Mechanism of Action

• D-Ala-D-Ala structural analog.
• Bind penicillin-binding proteins (transpeptidases) and blocks transpeptidase cross-linking or peptidoglycan cell wall.
• Activates autolytic enzymes.

Mechanism of Resistance

• Penicillinase in bacteria (a type of β-lactamase) cleaves β-lactam ring.

β-Lactamase Inhibitors

• Clavulonic acid, Avibactam, Sulbactam, Tazobactam
• Often added to penicillin antibiotics to protect antibiotic destruction by β-lactamase (penicillinase).
• Unasyn = ampicillin + sulbactam
• Zosyn = piperacillin + tazobactam
  • The only difference between sulbactam and tazobactam is the presence of a triazolyl moiety on the C2 β-methyl group of the later. Removal of the triazole group results in an inferior inhibitor.

Mechanism of Action

• β-lactam drugs that inhibit cell wall synthesis but less susceptible to penicillinases.
• Bactericidal

Clinical Use

• 1st generation: cefazolin (ancef), cephalexin (keflex)
• 2nd generation: cefaclor, cefoxitin, cefuroxime
• 3rd generation: ceftriaxone, cefotaxime, cefpodoxime, ceftazidime
• 4th generation: cefepime
• 5th generation: ceftaroline

Adverse Effects

• Hypersensitivity reactions, autoimmune hemolytic anemia, disulfiram-like reaction, vitamin K deficiency.
• Low rate of cross-reactivity even in penicillin-allergic patients.

Mechanism of Resistance

• Structural change in penicillin-binding proteins (transpeptidases).

Mechanism of Action

• Inhibits cell wall peptidoglycan formation by binding D-Ala-D-Ala portion of cell wall precursors.
• Bactericidal against most bacteria (bacteriostatic against C difficile).
• Not susceptible to β-lactamases.

Clinical Use

• Gram ⊕ bugs only
• Serious, multidrug-resistance organisms including MRSA, S epidermidis, sensitive Enterococcus species, and Clostridium difficile (oral dose for pseudomembranous colitis).

Adverse Effects

• Red man syndrome – diffuse flushing (largely preventable by pretreatment with antihistamines and slow infusion rate)/
• Nephrotoxic, Ototoxic, Thrombophlebitis

Mechanism of Resistance

• Occurs in bacteria via amino acid modification of D-Ala-D-Ala to D-Ala-D-Lac

Mechanism of Action

• Blocks peptide transfer (translocation) at 50S ribosomal subunit.
• Bacteriostatic.

Adverse Effects

• Pseudomembranous colitis (C difficile overgrowth), fever, diarrhea

Tetracycline, Doxycycline, Minocycline

Mechanism of Action

• Binds to 30S and prevents attachment of aminoacyl-tRNA
• Bacteriostatic.
• Do not take tetracyclines with milk (Ca2+), antacids (Ca2+ or Mg2+), or iron-containing preparations because divalent cations inhibit drugs’ absorption in the gut.

Adverse Effects

• GI distress, discoloration of teeth and inhibition of bone growth in children, photosensitivity.
• Contraindicated in pregnancy.

Mechanism of Resistance

• Decreased uptake or increased efflux out of bacterial cells by plasmid-encoded transport pumps.

Sulfamethoxazole, Sulfisoxazole, Sulfadiazine

Mechanism of Action

• Inhibit dihyrpteroate synthase, thus inhibitnig folate synthesis.
• Bacteriostatic (bacteriocidal when combined with trimethoprim).

Clinical Use

• Gram ⊕, gram ⊝, Nocardia. SMX for simple UTI.

Mechanism of Resistance

• Altered enzyme (bacterial dihydropteroate synthase), decreased uptake, or increased PABA synthesis

Mechanism of Action

• Inhibits bacterial dihydrofolate reductase.
• Bacteriostatic.

Clinical Use

• Used in combination with sulfonamides (trimethoprim-sulfamethoxazole) causing sequential block of folate synthesis.

Adverse Effects

• Megaloblastic anemia, leukopenia, granulocytopenia.