The killing effects of cefathiamidine or ampicillin alone and in combination with gentamicin against enterococci

The in-vitro activity of cefathiamidine against Streptococcus faecalis and Str. faecium were studied in comparison with other beta-lactams. All the 56 strains of Str. faecalis tested were inhibited by 2 mg/l of cefathiamidine. MICs of ampicillin were twofold higher than those of cefathiamidine and MICs of cephaloridine and cephazolin were 8-16-fold higher. No significant inoculum effect on MICs of cefathiamidine could be seen. Two isolates of Str. faecium showed resistance to the four antibiotics. The MBCs of cefathiamidine and ampicillin for ten strains of Str. faecalis showed that the ratios of MBC/MIC were greater than 64. The rates of killing of Str. faecalis were reduced at concentrations of cefathiamidine and ampicillin greater than the MIC. The most rapid killing was obtained at 2 mg/l cefathiamidine or 4 mg/l of ampicillin. With the addition of 1 mg/l gentamicin this paradoxical bacteriocidal effect was eliminated. Time killing studies showed 99.9% of the cells were killed within 6 h by a combination of aminoglycoside and beta-lactam. The paradoxical bacteriocidal effect of cefathiamidine and ampicillin was also demonstrated on solid media.