In Vitro Effect of Multiple Antibiotic/Antimicrobial Residues on the Selection for Resistance in Bacteria

Abstract

Abstract A method using a gram-positive and a gram-negative organism was used to investigate the selection for resistant populations after exposure to residue levels of 7 antibiotics and 1 antimicrobial. The organisms were exposed to individual compounds and combinations of 3 compounds for 14 days. The changes in minimum inhibitory concentration (MIC) of a panel of 8 antibiotics and 1 antimicrobial were used as the measure of resistance development/selection. For Staphylococcus aureus ATCC 9144, exposure to residue levels of oxytetracycline, tylosin, penicillin, and virginiamycin resulted in an increased MIC of the compound itself; most individual residues did not result in increased cross-resistance. With combinations of residues, 13 of 45 determinations resulted in significant increases in MIC. Enterobacter cloacae B520, which was much less sensitive to 4 of 9 markers, showed MIC increases only for tylosin and the combination of neomycin-sulfamethazine-oxytetracycline. The results indicate an interaction among residue levels of antibiotics in selection for resistance.