Antimicrobial, Antifungal and Antiviral Drugs
• Paul Ehrlich – Father of chemotherapy, used organoarsenicals – syphilis
• Domagk – sulfonamides
• Fleming – penicillin from a mold
• Waksman – streptomycin
• Antibiotic: a substance produced by an microorganism that suppress the growth of other
• synthetic compounds would be called antimicrobial.
• Gram positive and negative: bacteria that take up gram’s stain are G+, and those that do not are
◦ cell wall is different: G- cell wall doesn't take up gram stain, while G+ lacks a component of
the cell wall and ca
• Emergence of resistant strains:
◦ Longstanding problem.
◦ Due to organism mutating to have different properties.
◦ Over-use or under-use?
▪ prescribe usually for 8-10 days
▪ usually people feel better after ~5 days
▪ and stop taking drug: but organism still in body, more resistant ones!
• Most of the current drugs take advantage of a difference between the host and the organism
• All these targets have been discovered (common ones)
• New targets will be more difficult to develop and hence the appearance of drugs that act via
novel mechanisms could be rare
◦ Vancomysin resistant bacteria: problem b/c was main backu[
• Narrow spectrum: e.g. penicillin acts on G+ only.
• Broad spectrum: acts on both G+ and G–.
• Bactericidal: kill the organism
• Bacteriostatic: prevent multiplication of organism and defense mechanism of the host remove
• bacteria have rigid cell walls: have high osmotic pressure
• mammalian cells do not have cell walls
• thus, penicillin inhibits an enzyme involved in cell wall synthesis and bacteria are formed
without cell walls and cannot maintain the pressure, break open
◦ selective toxicity: penicillin resembles D-alanyl-D-alanine and thus inhibits the enyzme
(transpeptidation reaction- cross links the peptide chains) that would be used to make the
cell wall Gram negative
← Grampositive does not have this layer
inhibits the synthesis ofthis layer
Resistance:some organisms can produce enzyme beta-
lactamase that breaks down penicilin
Classification of Penicillins
• Penicillin G
◦ extracted from penicillium mold.
◦ narrow spectrum mainly G+ organisms.
◦ pneumoniae, middle ear infections and skin infections, meningitis, and syphilis.
• Penicillin V – semisynthetic
◦ altered to make the molecule resistant to acid in the stomach
◦ more bioavailable than Pen G
• penicillin developed to become resistant to beta-lactamase
• bacteria become resistant to antibiotics by developing an enzyme that destroys the antibiotic.
◦ betalactamase or penicillinase – an adaptive enzyme produced by penicillin resistant
organisms (staphylococcus aureus).
• Ampicillin and Amoxicillin
◦ broader spectrum than Pen G, include some G– bacteria
◦ useful in urinary tract infections and E. coli.
◦ broad spectrum penicillin derivative, effective in severe infections caused by G– organisms
◦ problem: use where penicillin G would be sufficient
◦ combination of amoxacillin and clavulinic acid (ie an inhibitor of penicillinase)
◦ can be used for penicillinase producing organisms Adverse Effects of Penicillins
• one of safest drugs
• allergic reactions – most common:
◦ rash, tongue and face swell, urticaria (wheels)
◦ also get difficulty in breathing and fall in blood pressure if severe
◦ most antiobiotics cause diarrhea
◦ antibiotic destroy normal gut flora
◦ also if take antiobiotics with oral contraceptives, sometimes interfere with efficacy partially
b/c of diarrhea
• Similar to penicillin in mechanism of action, but are more resistant to penicillinase.
• first generation: Cephalothin, good against G+ less effective against G–.
• CefamandoleL second generation, increased activity against G–.
• third generation: less active against G+ than first generation, but increased activity against G–.
• fourth generation: broader spectrum
Fluoroquinolones highly abused b/c it is broad spectrum, lots of
• Ciprofloxacin resistance
◦ broad spectrum G+ and G–
◦ inhibits DNAGyrase (ie topoisomerase II) and protein synthesis
Erythromycin and Congeners
• Severe G+ infections.
• Inhibits protein synthesis
• Used where individual allergic to penicillin.
• Also used for some G– infections. Gonococci and legionnaires bacillus (people caught at a
legionnaire conference when air conditioning unit was infected)
• Azithromycin and clarithromycin.
• Chemically modified from erythromycin, more effective than erythromycin but more expensive.
• Broad spectrum – bacteriostatic: don't kill organism, but stop their growth
• Resistance is a problem due to over use
• Inhibits bacterial protein synthesis
• High affinity for calcium in bone and teeth → can't use in children (teeth and bone formation)
and pregnant women
Oxygens/hydroxyls on rings can bind calcium chloramphenicol
• Broad spectrum, bacteriostatic antimicrobial