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 ofloxacin for treating multidrug-resistant (MDR, i.e., resistant to chloramphenicol, ampicillin, and cotrimoxazole) and nalidixic acid-resistant enteric fever, azithromycin (1 g once daily for 5 days at 20 mg/kg/day) and ofloxacin (200 mg orally twice a day for 5 days at 8 mg/kg/day) were compared in an open randomized study in adults admitted to a hospital with uncomplicated enteric fever. A total of 88 blood culture-confirmed patients were enrolled in the study (86 with Salmonella enterica serovar Typhi and 2 with S. enterica serovar Paratyphi A). Of these, 44 received azithromycin and 44 ofloxacin. A total of 68 of 87 (78%) isolates were MDR serovar Typhi, and 46 of 87 (53%) were nalidixic acid resistant. The MIC(90) (range) of azithromycin was 8 (4 to 16) microgram/ml for the isolates. The MIC(90) (range) of ofloxacin for the nalidixic acid-sensitive isolates was 0.03 (0.015 to 0.06) microgram/ml and for the nalidixic acid-resistant isolates it was 0.5 (0.25 to 1.0) microgram/ml. There was no significant difference in the overall clinical cure rate with 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 (17 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 264] versus 135 [72 to 186] h; P = 0.004) and had positive fecal cultures after the end of treatment (7 of 17 [41%] versus 0 of 19 [0%]; P = 0.002). Both antibiotics were well tolerated. A 5-day course of azithromycin was effective for the treatment of enteric fever due to MDR and nalidixic-acid-resistant serovar Typhi, whereas the ofloxacin regimen chosen was less satisfactory for these strains.
Chinh
N T
NT
Department of Infectious Diseases, Faculty of Medicine, University of Medicine and Pharmacy, Ho Chi Minh City, Vietnam.
Parry
C M
CM
Ly
N T
NT
Ha
H D
HD
Thong
M X
MX
Diep
T S
TS
Wain
J
J
White
N J
NJ
Farrar
J J
JJ
D000293:Adolescent; D000328:Adult; D000900:Anti-Bacterial Agents / Q000009:adverse effects / Q000627:therapeutic use*; D000890:Anti-Infective Agents / Q000009:adverse effects / Q000627:therapeutic use*; D017963:Azithromycin / Q000009:adverse effects / Q000627:therapeutic use*; D018432:Drug Resistance, Multiple; D005260:Female; D006801:Humans; D008297:Male; D009268:Nalidixic Acid / Q000494:pharmacology; D015242:Ofloxacin / Q000009:adverse effects / Q000627:therapeutic use*; D017063:Outcome Assessment, Health Care; D010865:Pilot Projects; D014435:Typhoid Fever / Q000188:drug therapy*
D000900:Anti-Bacterial Agents; D000890:Anti-Infective Agents; D009268:Nalidixic Acid; D017963:Azithromycin; D015242:Ofloxacin