- FTIR spectroscopy has been used by chemists as a powerful tool to characterize inorganic and organic compounds. In this study we examined the potential of FTIR microspectroscopy for early evaluation of the efficiency of anti-bacterial therapy. For this purpose, the effect of caffeic acid phenethyl ester ( CAPE ) and ampicillin on the development of bacterial infection in cell culture was examined. CAPE is one of the most active components of propolis which is a natural honeybee product with a potent anti-bacterial activity. Our results show early (2 h post-treatment), unique and significant spectral indicators for successful treatment with CAPE although some of these biomarkers showed different trends in Gram (−) compared with Gram (+) bacteria. For instance, the intensity of bands at 682 and 1316 cm −1 decreases in all examined Gram (−) bacterial strains while significantly increases in all examined Gram (+) bacterial strains. On the other hand, both Gram (+) and Gram (−) bacteria treated with ampicillin did not show any spectral differences compared with the control untreated bacteria. It seems that FTIR spectroscopy can be used as an effective tool for an early evaluation of the efficiency of the anti-bacterial effect of CAPE and probably other used drugs.