The mechanism of staphylococci resistance to methicillin: a critical analysis of dominant opinions

Resistance to methicillin has been reported to be constantly associated with production of a novel penicillin-binding protein (PBP), indicated as PBP2a. This PBP is always present in strains that are homogeneously resistant to the drug, but is also constantly present in the strains heterogeneously resistant, where by far the vast majority of the cells are indeed sensitive to the antibiotic. This apparent lack of correlation between the presence of PBP2a and methicillin resistance has led to the idea, shared by most scientists, that the presence of PBP2a alone cannot explain resistance of staphylococci to methicillin. This confusion has implications also for clinical microbiology. In fact in in-vitro assays, not rarely, strains that are resistant to methicillin appear sensitive to other beta-lactams. However, clinical experience has demonstrated that when infections caused by methicillin-resistant staphylococci, which, in in vitro assays, become sensitive to other beta-lactams, are treated with the latter antibiotics, the incidence of failures is higher than that observed when the same antibiotics are used to treat infections caused by staphylococci sensitive to methicillin. Also in consideration of the fact that the mechanism of resistance to methicillin is not yet understood, many authors recommend to consider methicillin-resistant staphylococci as being in-vivo resistant also to the beta-lactams to which they may become sensitive in in-vitro assays. In the opinion of the authors, the mechanism of staphylococcal resistance to methicillin is reasonably explainable at least in its fundamental aspects. The present dominant opinions concerning methicillin-resistant staphylococci will be critically analyzed on the basis both of data presented in the literature and of data obtained in the authors' laboratory.