Antimicrobial drug resistance of Salmonella enterica serovar typhi in asia and molecular mechanism of reduced susceptibility to the fluoroquinolones.
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.
Chau
Tran Thuy
TT
Oxford University Clinical Research Unit, Hospital for Tropical Diseases, 190 Ben Ham Tu, Ho Chi Minh City, Vietnam.
Campbell
James Ian
JI
Galindo
Claudia M
CM
Van Minh Hoang
Nguyen
N
Diep
To Song
TS
Nga
Tran Thu Thi
TT
Van Vinh Chau
Nguyen
N
Tuan
Phung Quoc
PQ
Page
Anne Laure
AL
Ochiai
R Leon
RL
Schultsz
Constance
C
Wain
John
J
Bhutta
Zulfiqar A
ZA
Parry
Christopher M
CM
Bhattacharya
Sujit K
SK
Dutta
Shanta
S
Agtini
Magdarina
M
Dong
Baiqing
B
Honghui
Yang
Y
Anh
Dang Duc
DD
Canh
Do Gia
DG
Naheed
Aliya
A
Albert
M John
MJ
Phetsouvanh
Rattanaphone
R
Newton
Paul N
PN
Basnyat
Buddha
B
Arjyal
Amit
A
La
Tran Thi Phi
TT
Rang
Nguyen Ngoc
NN
Phuong
Le Thi
LT
Van Be Bay
Phan
P
von Seidlein
Lorenz
L
Dougan
Gordon
G
Clemens
John D
JD
Vinh
Ha
H
Hien
Tran Tinh
TT
Chinh
Nguyen Tran
NT
Acosta
Camilo J
CJ
Farrar
Jeremy
J
Dolecek
Christiane
C
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
D000900:Anti-Bacterial Agents; D024841:Fluoroquinolones; D027101:DNA Topoisomerase IV; D027081:DNA Gyrase