The pneumococcus and the mouse-protection test: correlation of in vitro and in vivo activity for beta-lactam antibiotics, vancomycin, erythromycin and gentamicin.

The mouse-protection test with intraperitoneal inoculation of Streptococcus pneumoniae type 3 was employed to compare the effect in vivo and to correlate with activity in vitro of ampicillin, piperacillin, methicillin, cefuroxime, erythromycin, vancomycin and gentamicin. The MICs for these drugs were lowest for the beta-lactam antibiotics, highest for vancomycin and gentamicin. Relative to the MIC, gentamicin and vancomycin showed the highest bactericidal rates against the pneumococcus. Vancomycin was the most effective in vivo as measured by the 50% effective dose (ED50) after single doses 1 h post-inoculation. Serum vancomycin concentrations measured after doses equal to the ED50 were below the minimal concentration measurable by our bioassay (i.e. less than 3.7 micrograms/ml). For the other drugs, peak concentrations in serum were higher than those produced even by high doses in man. Among pharmacokinetic parameters studied at dosages equal to the ED50s, the period during which the serum concentration exceeded the MIC (delta T(MIC] was the factor which varied the least for the beta-lactam antibiotics (range, 2-5 h). For gentamicin and probably also for vancomycin the delta T(MIC) was below 20 min, while it was considerably longer (i.e. 19 h) for erythromycin, although the bactericidal activity of this drug in vitro was comparable to that of the beta-lactam antibiotics.