Download Chapter 16 Cholinesterase Inhibitors

Drugs That Weaken the Bacterial Cell
Wall II: Cephalosporins, Carbapenems,
Vancomycin, Telavancin, Aztreonam,
Teicoplanin, and Fosfomycin
Cephalosporins

Most widely used group of antibiotics





Beta-lactam antibiotics
Similar to penicillin structure
Bactericidal
Usually given parenterally
Toxicity is low
Cephalosporins

Mechanism of action



Bind to penicillin-binding proteins (PBPs), disrupt
cell wall synthesis, and cause cell lysis
Most effective against cells undergoing active
growth and division
Resistance

Beta-lactamases (cephalosporinases)
• Third- and fourth-generation agents more resistant than
first- and second-generation agents
Classification of Cephalosporins

First-generation


Second-generation


Cefaclor (Ceclor)
Third-generation


Cefazolin (Ancef)
Cefoperazone (Cefobid)
Fourth-generation

Cefepime (Maxipime)
Cephalosporins

Drug interactions





Probenecid
Alcohol
Drugs that promote bleeding
Calcium and ceftriaxone
Adverse effects



Allergy
Bleeding
Thrombophlebitis
Cephalosporins

Therapeutic uses




19 cephalosporins currently used in United States
First- and second-generation agents rarely used
for active infection
Third-generation
• Preferred therapy for several infections
• Highly active against gram-negative organisms
• Able to penetrate to cerebrospinal fluid (CSF)
Fourth-generation
• Broad spectrum
• Penetration to CSF is good
Carbapenems


Beta-lactam antibiotics have an extremely
broad antimicrobial spectrum with low toxicity
Not active against methicillin-resistant
Staphylococcus aureus (MRSA)




Imipenem (Primaxin)
Meropenem (Merrem IV)
Ertapenem (Invanz)
Doripenem (Doribax)
Vancomycin (Vancocin, Vancoled)

Action


Inhibits cell wall synthesis
Uses



Severe infections only
Methicillin-resistant Staphylococcus aureus or
Staphylococcus epidermidis
Oral dose used for Clostridium difficile if
metronidazole was tried and found ineffective
Vancomycin (Vancocin, Vancoled)

Adverse effects





Ototoxicity (reversible or permanent)
Red man syndrome
Thrombophlebitis (common)
Thrombocytopenia (rare)
Allergy
Monobactam

Aztreonam (Azactam)





Binds to penicillin-binding protein 3 (PBP3)
Narrow antimicrobial spectrum
Gram-negative aerobic bacteria only
Must be given parenterally
Adverse effects similar to those of other betalactam antibiotics
Teicoplanin (Targocid)





Similar in structure and actions to vancomycin
Does not have beta-lactam ring
MRSA and C. difficile are sensitive to drug
Not approved in United States (approved in
Japan and Europe)
No infusion-related reactions
Fosfomycin (Monurol)



Approved for single-dose therapy of
uncomplicated urinary tract infection (UTI)
caused by Escherichia coli or Enterococcus
faecalis
Disrupts the synthesis of peptidoglycan
polymer strands that compose the cell wall
Side effects

Most common: diarrhea, headache, vaginitis,
nausea