Open-label randomized trial of oral trimethoprim-sulfamethoxazole, doxycycline, and chloramphenicol compared with trimethoprim-sulfamethoxazole and doxycycline for maintenance therapy of melioidosis.
Melioidosis (infection caused by Burkholderia pseudomallei) requires a prolonged course of oral antibiotics following initial intravenous therapy to reduce the risk of relapse after cessation of treatment. The current recommendation is a four-drug regimen (trimethoprim [TMP], sulfamethoxazole [SMX], doxycycline, and chloramphenicol) and a total treatment time of 12 to 20 weeks. Drug side effects are common; the aim of this study was to compare the efficacy and tolerance of the four-drug regimen with a three-drug regimen (TMP-SMX and doxycycline). An open-label, randomized trial was conducted in northeast Thailand. A total of 180 adult Thai patients were enrolled, of which 91 were allocated to the four-drug regimen and 89 to the three-drug regimen. The trial was terminated early due to poor drug tolerance, particularly of the four-drug regimen. The culture-confirmed relapse rates at 1 year were 6.6% and 5.6% for the four- and three-drug regimens, respectively (P = 0.79). The three-drug regimen was better tolerated than the four-drug regimen; 36% of patients receiving four drugs and 19% of patients receiving three drugs required a switch in therapy due to side effects (P = 0.01). The duration of oral therapy was significantly associated with relapse; after adjustment for confounders, patients receiving less than 12 weeks of oral therapy had a 5.7-fold increase of relapse or death. A combination of TMP-SMX and doxycycline is as effective as and better tolerated than the conventional four-drug regimen for the oral treatment phase of melioidosis.
Chaowagul
Wipada
W
Medical Department, Sappasithiprasong Hospital, Ubon Ratchathani, Thailand.
Chierakul
Wirongrong
W
Simpson
Andrew J
AJ
Short
Jennifer M
JM
Stepniewska
Kasia
K
Maharjan
Bina
B
Rajchanuvong
Adul
A
Busarawong
Duangkaew
D
Limmathurotsakul
Direk
D
Cheng
Allen C
AC
Wuthiekanun
Vanaporn
V
Newton
Paul N
PN
White
Nicholas J
NJ
Day
Nicholas P J
NP
Peacock
Sharon J
SJ
D000293:Adolescent; D000328:Adult; D000368:Aged; D000900:Anti-Bacterial Agents / Q000009:adverse effects / Q000627:therapeutic use*; D000890:Anti-Infective Agents / Q000009:adverse effects / Q000627:therapeutic use*; D002701:Chloramphenicol / Q000009:adverse effects / Q000627:therapeutic use*; D004318:Doxycycline / Q000009:adverse effects / Q000627:therapeutic use*; D004359:Drug Therapy, Combination; D004361:Drug Tolerance; D005260:Female; D006801:Humans; D008297:Male; D008554:Melioidosis / Q000188:drug therapy* / Q000401:mortality; D008875:Middle Aged; D012008:Recurrence; D016896:Treatment Outcome; D015662:Trimethoprim, Sulfamethoxazole Drug Combination / Q000009:adverse effects / Q000627:therapeutic use*
D000900:Anti-Bacterial Agents; D000890:Anti-Infective Agents; D002701:Chloramphenicol; D015662:Trimethoprim, Sulfamethoxazole Drug Combination; D004318:Doxycycline