Download Chapter 20 Antimicrobial Drugs

Antibacterial Inhibitors of Cell Wall
Synthesis
– Very high therapeutic index
• Low toxicity with high effectiveness
• β- lactam Drugs
– Inhibit peptidoglycan synthesis
– Only effective against growing bacteria
– Vary in their spectrum of activity
•Some bacteria produce β- lactamase enzymes
•Destroys β- lactam ring which inactivates drug
•Greater variety produced by G- bacteria
Penicillinase cleaves the β–lactam ring from the
common nucleus of penicillin compounds
• Penicillins
– group of over 50 related antibiotics
– share a common core structure
– Natural penicillins
• have a narrow range of activity
– Semisynthetic penicillins
• overcome disadvantages
• Natural Penicillin
– Produced by the mold Penicillium chrysogenum
– Most common are Penicillin G and Penicillin V
– Narrow spectrum
• Effective against Gram + and few Gram – cocci
• Semi-synthetic Penicillin
– Penicilinase-resistant penicillins
• Methicillin – MRSA reduced use
– Penicillins + -lactamase inhibitors
• Augmentin
– Combines amoxicillin with clavulanic acid which inhibits
penicillinase
•Cephalosporins
•Produced by mold
Acremonium cephalosporium
•resemble penicillin
•broader spectrum
•Semi-synthetic versions
grouped as generations
•New generations less
susceptible to β -lactamases
• Polypeptide antibiotics
– Bacitracin
• Produced by species of Bacillus
• Topical application due to toxicity
• effective primarily against G+ bacteria
– Vancomycin
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Produced by species of Streptomyces
Has narrow spectrum similar to penicillin
Used to treat antibiotic-associated colitis
Important "last line" against MRSA and VRE
• Antimycobacterial drugs
– effective only against Mycobacterium
– Isoniazid
• Inhibits mycolic acid synthesis
– Ethambutol
• Inhibits incorporation of mycolic acid
Antibacterial Inhibitors of Protein Synthesis
• Bind 30S subunit
• Aminoglycosides
– Produced by Streptomyces spp.
– Broad spectrum
– Streptomycin, neomycin, gentamycin, tobramycin
• serious side effects
• Streptomycin is an alternative treatment for
tuberculosis
– resistant strains rapidly emerging
• Tetracyclines
– Produced by Streptomyces
– Oxytetracycline, Doxycycline
– Broadest spectrum of all anti-bacterial drugs
• Effective against most G- and G+ bacteria; rickettsias
and chlamydias
– Common animal feed additive
• Bind 50S subunit
• Chloramphenicol
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Produced by Streptomyces
Very simple chemical structure and inexpensive
Broad spectrum
Serious toxicity issues
• Macrolides
– Erythromycin , azithromycin
– Choice mycoplasmal pneumonia
• Oxazolidinones
– Narrow spectrum (mostly G+), totally synthetic
• resistance develops slower
• Useful against vancomycin and β- lactam resistant
bacteria
Antibacterial Injury to the Plasma Membrane
• Polymyxin B
– Useful against G- bacteria & G+
– One of the 1st antibiotics useful against GPseudomonas
– Topical
• Combined with bacitracin and neomycin in overthe-counter preparation (neosporin)
Antibacterial Inhibitors of Nucleic Acid
Synthesis
• Rifamycin
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Rifampin
Inhibits RNA synthesis in prokaryotes
Effective against Gram+, Gram- and mycobacterium
Used in treatment of tuberculosis and prophylactic
prevention of meningitis
• Penetrate tissues so capable of reaching cerebrospinal fluid and
abscesses
• Fluoroquinolones
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Synthetic Drugs
Broad spectrum
Ciprofloxacin
Inhibits enzyme needed for DNA replication
Adversely effect the development of cartilage
• limited use in children and pregnant women
Antibacterial Anti-metabolites
Sulfonamides (Sulfa
drugs)
• Broad spectrum
• Inhibit folic acid synthesis
Trimethoprim
• Used in combination with
sulfa drugs
– broader spectrum and
reduces the risk of
resistance