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ABSTRACT: Some studies have been published about the in vitro activity of zinc acetate (ZA), erythromycin (E) and their combination (ZA/E) against Propionibacterium spp., especially erythromycin resistant strains. The efficacy of topical ZA/E combination has been reported as well, but a comparison to ZA monotherapy is missing. Therefore, the MIC values of ZA, E and the ZA/E combination were determined for 15 erythromycin-resistant and 12 erythromycin-sensitive Propionibacterium strains using the agar dilution method and the checkerboard technique. Furthermore, the antimicrobial efficacy of ZA (1.2%) vs. the ZA/E (1.2%/4%) combination in an alcoholic solution was tested in a 7-day treatment administered to 32 acne patients. The MIC 100 for ZA was 1024 micrograms ZA/ml for both, erythromycin resistant and erythromycin sensitive Propionibacterium strains. The ZA, as well as the ZA/E solution showed efficacy reducing both the Propionibacterium spp., and the Micrococcaceae in the sebaceous gland infundibula of acne patients. There was no significant difference between the two treatments. As the MIC 100 of ZA/E was equal to the MIC 100 of ZA, the decrease of the erythromycin MIC of the ZA/E combination in erythromycin-resistant strains may be partly attributed to the addition of ZA to E. The in vivo antibacterial efficacy on 32 acne patients supports the hypothesis that the antibacterial effect of ZA/E in short-term treatment can be mostly attributed to ZA.