Nalidixic acid-resistant Salmonella typhi (NARST) was first isolated in Viet Nam in 1993. Analysis of the quinolone resistance-determining region of gyrA in 20 NARST isolates by polymerase chain reaction and single-stranded conformational polymorphism yielded two novel patterns: pattern II corresponding to a point mutation at nucleotide 87 Asp-->Gly (n = 17), and pattern III corresponding to a point mutation at nucleotide 83 Ser-->Phe (n = 3). In trials of short-course ofloxacin therapy for uncomplicated typhoid, 117 (78%) of 150 patients were infected with multidrug-resistant S. typhi, 18 (15%) of which were NARST. The median time to fever clearance was 156 hours (range, 30-366 hours) for patients infected with NARST and 84 hours (range, 12-378 hours) for those infected with nalidixic acid-susceptible strains (P < .001). Six (33.3%) of 18 NARST infections required retreatment, whereas 1 (0.8%) of 132 infections due to susceptible strains required retreatment (relative risk = 44; 95% confidence interval = 5.6-345; P < .0001). We recommend that short courses of quinolones not be used in patients infected with NARST.
An open, randomized comparison of ofloxacin (200 mg, every 12 h) given orally for 5 days and ceftriaxone (3 g, once daily) given intravenously for 3 days in the treatment of uncomplicated enteric fever was conducted in Ho Chi Minh City, Vietnam. Salmonella paratyphi type A was isolated from six patients. Salmonella typhi was isolated from 41 patients; 63% of these isolates were resistant to multiple antibiotics: ampicillin, chloramphenicol, sulfamethoxazole, trimethoprim, and tetracycline. Of the culture-confirmed cases, treatment with ofloxacin resulted in complete cure of all 22 patients, whereas 18 of 25 patients treated with ceftriaxone were completely cured (P < 0.01). In the ceftriaxone group, there were six acute treatment failures and one relapse. Mean +/- standard deviation fever clearance times were 81 +/- 25 h for ofloxacin and 196 +/- 87 h for ceftriaxone (P < 0.0001). Short-course treatment with oral ofloxacin (5 days) is significantly better than that with ceftriaxone (3 days) and will be of particular benefit in areas where multiresistant strains of S. typhi are encountered.
The diagnostic value of an acute-phase single-tube Widal test for suspected typhoid fever was evaluated with 2,000 Vietnamese patients admitted to an infectious disease referral hospital between 1993 and 1998. Test patients had suspected typhoid fever and a blood culture positive for Salmonella typhi (n= 1,400) orSalmonella paratyphi A (n = 45). Control patients had a febrile illness for which another cause was confirmed (malaria [n = 103], dengue [n = 76], or bacteremia due to another microorganism [n = 156] or tetanus (n = 265). An O-agglutinin titer of ≥100 was found in 18% of the febrile controls and 7% of the tetanus patients. Corresponding values for H agglutinins were 8 and 1%, respectively. The O-agglutinin titer was ≥100 in 83% of the blood culture-positive typhoid fever cases, and the H-agglutinin titer was ≥100 in 67%. The disease prevalence in investigated patients in this hospital was 30.8% (95% confidence interval, 26.8 to 35.1%); at this prevalence, an elevated level of H agglutinins gave better positive predictive values for typhoid fever than did O agglutinins. With a cutoff titer of ≥200 for O agglutinin or ≥100 for H agglutinin, the Widal test would diagnose correctly 74% of the blood culture-positive cases of typhoid fever. However, 14% of the positive results would be false-positive, and 10% of the negative results would be false-negative. The Widal test can be helpful in the laboratory diagnosis of typhoid fever in Vietnam if interpreted with care.
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