Background: We investigated the in vitro activities of nisin alone or in combination with vancomycin and ciprofloxacin against methicillin-resistant (MRSA) and -susceptible Staphylococcus aureus (MSSA) strains. Methods: The minimum inhibitory concentrations were determined by microbroth dilution technique. Antibiotic combinations were assessed using the checkerboard technique. The time-kill curve method was used for determining the bactericidal activity of nisin alone and in combination. Results: For both MSSA and MRSA strains, the minimum inhibitory concentrations of nisin ranged between 4 and 16 mg/l. With a fractional inhibitory concentration of ≧0.5 as borderline, synergistic interactions were seen in three of five isolates with nisin-ciprofloxacin compared to two of five isolates with nisin-vancomycin combinations against both MSSA and MRSA. No antagonism was observed. The results of time-kill curve analysis demonstrated concentration-dependent rapid bactericidal activity of nisin and synergism almost in all strains when nisin was used in combination with ciprofloxacin, and early synergistic interactions in some of the strains when it was used in combination with vancomycin. Conclusion: Nisin seems to be a good candidate for further investigations in the treatment of Gram-positive bacteria, alone or in combination with antibiotics.
The In vitro activities of two antimicrobial cationic peptides, melittin and nisin alone and in combination with frequently used antibiotics (daptomycin, vancomycin, linezolid, ampicillin, and erythromycin), were assessed against clinical isolates of methicillin-susceptible Staphylococcus aureus, methicillin-resistant S. aureus and Enterococcus faecalis. Using the broth microdilution method, minimum inhibitory concentration (MIC) ranges of melittin and nisin against all strains were 2-8 μg/ml and 2-32 μg/ml respectively. In combination studies performed with the microdilution checkerboard method using a fractional inhibitory concentration index of ≤ 0.5 as borderline, synergistic interactions occurred more frequently with nisin-ampicillin combination against MSSA and nisin-daptomycin combination against E. faecalis strains. The results of the time-killing curve analysis demonstrated that the concentration dependent rapid bactericidal activity of nisin, and that synergism or early synergism was detected in most strains when nisin or melittin was used in combination with antibiotics even at concentrations of 0.5 × MIC.
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