Lecture 9 Flashcards

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1
Q

Be able to define the following terms

Antimicrobial chemotherapy, prophylaxis,

antimicrobial drug, antibiotic, semisynthetic drug,

synthetic drug, narrow and broad spectrum

drugs.

A
  1. Chemotherapuetic Drug: Any
    chemical used in the treatment, relief,
    or prophylaxis of a disease.
  2. Prophylaxis: Use of a drug to prevent
    imminent infection of a person at risk
    (prophylactic drug).
  3. Antimicrobial chemotherapy: Use of
    chemotheraputic drugs to control
    microbial infectious disease.
4. Antimicrobial: All-inclusive term for 
any antimicrobial drug, regardless of 
its origin. Antibiotic: Substances 
produced by the natural metabolism 
of some microbes that can inhibit or 
kill other microbes. 
5. Semisynthetic drugs: Drugs that are 
chemically modified in the laboratory 
after being isolated from natural 
sources.  Synthetic drugs: Drugs 
produced entirely in the laboratory, 
not derived from living organisms. 
6. Spectrum of a drug: The breadth of 
different microbes that a given drug is 
effective on. Narrow spectrum 
(limited spectrum): Antimicrobials 
effective against a limited number of 
microbes, e.g. effective only on Gram-
positive bacteria. 
7. Broad spectrum (extended spectrum): 
Antimicrobials effective against a 
wide variety of microbial types e.g. 
Gram-positive and Gram-negative 
bacteria
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2
Q

Where are antibiotics found?

A

Bacteria and fungi

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3
Q

What organisms produce them?Bacteria and fungi

A

Streptomyces and Bacillus

Penicillium and Cephalosporium

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4
Q

Why do microbes produce antibiotics?

A

To inhibit the growth of competing microbes

in the same habitat

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5
Q

What are 2 examples of effects that chemical
modifications can have on semisynthetic
drugs?

A
  1. Make the antibiotic more stable.
  2. Increase or modify the spectrum of

the antibiotic

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6
Q

What is meant by the post antibiotic era?

A

Where antibiotics are no longer effective

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7
Q

What do MRSA, VRE, CRE stand for?

A

MRSA: Methicillin-resistant Staphylococcus

aureus

VRE: Vancomycin-resistant Enterococcus

CRE: Carbapenem-resistant

Enterobacteriaceae

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8
Q

What is meant by selective toxicity>

A

To administer a drug to an infected person

that destroys the infective agent without

harming the host’s cells

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9
Q

What are characteristics of an ideal

antimicrobial drug?

A

Selectively toxic to microbe but not to host

cells. • Doesn’t produce an allergic reaction

in the host. • Doesn’t predispose the host to

other infections. • Acts against the target

pathogen but not against the normal host

microbiota. • Microbicidal rather than
microbistatic. • Soluble, easily delivered to

the site of infection. • Active at low

concentrations in body tissues, fluids. • Is

stable (not easily degraded) and not quickly

excreted. • Doesn’t easliy lead to

development of antimicrobial resistance.

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10
Q

What are 3 factors to consider when

choosing antimicrobial chemotherapy?

A
  1. The nature of the microorganism

causing the infection

  1. The degree of the microorganism’s

sensitivity to various drugs

  1. The overall medical condition of the

patient

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11
Q

What are 2 examples of methods to test a

microbes drug susceptibility?

A
  1. Kirby-Bauer

2. Tube dilution tests

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12
Q

What are the steps of Kirby-Baeur test?

A

1) Plate of solid growth medium is spread

with a culture of the microbe to be tested

2) Discs with various compounds are placed

on the inoculated plate

3) Plate is incubated at appropriate growth

conditions for the microbe

4) Zone of inhibition of growth around discs

is measured and compared to standards

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13
Q

What is a zone of inhibition?

A

After incubation of the plates, zone of

inhibition surrounding the discs is measured

and compared with a standard for each drug

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14
Q

What are the steps in performing a tube

dilution test for drug susceptibility?

A

1) Liquid medium is inoculated with a culture

of the microbe to be tested

2) Different concentrations of an antibiotic

are added to the tubes (dilution series)

3) Tubes are incubated at appropriate growth

conditions for the microbe

4) The minimum amount of antibiotic that

inhibits all growth is the MIC (minimum

inhibitory concentration)

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15
Q

What is meant by a minimum inhibitory

concentration?

A

The smallest concentration (highest dilution)

of drug that visibly inhibits all growth

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16
Q

What is a therapeutic index of an

antimicrobial drug?

A

The ratio of the dose of the drug that is toxic

to humans as compared to its minimum

effective (therapeutic) dose

17
Q

What are 5 common targets of an

antimicrobial drugs?

A
  1. Inhibition of cell wall synthesis
  2. Inhibition of nucleic acid structure

and function

  1. Inhibition of protein synthesis
  2. Interference with cell membrane

structure and function

  1. Inhibition of folic acid synthesis (or

other biosynthetic pathways)

18
Q

Why might it be more difficult to achieve

selective toxicity for fungi than bacteria?

A

Bacteria are distantly related, have many

potential targets; Fungi are also animals, so

there are fewer potential targets.

