1. Wstęp. 2. Wankomycyna i inne glikopeptydy. 2.1. Charakterystyka antybiotyków. 2.2. Kryteria wrażliwości na glikopeptydy. 3. Nabyta oporność na wankomycynę. 3.1. Enterokoki VRE. 3.2. Transfer operonu vanA ze szczepów Enterococcus spp. do izolatów metycylino-opornych Staphylococcus aureus – możliwości i obawy. 3.3. Wankomycyno-oporne szczepy Staphylococcus aureus (VRSA). 3.3.1. Mechanizm oporności u VRSA warunkowany obecnością operonu vanA. 3.3.1.1. Heterologiczna ekspresja operonu vanA u wankomycyno-opornych S. aureus. 3.3.1.2. Wankomycyno-oporne S. aureus – analiza przypadków. 3.3.1.3. Epidemiologia szczepów VRSA vanA. 3.3.2. Szczepy VRSA – vanA-negatywne (dawne Staphylococcus aureus o obniżonej wrażliwości na wankomycynę, VISA) – pochodzenie oraz mechanizm oporności. 4. Szczepy Staphylococcus aureus wykazujące fenotyp hetero-VISA. 5. Opcje terapeutyczne leczenia ciężkich zakażeń o etiologii S. aureus, wobec których terapia wankomycyną pozostaje nieskuteczna. 6. Podsumowanie

Abstract: Until recently, vancomycin was perceived as an effective drug for the treatment of serious infections with MRSA etiology. For over 30 years, since the introduction of the antibiotics on the pharmaceutical market, there was no case of Staphylococcus aureus resistant to the glycopeptide and it seemed that strains of S. aureus are naturally sensitive to vancomycin. Problems began to appear at the beginning of the 90s of the twentieth century, when more and more treatment failures with the use of the glycopeptide antibiotics were being reported. Strains of S. aureus which may manifest decreased susceptibility or resistance to vancomycin and/or teicoplanin were recognized as the main cause of these failures. VRSA (vancomycin resistant S. aureus), with the genotype vanA conditioned by the presence of vanA operon transmitted from Enterococcus are extremely rare. More frequent are VISA (vancomycin intermediate S. aureus) or VRSA vanA-negative strains exhibiting thickened cell walls, increased content of free dipeptide D-Ala-D-Ala in peptidoglycans and disorders in autolytic processes, and hetero-VISA strains sensitive to vancomycin (MICVA ≤2 mg/L), but containing subpopulations of cells exhibiting MIC values at different levels. These effects are caused by different molecular mechanisms, which are related to different regulatory systems and manifested by diverse phenotypic features, but the result is always the lack of treatment efficacy. A review of the mechanisms leading to the formation and spread of S. aureus isolates for which the vancomycin treatment can be ineffective has become an essential objective of this monograph.

1. Introduction. 2. Vancomycin and other glycopeptides. 2.1. Characteristics of the antibiotics. 2.2. Criteria of sensitivity to glycopeptides. 3. Transferred resistance to vancomycin. 3.1. Enterococci VRE strains. 3.2. The vanA operon transfer from Enterococcus spp. to methicillinresistant Staphylococcus aureus strains – possibilities and apprehensions. 3.3. Vancomycin-resistant Staphylococcus aureus strains (VRSA). 3.3.1. Mechanism of resistance of VRSA strains – determination the presence of vanA genes. 3.3.1.1. Heterologic expression of vanA operon in vancomycin-resistant S. aureus. 3.3.1.2. Vancomycin-resistance of S. aureus – case studies. 3.3.1.3. Epidemiology of VRSA vanA strains. 3.3.2. VRSA strains – vanA-negative (previous vancomycin intermediate Staphylococcus aureus, VISA) – provenance and mechanism of resistance. 4. The hetero-VISA phenotype expression in Staphylococcus aureus strains. 5. Therapeutic options for the treatment of serious infections with S. aureus etiology for which vancomycin therapy remains ineffective. 6. Summary