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Introductory lecture
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what was the first antibiotic that was used?
salversan
why is salversan not used anymore?
toxic, too much work to create, which was also toxic and dangerous for the doctor preparing it, unstable
what is the mechanism of a bactericide?
they kill bacteria at safe plasma concentration levels
what is the mechanism of bacteriostatic?
inhibit, bacterial growth and the immune mechanisms eliminate the bacteria
what is a unique pathway/target?
This is only found in the pathogen
what is a similar pathway?
this is also found in humans, but there are some differences.
what is the target with the same pathway?
there is the same pathway but there is a different significance
what is the cell wall synthesis inhibition an example of?
unique pathway
what is the folic acid synthesis inhibition an example of?
unique pathway
what is the ergosterol synthesis inhibition an example of?
unique pathway
what is the binding to the membrane ergosterol mechanism an example of?
unique pathway
what is HIV protease inhibition an example of?
unique pathway
what pathway is targeted with neuraminidase inhibtion?
unique pathway
what pathway is targeted with the dihydrofolate reductase inhibtion?
similar pathway / same pathway
what pathway is targeted with the topoisomerase inhibition?
similar pathway
what pathway is the protein synthesis inhibition an example of?
similar pathway
what pathway is the DNA/RNA polymerase inhibition an example of?
similar pathway
what pathway is anti-metabolite nucleotides an example of?
same pathway
what pathway is DNA polymerase inhibition an example of?
same pathway
what are the questions asked to determine if the antimicrobial therapy is waarented for a given patient?
indicated, clinical specimens have been obtained, etiologic agentes, prevent further exposure, clinical evidence
What are the questions asked when there are is a specific species found?
narrower-spectrum agent, combination, optimal dose and duration, specific tests, adjunctive measures.
What are the principles of antimicrobial therapy?
proper dose ffor a proper time with a proper schedule
define empiric antimicrobial therapy
based on experience with particular clinical entity, when it is hard to identify specific pathogen
when are emperic antibiotic therapies indicated?
when there is significant risk of serious morbidity or mortality if withheld OR for public health reasons
what is the efficacy related to with time-dependent antibiotics?
to the time the concentration of a drug remains above the MIC
what is the efficacy related to with concentration dependent antibiotics?
to the peak concentration/minimum inhibitory concentration ratio
what is the post antibiotic effect(PAE)?
suppression of bacterial growth after brief antimicrobial exposure to microorganisms
What are possible mechanisms of PAE?
slow recovery, persistance of drug at binding site, unknown
which drugsposses concentration-dependent PAEs and with that can be given at high dose, once a day?
aminoglycosides, quinolones
what are pharmacokinetic considerations?
IV administration, distribution, TDM
What is the TDM approach?
personalized, but as that would be too invasive and only feasible in hospital there is Bayesian simulations
what are the reasons for the combination of drugs?
seriously ill, polymicrobial infections, decrease resistant strains, decrease dose-related toxicity, enhance inhibition or killing
what is important to prevent tolerance development
misuse of AB therapy: use it for viruses and patient compliance
What are mechanisms of obtained resistance?
mutation resulting in selection: enzyme production, change in target binding spot, decreased accumulation, correction of damage/decrease in apoptosis
what is another mechanism of tolerance between bacteria?
there can be tranfer between humans and between bacteria via plasmids
What are the nosocomial ESKAPE pathogens?
no treatment: Enterococcus faecium, Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa, Enterobacter species.
what are the superbugs?
multidrug resistance: MRSA, ESBL, MDRAB, VRE, CRE, CRAB
what is not true about therapeutic drug monitoring
a disadvantage is that it requires a high amount and frequent patient samples
in what cases is a bactericide therapy required?
endocarditis, meningitis, infections of immunocompromised patients
choose the true statement for bactericide agents
the main therapeutic effect is that they kill bacteria at safe plasma concentration levels
what is not a unique pathway that is targeted by some antimicrobial agents
dihydrofolate reductase inhibitors
what is PAE
suppression of bacterial growth after brief antimicrobial exposure to microorganisms
why is it extremely important that the patients adhere to the prescribed antimicrobial therapeutic regimen?
to avoid tolerance, to achieve proper therapeutic effects, to minimize side effects
what is the difference between gram positive and gram negative
positive has a thick peptidoglycan layer, negative has an outer membrane
what type of bacteria is Staphylococcus aureus
gram positive cocci: skin and wound infections, osteomyelitis, endocarditis
what type of bacteria is Streptococcus pyogenes
gram positive cocci: skin and wound infections, tonsillopharyngitis, scarlet fever
what type of bacteria is Streptococcus pneumonia?
gram positive cocci(Pneumococcus): respiratory infections
what type of bacteria is Streptococcus viridans group?
gram positive cocci: dental infections, caries(tooth decay), endocarditis
what type of bacteria is the Enterococcus?
gram positive cocci: urinary infections, endocarditis
what type of bacteria is corynebacterium diphtheria
gram positive bacillus: diphtheria
what type of bacteria is neisseria meningitidis
gram negative cocci: meningitis
what type of bacteria is Neissseria gonorrhoeae
gram negative cocci
what type of bacteria is Moraxella catarrhalis
gram negative cocci: respiratory infections
what type of bacteria is the Haemophilus influenza
gram negative: respiratory infections
what type of bacteria is the Helicobacter pylori?
gram negative : gastric ulcer
What type of bacteria are E. coli and Salmonella
gram negative
what type of bacteria is the pseudomonas aeruginosa
gram negative
what type of bacteria is the clostridium ssp.
anaerobe gram positive bacillus
what type of bacteria is the Bacteriodes fragilis?
anaerobe gram negative bacillus
wha type of bacteria is the propionibacter acnes
anaerobe gram negative
what are mycobacteria
they have cell walls with a waxy lipid-rich outer layer
what is true for gram positive bacteria
they have a thicker peptidoglycan layer, crystal violet gram staining
choose the pathogen of Lyme disease
Borrelia burgdorferi
which of the following bacteria might cause mainly respiratory infections?
Haemophilus influenzae, Streptococcus pneumonia, Moraxella catarrhalis