In vitro activities of antimicrobial combination against Pseudomonas pseudomallei.

ABSTRACT

P pseudomallei infection was treated empirically with an antimicrobial combination without hard evidence of a more favorable outcome over single drug regimens. The so-called "conventional' agents, namely kanamycin (K), chloramphenicol (C), doxycycline (D) and sulfamethoxazole/trimethoprim (SMZ/TMP) are often combined. We determined the effects of the combination of these agents by standard time-kill curve. Six combinations were tested, i.e. K and C, K and D, K and SMZ/TMP, C and D, C and SMZ/TMP, and lastly, D and SMZ/TMP. Three recent clinical isolates of P. pseudomallei were used. The antimicrobial concentration in the combination selected was one-fourth of the minimal inhibiting concentration (MIC). Colony counts were performed at times 0, 2, 4, 6 and 24 hours. The results were interpreted using standard definition, as synergistic, additive and antagonistic effects. It was found that at time 0 to 6 hours, all of the combinations only acted additively. At 24 hours, however, there were 3 effects observed. These were (1) synergistic effects for K and D, and C and D; (2) additive effect for K and C, K and SMZ/TMP, and D and SMZ/TMP; and (3) antagonistic effect for C and SMZ/TMP. None of the combinations showed rapid killing rates. The results, although subjected to precautious extrapolation of in vitro to in vivo situations, suggested that the combined regimens of "conventional' drugs often acted additively, and none of these combinations offered fast killing.