IMPORTANCE OF GENOTYPIC AND PHENOTYPIC TOLERANCE IN THE TREATMENT OF EXPERIMENTAL ENDOCARDITIS DUE TO STREPTOCOCCUS-GORDONII

Genotypic and phenotypic tolerance was studied in penicillin treatment of experimental endocarditis due to nontolerant and tolerant Streptoc occus gordonii and to their backcross transformants. The organisms wer e matched for in vitro and in vivo growth rates. Rats with aortic endo carditis 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 treat ment failed against both bacteria. However, a significant difference b etween the 2 organisms was restored when treatment was extended to 5 d ays. Thus, genotypic tolerance conferred a survival advantage in both fast- and slow-growing bacteria, demonstrating that the in vitro-defin ed tolerant phenotype also carried the risk of treatment failure in vi vo.