Tetracyclines

Broad spectrum

1ST – Rickettsia, Chlamydia

Good for intracellular bacteria because good penetration into host cells

Tigecycline 

-drug resistant Gram neg & MRSA; not good for UTI or blood (newest derivative, a glyclglycine) 

Spectinomycin

Spectinomycin:  MOA similar to aminoglycosides (aminocyclitol); Binds to 30S but is bacteriostatic.

Chloramphenicol 

Binds reversibly to 50S

Prevents peptide bond formation

BROAD SPECTRUM

Toxic effects – Aplastic anemia

Lincomycin and the derivative Clindamycin

• Mechanism of action:  Interference with peptide bond formation
• Effective against anaerobes:  e.g. Bacteriodesfragilis
• Problem:   May induce overgrowth of Clostridium difficile  

Macrolides

• reversible binding to 23S rRNA in 50S ribosomal subunit
• Erythromycin:  Primarily effective against Gram + bacteria
•      New derivatives: Azithromycin and Clarithromycin
• Erythromycin is the drug of choice for Mycoplasma  pneumoniae infections and Legionairre’s Disease  

Oxazolidinones

Linezolid - ZYVOX

A synthetic antimicrobial agent that is the first in a new class of agents – designed from scratch.  First new class in 40 years

Useful for Gram positive infections:  First new drug for Staphylococcus infections in years.  Tx: MRSA & VRE

Thought to attack an unexploited site:  The proper assembly of the fmet-tRNA with mRNA and the 30S subunit.  May also act by binding 50S and preventing 70S formation.

  TOTALLY NEW TARGET

Neither linezolid or its chemical relatives have been used for animal infections or as growth promoters.

YET: resistance already reported (LRE/LRVRE)!

Rifamycins (Rifampin=Rifampicin; cidal)

• Inhibit RNA synthesis by interacting with DNA-DEPENDENT, RNA POLYMERASE, preventing transcription; use with other drugs; used for TB, leprosy; prophylaxis of patient contacts of bacterial meningitis

Griseofulvin

Fungistatic agent that affects fungal microtubles, inhibiting DNA replication and mitosis. 

Ineffective if applied locally.  Must be given orally – Collects in keratin.  At the levels used, does not affect mammalian cells. 

Quinolones/Fluoroquinolones

• Active against Gram (-) or (+) bacteria:  BROAD SPECTRUM
• Pseudomonas aeruginosa, Methicillin-resistant Staphylococcus
• Inhibit DNA GYRASE (Neg.)/Topoisomerase (Pos.)

• Widespread use in agriculture has caused resistance; concern of becoming obsolete

Metronidazole

Anaerobes and Parasites: Must be reduced in the cytoplasm

by a nitroreductase to become active  (Use: Anaerobes, H. pylori, protozoa)

Intermediary Metabolism: Anti-folates

Sulfonamides  ------------> Synthetase

Trimethoprim ----------> Dihydrofolate Reductase 

Mechanisms of Resistance