exam 3 antibiotic Flashcards
Goal of antimicrobial chemotherapy?
administer a drug to an infected person that destroys the infective agent without harming the host’s cells
T or F - Antimicrobial drugs are produced naturally or synthetically
T
microbicidal
kills microbe
microbiostatic
inhibits the growth or multiplication of microbiota.
keep still, or stop growing → immune system
What are the ideal characteristics of a antimicrobial drug?
- Selectively toxic to the microbe but nontoxic to host cells
- microbicidal rather than microbistatic
- Remains potent long enough to act and is not broken down or excreted prematurely
- Is not subject to the development of antimicrobial resistance
- Complements or assists the activities of the host’s defenses (immune system)
- remains active even when diluted in body fluids and tissues
- readily delivered to the site of infection
- reasonably priced
- does not disrupt the host’s health by causing allergies or predisposing the host to other infectio
Define antibiotics
common metabolic products of aerobic bacteria and fungi
What bacteria genera are found in antibiotics?
- found in soil
- lot of bacteria in soil and kill competition
- not kill them = gene Ab^R
Streptomyces and Bacillus
What genera forms molds? by doing so they secrete antibiotics
Penicillium and Cephalosporium
By inhibiting the other microbes in the same habitat, antibiotic producers have less competition for____ and ____
nutrients and space
Antimicrobial drugs should be selectively toxic - meaning?
drugs should kill or inhibit microbial cells without simultaneously damaging host tissues
- remember microbiocidal
- microbistatis
Antimicrobial drugs should be selectively toxic - meaning?
drugs should kill or inhibit microbial cells without simultaneously damaging host tissues
- remember microbiocidal
- microbistatic
As the characteristics of the infectious agent become more similar to the vertebrate host cell, complete _____ _______ becomes more difficult to achieve and more side effects are seen
selective toxicity
List 5 major components that are useful drug targets in actively dividing cells
- Inhibition of cell wall synthesis
- Breakdown of the cell membrane structure or function
- Interference with functions of DNA and RNA
- Inhibition of protein synthesis
- Blockage of key metabolic pathways
why would be drug target for inhibition of cell wall synthesis be useful?
made of peptidoglycan
why would be drug target for breakdown of the cell membrane structure or function be beneficial?
the phospholipid bilayer
why would be drug target for interference with functions of DNA and RNA be beneficial?
look for differences
why would be drug target for Inhibition of protein synthesis be beneficial?
inhibition of ribosomes or tRNA
why would a drug target for blockage of key metabolic pathways be beneficial?
cell starves
define spectrum
range of activity of a drug
Narrow-spectrum drugs– effective on a
small range of microbes
Target a specific cell component found only in certain microbes
Medium or Broad-spectrum drugs has what type of range of activity?
greatest range of activity
Target cell components common to most pathogens
What antibiotic target cell with medium range?
ampicillin
What antibiotic target cell with broad range?
tetracycline ->targets all bacteria because they have 30S ribosome
A drug that targets lipopolysaccharides in a gram- negative cell would be considered:
- does not say specific LPS
a. Broad Spectrum
b. Narrow Spectrum
c. Selectively Toxic
d. Broad Spectrum and Selectively Toxic
e. Narrow Spectrum and Selectively Toxic
C. selectively toxic
Most bacterial cell walls contain peptidoglycan. Name bacteria that does not contain peptidoglycan.
Bacteria lacking peptidoglycan come into four main categories:
- Mycoplasmas
- bacterial L-forms
- halobacteria
- methanogenic bacteria.
What does penicillins and cephalosporins block the synthesis of? which causes the cell wall to lyse
peptidoglycan
doesn’t destroy block synthesis
cell wall needs maintenance
what type of cells are antimicrobial cell active on?
active on young, growing cells
w/ log phase
Some penicillins that do not penetrate the outer membrane. As a result they are less effective on what type of gram bacteria?
gram-negative bacteria because they are too big to move thru porins
what type of gram bacteria can broad spectrum penicillins and cephalosporins can cross the cell walls?
gram-negative bacteria
Describe Beta-lactam antimicrobials structure?
highly reactive 3 carbon, 1 nitrogen ring
What is the beta-lactam antimicrobial primary mode of action?
primary stop cross-linking of ppg
Greater than ½ of all antimicrobic drugs are what?
beta-lactams
what are the most prominent beta-lactams?
