Penicillin-binding protein (PBP) removes the terminal alanine in the process of forming a cross-link with a nearby peptide. Cross-links give the cell wall its structural rigidity. β-Lactam antibiotics covalently bind to the active site of PBP’s. This inhibits the transpeptidation reaction, halting peptidoglycan synthesis, and the cell dies.

Immediate hypersensitivity, rash, seizures (pts. with renal failure)

Allergic hypersensitivity

include anaphylactic shock (very rare), serum sickness-type reactions, fever, interstitial nephritis, eosinophilia, hemolytic anemia, hematologic disturbances

IV administration; Greatest activity against gram-positive organisms, gram-negative cocci, and non-β-lactamase producing anaerobes.

Oral form; Low systemic levels limit widespread use

Allergic hypersensitivity

Only used in minor infections due to poor bioavailability and narrow antibacterial spectrum

IV; resistant to staphylococcal β lactamases

“ Neutropenia

Allergic hypersensitivity

Β-lactamase producing staphylococci

resistant to staphylococcal β lactamases

“ Hepatitis

Allergic hypersensitivity

Greater activity against gram-negative bacteria; susceptible to β-lactamases

“ Non-allergic skin rashes

Allergic hypersensitivity

Urinary tract infections, sinusitis, otitis, lower respiratory tract infections

Used for penicillin-resistant pneumococci

Similar to penicillins but more stable to β lactamases

Broader spectrum of activity

2^nd gen. oral & IV; extend gram-negative coverage; ↑activity vs. Pneumococcus and H. influenzae

Active vs. H. influenza or Moraxella catarrhalis in sinusitis, otitis, and lower respiratory tract infections

Similar to penicillins but more stable to β lactamases

Broader spectrum of activity

3^rd generation; IV; expanded gram-negative coverage and good penetrance of blood-brain barrier

Many uses including pneumonia, meningitis, pyelonephritis, and gonorrhea

Similar to penicillins but more stable to β lactamases

Broader spectrum of activity

4^th generation; IV; ↑resistance to chromosomal β lactamses

Broad activity with ↑ stability to chromosomal β-lactamases

Prevents bacterial cell wall synthesis by binding to and inhibiting cell wall transpeptidases.

No cross allergenicity with penicllins

Infections caused by aerobic, gram-negative bacteria in patients with immediate hypersensitivity to penicillins

Potent inhibitors of many but not all bacterial β lactamases and can protect hydrolysable penicillins from inactivation.

Infections caused by a wide range of potential pathogens,

mixed aerobic/anaerobic infection

Potent inhibitors of many but not all bacterial β lactamases and can protect hydrolysable penicillins from inactivation.

Infections caused by a wide range of potential pathogens,

mixed aerobic/anaerobic infection

Potent inhibitors of many but not all bacterial β lactamases and can protect hydrolysable penicillins from inactivation.

Infections caused by a wide range of potential pathogens,

mixed aerobic/anaerobic infection

Prevents bacterial cell wall synthesis by binding to and inhibiting cell wall transpeptidases

Cilastatin added to prevent hydrolysis by renal dehydropeptidase

Seizures especially in renal failure or with high doses

Serious infections such as pneumonia and sepsis

Prevents bacterial cell wall synthesis by binding to and inhibiting cell wall transpeptidases

Cilastatin added to prevent hydrolysis by renal dehydropeptidase

Seizures especially in renal failure or with high doses

Serious infections such as pneumonia and sepsis

Longer half-life allows for once daily dosing

Lacks activity against pseudomonas and acinetobacter

Inhibits cell wall synthesis by binding to the D-Ala-D-Ala terminus of nascent peptidoglycan. This inhibits the transglycosylase preventing further elongation of peptidoglycan and cross-linking

“Red-man” or “red neck” syndrome (flushing caused by release of histamine)

Ototoxicity

Renal damage/renal failure

Infections caused by gram-positive bacteria including sepsis, endocarditis, and meningitis, Clostridium difficile colitis

Binds to cell membrane, causing depolarization with K⁺ efflux and rapid cell death

Myopathy, monitoring of weekly creatine phosphokinase levels recommended

Gram-positive bacteria including sepsis and endocarditis

Analog of phosphoenolpyruvate (PEP). Inhibits enolpyruvate transferase and blocks the addition of PEP to UDP-N-acetylglucosamine

Gram pos. and neg. synergistic w/ β-lactams, fluoroquinolones or

amionglycosides

interferes with dephosphorylation of the lipid carrier bactoprenol that transfers peptidoglycan subunits to the growing cell wall.

Gram positive, only topical

Structural analog of D-alanine. Inhibits the incorporation of D-alanine into peptidoglycan pentapeptide by inhibiting alanine racemase, which converts L-alanine to D-alanine, and D-alanyl-D-alanine ligase

Serious dose-related CNS toxicity with headaches, tremors, actue psychosis, and convulsions

Inhibits many gram-positive and negative organisms, but is used almost exclusively to treat TB caused by strains of Mycobacterium tuberculosis resistant to first-line agents