title: Differential response to benzylpenicillin in vivo of tolerant and non-tolerant variants of Streptococcus sanguis II.
abstract: A variant that was highly tolerant to benzylpenicillin was obtained from a non-tolerant clinical isolate of Streptococcus sanguis II by repeated exposure to penicillin. The rabbit model of endocarditis was used to investigate the efficacy of a high dose regimen of benzylpenicillin (250 mg/kg; peak serum concentration c. 25 mg/l) in the prophylaxis and treatment of endocarditis during challenge or infection with the non-tolerant parent strain or its tolerant variant. The two strains exhibited a similar capacity to initiate infection. A single dose of penicillin administered 0.5 h before bacterial challenge protected six of nine rabbits infected with the non-tolerant parent strain, but none of nine infected with the tolerant variant. Treatment of established infection with penicillin administered twice daily for four days cured eight of 13 (61%) rabbits infected with the non-tolerant parent strain, but only one of 14 (7%) rabbits infected with the tolerant variant. These results support the view that tolerance to penicillin has therapeutic implications.
authors.affiliation: Department of Microbiology, University Hospital, Queen's Medical Centre, Nottingham, UK.
authors.forename: J
authors.initials: J
authors.lastname: Meeson
authors.forename: A A
authors.initials: AA
authors.lastname: McColm
authors.forename: P
authors.initials: P
authors.lastname: Acred
authors.forename: D
authors.initials: D
authors.lastname: Greenwood
mesh_terms: D004361:Drug Tolerance; D004697:Endocarditis, Bacterial / Q000188:drug therapy; D014644:Genetic Variation; D010400:Penicillin G / Q000097:blood / Q000494:pharmacology / Q000627:therapeutic use*; D013290:Streptococcal Infections / Q000188:drug therapy; D013298:Streptococcus sanguis / Q000187:drug effects* / Q000235:genetics
chemical_list: D010400:Penicillin G