Penicillins and cephalosporins
what is the largest diverse group of compounds that could be synthesized in the laboratory?
pencillin and its relatives
What is an economical approach to obtain natural penicillin?
microbial fermentation and modify it to semi-synthetic forms
Pencillin contains 3 parts
- Thiazolidine ring
- Beta-lactam ring
- Variable side chain dictating microbial activity
what are the most important natural forms of penicillins?
Penicillins G and V
Penicillin is the drug of choice for what type of gram and morphology - there’s two
Penicillin is the drug of choice for gram-positive cocci (streptococci) and some gram-negative bacteria (meningococci and syphilis spirochete)
semisynthetic pencillins examples
ampicillin and amoxicillin have broader spectra – Gram-negative infections
Penicillinase-resistant examples
methicillin, nafcillin, cloxacillin
what is the primary problems of pencillin?
allergies and resistant strains of bacteria
addition of side chains of penicillin creates
semisynthetic penicillins
Normally, describe NAG and NAM in gram(+) cell walls
chains of NAM and NAG are linked together by cross bridges
Describe the effect of penicillin on gram (+) cell walls
exposure to penicillin; penicillin blocks cross-linking bridges; thus weakening the peptidoglycan
polymyxins
narrow-spectrum peptide antibiotics with a unique fatty acid component
What are polymyxins indicated for?
Indicated for drug-resistant Pseudomonas aeruginosa and severe UTI
ex. cystic fibrosis and burn patients
Why is polymyxin not selectively toxic as pencillin?
b/c it targets cell membrane
causing a breakage which results in the cell losing water and dies
What drugs block protein synthesis?
Erythromycin or Z-pack
Ribosomes of eukaryotes differ in size and structure from
prokaryotes
antimicrobics usually have a selective action against
prokaryotes
erythromycin or Z-pack can also damage the eukaryotic mitochondria meaning it affects
ribosomes
Aminoglycosides (streptomycin, gentamycin) insert on sites on what and causes what to happen?
Aminoglycosides (streptomycin, gentamycin) insert on sites on the 30S subunit and cause misreading of mRNA
Function of tetracyclines
Tetracyclines block attachment of tRNA on the A acceptor site and stop further synthesis
What drug Interferes with Protein Synthesis?
aminoglycosides
amnioglycosides are products of various species of soil ________
actinomycetes
Aminoglycosides type of spectrum?
Relatively broad-spectrum
Relatively broad-spectrum function
inhibit protein synthesis binding to one ribosomal subunit
What are amnioglycosides useful against?
aerobic gram-negative rods and certain gram-positive bacteria
What Non Beta-lactam Cell Wall Inhibitors is a narrow-spectrum, most effective in treatment of staphylococcal infections in cases of penicillin and methicillin resistance or if patient is allergic to penicillin; toxic and hard to administer; restricted use?
Vancomycin
What Non Beta-lactam Cell Wall Inhibitors narrow-spectrum produced by a strain of Bacillus subtilis; used topically in ointment?
bacitracin
What Non Beta-lactam Cell Wall Inhibitors works by interfering with mycolic acid synthesis; used to treat infections with Mycobacterium tuberculosis?
Isoniazid (INH)
NAME 3 Non Beta-lactam Cell Wall Inhibitors
Vancomycin
Bacitracin
Isoniazid
What type of spectrum and cliinical application is used for vancomycin?
narrow-spectrum, most effective in treatment of Staphylococcal infections in cases of penicillin and methicillin resistance or if patient is allergic to penicillin; toxic and hard to administer; restricted use
What type of spectrum and clinical application of Bacitracin?
narrow-spectrum produced by a strain of Bacillus subtilis; used topically in ointment
How does Isoniazid (INH) work?
works by interfering with mycolic acid synthesis; used to treat infections with Mycobacterium tuberculosis
What Antibiotics Damage Bacterial Cell Membranes?
polymyxins, narrow-spectrum peptide antibiotics with a unique fatty acid component
Clinical application of polymyxins
- Indicated for drug-resistant Pseudomonas aeruginosa and severe UTI
- cystic fibrosis
- burn patients
is polymyxin as selective as penicillin?
