Antibacterial Inhibitors of Cell Wall Synthesis Very high

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 • • 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 30 S 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 50 S subunit • Chloramphenicol – – 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 1 st antibiotics useful against GPseudomonas – Topical • Combined with bacitracin and neomycin in over-the -counter preparation (neosporin)

Antibacterial Inhibitors of Nucleic Acid Synthesis • Rifamycin – – 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 – – – 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