Interactions in vitro between agents used to treat melioidosis

Combinations of antimicrobial agents are usually recommended for the treatment of melioidosis. In Thailand, the conventional treatment regimen for Pseudomonas pseudomallei infections is a combination of chloramphenicol, doxycycline and cotrimoxazole. We have consistently observed antagonism between these agents during routine disc susceptibility testing. Interactions between these antimicrobials were studied further by a chequerboard microdilution method, using five clinical isolates of P. pseudomallei. Both trimethoprim and sulphamethoxazole antagonised the bacteriostatic activity of chloramphenicol and doxycycline. The combination of trimethoprim and sulphamethoxazole was synergistic, but not bactericidal. Bacteriostatic drugs antagonised the bactericidal activity of ceftazidime, which is undergoing clinical trials in severe melioidosis. These findings may be of therapeutic relevance.