CHAPTER 5: Lesson 16: Antimicrobial Therapy and Resistance Flashcards
is defined as that which minimizes the
development of resistance as well as resulting in a therapeutically successful
outcome
successful antimicrobial therapy
can be initiated as soon as specimens are collected
Chemotherapy
can, if necessary, be modified when laboratory data are at hand
empirical chemotherapy
arising from chemotherapy require careful
consideration in some species and also in young animals
Inherent Toxicity or Side Effects
Legal regulations in some
countries may prohibit the use of certain antibiotics, such as ________ in
food-producing animal
chloramphenicol
Classification of Antimicrobial Drugs
- Spectrum of activity against class of microorganism
- Antibacterial activity
- Bacteriostatic or bactericidal
- Pharmacodynamic activity
- Mechanism of action
are narrow spectrum because they inhibit only bacteria
Penicillins
are broader because they inhibit both bacteria and protozoa.
sulfonamides, trimethoprim, and
lincosamides
only inhibit fungi.
Polyenes
Some antibiotics are __________ in that they inhibit only
gram-positive (bacitracin and vancomycin) or mainly gram negative bacteria
(polymyxin)
Narrow Spectrum
Some antibiotics are narrow spectrum in that they inhibit only
gram-positive (bacitracin and vancomycin) or mainly gram negative bacteria. Give an example(s) of each type of bacteria.
*gram-positive (bacitracin and vancomycin) *gram negative bacteria
(polymyxin)
such as tetracyclines inhibit both gram positive and gram-negative bacteria
broadspectrum drugs
Example of a broadspectrum drug that inhibits both gram positive and gram-negative bacteria.
tetracyclines
Other drugs such as _____________ are most active against gram-positive bacteria but will inhibit some
gram-negatives.
Penicillin G or lincosamides
This distinction is an approximation that depends on
drug concentrations and the organism involved
Bacteriostatic or bactericidal
This drug is bactericidal
at high concentrations and bacteriostatic at lower ones.
penicillin
The distinction between
bactericidal and bacteriostatic is critical in certain circumstances, such as the
treatment of the _____________.
meningitis or of septicemia in neutropenic patients
: Antibacterial action is concentration or time dependent
Pharmacodynamic activity
: Like pharmacodynamic activity, this is dependent on the
drug class. This is probably the most useful of the classifications, since it determines
the previous four classification approaches
Mechanism of action
Narrow Spectrum & Broader Spectrum
Spectrum of activity against class of microorganism
Narrow Spectrum for either gram positive or gram negative bacteria
Broad Spectrum for both gram positive and gram negative bacteria
Antibacterial activity
Mechanism of Action of Antimicrobial Drugs
(1) inhibition of cell wall synthesis
(2) damage to cell membrane
function (3) inhibition of nucleic acid synthesis or function, and
(4) inhibition of protein synthesis
Purine synthesis
Sulfonamides trimethoprim
Example of drugs that Inhibit Cell Wall Synthesis
penicillins and cephalosporins (β-lactam antibiotics), bacitracin,
and vancomycin
It inhibits cross-linkage between peptidoglycans in the cell wall,
inhibiting division, and creating weak points during active growth and cell division.
Inhibition of Cell Wall Synthesis [penicillins and cephalosporins (β-lactam antibiotics), bacitracin,
and vancomycin.]
The cross-linkage between _________ gives the cell wall remarkable strength.
peptidoglycans
Antibiotics that damage the cell membrane function include
polymyxins,
monensin, and the antifungal polyenes (amphotericin, nystatin) and imidazoles
(fluconazole, itraconazole, ketoconazole, miconazole)
The ________ lies
beneath the cell wall, enclosing the cytoplasm
cell membrane
It controls the passage of materials
into or out of the cell. If its function is damaged, cellular contents (proteins,
nucleotides, ions) can leak from the cell and result in cell damage and death.
