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Antimicrobial Drugs
The dawn of antibiotics
• Paul Erlich (1910)
– Wanted to find the “magic
bullet” for syphilis
– proposed the idea of the
blood brain barrier
– Worked at staining tissues
and first to come up with
the idea behind “selective
toxicity”
– Nobel Prize in 1908
Alexander Fleming
• A physician who studied
bacterial action of blood
and antisepsis
• Discovered and named
Lysozyme
• Discovered mold growing
on an agan plate(1928)
• 1945 Nobel Prize in
Physiology or Medicine
along with Chain and
Florey
Chain and Florey
• 1940 developed a system for growing
Penicillium and purifying the drug
• Tested the drug in mice, passed all trials
• Received the Nobel Prize in 1945 with
Alexander Fleming for their work
Antibiotics
• A substance produced by a microorganism
that inhibits or kills other microbes
Microbes that produce antibiotics
Range of activity
• Narrow range: target one group of microbes
• Broad range: target a wide group of
different microbes
• Which one is the best?
Spectrum of activity
Targets of antimicrobial drugs
Targets of Cell Wall Synthesis
How does penicillin work?
• Inhibits formation of tetrapeptide side
chains….which means….
• What happens if you put a cell in a solution
with penicillin?
Some drugs target protein
synthesis
Penicillin weakens the cell wall
Beta-lactam ring common with
penicillins and cephalosporins
How organisms degrade
penicillins
Family of Penicillins
• Natural penicillins– Penicillin G and V
• Penicillinase-resistant penicillins
– Methicillin, Dicloxacillin
• Broad-spectrum penicillins
– Ampicillin, Amoxicillin
• Extended-spectrum penicillins
– Ticaricillin, Piperacillin
• Penicillins plus beta-lactamase inhibitors
– Augmentin (amoxicillin and clavulanic acid)
Side chain varies for
derivatives of penicillin
Cephalosporins
• Derived from fungus, Acremonium
cephalosporium
• Chemical structure makes them resistant to
beta-lactamase, low affinity for penicillin
binding proteins
• Grouped into first, second, third, and fourth
generation cephalosporins
Vancomycin
• Binds to the terminal amino acids of the
peptide chain of NAM molecules, blocks
peptidoglycan formation
Antibiotics that inhibit protein
synthesis
Aminoglycosides
• Bactericidal
• Irreversibly bind to 30S ribosome, cause
misreading of the mRNA
• Transported into cells that actively respire
(not effective against ananerobes,
streptococci, enterococci)
• Ex: streptomycin, gentamicin, tobramycin
Tetracyclines
• Bind reversibly to 30S, block attachment of
the tRNA to ribosome
• Actively transported into bacterial cells
• Effective against gram positive and gram
negative
• Resistance: due to decrease in uptake or
increase in excretion
• Ex: Doxycycline
Macrolides
• Reversibly bind to the 50S, prevent
continuation of protein synthesis
• Drug of choice for patients allergic to
penicillins
• Not good for Enterobacteriaceae
• Ex: Erythromycin, Azithromycin
• Resistance: enzymes that alter drug,
decreased uptake
Oxazolidinones
• Reversibly bind to the 50S subunit, interfere
with initiation of protein synthesis
• Used for treating gram positive infections
resistant to Beta-lactam drugs and
Vancomycin
• Ex: Linezolid
Antibiotics that inhibit nucleic
acid synthesis
• Fluoroquinolones
– Inhibit topoisomerase
• Rifamycins
– Blocks prokaryotic RNA polymerase from
initiating transcription
Antibiotics that inhibit metabolic
pathways
• Sulfonamides
• Trimethoprims
Sulfonamides (sulfa drugs)
• First synthetic drugs to treat microbial
infections
• Used to treat urinary tract infections (UTIs)
• Combination of trimethoprim and
sulfamethoxazole (TMP-SMZ) example of
synergism
Tests for microbial sensitivity
• Kirby-Bauer (disk diffusion method)
– We did this in lab
• Determining the Minimum Inhibitory
Concentration (MIC)
• E test
– easier way to determine the MIC
Kirby-Bauer tests for sensitivity
Determining the Minimum
Inhibitory Concentration (MIC)
E-test for MIC
What resistance
looks like…
Mechanisms of Drug resistance
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Destruction or inactivation of the drug
Prevention of penetration to target site
Alteration of target site (mutation)
Pumping of the drug out of the
bacterial cell
Emerging Antibiotic Resistance
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Enterococci
Staphylococcus aureus
Steptococcus pneumoniae
Mycobacterium tuberculosis
Targets of Viral drugs