Synergy with double and triple antibiotic combinations compared

Abstract

Combinations of two sets of antibiotics (gentamicin-carbenicillin-rifampicin and trimethoprim/sulphamethoxazole-carbenicillin-rifampicin) were tested against isolates of Pseudomonas maltophilia. An abbreviated checker-board method permitted tests with combinations of all three antibiotics and of each of the possible three pairs in each set. Triple combinations were usually synergistic, whereas 25% of combinations of pairs were antagonistic or additive. The modal degree of synergy was greater with combinations of three antibiotics than with combinations of any two. For any isolate, greater synergy was generally obtained with a triple than with a double combination, and the mean degree of synergy was always greater with triple than with double combinations. It was advantageous to add to double combinations even an antibiotic to which the organism was resistant. Organisms multiply resistant to three antibiotics were also resistant to 25% of combinations of pairs, but never resistant to combinations of all three. Synergy was more likely to be present at all antibiotic ratios with triple than with double combinations. Since ratios at the site of action may differ greatly from that of the administered combination, there would be substantial clinical benefit in identifying sets of antibiotics of which combinations at all ratios showed synergy. The search for these may entail exploring multicomponent combinations and, with conventional methods, this raises a considerable logistic problem. A strategy is therefore proposed, designed to find antibiotic sets showing synergy at all ratios.

Rutin-enhanced Antibacterial Activities of Flavonoids againstBacillus cereusandSalmonella enteritidis

“…[11][12][13][14] The advantage of such a synergistic eŠect is not only stronger activity, but also a reduction in the quantity of the agent and fewer consequent side eŠects. 15,16) It was found in the present study that the antibacterial activity was reinforced by ‰avonoids when using S. enteritidis and B. cereus as test bacteria. Natural ‰avonoid preparations are mixtures, and their activity is greater than that of pure ‰avonoids.…”

“…20) Fractional inhibitory concentration (FIC). It was investigated by evaluating FIC 12,16) whether the increase in antibacterial activity observed with a mixture of two ‰avonoids was synergistic or additive. FIC is expressed by the following formula: FIC＝A W Ma+B W Mb, where A and B are the respective amounts of compounds A and B at the MIC for the mixture, and Ma and Mb are the respective MIC values of compounds A and B.…”

Accelerated evolution of resistance in multidrug environments

“…In addition, we used the fact that for any drug pair, including strongly synergistic or antagonistic ones, the strength of interactions varies for different drug ratios and dosages (26). Therefore, for all drug pairs, for each combination of concentrations of two drugs, we measured the degree of synergy (S, defined in Materials and Methods and in Fig.…”

High-Level Gentamicin-Resistant Enterococci: In vitro Activity of Double and Triple Combinations of Antimicrobial Drugs

“…Detailsof thetesting method were taken from studies of Yu et al [17] and Berenbaum et al [18]. Double and triple combinations were contempo raneously evaluated against all strains as indicated: meropenem-gentamicin, teicoplanin-gentamicin.…”