetics*; D024841:Fluoroquinolones / Q000494:pharmacology*; D006801:Humans; D007194:India; D007214:Indonesia; D007812:Laos; D008826:Microbial Sensitivity Tests; D009154:Mutation; D009390:Nepal; D010154:Pakistan; D012485:Salmonella typhi / Q000187:drug effects* / Q000235:genetics*; D014744:Vietnam
chemical_list: D000900:Anti-Bacterial Agents; D024841:Fluoroquinolones; D027101:DNA Topoisomerase IV; D027081:DNA Gyrase