pH-dependent penicillin tolerance may protect intraleukocytic Staphylococcus aureus from killing by cloxacillin.

Exposure of Staphylococcus aureus to cloxacillin at neutral pH rendered the bacteria more susceptible to subsequent lysis by lysostaphin. This sensitization effect also occurred at lower pH levels which were nonpermissive for the bactericidal action of cloxacillin, but the effect disappeared at pH 5.0. These findings elucidate previous observations on the protection of intraleukocytic S. aureus from killing by cloxacillin and indicate that low pH in the phagolysosomes may be involved.