title: Importance of genotypic and phenotypic tolerance in the treatment of experimental endocarditis due to Streptococcus gordonii.
abstract: Genotypic and phenotypic tolerance was studied in penicillin treatment of experimental endocarditis due to nontolerant and tolerant Streptococcus gordonii and to their backcross transformants. The organisms were matched for in vitro and in vivo growth rates. Rats with aortic endocarditis were treated for 3 or 5 days, starting 12, 24, or 48 h after inoculation. When started at 12 h, during fast intravegetation growth, 3 days of treatment cured 80% of the nontolerant parent compared with <30% of the tolerant derivative (P < .005). When started at 24 or 48 h and if intravegetation growth had reached a plateau, 3 days of treatment failed against both bacteria. However, a significant difference between the 2 organisms was restored when treatment was extended to 5 days. Thus, genotypic tolerance conferred a survival advantage in both fast- and slow-growing bacteria, demonstrating that the in vitro-defined tolerant phenotype also carried the risk of treatment failure in vivo.
authors.affiliation: Department of Internal Medicine, Centre Hospitalier Universitaire Vaudois, Lausanne, Switzerland.
authors.forename: J M
authors.initials: JM
authors.lastname: Entenza
authors.forename: I
authors.initials: I
authors.lastname: Caldelari
authors.forename: M P
authors.initials: MP
authors.lastname: Glauser
authors.forename: P
authors.initials: P
authors.lastname: Francioli
authors.forename: P
authors.initials: P
authors.lastname: Moreillon
mesh_terms: D000818:Animals; D000900:Anti-Bacterial Agents / Q000494:pharmacology; D001021:Aortic Valve / Q000382:microbiology; D016470:Bacteremia / Q000382:microbiology; D004352:Drug Resistance, Microbial; D004361:Drug Tolerance; D004697:Endocarditis, Bacterial / Q000188:drug therapy / Q000382:microbiology*; D005260:Female; D005838:Genotype; D008826:Microbial Sensitivity Tests; D009154:Mutation; D010406:Penicillins / Q000097:blood / Q000494:pharmacology* / Q000627:therapeutic use; D010641:Phenotype; D051381:Rats; D017208:Rats, Wistar; D015610:Serum Bactericidal Test; D013154:Spleen / Q000382:microbiology; D013290:Streptococcal Infections / Q000188:drug therapy / Q000382:microbiology*; D013291:Streptococcus / Q000187:drug effects* / Q000235:genetics / Q000254:growth & development; D013298:Streptococcus sanguis / Q000187:drug effects / Q000235:genetics / Q000254:growth & development; D013307:Streptomycin / Q000494:pharmacology; D014169:Transformation, Bacterial; D017211:Treatment Failure
chemical_list: D000900:Anti-Bacterial Agents; D010406:Penicillins; D013307:Streptomycin