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An in-depth exploration of various factors that influence the choice of antimicrobials, including their efficacy, susceptibility, pharmacokinetics, pharmacodynamics, and toxicity. The text also covers antimicrobial susceptibility testing methods, determination of minimal inhibitory concentration (mic), and common mechanisms of antimicrobial resistance. Additionally, it discusses genetic variability of microbes and their mechanisms of genetic variation, as well as the role of dna replication errors and genetic recombination in antimicrobial resistance.
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Efficacy / sensitivity / pharmacokinetics & pharmacodynamics ToxicityCost TERM 2
DEFINITION 2 depends on microbe, achievable serum level, and ultimately clinical response TERM 3
DEFINITION 3
DEFINITION 4 2. Kirby-Bauer Disk Diffusion Technique Measure diameter of zone of inhibitionCompare with chart to determineCLINCAL SUSCEPTIBILITYResult reported are qualitaitivesensitive, intermediate, or resistant TERM 5
DEFINITION 5
DEFINITION 7 Intrinsic - innate or naturally-occurring resistance Ex. Pseudomonas aeruginosa has always been resistant to penicillin dueto the restricted (small) size of its porin channels in the outer membrane Acquired - once susceptible microbes develop resistance Ex. prior to 1945 practically all strains of Staphylococcus aureus were susceptible to penicillin G, today practically all hospital-acquired isolates are resistant to penicillin G TERM 8
DEFINITION 8 Mutational Resistance (random mutation & selection) Acquisition of New DNA (new genes provide mechanisms of antimicrobial resistance) Transformation Transduction - bacteriophage Conjugation - plasmids & transposons TERM 9
DEFINITION 9 Microbes have the ability to rapidly change their genomes and thus express altered or different proteins that may: increase their pathogenicty aid in avoiding the immue system mediate resistant to antimicrobial drugs TERM 10
DEFINITION 10 Spontaneous Mutation replication errors Movement of DNA segments (rearrangements) (1) movement of DNA segments within a genome (intracellular) inversion translocation (2) movement of DNA segments between genomes (intercellular) transformation conjugation / plasmids transposition / transposons transduction / bacteriophages
large DNA sequence rearrangements result from movement of blocks of DNA from one position to anotherrequires genetic recombination genetic recombination mediates a wide variety of other fundamental processes (a) exchange between homologous chromosomes during meiosis(b) the repair of damaged DNA (c) the assembly of active genes during differentiation (d) chromosomal integration of extrachromosomal elements TERM 17
DEFINITION 17 (a) within a single DNA molecule ex. translocation & inversion(b) between DNA molecules ex. transformation & transposition TERM 18
DEFINITION 18 DNA rearrangements within a single DNA molecule (1) translocation a segment of DNA moves from one location to anotheri.e. from silent storage sites to active expression sites (analogy - CD or cassette player) ex. Neisseria gonorrhoeae & trypanasomes used by several microbes to vary the expression of their surface proteins (antigens) and thus evade the immune response TERM 19
DEFINITION 19 DNA rearrangements within a single DNA molecule (2) inversion a segment of DNA changes orientation by 180E (only 1 vinyl record in your collection) Salmonella typhimurium alternates its expression of two differentflagellar antigens by inversion of a segment that contains a promoter TERM 20
DEFINITION 20 DNA rearrangement between DNA molecule &/or between bacterial cells (1) Transformation uptake & incorporation of naked DNA from the environment recombination between incoming DNA & recipient genomeincorporation of exogenous DNA sequence information
DNA rearrangement between DNA molecules &/or between bacterial cells (2) Conjugation many plasmids carry genes which enable them to transfer copies of themselves from donor bacterium to a recipient bacterium specialized pilus which mediates plasmid transfer and DNA mobilizing enzymes required for DNA transfer TERM 22
DEFINITION 22 conjugative plasmids that carry multiple drug resistance genessome conjugative plasmids have a broad host rangethey can replicate in many different bacterial species &become widely distributed TERM 23
DEFINITION 23 high frequency of recombination movement of chromosomal genes by conjugation TERM 24
DEFINITION 24 self-mobilizable segments of DNAmay be present on plasmids or on chromosomecan move (transpose) from one position to a different positionwithin a single DNA molecule or between two DNA moleculescomposite transposons often carry genes that encode antibiotic resistance and toxin productionplasmids & transposons responsible for rapid spread of resistance to antimicrobials TERM 25
DEFINITION 25 genetic variation mediated by bacteriophages bacteriophages can contribute to genetic variation by(1) transducing (moving) chromosomal genes between bacterial cells &/or(2) expression of viral genes during lysogenic infection