Fina: Ch 10: Antimicrobial Treatment

Question 1

Origins of Antimicrobial therapy

Answer 1

naturally occurring antimicrobials:
-metabolic products of bacteria and fungi
-microbes produce antibiotics (their weapons) to reduce competition for nutrients and space
derived from:
-bacteria & molds
first systemic attempt to find specific antimicrobials occurred in early 1990s

Question 2

Antibiotic

Answer 2

substance produced by microorganisms that in small amounts inhibits another microorganism
microbes produce antibiotics (their weapons) to reduce competition for nutrients and space

Question 3

History of Chemotherapy

Answer 3

1910: Paul Erhlich “father of chemo” discovered that Salvarsan could treat syphilis
1935: Sulfa drugs were discovered
1928-1940: Alexander Flemming discovered antimicrobial action from the mold Penicillium, however many years passed before penicillin was purified and produced

Question 4

Qualities of the ideal antimicrobial

Answer 4

selective toxicity
solubility in bodily fluids
toxicity not easily altered by bacteria
non-allergenic
stability
resistance by microorganisms not easily required
long shelf life
reasonable cost

Question 5

Selective toxicity

Answer 5

drug kills the pathogen without damaging the host

Question 6

Stability

Answer 6

maintenance of a constant, therapeutic concentration in blood and tissue fluids

Question 7

The action of microbial drugs

Answer 7

1. inhibition of cell wall synthesis
2. disruption of cell membrane function
3. inhibition of protein synthesis
4. inhibition of nucleic acid synthesis
5. action as antimetabolites

Question 8

Inhibition of cell wall synthesis

Answer 8

the cell wall is a good, selective target b/c eukaryotes dont have peptidoglycan
penicllin and cephalosporins inhibit the peptide crosslinks that hold the carb units together (similar to taking a blow torch and cutting links in a chain link fence)

Question 9

Penicillin: Inhibition of cell wall synthesis

Answer 9

produced by the mold Penicillium chrysogenum
-a diverse group (1st, 2nd, 3rd generations)
-natural: penicillin G and V
-semisynthetic: ampicillin and Augmentin
-structure - beta-lactam ring
the R group is responsible for the activity of the drug, and cleavage of the beta-lactam ring will render the drug inactive

Question 10

Injury to the plasma membrane

Answer 10

change in permeability of plasma membrane causes loss of important metabolites from cell

• interact with membrane phospholipids
• distorts the cell surface
• leakage of proteins and nitrogen bases

Question 11

Inhibition of protein synthesis

Answer 11

exploit difference in ribosomes:

• drugs specifically bind to 70S and not 80S because of specific shape of ribosomes
• erythromycin, streptomycin, tetracycline, chloramphenical
• some toxicity since mitchondria have 70S ribosomes

Question 12

Inhibition of nucleic acid synthesis

Answer 12

inhibition of DNA replication
inhibition of transcription of RNA
-modes of action include:
-Quinolones: inhibits DNA unwinding enzymes
-Rifampicin: inhibits bacterial RNA polymerase

Question 13

Inhibition of folic acid synthesis

Answer 13

Sulfonamides (sulfa drug) and trimethoprim

-competitive inhibition preventing the metabolism of DNA, RNA and amino acid

Question 14

Biolfilm Effects on antibiotic treatment

Answer 14

Biofilms - unaffected by the same antimicrobials that work against them when they are free living
-penetration of the biofilm
-different phenotype is expressed by biofilm bacteria, giving them different antibiotic sensitivity
Strategies for treating biofilm infections:
-interrupting quorum sensing signals
-adding DNase to antibiotics helps with penetration
-impregnating devices with antibiotics

Question 15

Bioavailability effects on antibiotic treatment

Answer 15

the chemical structure of a drug AND the mode of entry of a drug influence:

• concentration of drug in blood
• time of drug in blood

Question 16

Actions of antimicrobial drugs: eukaryotic pathogens

Answer 16

treatment of eukaryotic pathogens is more difficult because they are more similar to human cells

• need to target the few differences between cells
  
  • target sterols in cell membrane in fungi
  • target protein gates in invertebrate nervous system

Question 17

Actions of antimicrobial drugs: viral pathogens

Answer 17

treatment of viral pathogens is more difficult because they find protection inside the human cell

• limited drugs available
• difficult to maintain selective toxicity
• effective drugs: target viral replication cycle
  
  • entry
  • nucleic acid synthesis
  • assembly/release

Question 18

Drug-Host interaction

Answer 18

be cautious of toxicity to organs
some drugs can cause allergic reactions (especially penicillin and sulfa drugs)
many times, drugs will suppress or alter the normal microflora (good to take extra sources of live cultures lto replenish flora - like lactobaccillus acidophilus found in yogurt and milk)
need effective drugs: be mindful to use the best drug for the job

