Interventions for treating melioidosis.
BACKGROUND
Melioidosis is an infectious disease that occurs in tropical regions, particularly in Thailand. It is caused by the bacterium Burkholderia pseudomallei and is a serious condition which can be fatal. Beta-lactam antibiotics have dramatically reduced the risk of death, but mortality still remains high.


OBJECTIVE
To summarize reliable evidence on the effects of treatment regimens on death and relapse.


METHODS
We searched the Cochrane Infectious Diseases Group trials register (July 2002), the Cochrane Controlled Trials Register (Issue 3, 2002), MEDLINE (1966 to July 2002), EMBASE (1980 to May 2002), BIOSIS (up to July 2002), Health Star (up to July 2002), and reference lists of articles. We also contacted pharmaceutical companies and researchers in the field.


METHODS
Randomized and quasi-randomized controlled trials comparing antibiotic regimens in people with melioidosis.


METHODS
We independently assessed the eligibility of studies and the methodological quality of the trials. Adverse effects information was collected from the trials.


RESULTS
Nine trials, all from Thailand, involving a total of 872 participants were included. For intravenous therapy in the acute phase, we identified six trials with a total of 619 participants. Chloramphenicol, doxycycline, and co-trimoxazole (trimethoprim-sulphamethoxazole) combination regimens were associated with a mortality of 50% or more (two studies). Participants randomized to regimens including ceftazidime were more likely to survive (relative risk [RR] 0.46; 95% confidence interval [CI] 0.30 to 0.71). When ceftazidime-containing regimens were compared with beta-lactam or alternative beta-lactamase inhibitor regimens such as co-amoxiclav (amoxycillin-clavulanic acid) and cefoperazone-sulbactam, or with imipenem, mortality rates were similar (RR 1.06; 95% CI 0.81 to 1.39). For oral therapy in the maintenance phase, we found three trials of 253 participants. They compared the conventional regimen (chloramphenicol, doxycycline, and trimethoprim-sulphamethoxazole) with other regimens (amoxycillin-clavulanic acid, ciprofloxacin-azithromycin, and doxycycline alone). There were fewer deaths with the conventional regimen, but no statistically significant differences demonstrated.


CONCLUSIONS
Regimens for the acute phase of illness should contain ceftazidime or imipenem. It is not yet clear if combinations of treatments in the early phase reduce relapse. For oral therapy after the acute phase of treatment, trials suggest that conventional four drug regimens can be used for treatment.
Samuel
M
M
Clinical Trials & Epidemiology Research Unit, Ministry of Health, 226 Outram road, Block A #02-02, Singapore, South East Asia, Singapore. miny@cteru.gov.sg
Ti
T Y
TY
D000284:Administration, Oral; D002442:Ceftazidime / Q000008:administration & dosage; D004359:Drug Therapy, Combination / Q000627:therapeutic use*; D006801:Humans; D015378:Imipenem / Q000008:administration & dosage; D007275:Injections, Intravenous; D008554:Melioidosis / Q000188:drug therapy* / Q000401:mortality; D016032:Randomized Controlled Trials as Topic
D015378:Imipenem; D002442:Ceftazidime