Effect of Rifampin and Oxacillin on the Ultrastructure and Growth of Staphylococcus aureus

The minimal inhibitory concentrations (MICs) of rifampin for 12 strains of Staphylococcus aureus ranged from 0.005 microgram/ml to 0.02 microgram/ml, and the minimal antibiotic concentrations (i.e., those that inhibited growth by 90% in comparison with control values) ranged from one-fifth to one-half the MICs. Rifampin alone produced a 1-log (90%) decrease in the staphylococcal population after incubation for 6.5 hr, and the inhibitory effect after removal of the antibiotic lasted for 5 hr. Regardless of whether rifampin was used simultaneously with, before, or after exposure to oxacillin, the latter drug partially or totally prevented the overgrowth of rifampin-resistant staphylococci. The use of this combination in therapy is therefore justified. Staphylococci exposed to rifampin at concentrations equal to three or 20 times the MIC developed a cell wall that was four times thicker than normal and had a peripheral undulated dense layer. The cross walls were also two to 10 times thicker than normal but had a normal central dense zone. Exposure of staphylococci to oxacillin produced large cells with multiple cross walls that underwent autolysis when the organisms were transferred to drug-free medium. When exposure to oxacillin was preceded by exposure to rifampin, cells did not become enlarged. When the large cells produced by oxacillin were transferred to medium containing rifampin, the cross walls did not lyse.