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Glycopeptide resistance in staphylococci
Rozsypálková, Adéla ; Tkadlec, Jan (advisor) ; Balíková Novotná, Gabriela (referee)
The aim of this thesis is to describe the mechanism of the resistance to glycopeptide antibiotics in a genus Staphylococcus, especially in a species Staphylococcus aureus which is common cause of nosocomial infections resulting frequently in expensive and long-term treatment. This pathogen is dangerous due to its ability to acquire resistance to most antibiotics used in a clinical practice. The resistance of these microorganisms can develop very easily due to inappropriate treatment (administration, drug concentration, duration), which, if not detected, could ultimately results in treatment failure and the death of the patient. The vancomycin resistance of S. aureus could be divide into groups according to their values of vancomycin MIC: VSSA, VISA, hVISA and VRSA. Vancomycin intermediate resistance is associated with mutation, e.g., which affect cell wall synthesis. In contrast, VRSA is associated with the transfer of the mobile genetic element with the vanA or vanB operon from genus Enterococcus. This transmission is due to co-infection with both pathogens. Glycopeptide resistance has also been shown to be very common in coagulase-negative staphylococci (CNS), such as S. capitis, which cause infection in preterm infants. Glycopeptide resistance in CNS and intermediate resistance of S. aureus is...
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Stability of controlled drug release systems based on plasticized starch
Zhukouskaya, Hanna ; Štěpánek, Miroslav (advisor) ; Hrubý, Martin (referee)
The thesis is focused on the research of stability of controlled drug release systems based on a blend of plasticized starch/polycaprolactone (TPS/PCL) that served as a carrier. Antibiotic vancomycin was used as a model drug, and its release from TPS/PCL pellets into aqueous environment was followed by UV-spectroscopy and the obtained time dependences were treated by a simple kinetic model. Moreover, the simultaneous release of starch particles to the surrounding liquid phase was studied by static and dynamic light scattering as well as transmission electron microscopy (TEM) in order to obtain information on the stability of biodegradable matrix and on the structure of the products of the pellet decomposition on a nanoscale level. Key words: vancomycin, starch, drug delivery system, polycaprolactone (PCL), particle release, dynamic light scattering (DLS), static light scattering (SLS)
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Development and genetic basis of glycopeptide resistance in coagulase-negative staphylococci
Prášilová, Jana ; Balíková Novotná, Gabriela (advisor) ; Lišková, Petra (referee)
Glycopeptides are the so-called last-resort antibiotics in clinical practice used to treat heavier, predominantly nosocomial infections caused by multi-resistant coagulase-negative staphylococci. The origin and genetic basis of resistance to glycopeptide antibiotics has not yet been elucidated within coagulase-negative staphylococci. Research on Staphylococcus aureus has shown, that intermediate resistance to glycopeptide antibiotics is associated with the presence of one or more mutations, rather than being conditioned by the support of a particular genetic element, such as in enterococci. By using various types of in vitro resistant mutant selection, we were able to obtain isogenic pairs of glycopeptide sensitive and resistant strains of Staphylococcus epidermidis and Staphylococcus haemolyticus. By sequencing the genomes of these pairs, one nucleotide polymorphisms were identified and predominantly found in metabolic and cell wall control systems. Phenotypic analysis did not reveal a direct association of glycopeptide resistance with increased biofilm formation. In clinical practice, the cross-resistance of glycopeptides and other antibiotics is problematic. For the non-glycopeptide antibiotics imipenem and rifampicin, the incidence of cross-resistance with glycopeptide antibiotics in S. aureus...
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Determination of vancomycin and its crystalline degradation products by HPLC
Neščáková, Monika ; Klapková, Eva (advisor) ; Kotaška, Karel (referee)
The aim of this bachelor thesis was to introduce and validate the method for the determination of vancomycin and its crystalline degradation products by high performance liquid chromatography with detection by diode-array detector. This method is able to reliably detect and distinguish the crystalline degradation products of vancomycin, which lack the necessary therapeutic effect. The long-term using of vancomycin or renal insufficiency lead to their accumulation in the patient's body. Another target of this bachelor thesis was to monitor the release profile of vancomycin concentration and its crystalline degradation products from local carrier of antibiotics that are used in some complicated orthopedic surgeries such as prevention of inflammatory infections caused by Staphylococcus aureus. We compared in vitro release of vancomycin from two bone grafts, two different bone cements and from one synthetic bone graft. The aim was to determine if the examine material releases the quantity of vancomycin, which ensure the long-term local concentrations of vancomycin higher than is the MIC of vancomycin-resistant Staphylococcus aureus (VRSA). Powered by TCPDF (www.tcpdf.org)
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The effect of vanZTei and vanZg expression on resistance to glycopeptide antibiotics in Staphylococcus aureus
Zieglerová, Leona ; Balíková Novotná, Gabriela (advisor) ; Lichá, Irena (referee)
A membrane protein VanZTei which is encoded by the gene vanZ from the vanA glycopeptide resistance gene cluster is a part of the large family of VanZ proteins. VanZTei confers resistance to teicoplanin in Enterococcus faecalis without the presence of other proteins encoded by the cluster. The aim of my work was to compare the ability of two orthologous proteins VanZTei and VanZg (from the genome of Enterococcus faecium) to confer resistance to glycopeptides in Staphylococcus aureus RN4220 and Enterococcus faecium. We have shown that VanZg increases resistance to teicoplanin (Tei) 8 to 16 times the and also to dalbavancin (Dalb) 8 times. VanZTei also confers resistance to Tei and Dalb, but the increase is only twofold. Conversely VanZTei confers resistance to newly synthetized glycopeptides more effectively than VanZg (fourfold increase of resistance confered by VanZTei and two to fourfold increase of resistance confered by VanZg). It suggests that both proteins have different specificity to antibiotics. In despite the mutants of S. aureus RN4220 VanZTei pRMC2 with increased resistance to teicoplanin (MICTei> 8 µg/ml) in which the resistance is dependent on vanZTei expression were selected. These resistant mutants do not carry mutation in a gene vanZTei or in its ribosomal binding site. Neither of the...
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