Cephalosporins Overview

Cephalosporins

• Cephalosporins are cell wall synthesis inhibitors.
• Different generations of cephalosporins have varying spectra of activity and pharmacological properties.
• The mechanism of action and resistance, as well as the broader pharmacology, are similar to penicillins.
• First-generation cephalosporins are effective against susceptible staphylococci and streptococci, and have modest activity against gram-negative bacteria. They are generally given intravenously (IV) or intramuscularly (IM). They are excreted by the kidneys, unmetabolized.
• Second-generation cephalosporins exhibit modest activity against gram-positive bacteria and increased activity against gram-negative bacteria and anaerobes. Absorption and excretion profiles are similar to first-generation.
• Third-generation cephalosporins have a broad spectrum, and are often the drugs of choice for serious infections, especially those caused by gram-negative bacteria. Cefpodoxime and cefixime are oral, while others are administered parentally.
• Fourth generation cephalosporins, like cefepime, have similar activity to third generation but resist more beta-lactamases. They are administered parentally and have excellent penetration into the cerebrospinal fluid (CSF).
• Fifth-generation cephalosporins, such as cetobiprole, are generally effective against a wider array of resistant organisms.

Toxicity/Contraindications

• Hypersensitivity reactions to cephalosporins are similar to those seen with penicillins, although uncommon.
• Cross-reactions can occur between cephalosporins and penicillins.
• Common side effects such as nausea and vomiting may occur.
• Pain at the injection site, and phlebitis after IV administration are side effects.
• Some cephalosporins (containing methylthiotetrazole), can cause hypoprothrombinemia and disulfiram-like reactions.
• When administered with aminoglycosides, they may increase nephrotoxicity.

Carbapenems (Imipenem, Meropenem, Ertapenem)

• Carbapenems, like imipenem, are similar to penicillins in their effect on microbes and their pharmacology, but have a broader spectrum of activity against gram-positive, gram-negative and anaerobic bacteria.
• Useful in treating pseudomonal infections where they're often administered with aminoglycosides.
• Usually administered parenterally.
• They are often the drugs of choice for infections caused by Enterobacter.

Monobactam (Aztreonam)

• Specifically active against gram-negative bacteria, including Pseudomonas.
• Useful for treating G- infections where a beta-lactam is needed but hypersensitivity reactions are a concern.

Cell Wall Synthesis Inhibitors (Non-β-Lactams)

• Vancomycin
  • A tricyclic glycopeptide
  • Effective against multiple drug-resistant organisms such as MRSA and enterococci
  • Concerns exist about the emergence of vancomycin resistance.
  • Mode of action: Inhibits peptidoglycan polymerization by binding to the D-Ala-D-Ala side chain of the precursor pentapeptide. It also affects transglycosylation steps of peptidoglycan, weakening the cell wall.
• Daptomycin
• Teicoplanin
• Telvancin
• Bacitracin

Pharmacokinetics of Vancomycin

• Usually administered intravenously (IV) over an hour.
• Can be administered orally for pseudomembranous colitis.
• 30% of the drug binds to serum proteins.
• Appears in various bodily fluids, including the CSF.
• Excretion is via the kidneys.

Toxicity/Contraindications of Vancomycin

• Red Man Syndrome (erythematous or urticarial reaction) is a common side effect when given quickly.
• Ototoxicity and nephrotoxicity are less common but can occur to higher doses.

Other Vancomycin Inhibitors

• Treatments for vancomycin-resistant organisms
• Daptomycin
• Quinopristin/dalfopristin
• Linezolid
• Synergistic use with aminoglycosides in enterococcal endocarditis treatment

This quiz covers the different generations of cephalosporins, their mechanism of action, and pharmacological properties. It discusses the spectrum of activity for first, second, and third-generation cephalosporins, including their efficacy against gram-positive and gram-negative bacteria. Test your knowledge on this important class of antibiotics.