Resistance to methicillin in Staphylococcus is related to the expression of the mecA gene, and involves resistance to all beta-lactams, with the exception of the new cephalosporins, ceftobiprole and ceftaroline. Breakpoints for interpretation of this mechanism differ in S. aureus and in coagulase-negative species. For macrolides-lincosamides-streptogramins B, (MLSB) the most frequent mechanism among resistant strains is expression of methylases (erm genes). Topoisomerase changes caused by point mutations and expression of the efflux pump NorA determine resistance to quinolones, but there are great differences in the activity of different compounds, which makes interpretative reading difficult. Strains of S. aureus with intermediate susceptibility to glycopeptides (GISA strains) have been described, as well as highlyvancomycin-resistant isolates (vanA isolates). In Spain, there is a high percentage of S. pneumoniae strains intermediate or resistant to penicillin, and a low percentage of strains intermediate or resistant to third generation cephalosporins, due to mutations in genes encoding penicillin-binding proteins. The most frequent phenotype of resistance to MLSB in this species is caused by methylase production. Resistance to quinolones is still uncommon, and is mainly related to mutations in parC/parE (low level) and in gyrA .I t is important to detect low level resistance due to its clinical implications. No strains of S. pyogenes resistant to penicillin have yet been described. In Spain the most common phenotype of resistance to macrolides in S. pyogenes is determined by efflux pumps (mef genes), affecting 14- and 15-membered macrolides. E. faecalis is usually susceptible to ampicillin, in contrast to E. faecium. Enterococci show intrinsic low-level resistance to aminoglycosides, but still remain susceptible to the combination of these antimicrobials and cell-wall active agents. Strains expressing different aminoglycoside-modifying enzymes (high-level resistance) became resistant to the combination. Glycopeptide-resistant strains of enterococci are www.elsevier.es/eimc