Chapter 70 – Basic Principles of Antimicrobial Therapy
Antibiotic is a chemical that is produced by 1 microbe and has the ability to harm
other microbes; by definition only compounds that are made by microorganisms
qualify as antibiotics, therefore cellphone amines which are produced in a lab would
not be considered antibiotics under these strict definition
antimicrobials is any agent natural or synthetic that has the ability to kill or suppress
microorganisms; under this definition there is no distinction between compounds
produced by microbes or those made in a lab
there is no benefit in distinguishing the drugs therefore the terms are used
interchangeably
selective toxicity
the ability of a drug to injure a target without injuring other cells or organisms that
are in intimate contact with the target
For antimicrobial drugs selective toxicity indicates the ability of an antibiotic to kill or
suppress microbial pathogens without causing harm to the host
selective toxicity is what makes antibiotics valuable; if they did not have selective
toxicity they would be harmful to the host and have no therapeutic utility
achieving selective toxicity
Differences in cellular chemistry of mammals and microbes allow a drug to be toxic to
microbes and harmless to the host
o Disruption of the bacterial cell wall
bacteria are enclosed in a rigid cell wall unlike mammalian cells
within the cells the protoplasm has a high concentration of solutes
making the osmotic pressure within the bacterium high
if it weren't for the cell wall bacteria would absorb water swell and
burst
some families of drugs like penicillins and cephalosporins weaken the
cell wall which promotes bacterial lysis
because mammalian cells don't have a cell wall drugs directed at this
structure do not affect humans
o inhibition of an enzyme unique to bacteria
sulfonamides are selectively toxic because they inhibit an enzyme
needed to make folic acid which is required by all cells mammalian and
bacterial
Humans use folic acid from dietary sources but bacteria must
synthesize folic acid themselves; to begin bacteria take up para-
aminobenzoic acid (PABA) which is a precursor of folic acid and then
convert it into folic acid; sulfonamides block this conversion; because
humans do not engage in process, sulfonamide toxicity is only limited
to microbes
o disruption of bacterial protein synthesis
protein synthesis is completed by ribosomes in mammalian and
bacterial cells, however the ribosomes are not identical allowing us to
make drugs that disrupt the function of one but not the other
classification of antimicrobial drugs
, classification by susceptible Organism
o narrow spectrum antibiotics
active against only a few species of microorganisms; generally
preferred to broad spectrum drugs
Gram+ cocci and gram+ bacilli
Gram- aerobes
Mycobacterium tuberculosis
o broad spectrum antibiotics
active against a wide variety of microbes
Gram+ cocci and gram- bacilli
o Antiviral drugs
drugs for HIV infection
drugs for influenza
other antiviral drugs like acyclovir, ribavirin, interferon-a
o antifungal drugs
classification by mechanism of action
o drugs that inhibit bacterial cell wall synthesis or activate enzymes that disrupt
the cell wall
weaken the cell wall and promote bacterial lysis and death
penicillins and cephalosporins
o drugs that increase cell membrane permeability
increase permeability of cell membranes causing leaking of in cellular
material
amphotericin B
o drugs that cause lethal inhibition of bacterial protein synthesis
Aminoglycosides are the only drugs in this group
it is unknown why inhibition of protein synthesis by these drugs result
in cell death
o drugs that cause non lethal inhibition of protein synthesis
inhibit bacterial protein synthesis but unlike aminoglycosides these
agents only slow microbial growth; they do not kill bacteria at clinically
achievable concentrations
tetracyclines
o drugs that inhibit bacterial lysis of DNA and RNA or disrupt DNA function
inhibit synthesis of DNA or RNA by binding directly to nucleic acids or
by interacting with enzymes required for nucleic acid synthesis; can
also bind with DNA and disrupt its function
rifampin metronidazole fluoroquinolones like ciprofloxacin
o Antimetabolites
Disrupt specific biochemical reactions resulting in either a decrease in
the synthesis of essential cell constituents or synthesis of non
functional analogs of normal metabolites
trimethoprim and sulfonamides
o drugs that suppress viral replication
inhibit specific enzymes required for viral replication and infectivity like
DNA polymerase, reverse transcriptase, protease, integrase, or
neuraminidase
When choosing an antibacterial drug you should distinguish between agents that are
bactericidal and bacteriostatic
o bactericidal drugs are lethal to bacteria at clinically achievable concentrations
