Experimental group B streptococcal endocarditis treated with penicillin G versus ceftizoxime. In vitro-in vivo disparity.
Aortic valve endocarditis due to a penicillin G (PNC) and ceftizoxime (CZ)-sensitive group B streptococcus (GBS) was induced in 72 rabbits. Animals received either procaine PNC (300 mg/kg per day) or CZ (150 mg/kg/day) for 3, 6, or 9 days. PNC rapidly sterilized blood cultures (less than or equal to 3 days) and significantly reduced vegetation GBS titers versus controls at all three sacrifice times (p less than 0.0005). In contrast, CZ exerted a slow in vivo bactericidal effect with vegetation titers not significantly different from controls until day 9 of therapy. By day 9 of therapy, 65/89 (73%) of vegetations were sterilized by PNC versus only 24/94 (26%) sterilized by CZ (p less than 0.0005). This marked in vitro-in vivo disparity in CZ-treated animals occurred despite 100% of individual serum bactericidal titers greater than or equal to 1:32 and 100% of individual CZ serum levels greater than or equal to 100 times the GBS MBC. The suboptimal CZ in vivo effect was not related to: (1) development of CZ resistance on therapy; (2) CZ inactivation, or (3) inoculum-growth phase effect.
D000818:Animals; D002439:Cefotaxime / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000627:therapeutic use; D015296:Ceftizoxime; D004697:Endocarditis, Bacterial / Q000188:drug therapy*; D005260:Female; D008826:Microbial Sensitivity Tests; D010400:Penicillin G / Q000494:pharmacology / Q000627:therapeutic use*; D011817:Rabbits; D013290:Streptococcal Infections / Q000188:drug therapy*; D013292:Streptococcus agalactiae / Q000187:drug effects; D013997:Time Factors
D015296:Ceftizoxime; D002439:Cefotaxime; D010400:Penicillin G