Azithromycin versus Ciprofloxacin for Treatment of Uncomplicated Typhoid Fever in a Randomized Trial in Egypt That Included Patients with Multidrug Resistance

Abstract

To compare clinical and bacteriological efficacies of azithromycin and ciprofloxacin for typhoid fever, 123 adults with fever and signs of uncomplicated typhoid fever were entered into a randomized trial. Cultures of blood were positive for Salmonella typhi in 59 patients and for S. paratyphi A in 3 cases; stool cultures were positive for S. typhi in 11 cases and for S. paratyphi A in 1 case. Multiple-drug resistance (MDR; resistance to ampicillin, chloramphenicol, and trimethoprim-sulfamethoxazole) was present in isolates of 21 of 64 patients with positive cultures. Of these 64 patients, 36 received 1 g of azithromycin orally once on the first day, followed by 500 mg given orally once daily on the next 6 days; 28 patients received 500 mg of ciprofloxacin orally twice daily for 7 days. Blood cultures were repeated on days 4 and 10 after the start of therapy, and stool cultures were done on days 4, 10, and 28 after the start of therapy. All patients in both groups improved during therapy and were cured. Defervescence (maximum daily temperatures of ≤38°C) occurred at the following times [mean ± standard deviation (range)] after the start of therapy: 3.8 ± 1.1 (2 to 7) days with azithromycin and 3.3 ± 1.0 (1 to 5) days with ciprofloxacin. No relapses were detected. Cultures of blood and stool during and after therapy were negative in all cases, except for one patient treated with azithromycin who had a positive blood culture on day 4. These results indicated that azithromycin and ciprofloxacin were similarly effective, both clinically and bacteriologically, against typhoid fever caused by both sensitive organisms and MDRS. typhi.

Short‐Course Azithromycin for the Treatment of Uncomplicated Typhoid Fever in Children and Adolescents

“…These findings are consistent with reports in the literature of relapse rates of 5%-15% for patients treated with ceftriaxone [14,[20][21][22]. Although the sample size in the present study is small, combining these results with those of our previous trials [13,14], along with those of studies by Chinh et al [15] and Butler et al [23], nearly 200 patients with blood culture-confirmed typhoid fever have been treated with azithromycin, and no relapses have occurred. The concentration of azithromycin within cells and its secretion into the biliary tree, in conjunction with the long half-life of the drug, likely explain why relapses have not occurred when treating a principally intracellular infection such as typhoid fever [14,15].…”

“…Combining the results of 2 previous typhoid fever treatment trials, 69 patients with blood culture-proven typhoid fever were treated with azithromycin, and only 2 remained bacteremic 4 days after starting antibiotic therapy [13,14]. In the current study, because the duration of treatment was shortened from 7 to 5 days, the ontherapy blood samples were obtained for culture on day 3, one day sooner than treatment was ended in our previous trials [13,14]. The fact that blood samples were obtained for culture earlier in the present study is postulated to be the reason for the apparent, rather than actual, prolongation of bacteremia.…”

“…Previous studies have demonstrated that a 7-day treatment course of azithromycin was highly effective against uncomplicated typhoid fever in adults and children [12][13][14].…”

Current trends in typhoid fever

“…Azithromycin (1000 mg/d for 1 day, then 500 mg/d for 6 days) may also be effective [70][71][72]; however, clinical failure has been described despite the high leukocyte intracellular concentrations achieved with this antibiotic [73]. Aztreonam and cefixime have had variable success rates and are not considered first-line therapy [65,[74][75][76].…”

Salmonella spp.

“…It was also effective in cases of MDR typhoid. This provides a useful alternative for the management of children with uncomplicated typhoid in developing countries , Girgis et al, 1999, Frenck et al, 2000.…”