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

Penicillinase cleaves the β–lactam ring from the common nucleus of penicillin compounds Some bacteria produce β- lactamase enzymes Destroys β- lactam ring which inactivates drug Greater variety produced by G- bacteria

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

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 Antibacterial Inhibitors of Protein Synthesis

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 –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 G- Pseudomonas –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