Two strains of Staphylococcus aureus expressing borderline or low-level methicillin resistance by one or more in vitro test methods were examined for resistance in vivo and for biochemical and
genetic markers of methicillin resistance. In vivo,
nafcillin was equally effective against experimental aortic valve
endocarditis in rabbits, regardless of whether they were infected by a fully susceptible or a low-level-resistant strain. Resistance did not emerge during
therapy. For the more resistant of the two low-level-resistant strains,
methicillin was as effective as
nafcillin.
Nafcillin was ineffective against
endocarditis caused by a truly methicillin-resistant strain, and resistance emerged on
therapy. The low-level-resistant strains did not produce the low-affinity
penicillin-binding protein 2a that is associated with methicillin resistance and did not contain
DNA that hybridized with probes that recognized the methicillin resistance determinant. Low-level resistance in S. aureus is a phenomenon that is biochemically and genetically distinct from true methicillin resistance. These strains actually are susceptible to
beta-lactam antibiotics. The clinical problem posed by these strains is not a therapeutic one but, instead, one of how to differentiate them from those that are truly methicillin resistant.