Methicillin and glycopeptide resistance in staphylococci: a new threat?

Methicillin resistance in staphylococci is an intrinsic resistance that extends to all P-lactam antibiotics. The biochemical correlate of this resistance is penicillin-binding protein (PBP)-2'. This abnormal protein has a low affinity to P-lactam antimicrobials, and appears to take over the function of normal penicillin-binding proteins. PBP-2' is encoded by the mecA, which is part of the chromosomal DNA sequence mec, a 30- to 40-kb piece of DNA. The origin of this sequence is unknown at present. Production of PBP-2' can be negatively regulated by the product of mecl, a part of the mec sequence in some strains, and also by the repressor Blal, which is encoded by the penicillinase transposon of penicillinase plasmids. The methicillin-resistant phenotype is further controlled by factors essential for methicillin resistance (Fern), encoded by genes which are not part of mec but located elsewhere on the chromosome. The contribution made by these factors to methicillin resistance is still unknown. The frequency of methicillin-resistant Staphylococcus aureus infection among all staphylococcal infections varies geographically, from hospital to hospital, and over time, mainly because there are only a few epidemic clones. Once such a clone is introduced into a hospital, it can spread, causing an outbreak. The patients most at risk are those in tertiary care hospitals, especially the elderly with severe underlying disease. The glycopeptide antibiotics, vancomycin and teicoplanin, are the drugs of choice for the treatment of methicillin-resistant Staphylococcus aureus infections because these organisms are always resistant to other commonly used antibiotics. Resistance to glycopeptides in staphylococci seems to develop by multiple mutational events in chromosomally located genes. At present, only low-level resistance to glycopeptides has been reported to occur very sporadically. For the near future, there seems to be no threat for patients from multiresistant glycopeptide-resistant strains of staphylococci.