19
Q

What are the targets and uses/characteristics

of the following antimicrobial drugs?:

Penicillin, methicillin, vancomycin,

clindamycin, streptomycin, tetracyclines,

linezolid, sulfonamides, polymyxins, rifampin,

ciprofloxacin.

A

Penicillin Cell wall synthesis

Methicillin Cell wall synthesis

Vancomycin Cell wall synthesis

Clindamycin Protein synthesis (50S ribosome

subunit)

Streptomycin (an aminoglycoside) Protein

synthesis (30S ribosome subunit)

Tetracyclines Protein synthesis (30S ribosome

subunit)

Linezolid Protein synthesis

Sulfonamides (sulfa drugs) Folic acid

synthesis

Polymyxins Membranes (some specificity for

LPS in outer membrane)Rifampin (rifamycin) Transcription (RNA

polymerase)

Ciprofloaxcin (a fluoroquinolone) DNA

replication (unwinding by DNA gyrase)

20
Q

What functional chemical group do penicilins

contain? (ring?)

A

Beta- lactam ring

21
Q

What effect do these drugs have on the

transpeptidase and on the cell wall synthesis

and growth?

A

The beta-lactam ring interacts with and

inactivates transpeptidase. Transpeptidase

makes crosslinks between peptide chains in

the cell wall. Inactivation results in faulty cell

wall synthesis, cell lysis (microbicidal)

22
Q

What type of enzyme provides resistant to

penicillin and how is the resistance achieved?

A

Penicillinase and beta-lactamses. They cleave

the b-lactam ring, allow for resistance

23
Q

What are the 2 ways in which semisynthetic

derivatives of penicillins improve or modify

the action of these drugs?

A
  1. Achieved by changing functional
    groups attached to the beta-lactam
    ring
2.  Broader spectrum: allow for better 
penetration of the outer membrane, 
and thus can affect some Gram 
negative bacteria as well as Gram 
positives
24
Q

Would you generally expect an antibiotic that
is effective against bacteria to be effective
against fungi?

A

no

25
Q

What do these drugs do: Macrolide Polyenes,

Azoles, and Echinocandins

A
1. Macrolide polyenes (e.g. 
amphotericin B) • Bind to fungal 
membranes, causing loss of selective 
permeability Specifically interacts 
with fungi-specific sterols 
  1. Azoles (e.g. miconazole, clotrimazole)
    Interferes with sterol synthesis, affect
    membrane integrity
  2. Echinocandins (e.g. caspofungin) •
    Inhibit fungal cell wall synthesis
26
Q

What are the 3 major models of action of

antiviral drugs?

A

1) Interacting with receptor “spike” proteins

on the virion surface

2) Blocking transcription and translation ofviral DNA/RNA
3) Preventing maturation of viral particles

27
Q

What are 2 reasons why cells in a biofilm
might be more resistant to antimicrobial
drugs than free living cells?

A
  1. Penetration of the biofilm is a

factor

  1. Different phenotype is expressed

by biofilm bacteria, giving them

different antibiotic sensitivity

28
Q

What are the 3 strategies for testing biofilm

infections?

A
  1. Interrupting quorum sensing signals

to impede biofilm formation

    1. Treating with enzymes that will

digest and weaken or disrupt the

biofilm matrix (extracellular

deposits/glycocalyx)

  1. Impregnating devices where biofilms

can grow with antibiotics

29
Q

How might a microbe become resistant to an

antimicrobial drug?

A

Microbes that produce antibiotics have

resistance mechanisms to the antibiotics that

they produce

30
Q

What role do nonpathogenic microbes play in
the spread of antimicrobial drug resistance to
pathogenic microbes?

A

Non-disease-causing flora of humans and

animals can harbor antibiotic resistance

genes that can be transferred to pathogenic

bacteria with which they share space

31
Q

What are the 5 major mechanisms of drug

resistance?

A

1) Enzymatic degradation of antibiotics
2) Preventing uptake of antibiotics Major
mechanisms of drug resistance
3) Efflux (pumping out) of antibiotics form
the cytoplasm
4) Alteration of binding site for antibiotics
5) Use of alternative biosynthetic pathways

32
Q

What are 4 examples of new approaches to

antimicrobial therapy?

A
  1. Mining natural microbes for new

antibiotics

  1. Targeting iron scavenging capabilities

of bacteria

  1. Mimicking defense peptides
  2. Using bacteriophages
33
Q

What is a superinfection?

A

microbes that were once small in number

overgrow when normal resident biota aredestroyed by broad-spectrum antimicrobials

34
Q

What are problems with overuse or misuse of

antimicrobial drugs?

A
  1. Antimicrobial drugs are often seen as

a “cure-all” • May be used for

infections such as the common cold

and acne where the antimicrobial

drug may have little or no beneficial

effect

  1. Physicians have used a “shotgun”

approach, using broad-spectrum

antimicrobial therapy for minor

infections • This can lead to

superinfections and other adverse

reactions • It can cause the

development of resistance in

“bystander” microbes (normal biota)

that were exposed to the drug as well

• Leads to the spread of resistance

among potential pathogens