not as selectively toxic as pencillin bc targets cell membrane
Drugs That Block Protein Synthesis
Erythromycin or Z-pack (Azythromycin)
Ribosomes of eukaryotes differ in size and structure from
prokaryotes
antimicrobics usually have a _____ action against prokaryote
selective
Erythromycin can also damage the ______ mitochondria
eukaryotic
Function of aminoglycosides (streptomyin, gentamycin)
nsert on sites on the 30S subunit and cause misreading of mRNA
Tetracyclines function
block attachment of tRNA on the A acceptor site and stop further synthesis
What makes the unique scent of spring?
actinomycetes
Various species of actinomycetes come from where
soil
what is the spectrum of actinomycetes?
broad-spectrum because inhibit protein synthesis binding to one ribosomal subunit
what are actinomycetes useful against?
aerobic gram-negative rods and certain gram-positive bacteria
What is erythromycin? what does it attach to?
lactone ring with sugars; attaches to ribosomal 50s subunit → large subunit of ribosome
function of erythromycin?
Ribosome is prevented from translocating.
- exiting is stop so no tRNA can come in = prevent protein synthesis
Define drug-resistance
Drug-resistance is an adaptive response in which microorganisms begin to tolerate an amount of drug that would ordinarily be inhibitory
Drug -resistance is a result of what
Result of genetic versatility and adaptability of microbial populations
Drug-resistance two characteristics
Can be intrinsic and acquired
How Does Drug Resistance Develop?
- Spontaneous mutations in critical chromosomal genes
- Acquisition of new genes or sets of genes via transfer from another species
Describe intermicrobial transfer
- Through intermicrobial transfer:
- Transfer of resistance (R) factors (plasmids) encoded with drug resistance
- Transposons duplicated and inserted from one plasmid to another or from a plasmid to the chromosome
Mechanism of acquired drug resistance - drug inactivation describe
Inactivation of a drug like penicillin by penicillinase, an enzyme that cleaves a portion of the molecule and renders it inactive.
needs gene→ to make enzyme that cleaves to make inactive
Mechanism of acquired drug resistance → decreased permeability
The receptor that transports the drug is altered, so that the drug cannot enter the cell.
Mechanism of acquired drug resistance → Activation of drug pumps (Efflux pump)
Specialized membrane proteins are activated and continually pump the drug out of the cell.
Mechanism of acquired drug resistance →Change in drug binding site
Binding site on target (ribosome) is altered so drug has no effect.
Mechanism of acquired drug resistance → use of alternate metabolic pathway
The drug has blocked the usual metabolic pathway (green), so the microbe circumvents it by using an alternate, unblocked pathway that achieves the required outcome (red).
Given - a large populations of microbes likely to include drug resistant cells due to prior mutations or transfer of plasmids so there is no growth
what happens if exposed
- If exposed, sensitive cells are inhibited or destroyed while resistance cells will survive and proliferate.
- Eventually population will be resistant – natural selection
Remember figure of natural selection and drug resistance
three petri dish -> exposure to drug and continued exposure to drug
- Microbial cells involved in an infection
- Most sensitive cells are eliminated by drug (early); resistant cells survive and begin to grow (late)
- Most new cells are resistant; infection will no longer respond to drug
Kirby-Bauer Tests - list 5 steps
- spreading bacteria to make a lawan
- disks with abx
- incubate
- examine growth patterns
a. little zone of inhibition → resistance
big zone of inhibition → sensitive
Tube dilution test increasing minimum inhibitory concentrate means
the least amount of antibiotic that is still effective
The tube dilution test is the standard method for determining levels of resistance to an antibiotic
purpose of dilution testing
Dilution testing is used to quantitatively determine the minimal concentration (in mg/ml) of antimicrobial agent to inhibit or kill the bacteria.
In a tube dilution test, the MIC is the _____ of a drug that is required to inhibit growth of a microbe.
Smallest concentration
lowest you can go and still see cell death
what is the control for tube dilution test?
no antibiotic so you see growth
What does not growth look like in tube dilution test?
looks like clear transparent
not cloudy
In vitro activity (in test tube) of a drug is not always correlated with in vivo (in patient) effect true or false
true
for MIC and therapeutic index
If therapy fails - what happens?
a different drug, combination of drugs, or different administration must be considered
for MIC and therapeutic index
what is best to chose a drug with?
Best to chose a drug with highest level of selectivity but lowest level toxicity – measured by therapeutic index (TI) – the ratio of the dose of the drug that is toxic to humans as compared to its minimum effective dose
what is therapeutic index (TI) ?
the ratio of the dose of the drug that is toxic to humans as compared to its minimum effective dose
what type of index is desirable?
High index is desirable
