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In vitro activities of antimicrobial combination against Pseudomonas pseudomallei
N Aswapokee1, S Pruksachatvuthi, W Susaengrat
1Department of Medicine, Faculty of Medicine, Siriraj Hospital, Mahidol University, Bangkok, Thailand.
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.
Insights
Combinations of conventional antibiotics for P. pseudomallei infections showed additive effects, not synergistic ones. These drug combinations did not demonstrate rapid killing rates in vitro.
Area of Science:
- Microbiology
- Infectious Diseases
- Pharmacology
Background:
- Empirical antimicrobial combinations are used for P. pseudomallei infections without strong evidence of superior outcomes.
- Conventional agents like kanamycin, chloramphenicol, doxycycline, and sulfamethoxazole/trimethoprim are frequently combined.
Purpose of the Study:
- To determine the in vitro effects of specific combinations of conventional antimicrobial agents against P. pseudomallei.
- To evaluate if common drug combinations offer synergistic or additive benefits over single agents.
Main Methods:
- Standard time-kill curves were employed using three clinical isolates of P. pseudomallei.
- Six combinations (K+C, K+D, K+SMZ/TMP, C+D, C+SMZ/TMP, D+SMZ/TMP) were tested at 1/4 MIC.
- Colony counts were assessed at 0, 2, 4, 6, and 24 hours.
Main Results:
- All tested combinations exhibited only additive effects between 0 and 6 hours.
- At 24 hours, synergistic effects were observed for kanamycin/doxycycline and chloramphenicol/doxycycline.
- Additive effects were seen for kanamycin/chloramphenicol, kanamycin/SMZ/TMP, and doxycycline/SMZ/TMP.
- Chloramphenicol/SMZ/TMP showed antagonistic effects at 24 hours.
- None of the combinations demonstrated rapid killing rates.
Conclusions:
- In vitro, conventional antibiotic combinations for P. pseudomallei often act additively rather than synergistically.
- The tested combinations do not provide a significant advantage in terms of rapid bacterial killing.
- Further in vivo studies are needed to cautiously extrapolate these in vitro findings.