Lecture 12 - Drugs, Microbes and Hosts

Question 1

Three factors must be known before starting antimicrobial therapy:

Answer 1

• The identity of the microorganism causing the infection
• the degree of the microorganisms susceptibility to various drugs
• the overall medical condition the patient

Question 2

Small discs containing premeasured amounts of antibiotics are dispensed onto the bacterial lawn
A zone of inhibition formed during incubation is measured and compared with a standard for each drug

Answer 2

kirby-bauer technique

Question 3

profile of antimicrobial sensitivity

Answer 3

antibiogram

Question 4

• the smallest concentration (highest dilution) of drug that visibly inhibits growth
• Useful in determining the smallest effective dosage of a drug
• Provides a comparative index against other antimicrobials
• performed by automated machinery

Answer 4

tube dilution tests - minimum inhibitory concentration

Question 5

reasons why treatment can fail

Answer 5

• inability of the drug to diffuse into that body comportment
• resistant microbes the infection that didn’t make it into the sample collected for testing
• an infection caused by more than one pathogen

Question 6

• The ratio of the dose of the drug that is toxic to humans to its minimum effective dose
• The closer these two figures are to each other (the smaller the ratio), the greater potential for toxic drug reactions

Answer 6

therapeutic index

Question 7

• Central concept in antibiotic treatment
• Antimicrobial drugs should kill or inhibit microbial cells without simultaneously damaging host tissues
• The best drugs in current use block the actions or synthesis of molecules in microorganisms but not vertebrate cells

Answer 7

selective toxicity

Question 8

• Effective against more than one group of bacteria Example: tetracyclines

Answer 8

Broad spectrum drugs:

Question 9

• Only target a specific group

- Examples: polymyxin and penicillins

Answer 9

narrow spectrum drugs

Question 10

Can be obtained naturally or synthesized in the laboratory
Consist of three parts: Thiazolidine ring
Beta lactam ring
Variable side chain

Answer 10

penicillin

Question 11

Isolated in the 1940s from Cephalosporium
acremonium
Have a beta-lactam ring that can be chemically altered
Similar mode of action to penicillins

Answer 11

cephalosporins

Question 12

Derived from Bacillus polymyxa Toxic to the kidney

Answer 12

polymyxins

Question 13

High potency
  Broad spectrum
  Readily absorbed from the intestine
  Side effects:
  Seizures and other brain disturbances

Answer 13

fluoroquinolones

Question 14

Composed of one or more amino sugars and an aminocyclitol ring
Products of actinomyces Streptomyces
Micromonospora
Broad antimicrobial spectrum

Answer 14

amino glycoside drugs

Question 15

Natural parent compound and synthetic derivatives
Broad spectrum effects
Side effects:
Gastrointestinaldisruption Deposition in hard tissues

Answer 15

tetracyclines

Question 16

Newer derivatives of tetracyclines
Block 30s ribosomal subunit
Effective against bacteria that have become resistant to tetracyclines

Answer 16

glycylcyclines

Question 17

Macrolide ring

Broad spectrum, low toxicity

Answer 17

erythromycin

Question 18

adverse reactions theGI tract limits its use

Answer 18

clindamycin

Question 19

respiratory tract infections suspected to be caused by resistant microbes

Answer 19

telithromycin

Question 20

Synthetic: do not originate from bacteria or fungi

Answer 20

sulfonamides

Question 21

Interrupting quorum sensing pathways

Adding DNase to antibiotics Pretreatment

Answer 21

treatment of biofilms

Question 22

Quinine: principal treatment for hundreds of years Replaced by chloroquine and primaquine: less toxicity

Answer 22

antimalarial drugs

Question 23

chemotherapy for other protozoa infections

Answer 23

metronidazole: amoebicide

Question 24

anthelminthic drug therapy:

Answer 24

Mebendazole and albendazole
Pyrantel
Praziquantel

Question 25

Three major modes of action in antiviral chemotherapeutic agents:

Answer 25

Barring penetration of the virus into the host cell
Blocking the transcription and translation of viral molecules
Preventing maturation of viral particles

Question 26

how does drug resistance develop

Answer 26

resistance through

• spontaneous mutation
• horizontal transfer
• sharing of resistance genes

Question 27

Plasmids that are transferred through conjugation, transformation,
or transduction

Answer 27

resistance factors

Question 28

duplicated and inserted from one plasmid to another or from the plasmid to the chromosome

Answer 28

transposable drug resistance sequences

Question 29

new enzymes are synthesized

Answer 29

• inactivate the drugs

- only occurs when new genes are acquired

Question 30

permeability or uptake of the drug into a bacterium is decrease

Answer 30

• occurs via mutation

Question 31

• drug is immediately eliminated

Answer 31

• acquisition of new genes

Question 32

• binding sites for drugs are decreased in number or affinity

Answer 32

can occur via mutation or acquisition of new genes

Question 33

an affected metabolic pathway is shut down or alternative pathway is used

Answer 33

• occurs due to mutation of original enzyme or enzymes

Question 34

long term strategies to control drug resistance

Answer 34

• restriction of the use of first line antibiotics

- enhanced surveillance mechanisms

Question 35

• PulseNet, WHONET
• Track foodLborne pathogens and pathogenic microbial populations
• Provides up to date views of the changes in resistance genes

Answer 35

surveillance mechanisms

Question 36

Finding new targets in the bacterial cell

Customizing drugs that aim for these new targets

Answer 36

past approach

Question 37

Disabling host molecules that the invaders use to enhance their position

Answer 37

novel approach

Question 38

Using bacteriophages in Eastern European countries
Incorporating phage into wound dressings
Phage are extremely specific and only infect one species of bacteria, leaving normal microbiota alone

Answer 38

low tech solutions

Question 39

Preparations of live microorganisms fed to animals and humans to improve intestinal biota
Replace microbes lost during antimicrobial therapy
Augment the biota already there

Answer 39

probiotics

Question 40

Nutrients that encourage the growth of beneficial

microbes in the intestine

Answer 40

prebiotics

Question 41

Bind to the enamel of teeth, causing a permanent gray to brown discoloration
Cause liver damage in pregnant women
Cross the placenta and are deposited in fetal bones and teeth

Answer 41

tetracycline

Question 42

Most common complaint associated with oral antimicrobial therapy
Can progress to severe intestinal irritation or colitis
Some drugs directly irritate the intestinal lining
Also caused by disruption of the intestinal microbiota

Answer 42

diarrhea

Question 43

Drug acts as an antigen that stimulates the allergic
response
Can be provoked by the intact drug molecule or alteration of the drug

Answer 43

allergy

Question 44

Treats infection

Destroys normal biota, even those far removed from the original infection

Answer 44

broad spectrum antimicrobial

Question 45

Beneficial resident species are destroyed through
antibiotic therapy
Microbes once small in number begin to overgrow and cause disease

Answer 45

superinfection