Cooperative Behavior of Fluoroquinolone Combinations against <i>Escherichia coli</i> and <i>Staphylococcus aureus</i>

Abstract

The effects of different combinations of ciprofloxacin (CIP) and norfloxacin (NOR) against Escherichia coli and Staphylococcus aureus were studied using checkerboard, fractional inhibitory concentration (FIC) and time-kill analysis methods. Results obtained by the checkerboard method showed that the more effectives combinations against Escherichia coli were 0.0009 µg/mL CIP 0.0312 µg/mL NOR and 0.0037 µg/mL CIP 0.0075 µg/mL NOR with a FIC index of 0.62. For Staphylococcus aureus, the combination of 0.0625 µg/mL CIP 0.2500 µg/mL NOR showed a synergistic effect, with a FIC index of 0.50. The results of the time-kill method demonstrated either indifference or additivity of the combinations 0.0009 µg/mL CIP 0.0312 µg/mL NOR, 0.0018 µg/mL CIP 0.0312 µg/mL NOR, 0.0037 µg/mL CIP 0.0075 µg/mL NOR and 0.0037 µg/mL CIP 0.0156 µg/mL NOR at 24 h against E. coli. The combination 0.0037 µg/mL CIP 0.0312 µg/mL NOR showed synergistic activity. All the analyzed combinations evidenced bactericidal effects at 4 h. The combinations 0.0625 µg/mL CIP 0.2500 µg/mL NOR and 0.0625 µg/mL CIP 0.0625 µg/mL NOR showed indifference or additivity against S. aureus. None of them generated bactericidal effect at 4 h. Moreover, this last equimolecular combination (equivalent to 1/4 minimum inhibitory concentration (MIC) CIP 1/16 MIC NOR) generated higher reduction of nitro blue tetrazolium than drugs alone. By another way, combinations not equimolecular of CIP and NOR assayed, generated less levels of reactive oxygen species (ROS) than the components alone.

Supramolecular complex of norfloxacin and sulfamethoxazole: Synthesis, characterization, and evaluation of the antibacterial activity

“…Results of the checkerboard method showed synergistic effect, with a FIC index of 0.40. 3 These results are very promising so we continue developing new biopharmaceutical assays.…”

Preliminary Investigation of the Antibacterial Activity of Antitumor Drug 3-Amino-1,2,4-Benzotriazine-1,4-Dioxide (Tirapazamine) and its Derivatives

“…The combinations of TPZs with conventional antibiotics were conducted at varying concentrations of TPZs (by serial two-fold dilution) in the presence of several fixed sub-inhibitory concentrations of antibiotics.The inhibitory activities were assessed by the same method as described above. The obtained results were expressed in terms of the fractional inhibitory concentration index (FICI): FICI = FIC A + FIC B , where FIC A = (MIC of compound A in combination with B)/(MIC of A used alone) and FIC B = (MIC of compound B in combination with A)/(MIC of B used alone), and interpreted as synergism (FICI ≤ 0.5), partial synergism (0.5 ≤ FICI ≤ 0.75), additive (0.75 ≤ FICI ≤1) and indifferent (non-interactive) effect (1 < FICI ≤ 2) ( [31][32][33], and refs. therein).…”

“…Table 1 provides the inhibitory potencies of TPZ (1) and a set of its 3-amino substituted derivatives (compounds 2-10) against a panel of E. coli, S. enterica and S. aureus strains in terms of minimum inhibitory concentrations (MICs), which varied in the range of 1.1 µM (0.25 µg/mL)-412.6 µM (128.0 µg/mL). Note that the activities of the antibacterial compounds are considered significant when the MIC ≤ 10 µg/mL, moderate when the MIC varies in the range of 10-100 µg/mL, and insignificant when the MIC > 100 µg/mL [33,34]. TPZ (1) showed significant activity towards Gram-negative E. coli and S. enterica strains (with MICs of 44.9 µM (8.0 µg/mL)), which was twice as high as that as defined against the Gram-positive S. aureus strain (MIC = 89.8 µM (16.0 µg/mL)).…”

“…The use of combination therapy is commonly justified by the following reasons: to extend the spectrum of drug action (important for heavy infections where early treatment is critical); to prevent or delay the emergence of drug resistance and achieve enhanced (partial or complete synergistic) or at least additive effects, which should allow for the use of a lower dosage of single agents (thereby reducing the risk of their toxic and other side effects) ( [14,[31][32][33]48], and refs. therein).…”

Recent updates of fluoroquinolones as antibacterial agents

“…It is very important to indicate the pharmacophore structure that is essential for retaining antibacterial activity (Figure ). Position 1 is part of the enzyme‐DNA binding complex and has a hydrophobic interaction with the major grove of DNA . A cyclopropyl moiety is now considered the most potent modification here, followed by 2,4‐difluorophenyl moiety which is favored against anaerobic bacteria .…”