Cell membrane
Examples of Drugs That Inhibit Nucleic Acid Function are
*nitroimidazoles,
*nitrofurans,
“nalidixic acid,
“flfluoroquinolones (ciproflfloxacin, danoflfloxacin,
diflfloxacin, enroflfloxacin, orbiflfloxacin, saraflfloxacin),
*novobiocin,
*rifampin,
*sulfonamides,
*trimethoprim, and
*5-flflucytosine
mechanisms of these are similar in all cells
Nucleic
acid Synthesis, Replication, and Transcription
drugs affecting
_________ function have poor selective toxicity
Nucleic Acid
Drugs with greater selective toxicity
sulfonamides and trimethoprim
which inhibits the synthesis of folic acid
sulfonamides and trimethoprim
Examples of drugs that inhibit protein synthesis
- tetracyclines;
- aminoglycosides (amikacin, gentamicin, kanamycin, neomycin, streptomycin,
tobramycin, and others); - aminocyclitols (spectinomycin);
- chloramphenicol;
- lincosamides (clindamycin, lincomycin); and * macrolides (azithromycin, clarithromycin, erythromycin, tylosin, tiamulin)
Antibiotics affecting protein synthesis can be divided into those affecting the _________
- 30S
ribosome (tetracyclines, aminoglycosides, aminocyclitols) and those affecting the - 50S ribosome (chloramphenicol, macrolides, lincosamides).
are matters relevant to the veterinarian and the owner.
Route and frequency of administration of the drug,
cost of treatment, adverse effects on the host and public health aspects of treatment
pathogenic bacteria that commonly exhibit drug resistance ,
staphylococci, members of the Enterobacteriaceae and pseudomonads
Anti-microbial Drug Interaction
Combination of the use of antimicrobial drug may produce a different effect
from that achieved by the individual drugs used separately such as:
Indifference
Additive
Synergism
Antagonism
: where the combined action is no greater than that of the more
effective drug used alone
Indifference
: where the combined action is equivalent to the sum of the actions of
each drug when used alone
Additive
: where the combined action is significantly greater than the sum of
both effects
Synergism
: where the combined action is less than that of the more effective
agent when used alone. Ex: bacteriostatic drugs (chloramphamicol or a
tetracycline) and bactericidal drugs (penicillin or an aminoglycoside).
Antagonism
ANTAGONISM DRUGS
Ex: bacteriostatic drugs (chloramphamicol or a
tetracycline) and bactericidal drugs (penicillin or an aminoglycoside).
Forms of Antimicrobial Synergy
- Two drugs may sequentially block a microbial metabolic pathway
- One drug may prevent the inactivation of a second drug by microbial
enzymes - One drug may promote the uptake of a second drug thereby increasing the
overall antimicrobial effect - One drug may affect the cell membrane and facilitate the entry of a second
drug. - A drug combination may also prevent the emergence of resistant
populations.
Two drugs may sequentially block a microbial metabolic pathway. Ex:
sulphonamide with
trimethoprim (Folate antagonists)
(synthesis of dihydrofolate needed for the growth of bacteria)
sulphonamide
(Folate antagonists)
trimethoprim
One drug may prevent the inactivation of a second drug by microbial
enzymes. Ex:
Inhibition of beta-lactamases by clavulanic acid
can protect
penicillin G or other susceptible antibiotics from inactivation by bacteria that
produce beta-lactamase.
Inhibition of beta-lactamases by clavulanic acid
One drug may promote the uptake of a second drug thereby increasing the
overall antimicrobial effect.Ex:
Penicillins
It enhance aminoglycosides by for the
treatment of enterococcal endocarditis.
Penicillin
One drug may affect the cell membrane and facilitate the entry of a second
drug. Ex:
Amphotericin B
may be synergistic with flucytosine against
Cryptococcus neoformans.
Amphotericin B
A drug combination may also prevent the emergence of resistant
populations. Ex:
erythromycin-rifampicin
Drug against Rhodococcus equi infection in
foals.
erythromycin-rifampicin
erythromycin-rifampicin against ________ infection in
foals.
Rhodococcus equi
Considerations when administering two antimicrobial drugs
- Drugs are not antagonistics to each other;
- Treatment of mixed bacterial infections, where each drug has activity against
one of the pathogens; - Treatment of severe infections of uncertain aetiology;
- Use of synergistic combinations with documented efficacy against specific
infections.
Take note of the inherent disadvantages in combined antimicrobial treatment
regimens such as ___________ from the drugs used
additive toxic effect
disadvantages in combined antimicrobial treatment
regimens such as increased risk of
superinfection with overgrowth of fungi or resistant bacteria and a danger of
enhanced spread of __________.
R plasmids