Antibiotic is a chemical that is produced by 1 microbe and has the ability to harm
other microbes; by definition only compounds that are made by microorganisms
qualify as antibiotics, therefore cellphone amines which are produced in a lab would
not be considered antibiotics under these strict definition
antimicrobials is any agent natural or synthetic that has the ability to kill or suppress
microorganisms; under this definition there is no distinction between compounds
produced by microbes or those made in a lab
there is no benefit in distinguishing the drugs therefore the terms are used
interchangeably
selective toxicity
the ability of a drug to injure a target without injuring other cells or organisms that
are in intimate contact with the target
For antimicrobial drugs selective toxicity indicates the ability of an antibiotic to kill or
suppress microbial pathogens without causing harm to the host
selective toxicity is what makes antibiotics valuable; if they did not have selective
toxicity they would be harmful to the host and have no therapeutic utility
achieving selective toxicity
Differences in cellular chemistry of mammals and microbes allow a drug to be toxic to
microbes and harmless to the host
o Disruption of the bacterial cell wall
bacteria are enclosed in a rigid cell wall unlike mammalian cells
within the cells the protoplasm has a high concentration of solutes
making the osmotic pressure within the bacterium high
if it weren't for the cell wall bacteria would absorb water swell and
burst
some families of drugs like penicillins and cephalosporins weaken the
cell wall which promotes bacterial lysis
because mammalian cells don't have a cell wall drugs directed at this
structure do not affect humans
o inhibition of an enzyme unique to bacteria
sulfonamides are selectively toxic because they inhibit an enzyme
needed to make folic acid which is required by all cells mammalian and
bacterial
Humans use folic acid from dietary sources but bacteria must
synthesize folic acid themselves; to begin bacteria take up para-
aminobenzoic acid (PABA) which is a precursor of folic acid and then
convert it into folic acid; sulfonamides block this conversion; because
humans do not engage in process, sulfonamide toxicity is only limited
to microbes
o disruption of bacterial protein synthesis
protein synthesis is completed by ribosomes in mammalian and
bacterial cells, however the ribosomes are not identical allowing us to
make drugs that disrupt the function of one but not the other
classification of antimicrobial drugs
, classification by susceptible Organism
o narrow spectrum antibiotics
active against only a few species of microorganisms; generally
preferred to broad spectrum drugs
Gram+ cocci and gram+ bacilli
Gram- aerobes
Mycobacterium tuberculosis
o broad spectrum antibiotics
active against a wide variety of microbes
Gram+ cocci and gram- bacilli
o Antiviral drugs
drugs for HIV infection
drugs for influenza
other antiviral drugs like acyclovir, ribavirin, interferon-a
o antifungal drugs
classification by mechanism of action
o drugs that inhibit bacterial cell wall synthesis or activate enzymes that disrupt
the cell wall
weaken the cell wall and promote bacterial lysis and death
penicillins and cephalosporins
o drugs that increase cell membrane permeability
increase permeability of cell membranes causing leaking of in cellular
material
amphotericin B
o drugs that cause lethal inhibition of bacterial protein synthesis
Aminoglycosides are the only drugs in this group
it is unknown why inhibition of protein synthesis by these drugs result
in cell death
o drugs that cause non lethal inhibition of protein synthesis
inhibit bacterial protein synthesis but unlike aminoglycosides these
agents only slow microbial growth; they do not kill bacteria at clinically
achievable concentrations
tetracyclines
o drugs that inhibit bacterial lysis of DNA and RNA or disrupt DNA function
inhibit synthesis of DNA or RNA by binding directly to nucleic acids or
by interacting with enzymes required for nucleic acid synthesis; can
also bind with DNA and disrupt its function
rifampin metronidazole fluoroquinolones like ciprofloxacin
o Antimetabolites
Disrupt specific biochemical reactions resulting in either a decrease in
the synthesis of essential cell constituents or synthesis of non
functional analogs of normal metabolites
trimethoprim and sulfonamides
o drugs that suppress viral replication
inhibit specific enzymes required for viral replication and infectivity like
DNA polymerase, reverse transcriptase, protease, integrase, or
neuraminidase
When choosing an antibacterial drug you should distinguish between agents that are
bactericidal and bacteriostatic
o bactericidal drugs are lethal to bacteria at clinically achievable concentrations
