Cephalosporins Flashcards
What is the mechanism of action of cephalosporins?
Cephalosporins are beta-lactam antibiotics that inhibit bacterial cell wall synthesis. They bind penicillin-binding proteins (PBPs) and block peptidoglycan cross-linking, leading to cell wall instability and bactericidal activity. They have beta-lactamase resistance.
How does the antimicrobial spectrum change across cephalosporin generations?
As generation increases (1st→3rd), Gram+ coverage tends to decrease while Gram- coverage increases.
- 1st gen: good Gram+ and modest Gram-.
- 2nd gen: adds more Gram- while still covering anaerobes and Gram+.
- 3rd gen: strong Gram- coverage with reduced Gram+.
- 4th gen: broad Gram- including Pseudomonas and good Gram+.
- 5th gen: broad like 3rd gen but also covers MRSA and penicillin-resistant pneumococcus; not Pseudomonas.
Which organisms are not covered by early-generation cephalosporins?
LAME: Listeria, Atypicals (Chlamydia, Mycoplasma), MRSA, Enterococci are not covered by 1st-4th gen cephalosporins.
Exception: Ceftaroline, a 5th gen, covers MRSA.
What are common clinical indications for first generation cephalosporins (cefazolin and cephalexin)?
- Cefazolin: surgical prophylaxis, MSSA skin infections (erysipelas, cellulitis, abscesses)
- Cephalexin: skin/soft tissue infections and UTIs (proteus, klebsiella, e coli)
- Second line for strep throat
What are common clinical indications for second generation cephalosporins (cefaclor, cefoxitin, cefuroxime)?
- Cefuroxime: otitis and sinusitis
- Cefoxitin/cefotetan: peritonitis, diverticulitis and intra-abdominal/pelvic infections
- Cover the gram positive infections along with Haemophilus, Neisseria, and Serratia (HENS)
- Can be used for lower respiratory infections (Strep pneumo, Haemophilus influenzae, Moraxella, Klebsiella)
What are common clinical indications for third generation cephalosporins (Ceftriaxone, Ceftazidime, Cefotaxime, Cefdinir)?
- Ceftriaxone: IV: meningitis and SBP, IM: gonorrhea
- Cefotaxime: IV pediatric sepsis and meningitis
- Ceftazidime: Pseudomonas infections
- Lyme disease, Pneumonia (CAP, HAP, VAP)
- Endocarditis from viridans and HACEK
- Salmonella and shigella if antibiotics are indicated (usually these are treated with supportive treatment)
What are common clinical indications for fourth generation cephalosporins (cefepime)?
Cefepime: nosocomial infections that also covers pseudomonas
What are common clinical indications for fourth generation cephalosporins (ceftaroline, ceftolozane)?
ceftaroline and ceftolozane are broad spectrum and include MRSA skin infections
What is a useful mnemonic to remember cephalosporin coverage gaps?
LAME organisms are not covered by 1st-4th generation cephalosporins: Listeria, Atypicals, MRSA, Enterococci.
Ceftaroline covers MRSA as an exception.
How do bacteria develop resistance to cephalosporins?
Resistance can occur via beta-lactamase production, mutations in PBPs, and porin changes in Gram-negatives that reduce drug entry.
Outline key pharmacokinetic features of cephalosporins.
Many cephalosporins are given parenterally; some are oral. Later generations achieve good CNS levels. Elimination is primarily renal, except ceftriaxone. Ceftriaxone has a long half-life allowing once daily dosing, while others often require multiple daily doses.
What are notable drug interactions involving cephalosporins?
- Some cephalosporins can cause a disulfiram-like reaction with alcohol and impair vitamin K metabolism.
- Cephalosporins can enhance nephrotoxicity of aminoglycosides.
- Probenecid can prolong cephalosporin levels.
- Ceftriaxone can form precipitates with calcium-containing IV solutions.
What are contraindications or cautions when using cephalosporins?
- Patients with a history of anaphylactic reaction to penicillins should avoid cephalosporins.
- Some patients can develop an allergic reaction, but minor allergic reactions are not a contraindication.
- Dosage adjustments for renal impairment are needed for most cephalosporins.
- Ceftriaxone is contraindicated in neonates.
List major adverse effects of cephalosporins.
Hypersensitivity reactions are most common; GI upset can occur. Cefotetan and cefoperazone can cause disulfiram-like reactions with alcohol. High doses can cause seizures. Rarely, interstitial nephritis or hemolytic anemia can occur.
