Amoxycillin-clavulanic acid treatment of melioidosis

Abstract
Melioidosis is a serious infection with high acute mortality, and a high rate of relapse despite protracted antimicrobial treatment. The current recommended conventional oral treatment regimen is a 4-drug combination of high-dose chloramphenicol, doxycycline and trimethoprim-sulphamethoxazole given for between 6 weeks and 6 months. We have evaluated prospectively the use of amoxycillin-clavulanic acid, to which Pseudomonas pseudomallei is consistently sensitive in vitro, for the oral maintenance treatment of melioidosis. Amoxycillin-clavulanic acid was used either as sole treatment of localized disease, or as maintenance therapy following either parenteral ceftazidime or the conventional 4-drug regime; 20 patients with localized infections and 26 with septicaemic melioidosis received a median of 7.5 (2-12) weeks treatment. After a mean follow-up period of 6 months (range 1-19), 31 patients (67%) remain free of disease. The drug was well tolerated. Three patients had fatal relapses, one other died suddenly at home, and another died from underlying promyelocytic leukaemia. The remaining 10 relapses were treated successfully. Resistance developed in one case. Amoxycillin-clavulanic acid is a safe alternative to the conventional 4-drug antimicrobial combination for the oral treatment of melioidosis. It may be of particular value in children, pregnant women, and in infections with Ps. pseudomallei resistant to the potentially toxic conventional regimen, but the optimum dose and duration of therapy need to be established.