Role of Tolerance in Cloxacillin Treatment of Experimental Staphylococcus aureus Endocarditis

The roleofStaphylococcus aureus tolerance wasinvestigated in endocarditis in rats. Theeffica-ciesofcloxacillin, gentamicin,and a combination ofthe twowere comparedforanimalsinfected with a tolerant strain, its kill-sensitive variant, or a nonisogenic nontolerantstrain ofS. aureus. Cloxacillin wassignificantly lesseffective fortreatingthe tolerantthan forthe nontolerantstrains. The addition of gentamicin to cloxacillin reduced bacterialnumbersin endocardialvegetations forthe tolerantstrain comparable to the reduction bycloxacillin aloneforthe nontolerant strains, but had no additional effect for the nontolerantstrains. Isolatesfrom animals infected with the tolerantor nontolerant strainsduringanabiotictreatmentremained tolerantor nontolerant. These results show that the in vitro phenomenon of tolerance is relevant in vivo. Tolerance was first described by Tomasz et al. [1] in a mu-tant strain of Streptococcus pneumoniae in which growth was inhibited but not killed by penicillin in the usual bactericidal concentration. The authors related this phenomenon to defects in the autolytic system of the bacteria [1]. Since then, toler-ance has been described in several bacterial species includ