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Development and Validation of Methods for Rapid Detection of β-lactamases Using MALDI-TOF Mass Spectrometry for the Early Detection of Infectious Disease Agents and Their Antibiotic Resistance
Pašková, Veronika ; Hrabák, Jaroslav (advisor) ; Kolář, Milan (referee) ; Dolejská, Monika (referee)
The discovery of antibiotics and their subsequent clinical use has had a tremendous and beneficial impact on human health. β-lactam antibiotics are considered the most widely used therapeutic class of antibacterials prescribed in human and veterinary clinical practices due to their excellent safety profile and broad antimicrobial spectrum. β-lactams have undergone continuous development since their introduction in order to improve properties such as potency, spectrum of activity, pharmacokinetic and safety profiles and to counter the emergence of resistance. Resistance can occur by multiple mechanisms, including, notably, the production of β-lactamases and modification of β-lactam receptors - penicillin-binding proteins. The resistance of bacterial pathogens to common antimicrobial therapies and the emergence of multidrug- resistant bacteria are increasing at an alarming rate in Czechia. Understanding the mechanisms of resistance in clinical isolates is critical to the design of novel therapeutics and the improvement of detection techniques. Insight into the genetic basis of resistance can also reveal drug design strategies for curtailing the spread of resistance and combatting multidrug-resistant organisms. This dissertation thesis concerns different thematic investigations, beginning with the...

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