A randomized controlled comparison of azithromycin and ofloxacin for treatment of multidrug-resistant or nalidixic acid-resistant enteric fever

To examine the efficacy and safety of short courses of azithromycin and ofl oxacin for treating multidrug-resistant (MDR, i.e,, resistant to chloramphe nicol, ampicillin, and cotrimoxazole) and nalidixic acid-resistant enteric fever, azithromycin (1 g once daily for 5 days at 20 mg/kg/day) and ofloxac in (200 mg orally twice a day for 5 days at 8 mg/kg/day) were compared in a n open randomized study in adults admitted to a hospital with uncomplicated enteric fever. A total of 88 blood culture-confirmed patients were enrolle d in the study (86 with Salmonella enterica serovar Typhi and 2 with S, ent erica serovar Paratyphi A), Of these, 44 received azithromycin and 44 oflox acin, A total of 68 of 87 (78%) isolates were MDR serovar Typhi, and 46 of 87 (53%) were nalidixic acid resistant. The MIC90 (range) of azithromycin w as 8 (4 to 16) mu g/ml for the isolates. The MIC90 (range) of ofloxacin for the nalidixic acid-sensitive isolates,vas 0.03 (0.015 to 0.06) mu g/ml and for the nalidixic acid-resistant isolates it was 0.5 (0.25 to 1.0) mu g/ml . There was no significant difference in the overall clinical cure rate wit h ofloxacin and azithromycin (38 of 44 [86.4%] versus 42 of 44 [95.5%]; P = 0.27) or in the patients infected with nalidixic acid-resistant typhoid (1 7 of 21 [81.0%] versus 24 of 25 [96.0%]; P = 0.16), However, patients with nalidixic acid-resistant typhoid treated with ofloxacin had a longer fever clearance time compared with those treated with azithromycin (174 [60 to 26 4] versus 135 [72 to 186] h; P = 0.004) and had positive fecal cultures aft er the end of treatment (7 of 17 [41%] versus 0 of 19 [0%]; P = 0.002). Bot h antibiotics were well tolerated. A 5 day course of azithromycin was effec tive for the treatment of enteric fever due to MDR and nalidixic-acid-resis tant serovar Typhi, whereas the ofloxacin regimen chosen was less satisfact ory for these strains.