Question 19

Tests to guide chemotherapy

Answer 19

Disk-diffusion method (Kirby-Bauer technique)
same as testing disinfectants
Zone of inhibition surrounding the discs is measured and compared w/a standard for each drug
E test - uses a strip that contains a gradient of antimicrobial chemical
Indicates the concentration of antimicrobial needed to inhibit growth

Question 20

The future of chemotherapeutic agents

Answer 20

many disease have become resistant to antibiotics

chemicals produced by plants and animals are providing new antimicrobial agents

Question 21

Therapeutic index

Answer 21

the ratio of the dose of the drug that is toxic to humans as compared to its minimum effective (therapeutic) dose
the smaller the ratio, the greater the potential for drug reactions
the drug with the highest therapeutic index has the widest margin of safety

Question 22

the MIC and the therapeutic index

Answer 22

in vitro activity of a drug is not always correlated with the in vivo effect

Question 23

Failure of antimicrobial agents is due to:

Answer 23

the inability of the drug to diffuse into that body compartment (brain, joints, skin)
resistant microbes in the infection that didnt make it into the sample collected for testing
an infection caused by more than one pathogen (mixed) some of which are resistant to the drug

Question 24

How drug resistance develops

Answer 24

resistance to penicllin developed in bacteria as early as 1940
microbes become newly resistant to a drug after one of the following occurs:
-spontaneous mutations in critical chromosomal genes
-acquisition of entire new genes or sets of genes via horizontal transfer from another species

Question 25

Chromosomal drug resistance

Answer 25

usually results from spontaneous random mutation
can be the result of phenotypic, rather than a genotypic change - slowing or stopping of metabolism so that the microbe cant be harmed by the antibiotic

Question 26

Resistance thru horizontal transfer

Answer 26

Resistance (R) factors - plasmids containing antibiotic resistance genes (some have 6-7 resistance genes)
can be transferred thru conjugation, transformation or transduction
plasmids encoded w/drug resistance are naturally present in microbes before they have been exposed to an antibiotic
transposons that have duplicated and inserted genes for drug resistance into plasmids
Superbug!

Question 27

Antibiotic resistant strain propagation

Answer 27

antimicrobial exposure causes pressure to select resistant strains
without antibiotics, selective pressure decreases and antibiotic resistance genes may be lost

can have intermicrobial transfer of plasmids containing resistance genes
clinical implications in the development of drug resistant Steph aureus – how do we treat S. aureus infections when they become completely resistant to our last line antibiotic, Vancomycin?

Question 28

Synthetic advances in antibiotics (penicillins)

Answer 28

original penicillin was narrow spectrum and susceptible to microbial counterattacks
molecule has been altered and improved upon over the years
later penicillins overcome the limitations of the original molecule

beta-lactamase breaks the beta-lactam ring and renders penicillin inactive

Question 29

The future of chemotherapeutic agents

Answer 29

some drugs are actually a combo of 2 drugs

can start with one antibiotic then if it is being degraded, a second one can be released

Question 30

Superinfection

Answer 30

a second infection that occurs due to treatment of a first bacterial infection
antibiotics are taken for the first infection that selects for the second bacterial species

Question 31

Chemotherapeutic drug

Answer 31

any chemical used in the treatment, relief or propholaxis of a disease

Question 32

Antimicrobials

Answer 32

any microbial drug, regardless of its origin

Question 33

Antibiotics

Answer 33

substance produced by microorganisms that in small amounts inhibits another microorganism

Question 34

Semisynthetic drugs

Answer 34

drugs that are chemically modified in the lab after being isolated from natural sources

Question 35

Synthetic drugs

Answer 35

drugs produced entirely by chemical reactions

Question 36

Narrow spectrum

Answer 36

target a specific group

Question 37

Broad spectrum

Answer 37

effective against more than one group of bacteria

Question 38

3 factors to know before beginning antimicrobial therapy

Answer 38

1. the nature of the microorganisms causing the infection
2. the degree of the microorganisms susceptibility to various drugs
3. the overall medical condition of the patient

Question 39

5 mechanisms of drug resistance

Answer 39

1. drug inactivation
2. decreased permeability
3. activation of drug pumps
4. change in drug binding site
5. use of alternative metabolic pathways

Question 40

How does natural selection increase the under of resistant bacteria in a population treated with antibiotics?

Answer 40

if population is exposed to a drug, sensitive individuals are inhibited or destroyed, the resistant forms survive and proliferate
offspring will have these resistant genes

Question 41

Probiotic

Answer 41

preparations of live microorganisms that are fed to humans and animals to improve the intestinal biota

Question 42

Prebiotic

Answer 42

nutrients that encourage the growth of beneficial microbes in the intestine