Lecture 9 Flashcards
Be able to define the following terms
Antimicrobial chemotherapy, prophylaxis,
antimicrobial drug, antibiotic, semisynthetic drug,
synthetic drug, narrow and broad spectrum
drugs.
- Chemotherapuetic Drug: Any
chemical used in the treatment, relief,
or prophylaxis of a disease. - Prophylaxis: Use of a drug to prevent
imminent infection of a person at risk
(prophylactic drug). - 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
Where are antibiotics found?
Bacteria and fungi
What organisms produce them?Bacteria and fungi
Streptomyces and Bacillus
Penicillium and Cephalosporium
Why do microbes produce antibiotics?
To inhibit the growth of competing microbes
in the same habitat
What are 2 examples of effects that chemical
modifications can have on semisynthetic
drugs?
- Make the antibiotic more stable.
- Increase or modify the spectrum of
the antibiotic
What is meant by the post antibiotic era?
Where antibiotics are no longer effective
What do MRSA, VRE, CRE stand for?
MRSA: Methicillin-resistant Staphylococcus
aureus
VRE: Vancomycin-resistant Enterococcus
CRE: Carbapenem-resistant
Enterobacteriaceae
What is meant by selective toxicity>
To administer a drug to an infected person
that destroys the infective agent without
harming the host’s cells
What are characteristics of an ideal
antimicrobial drug?
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.
What are 3 factors to consider when
choosing antimicrobial chemotherapy?
- The nature of the microorganism
causing the infection
- The degree of the microorganism’s
sensitivity to various drugs
- The overall medical condition of the
patient
What are 2 examples of methods to test a
microbes drug susceptibility?
- Kirby-Bauer
2. Tube dilution tests
What are the steps of Kirby-Baeur test?
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
What is a zone of inhibition?
After incubation of the plates, zone of
inhibition surrounding the discs is measured
and compared with a standard for each drug
What are the steps in performing a tube
dilution test for drug susceptibility?
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)
What is meant by a minimum inhibitory
concentration?
The smallest concentration (highest dilution)
of drug that visibly inhibits all growth
What is a therapeutic index of an
antimicrobial drug?
The ratio of the dose of the drug that is toxic
to humans as compared to its minimum
effective (therapeutic) dose
What are 5 common targets of an
antimicrobial drugs?
- Inhibition of cell wall synthesis
- Inhibition of nucleic acid structure
and function
- Inhibition of protein synthesis
- Interference with cell membrane
structure and function
- Inhibition of folic acid synthesis (or
other biosynthetic pathways)
Why might it be more difficult to achieve
selective toxicity for fungi than bacteria?
Bacteria are distantly related, have many
potential targets; Fungi are also animals, so
there are fewer potential targets.
What are the targets and uses/characteristics
of the following antimicrobial drugs?:
Penicillin, methicillin, vancomycin,
clindamycin, streptomycin, tetracyclines,
linezolid, sulfonamides, polymyxins, rifampin,
ciprofloxacin.
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)
What functional chemical group do penicilins
contain? (ring?)
Beta- lactam ring
What effect do these drugs have on the
transpeptidase and on the cell wall synthesis
and growth?
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)
What type of enzyme provides resistant to
penicillin and how is the resistance achieved?
Penicillinase and beta-lactamses. They cleave
the b-lactam ring, allow for resistance
What are the 2 ways in which semisynthetic
derivatives of penicillins improve or modify
the action of these drugs?
- 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
Would you generally expect an antibiotic that
is effective against bacteria to be effective
against fungi?
no
What do these drugs do: Macrolide Polyenes,
Azoles, and Echinocandins
1. Macrolide polyenes (e.g. amphotericin B) • Bind to fungal membranes, causing loss of selective permeability Specifically interacts with fungi-specific sterols
- Azoles (e.g. miconazole, clotrimazole)
Interferes with sterol synthesis, affect
membrane integrity - Echinocandins (e.g. caspofungin) •
Inhibit fungal cell wall synthesis
What are the 3 major models of action of
antiviral drugs?
1) Interacting with receptor “spike” proteins
on the virion surface
2) Blocking transcription and translation ofviral DNA/RNA
3) Preventing maturation of viral particles
What are 2 reasons why cells in a biofilm
might be more resistant to antimicrobial
drugs than free living cells?
- Penetration of the biofilm is a
factor
- Different phenotype is expressed
by biofilm bacteria, giving them
different antibiotic sensitivity
What are the 3 strategies for testing biofilm
infections?
- Interrupting quorum sensing signals
to impede biofilm formation
- Treating with enzymes that will
digest and weaken or disrupt the
biofilm matrix (extracellular
deposits/glycocalyx)
- Impregnating devices where biofilms
can grow with antibiotics
How might a microbe become resistant to an
antimicrobial drug?
Microbes that produce antibiotics have
resistance mechanisms to the antibiotics that
they produce
What role do nonpathogenic microbes play in
the spread of antimicrobial drug resistance to
pathogenic microbes?
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
What are the 5 major mechanisms of drug
resistance?
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
What are 4 examples of new approaches to
antimicrobial therapy?
- Mining natural microbes for new
antibiotics
- Targeting iron scavenging capabilities
of bacteria
- Mimicking defense peptides
- Using bacteriophages
What is a superinfection?
microbes that were once small in number
overgrow when normal resident biota aredestroyed by broad-spectrum antimicrobials
What are problems with overuse or misuse of
antimicrobial drugs?
- 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
- 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
