Methicillin-resistant Staphylococcus aureus (MRSA) strains are most often found as hospital- and community-acquired infections. The danger of MRSA infections results from not only the emergence of multidrug resistance but also the occurrence of bacteria that form strong biofilms. We investigated the in vitro activities of antibiotics (daptomycin, linezolid, teichoplanine, azithromycin, and ciprofloxacin) and antimicrobial cationic peptides {AMPs; indolicidin, CAMA [cecropin (1-7)–melittin A (2-9) amide], and nisin} alone or in combination against MRSA ATCC 43300 biofilms. The MICs and minimum biofilm eradication concentrations (MBECs) were determined by the broth microdilution technique. Antibiotic and AMP combinations were assessed using the checkerboard technique. For MRSA planktonic cells, MICs of antibiotics and AMPs ranged between 0.125 and 512 and 8 and 16 mg/liter, respectively, and the MBEC values were between 512 and 5,120 and 640 mg/liter, respectively. With a fractional inhibitory concentration of ≤0.5 as the borderline, synergistic interactions against MRSA biofilms were frequent with almost all antibiotic-antibiotic and antibiotic-AMP combinations. Against planktonic cells, they generally had an additive effect. No antagonism was observed. All of the antibiotics, AMPs, and their combinations were able to inhibit the attachment of bacteria at 1/10 MIC and biofilm formation at 1× MIC. Biofilm-associated MRSA was not affected by therapeutically achievable concentrations of antimicrobial agents. Use of a combination of antimicrobial agents can provide a synergistic effect, which rapidly enhances antibiofilm activity and may help prevent or delay the emergence of resistance. AMPs seem to be good candidates for further investigations in the treatment of MRSA biofilms, alone or in combination with antibiotics.

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.

Background: Because of increasing antibiotic resistance, herbal teas are the most popular natural alternatives for the treatment of infectious diseases, and are currently gaining more importance. We examined the antimicrobial activities of 31 herbal teas both alone and in combination with antibiotics or antifungals against some standard and clinical isolates ofPseudomonas aeruginosa,Acinetobacter baumannii,Escherichia coli,Klebsiella pneumoniae,Enterococcus faecalis, methicillin susceptible/resistantStaphylococcus aureusandCandida albicans.Methods: The antimicrobial activities of the teas were determined by using the disk diffusion and microbroth dilution methods, and the combination studies were examined by using the microbroth checkerboard and the time killing curve methods.Results: Rosehip, rosehip bag, pomegranate blossom, thyme, wormwood, mint, echinacea bag, cinnamon, black, and green teas were active against most of the studied microorganisms. In the combination studies, we characterized all the expected effects (synergistic, additive, and antagonistic) between the teas and the antimicrobials. While synergy was observed more frequently between ampicillin, ampicillin-sulbactam, or nystatine, and the various tea combinations, most of the effects between the ciprofloxacin, erythromycin, cefuroxime, or amikacin and various tea combinations, particularly rosehip, rosehip bag, and pomegranate blossom teas, were antagonistic. The results of the time kill curve analyses showed that none of the herbal teas were bactericidal in their usage concentrations; however, in combination with antibiotics they showed some bactericidal effect.Discussion: Some herbal teas, particularly rosehip and pomegranate blossom should be avoided because of their antagonistic interactions with some antibiotics during the course of antibiotic treatment or they should be consumed alone for their antimicrobial activities.