Frequency and clinical significance of co-trimoxazole resistance in clinical isolates of Burkholderia Pseudomallei

Abstract

Co-trimoxazole is commonly used for the treatment of melioidosis. Antibiotic susceptibility testing using the disc diffusion method is commonly used in Thailand, but this leads to an over-estimation of resistance to co-trimoxazole. We have recently introduced the E-test to determine minimum inhibitory concentration (MIC) to this drug in routine clinical practice. The aim of this study was to describe rates of resistance in B. pseudomallei isolates, and to retrospectively examine the effect on outcome of prescribing co-trimoxazole to patients infected with an organism demonstrated to have in vitro resistance. A total of 1,915 isolates from patients with melioidosis presenting to Sappasithiprasong Hospital, Ubon Ratchathani spanning the years 1992-2004 were tested by co-trimoxazole E-test (susceptible ≤2/38 µg/ml, resistant ≥4/76 µg/ml) and disc diffusion (susceptible ≥16 mm, resistant ≤10 mm). By E-testing, 86% of isolates were susceptible and 14% were resistant. This contrasted with disc diffusion testing, in which 70% of isolates were resistant. An analysis was performed to determine the clinical impact of being infected by a co-trimoxazole resistant isolate but being treated with this drug during the oral treatment phase. For this we used data from a recent clinical trial of 180 patients randomized to receive conventional 4-drug therapy or co-trimoxazole plus doxycycline. In a model adjusting for known confounders, patients infected with resistant strains had a shorter time to relapse, but this difference did not reach statistical significance.