A prospective, open-label, randomized trial of doxycycline versus azithromycin for the treatment of uncomplicated murine typhus

Murine typhus, or infection with Rickettsia typhi, is a global but neglected disease without randomized clinical trials to guide antibiotic therapy.; A prospective, open, randomized trial was conducted in nonpregnant, consenting inpatient adults with rapid diagnostic test evidence of uncomplicated murine typhus at 2 hospitals in Vientiane, Laos. Patients were randomized to 7 days (D7) or 3 days (D3) of oral doxycycline or 3 days of oral azithromycin (A3). Primary outcome measures were fever clearance time and frequencies of treatment failure and relapse.; Between 2004 and 2009, the study enrolled 216 patients (72 per arm); 158 (73.2%) had serology/polymerase chain reaction (PCR)-confirmed murine typhus, and 52 (24.1%) were R. typhi PCR positive. The risk of treatment failure was greater for regimen A3 (22.5%; 16 of 71 patients) than for D3 (4.2%; 3 of 71) or D7 (1.4%; 1 of 71) (P < .001). Among R. typhi PCR-positive patients, the area under the time-temperature curve and the fever clearance time were significantly higher for A3 than for D3 (1.8- and 1.9-fold higher, respectively; P = .005) and D7 (1.5- and 1.6-fold higher; P = .02). No patients returned with PCR-confirmed R. typhi relapse.; In Lao adults, azithromycin is inferior to doxycycline as oral therapy for uncomplicated murine typhus. For doxycycline, 3- and 7-day regimens have similar efficacy. Azithromycin use in murine typhus should be reconsidered. Investigation of genomic and phenotypic markers of R. typhi azithromycin resistance is needed.; ISRCTN47812566

Rickettsial Infections and Fever, Vientiane, Laos

Rickettsia spp. are an underrecognized cause of undifferentiated febrile illness

A randomized comparison of oral chloramphenicol versus ofloxacin in the treatment of uncomplicated typhoid fever in Laos

We conducted a randomized open trial of oral chloramphenicol (50mg/kg/day in four divided doses for 14 days) versus ofloxacin (15 mg/kg/day in two divided doses for 3 days) in 50 adults with culture-confirmed uncomplicated typhoid fever in Vientiane, Laos. Patients had been ill for a median (range) of 8 (2-30) days. All Salmonella enterica serotype typhi isolates were nalidixic acid-sensitive, four (8%) were chloramphenicol-resistant and three (6%) were multidrug-resistant. Median (range) fever clearance times were 90 (24-224) hours in the chloramphenicol group and 54 (6-93) hours in the ofloxacin group (P&lt;0.001). One patient in the chloramphenicol group developed an ileal perforation. Three days ofloxacin was more effective than 14 days chloramphenicol for the in-patient treatment of typhoid fever, irrespective of antibiotic susceptibility, and was of similar cost.</p