Cephalosporins

If penicillins are the friendly old neighbors of the antibiotic world, cephalosporins are their well-dressed cousins: broad coverage, versatile, and ready to step in when things get serious.

• Class: β-lactam antibiotics (same core structure as penicillins; inhibit bacterial cell wall synthesis by binding PBPs).
• Mechanism: Bactericidal, time-dependent killing.
• General Trends by Generation:
  • ↑ Gram-negative coverage as you move from 1st → 4th generation.
  • Gram-positive coverage generally decreases as you move up, with some exceptions (5th gen regains MRSA coverage).
  • None cover Enterococcus (except ceftaroline weakly against some strains).
  • No coverage of atypicals (Chlamydia, Mycoplasma, Legionella).

Generations

First Generation

Examples:

• Cefazolin (IV) - surgical prophylaxis, MSSA, skin infections.
• Cephalexin (PO) - skin/soft tissue infections, strep pharyngitis.

Coverage:

• Gram+: Strong (MSSA, Streptococcus spp.)
• Gram -: Limited (Proteus, E. coli, Klebsiella — "PEcK").

High-Yield Pearl:

• Cefazolin is your go-to for pre-op prophylaxis (except bowel surgery).

Second Generation

Examples:

• Cefuroxime (PO/IV) - URIs, community-acquired pneumonia.
• Cefoxitin and Cefotetan - anaerobic coverage, intra-abdominal infections.

Coverage:

• Gram+: Slightly less than 1st gen.
• Gram-: More (PEcK + H. influenzae, Enterobacter, Neisseria - "HEN PEcK").
• Cefoxitin/cefotetan cover Bacteroides.

High-Yield Pearl:

• Cefoxitin & cefotetan are used for prophylaxis in colorectal surgery because of anaerobic coverage.

Third Generation

Examples:

• Ceftriaxone - meningitis, gonorrhea, CAP, Lyme disease (late stages).
• Cefotaxime - meningitis (safe in neonates).
• Ceftazidime - anti-Pseudomonal.

Coverage:

• Gram-: Excellent (broad Enterobacteriaceae).
• Gram+: Good (Strep, some MSSA).
• Special:
  • Ceftriaxone: long half-life, biliary excretion.
  • Ceftazidime: Pseudomonas coverage but weaker Gram+.

High-Yield Pearl:

• Avoid ceftriaxone in neonates (risk of kernicterus from bilirubin displacement).
• First-line for N. gonorrhoeae (single IM dose ceftriaxone).

Fourth Generation

Example:

• Cefepime - broad-spectrum big gun.

Coverage:

• Gram+: MSSA, Streptococci.
• Gram-: Excellent, including Pseudomonas, Enterobacter, Citrobacter.
• Resistant to many β-lactamases (but not carbapenemases).

High-Yield Pearl:

• Used in febrile neutropenia, nosocomial infections, and severe sepsis with suspected Pseudomonas.

Fifth Generation

Example:

• Ceftaroline - the MRSA cephalosporin.

Coverage:

• Gram+: MRSA, MSSA, Strep.
• Gram-: Similar to ceftriaxone but no Pseudomonas.

High-Yield Pearl:

• Only β-lactam that binds PBP2a (MRSA target).
• Used for MRSA bacteremia, endocarditis, and skin infections.

Adverse Effects & Warnings

• Hypersensitivity: Cross-reactivity with penicillins (~1%).
• GI upset, diarrhea.
• Cefotetan/Cefoperazone: Disulfiram-like reaction with alcohol + hypoprothrombinemia (vitamin K inhibition).
• Ceftriaxone: Biliary sludging, avoid in neonates.