Emerging Drug Resistance and Vaccination for Typhoid Fever

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 Zenilman¹ discussed 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 - 4} Quinolone resistance in isolates from patients returning from the Indian subcontinent have been reported since 1991.⁴ Interestingly, 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.