BMJ  2006;333:353-354 (12 August), doi:10.1136/bmj.333.7563.353-b

Letter

Fluoroquinolone resistance in Salmonella Typhi

EDITOR—As Parry et al point out,^{1 2} appropriate laboratory methods are crucial in detecting clinically important quinolone resistance.

We highlight the emergence of strains of Salmonella enterica serovar Typhi (S Typhi) that show reduced susceptibility to the fluoroquinolones but are susceptible to nalidixic acid (minimum inhibitory concentration < 16 mg/l). In a review of all 692 isolates of S Typhi sent to the Laboratory for Enteric Pathogens at the Health Protection Agency in London between 2000 and 2003 we detected 49 isolates that were susceptible to nalidixic acid but had reduced susceptibility to fluoroquinolone (minimum inhibitory concentration 0.125-1.0 mg/l; table).³ When the country of acquisition was known, 18 of these isolates were from patients who had visited India; eight, Pakistan; four, Bangladesh; and one, Kenya.

View this table: [in this window] [in a new window]   S Typhi susceptible to nalidixic acid but with reduced fluoroquinolone susceptibility imported into England, Scotland, and Wales, 2000-3

 

Overall, of 271 isolates with reduced susceptibility to fluoroquinolone, 18% were susceptible to nalidixic acid and therefore would not have been detected by routine screening with a nalidixic acid disc. No clinical outcome data are available and so the clinical relevance of these strains is uncertain, but an enhanced surveillance study is being undertaken by the Health Protection Agency.⁴

Although resistance to nalidixic acid (minimum inhibitory concentration > 256 mg/l) remains an important marker for failure of fluoroquinolone treatment in typhoid fever, several isolates show reduced susceptibility to fluoroquinolone while remaining susceptible to nalidixic acid. This is particularly true for isolates from the Indian subcontinent. Furthermore, in six of the 49 such isolates (table), none of the mutations in gyrA and parC commonly associated with reduced resistance to fluoroquinolone were present using the GAMA method.⁵ Therefore a new mechanism of fluoroquinolone resistance, which might not confer nalidixic acid resistance, may be emerging in S Typhi. Our findings underscore the importance of estimating the minimum inhibitory concentration of the agent selected for treatment.

fiona{at}sanger.ac.uk, Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Cambridge CB10 1SA

Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Cambridge CB10 1SA

Health Protection Agency, Centre for Infections, London NW9 5HT

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Competing interests: None declared.

References

1. Parry CM, Karunanayake L, Coulter JB, Beeching NJ. Test for quinolone resistance in typhoid fever. BMJ 2006; 333: 260-1. (29 July.)[Free Full Text]
2. Bhutta ZA. Current concepts in the diagnosis and treatment of typhoid fever. BMJ 2006;333: 78-82. (8 July.)[Free Full Text]
3. Cooke FJ, Day M, Wain J, Ward LR, Threlfall EJ. Cases of typhoid fever imported into England, Scotland and Wales (2000-2003). Trans R Soc Trop Med Hyg (in press).
4. Anonymous. A pilot of enhanced surveillance of enteric fever in England, Wales and Northern Ireland. Commun Dis Rep CDR Wkly 2006;16(18): 3-4.
5. Walker RA, Skinner JA, Ward LR, Threlfall EJ. LightCycler gyrA mutation assay (GAMA) identifies heterogeneity in GyrA in Salmonella enterica serotypes Typhi and Paratyphi A with decreased susceptibility to ciprofloxacin. Int J Antimicrob Agents 2003;22(6): 622-5.[CrossRef][ISI][Medline]

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