In vitro and in vivo activities of cefazolin (CEZ) and cefmetazole (CMZ) against methicillin resistant Staphylococcus aureus (MRSA) were studied.
(1) The MIC of CEZ for 54 of 100 strains of S. aureus isolated in 1985 was 0.39μg/ml and that of CMZ for 59 strains was 1.56μg/ml.
(2) For 11 strains of MRSA, the therapeutic effect (ED₅₀) of CEZ against systemic infections in mice was similar to that of CMZ although the MICs of CEZ were about two times higher than those of CMZ. Correlation of MIC and ED₅₀was:
CEZ; log ED₅₀=0.69log MIC-0.069 (Correlation 0.80)
CMZ; log ED₅₀=0.85log MICA+0.23 (Correlation 0.55)
These results suggest that the in vivo activity against in vitro activity of CEZ was superior to that of CMZ.
(3) The therapeutic effect of CEZ against granuloma pouch infection in rats, pyelonephritis and skin abscess in mice were similar or significantly superior to those of CMZ although the MICs of CEZ were higher than those of CMZ.
(4) The concentrations of CEZ in the serum and kidney of mice and in granuloma pouch exudate of rats were higher and longer lating than those of CMZ.
(5) The in vitro synergistic effect of sub-MICs of CEZ and PMN leukocytes of rabbits was markedly superior to that of CMZ. Bactericidal effect of CEZ in combination with PMN leukocytes appeared at 1/2 to 1/32 the MICs. In contrast, CMZ was bactericidal at 1/2 to 1/8 the MIC. CEZ was more effective than CMZ when given in combination with PMN leukocytes.
As above-mentioned, although the in vitro antibacterial activity of CEZ against MRSA was weaker than that of CMZ, the in vivo therapeutic activity of CEZ against MRSA infections was superior to that of CMZ. This paradoxical phenomenon shows that the good distributions of CEZ in rats and mice and the strong bactericidal activity of CEZ with the aid of phagocytes in the host brought about its excellent therapeutic effect against systemic and local infections with MRSA.

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The in vitro and in vivo combined antibacterial action of penicillins and pyridone carboxylic acids against clinical isolates of Serratia marcescens were studied. The combination of norfloxacin or ofloxacin and piperacillin or mezlocillin exhibited synergistic activity in checkerboard dilution method
The combination of piperacillin and norfloxacin showed markedly synergistic bactericidal activity. This synergism was comformed to the phase-contrast microscopic observation. The synergistic activity of piperacillin and norfloxacin was also observed in protective effect against experimental infection in mice.

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We measured serum and prostate concentrations of cefoperazone (CPZ) following its intravenous administration to 53 patients with benign prostatic hyperplasia.
High concentrations of CPZ were sustained in serum. The drug's biological half-life T_1/2βwas 133 min.
In patients who underwent retropubic prostatectomy, the concentrations of CPZ in the right and left lobes reached maximum values of 33.3 and 30.5 μg/g, respectively, at 8.6 min after administration. In the surgical capsule, the maximum concentration was 34.3 μg/g at 10.3 min. In patients who underwent transurethral resection, the concentration attained a maximum value of 39.8 μg/g at 2.3 min after administration. In all three patient groups, the concentration of CPZ in the prostate declined in parallel with that in serum. According to our findings concerning its bacterial inhibitory capacity and its penetration into prostate, CPZ may be effective against the bacteria that cause prostatitis and/or are detected in urine after operation for benign prostatic hyperplasia.

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