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Cephalosporins (cephalexin, cefazolin, ceftriaxone, cefepime)
Mechanism of action
Bind penicillin-binding proteins and block bacterial cell wall synthesis, like penicillins. Generations broaden the spectrum: 1st gen (cefazolin, cephalexin) — gram-positive plus some gram-negative, surgical prophylaxis; 2nd gen (cefuroxime) — broader gram-negative; 3rd gen (ceftriaxone, ceftazidime) — major gram-negative coverage, ceftriaxone for meningitis/CAP/gonorrhea; 4th gen (cefepime) — Pseudomonas plus broad spectrum; 5th gen (ceftaroline) — MRSA coverage.
Adverse effects
Life-threatening / NCLEX-tested
- Anaphylaxis — cross-reactivity with penicillin allergy is real but often overstated; in true IgE-mediated penicillin anaphylaxis, avoid 1st generation; later generations are usually safe but discuss with the team
- C. difficile colitis — cephalosporins (especially 3rd-gen) are among the highest-risk antibiotics
- Stevens-Johnson syndrome / TEN / DRESS
- Acute interstitial nephritis
- Disulfiram-like reaction with alcohol (cefotetan, cefoperazone — older agents, classic test point)
- Coagulopathy (vitamin K dependent, with cefotetan)
- Ceftriaxone biliary sludging / pseudolithiasis in children
Side effects
Common — what to teach
- Diarrhea
- Nausea, vomiting
- Maculopapular rash
- Yeast vaginitis or thrush
- Pain at IM injection site
- Phlebitis at IV site
Food & drug interactions
Probenecid raises levels (blocks renal tubular secretion). Aminoglycosides synergize for serious gram-positive infections. Anticoagulants — some cephalosporins (cefotetan) potentiate warfarin via vitamin K interference. Calcium-containing IV fluids should NOT be co-infused with ceftriaxone (precipitate, fatal in neonates). Alcohol with cefotetan/cefoperazone causes a disulfiram-like reaction.
Nursing implications
Assessment, monitoring, patient teaching
- Clarify penicillin allergy thoroughly — IgE anaphylaxis to PCN is the main contraindication for cephalosporins, especially 1st gen; non-anaphylactic PCN history usually allows cautious cephalosporin use with MD agreement
- Observe for 30 minutes after the first IV dose for anaphylaxis
- Complete the FULL course; counsel on C. diff warning signs (severe, watery, sometimes bloody diarrhea — call urgently)
- Counsel against alcohol during course of cefotetan, cefoperazone — disulfiram-like reaction (flushing, nausea, palpitations)
- Ceftriaxone: do NOT co-administer with calcium-containing solutions (LR, calcium gluconate) — precipitation; in neonates, ceftriaxone is contraindicated with calcium-containing fluids
- Take oral forms with food to limit GI upset; some (cefuroxime axetil) need food for absorption
- Renal dose adjustment for many; ceftriaxone is the exception (biliary excretion)
When to hold / contraindications
- Documented IgE-mediated cephalosporin or severe penicillin allergy (consult before re-challenge)
- Severe rash, fever, mucosal involvement (suspect SJS/TEN/DRESS)
- Active C. difficile infection until provider review
- Concurrent calcium-containing IV solution with ceftriaxone (especially neonates)
- Severe acute kidney injury without dose adjustment
Memory anchor
Cephalosporins start with "cef-" or "ceph-". "Cef + alcohol = flushing" (cefotetan/cefoperazone). "Cef + Ca²⁺" precipitate (ceftriaxone). Highest C. diff risk class.
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