title: Molecular analysis of high-level ciprofloxacin resistance in Salmonella enterica serovar Typhi and S. Paratyphi A: need to expand the QRDR region?
abstract: Fourteen strains of S. Typhi (n=13) and S. Paratyphi A (n=1) resistant to ciprofloxacin were compared with 30 ciprofloxacin decreased-susceptibility strains on the basis of qnr plasmid analysis, and nucleotide substitutions at gyrA, gyrB, parC and parE. In ciprofloxacin-resistant strains, five S. Typhi and a single S. Paratyphi A showed triple mutations in gyrA (Ser83-->Phe, Asp87-->Asn, Glu133-->Gly) and a novel mutation outside the quinolone resistance determining region (QRDR) (Met52-->Leu). Novel mutations were also discovered in an isolate (minimum inhibitory concentration 8 microg/ml) in gyrA gene Asp76-->Asn and outside the QRDR Leu44-->Ile. Out of 30 isolates with reduced susceptibility, single mutation was found in 12 strains only. Genes encoding qnr plasmid (qnr A, qnr B, AAC1-F) were not detected in ciprofloxacin-resistant or decreased-susceptibility strains. Antimicrobial surveillance coupled with molecular analysis of fluoroquinolone resistance is warranted for reconfirming novel and established molecular patterns of resistance, which is quintessential for reappraisal of enteric fever therapeutics.
authors.affiliation: Department of Microbiology, Vardhman Mahaveer Medical College and Safdarjung Hospital, New Delhi, India.
authors.forename: M R
authors.initials: MR
authors.lastname: Capoor
authors.forename: D
authors.initials: D
authors.lastname: Nair
authors.forename: N S
authors.initials: NS
authors.lastname: Walia
authors.forename: R S
authors.initials: RS
authors.lastname: Routela
authors.forename: S S
authors.initials: SS
authors.lastname: Grover
authors.forename: M
authors.initials: M
authors.lastname: Deb
authors.forename: P
authors.initials: P
authors.lastname: Aggarwal
authors.forename: P K
authors.initials: PK
authors.lastname: Pillai
authors.forename: P J
authors.initials: PJ
authors.lastname: Bifani
mesh_terms: D000293:Adolescent; D000328:Adult; D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D001426:Bacterial Proteins / Q000235:genetics; D001483:Base Sequence; D002648:Child; D002939:Ciprofloxacin / Q000494:pharmacology*; D004269:DNA, Bacterial / Q000235:genetics; D024881:Drug Resistance, Bacterial / Q000235:genetics*; D005260:Female; D006801:Humans; D008297:Male; D009154:Mutation; D012482:Salmonella paratyphi A / Q000187:drug effects* / Q000235:genetics; D012485:Salmonella typhi / Q000187:drug effects* / Q000235:genetics; D055815:Young Adult
chemical_list: D000900:Anti-Bacterial Agents; D001426:Bacterial Proteins; D004269:DNA, Bacterial; D002939:Ciprofloxacin