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February 25, 1998

Emerging Drug Resistance and Vaccination for Typhoid Fever

Author Affiliations

Margaret A.WinkerMD, Senior EditorIndividualAuthorPhil B.FontanarosaMD, Senior EditorIndividualAuthor

JAMA. 1998;279(8):579-580. doi:10.1001/jama.279.8.579

To the Editor.—We read with interest the recent presentation and review of a case of Salmonella typhiinfection in a pregnant woman returning from India. Dr Zenilman1discussed multidrug resistance (MDR) in S typhiand reinforced the general view that fluoroquinolones are effective first-line therapy in the treatment of such infections.

We recently cared for a 52-year-old man who had arrived 1 week previously from the Punjab region of northern India. He had had fever and headache for 6 days. Blood cultures grew S typhi,and he was treated with oral ciprofloxacin (500 mg twice a day at presentation, increasing to 750 mg twice a day on day 3). Despite some clinical improvement he remained febrile after 17 days of treatment. Ceftriaxone, 1 g once daily, was added to his regimen, and his fever resolved within 3 days.

The S typhiisolate was sensitive in vitro to trimethoprim, ampicillin, and ciprofloxacin. The minimum inhibitory concentration (MIC) for ciprofloxacin, as determined by an E-test (AB Biodisk, Solna, Sweden), was 0.25 mg/L. This MIC means that the isolate is "susceptible" using the National Committee for Clinical Laboratory Standards breakpoint for ciprofloxacin of 1.0 mg/L. The usual range of MICs for S typhi to ciprofloxacin, however, is from 0.0075 to 0.03 mg/L.2 Others have also recently reported clinical failure with ciprofloxacin in S typhiinfections when the MIC has been between 0.25 and 1 mg/L.3,4Quinolone resistance in isolates from patients returning from the Indian subcontinent have been reported since 1991.4Interestingly, although a reduced duration of fever has been a feature of fluoroquinolone therapy in typhoid fever, an increase in the time to defervescence while receiving ciprofloxacin has been noted in India.5 This may be indicative of gradually rising MICs for treatment of S typhi.

Ciprofloxacin remains a first-line antibiotic for the treatment of MDR S typhi. However, we recommend that a ciprofloxacin MIC should be determined on all isolates of S typhifrom patients returning from the Indian subcontinent. Clinicians should be aware that clinical failure with fluoroquinolones may occur despite reported sensitivity.

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Mitchell  DM Ciprofloxacin resistant Salmonella typhi: an emerging problem. Med J Aust. 1997;167172
Rowe  BWard  LRThrelfall  JE Multidrug-resistant Salmonella typhi: a world epidemic. Clin Infect Dis. 1997;24 (suppl 1) S106- S109Article
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