This study highlights clinical factors associated with an increased likelihood of relapse and provides evidence for optimal oral antimicrobial therapy.

Human melioidosis is associated with a high rate of recurrent disease, despite adequate antimicrobial treatment. Here, we define the rate of relapse versus the rate of reinfection in 116 patients with 123 episodes of recurrent melioidosis who were treated at Sappasithiprasong Hospital in Northeast Thailand between 1986 and 2005. Pulsed-field gel electrophoresis was performed on all isolates; isolates from primary and recurrent disease for a given patient different by one or more bands were examined by a sequence-based approach based on multilocus sequence typing. Overall, 92 episodes (75%) of recurrent disease were caused by the same strain (relapse) and 31 episodes (25%) were due to infection with a new strain (reinfection). The interval to recurrence differed between patients with relapse and reinfection; those with relapses had a median time to relapse of 228 days (range, 15 to 3,757 days; interquartile range [IQR], 99.5 to 608 days), while those with reinfection had a median time to reinfection of 823 days (range, 17 to 2,931 days; IQR, 453 to 1,211 days) (P ‫؍‬ 0.0001). A total of 64 episodes (52%) occurred within 12 months of the primary infection. Relapse was responsible for 57 of 64 (89%) episodes of recurrent infection within the first year after primary disease, whereas relapse was responsible for 35 of 59 (59%) episodes after 1 year (P < 0.0001). Our data indicate that in this setting of endemicity, reinfection is responsible for one-quarter of recurrent cases. This finding has important implications for the clinical management of melioidosis patients and for antibiotic treatment studies that use recurrent disease as a marker for treatment failure.Melioidosis is a severe infection caused by the gram-negative bacillus Burkholderia pseudomallei, an environmental saprophyte present in Southeast Asia and northern Australia (17). A major feature of human disease is that bacterial eradication is difficult to achieve. The clinical response to intravenous antibiotics is slow, with a median fever clearance time in our patient population of 8.5 days. Although prolonged courses of antibiotic treatment (at least 10 days of intravenous antibiotics, followed by 12 to 20 weeks of oral antibiotics) are recommended, recurrent disease is common (at a rate of Ն6% in the first year) (2, 5). A prolonged period of dormancy of up to 62 years may also occur between a presumed exposure to B. pseudomallei and clinical manifestations of infection (9).Bacterial mechanisms and host susceptibility for recurrent melioidosis are poorly understood. However, the ability of B. pseudomallei to survive in the human host supports the idea that recurrence is more likely to be associated with a relapse caused by bacteria persisting within a sequestered focus than to reinfection with a different strain. This is consistent with previous small studies in which isolates from the first and second episodes of infection in a given patient usually had the same genotype (5,6,14). Here, we report the results of a large genotyping study of isolates fr...

Disc diffusion testing of B. pseudomallei may be useful as a limited screening tool in resource poor settings. Isolates assigned as 'susceptible' or 'intermediate' by disc diffusion may be viewed as 'susceptible'; those assigned as 'resistant' require further evaluation by MIC methodology.

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.Melioidosis, the infection caused by Burkholderia pseudomallei, is endemic to southeast Asia and northern Australia. Large numbers of cases are seen in northeast Thailand, where it constitutes almost 20% of community-acquired bacteremia (2). An important feature of disease is that recurrence is common after completion of antibiotic treatment and apparent cure, occurring in 3 to 25% of patients. Molecular typing indicates that most cases of recurrence are due to recrudescence of the original infecting strain (relapse) (3,8). Prolonged therapy has been demonstrated to reduce relapse. Current treatment recommendations include administration of intravenous antibiotics (ceftazidime or a carbapenem) for at least 10 days, followed by oral antibiotics for at least 12 weeks.Our current oral regimen is a four-drug combination of trimethoprim-sulfamethoxazole (TMP-SMX), doxycycline, and chloramphenicol. This regimen is associated with high rates of adverse events, including gastrointestinal intolerance, anemia, and allergic reactions. In other centers, the use of a three-drug regimen or even TMP-SMX alone has been associated with low relapse rates (6, 7). Higher relapse rates have been found during clinical trials of amoxicillin-clavulanate with supplemental amoxicillin, doxycycline monotherapy, and a combination of azithromycin and ciprofloxacin (5, 6, 11). The aim of this study was to examine the efficacy and side effects associated with the four-drug (TMP-SMX, doxycycline, and chl...