Scientific Publications - Work Done by Microbiology Reader Bioscreen C

N. Geisler, R. Gattringer, W. Graninger, A. Georgopoulos,
Linezolid in combination with vancomycin and teicoplanin against MRSA by spectrophotometric optical density measurements, Austrian Health Communication, Antibiotika Monitor - 3/4/2003, 10th Scientific Meeting of European Society of Chemotherapy, Poster Session, Poster P 80

ABSTRACT

Objective: The Checkerboard method to assess antimicrobial combinations is based on linear dose-response curves and therefore on the FIC (fractional inhibitory concentration) of the tested antimicrobial agents. Using a spectrophotometric method for synergy experiments is a more appropriate way, because it considers not only non-linear dose response curves, but also shows a more kinetic view of the tested antimicrobial combination.

Methods: In these studies we used the BIOSCREEN C Analyzer to measure the effects of antimicrobial combinations on the growth rate constant of 5 strains of MRSA. Growth rate constants were calculated from plots of the logarithm of the optical density (OD) versus time. The growth rate constant is defined by OD(t) = OD(0)egt. The effects of antimicrobial combinations were assessed using increasing concentrations of one drug plus a fixed concentration of the other drug which leads to a 50% reduction in the value of g compared with the control value of g (in the absence of antimicrobial agents). The results were plotted in diagrams by using a logarithmic scale of drug concentration on the x-axis and the percent reduction of growth rate constant on the y-axis. We tested Linezolid in combination with Teicoplanin and Vancomycin, once increasing concentrations of Linezolid combined with a fixed concentration of either Teicoplanin or Vancomycin and then the converse experiment, with varied concentrations of Teicoplanin/Vancomycin and a fixed concentration of Linezolid.

Results: Increasing concentrations of Teicoplanin and an intermediate concentration of Linezolid showed synergy, but Linezolid combined with the IC50 of Teicoplanin produced an autonomous or slight additive response. Vancomycin produced an antagonistic response when combined with Linezolid. The results were better with the fixed concentration of Vancomycin, but showed a large variability.

Conclusion: The combination of Linezolid with Teicoplanin and its once a day or even three times a week administration might be an interesting alternative treatment of chronic osteomyelitis or endocarditis. Another advantage would be the possibility of outpatient therapy to save costs and prevent the spread of resistant strains throughout the hospital during a long stay.

(Abstract online)

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Last modified: May 25, 2005