title: Suitable disk antimicrobial susceptibility breakpoints defining Salmonella enterica serovar Typhi isolates with reduced susceptibility to fluoroquinolones.
abstract: Infections with Salmonella enterica serovar Typhi isolates that have reduced susceptibility to ofloxacin (MIC ≥ 0.25 μg/ml) or ciprofloxacin (MIC ≥ 0.125 μg/ml) have been associated with a delayed response or clinical failure following treatment with these antimicrobials. These isolates are not detected as resistant using current disk susceptibility breakpoints. We examined 816 isolates of S. Typhi from seven Asian countries. Screening for nalidixic acid resistance (MIC ≥ 16 μg/ml) identified isolates with an ofloxacin MIC of ≥0.25 μg/ml with a sensitivity of 97.3% (253/260) and specificity of 99.3% (552/556). For isolates with a ciprofloxacin MIC of ≥0.125 μg/ml, the sensitivity was 92.9% (248/267) and specificity was 98.4% (540/549). A zone of inhibition of ≤28 mm around a 5-μg ofloxacin disc detected strains with an ofloxacin MIC of ≥0.25 μg/ml with a sensitivity of 94.6% (246/260) and specificity of 94.2% (524/556). A zone of inhibition of ≤30 mm detected isolates with a ciprofloxacin MIC of ≥0.125 μg/ml with a sensitivity of 94.0% (251/267) and specificity of 94.2% (517/549). An ofloxacin MIC of ≥0.25 μg/ml and a ciprofloxacin MIC of ≥0.125 μg/ml detected 74.5% (341/460) of isolates with an identified quinolone resistance-inducing mutation and 81.5% (331/406) of the most common mutant (carrying a serine-to-phenylalanine mutation at codon 83 in the gyrA gene). Screening for nalidixic acid resistance or ciprofloxacin and ofloxacin disk inhibition zone are suitable for detecting S. Typhi isolates with reduced fluoroquinolone susceptibility.
authors.affiliation: The Hospital for Tropical Diseases, Wellcome Trust Major Overseas Programme, Oxford University Clinical Research Unit, 190 Ben Ham Tu, Quan 5, Ho Chi Minh City, Vietnam. cmparry59@gmail.com
authors.forename: Christopher M
authors.initials: CM
authors.lastname: Parry
authors.forename: Chau Tran
authors.initials: CT
authors.lastname: Thuy
authors.forename: Sabina
authors.initials: S
authors.lastname: Dongol
authors.forename: Abhilasha
authors.initials: A
authors.lastname: Karkey
authors.forename: Ha
authors.initials: H
authors.lastname: Vinh
authors.forename: Nguyen Tran
authors.initials: NT
authors.lastname: Chinh
authors.forename: Pham Thanh
authors.initials: PT
authors.lastname: Duy
authors.forename: Tran Vu
authors.initials: TV
authors.lastname: Thieu Nga
authors.forename: James I
authors.initials: JI
authors.lastname: Campbell
authors.forename: Nguyen
authors.initials: N
authors.lastname: Van Minh Hoang
authors.forename: Amit
authors.initials: A
authors.lastname: Arjyal
authors.forename: Zulfiqar A
authors.initials: ZA
authors.lastname: Bhutta
authors.forename: Sujit K
authors.initials: SK
authors.lastname: Bhattacharya
authors.forename: Magdarina D
authors.initials: MD
authors.lastname: Agtini
authors.forename: Baiqing
authors.initials: B
authors.lastname: Dong
authors.forename: Do Gia
authors.initials: DG
authors.lastname: Canh
authors.forename: Aliya
authors.initials: A
authors.lastname: Naheed
authors.forename: John
authors.initials: J
authors.lastname: Wain
authors.forename: Tran
authors.initials: T
authors.lastname: Tinh Hien
authors.forename: Buddha
authors.initials: B
authors.lastname: Basnyat
authors.forename: Leon
authors.initials: L
authors.lastname: Ochiai
authors.forename: John
authors.initials: J
authors.lastname: Clemens
authors.forename: Jeremy J
authors.initials: JJ
authors.lastname: Farrar
authors.forename: Christiane
authors.initials: C
authors.lastname: Dolecek
authors.forename: Stephen
authors.initials: S
authors.lastname: Baker
mesh_terms: D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D001426:Bacterial Proteins / Q000235:genetics; D002939:Ciprofloxacin / Q000494:pharmacology; D027081:DNA Gyrase / Q000235:genetics; D027101:DNA Topoisomerase IV / Q000235:genetics; D024881:Drug Resistance, Bacterial; D024841:Fluoroquinolones / Q000494:pharmacology*; D006801:Humans; D008826:Microbial Sensitivity Tests; D009154:Mutation / Q000235:genetics; D009268:Nalidixic Acid / Q000494:pharmacology; D015242:Ofloxacin / Q000494:pharmacology; D012485:Salmonella typhi / Q000187:drug effects* / Q000235:genetics
chemical_list: D000900:Anti-Bacterial Agents; D001426:Bacterial Proteins; D024841:Fluoroquinolones; D009268:Nalidixic Acid; D002939:Ciprofloxacin; D015242:Ofloxacin; D027101:DNA Topoisomerase IV; D027081:DNA Gyrase