Bacterial resistance to antimicrobial drugs is an increasing health and economic problem. Bacteria may be innate resistant or acquire resistance to one or few classes of antimicrobial agents. Acquired resistance arises from: (i) mutations in cell genes (chromosomal mutation) leading to cross-resistance, (ii) gene transfer from one microorganism to other by plasmids (conjugation or transformation), transposons (conjugation), integrons and bacteriophages (transduction). After a bacterium gains resistance genes to protect itself from various antimicrobial agents, bacteria can use several biochemical types of resistance mechanisms: antibiotic inactivation (interference with cell wall synthesis, e.g., β-lactams and glycopeptide), target modification (inhibition of protein synthesis, e.g., macrolides and tetracyclines; interference with nucleic acid synthesis, e.g., fluoroquinolones and rifampin), altered permeability (changes in outer membrane, e.g., aminoglycosides; new membrane transporters, e.g., chloramphenicol), and “bypass” metabolic pathway (inhibition of metabolic pathway, e.g., trimethoprim-sulfamethoxazole).

Aim: To determine clinically significant factors which may alter the effect of dual antiplatelet therapy with aspirin and ticagrelor or clopidogrel in patients who had undergone percutaneous coronary intervention and stent implantation. Materials & methods: The study included 378 patients. All the patients had undergone percutaneous coronary intervention and stent implantation. Platelet aggregation and genotyping for CYP2C19 *2 (rs4244285) and CYP4F2 (rs2108622, rs1558139, rs3093135 and rs2074902) was performed. Results: Significantly lower platelet aggregation values (% agr ) were detected in ticagrelor users who carried CYP4F2 rs3093135 TT variant (14.67 ± 5.07% agr ) versus AA (22.88 ± 6.30% agr ), p = 0.0004, or AT (20.56 ± 6.51% agr ), p = 0.0126. Conclusion: Results of the current study showed that CYP4F2 rs3093135 TT variant carriers had a higher antiplatelet effect of ticagrelor, and more frequently had nonprocedural bleeding during ticagrelor therapy, as compared with AA and AT variant carriers. Dual antiplatelet therapy (DAPT) with aspirin and ADP receptor blocker (ticagrelor, prasugrel or clopidogrel) is recommended for the secondary prevention of ischemic complications in patients with acute coronary syndromes, following percutaneous coronary intervention (PCI) and stent implantation. In large trials, prasugrel and ticagrelor have showed superior therapeutic effect compared with clopidogrel. Prasugrel reduced primary end point (cardiovascular death, nonfatal myocardial infarction (MI) or stroke) in the Trial to Assess Improvement in Therapeutic Outcomes by Optimizing Platelet InhibitionThrombolysis In Myocardial Infarction 38 [1]. Ticagrelor was shown to reduce primary end point in the Platelet Inhibition and Patient Outcomes (PLATO) trial [2]. Thus, the European Society of Cardiology issued guidelines for the diagnosis and treatment of ST-elevation myocardial infarction (STEMI) [3], non-STEMI (NSTEMI) [4] and myocardial revascularization [5]. According to these guidelines, ticagrelor or prasugrel is now preferred over clopidogrel due to their increased antiplatelet activity and lower risk of vascular thrombotic events. However, ticagrelor or prasugrel may cause higher incidence of nonprocedural noncoronary artery bypass grafting bleeding [1,2,6].Clopidogrel, a key antagonist of platelet ADP receptors, has been in use over the past two decades. This prodrug is metabolized by two main competing pathways. The major one is via human hepatic carboxylesterase 1, which hydrolyze clopidogrel into inactive clopidogrel acid metabolite. The minor one consists of two CYP450-dependent steps [7,8]. During the first step, clopidogrel is metabolized into a thiolactone (2-oxo-clopidogrel) by CYP1A2, CYP2B6 and CYP2C19. The second step involves CYP2B6, CYP2C9, CYP2C19 and CYP3A4, which forms active thiol-containing metabolite [7]. In total,

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(2009). Nationwide survey of extendedspectrum b-lactamase-producing Enterobacteriaceae in the French community setting.

This study demonstrates the predominance of the ST131 clone among CTX-M β-lactamase-producing E. coli isolates. Dissemination of bla genes in ST131 strains can be linked not only to highly adapted IncF plasmids such as FII/FIB and FII, but also to plasmid replicon types A/C, L/M and HI1.