PharmacologyTier 1Medical Sciences concept

Cephalosporin generations - spectrum and renal dosing (anti-pseudomonal, anti-MRSA, no renal adjustment)

Core concept

Cephalosporin generations track a shift from Gram-positive to Gram-negative cover, with later generations regaining specific niche activity (anti-pseudomonal, anti-MRSA)
1st: cefazolin, cephalexin -- strong Gram-positive (staph/strep), surgical prophylaxis, skin infection
2nd: cefuroxime, cefoxitin -- broader Gram-negative + some anaerobic cover, respiratory infection

Generation	Examples	Distinguishing spectrum
1st	Cefazolin, cephalexin	Gram-positive-heavy; minimal Gram-negative
2nd	Cefuroxime, cefoxitin	Adds Gram-negative + anaerobic (cefoxitin)
3rd	Ceftriaxone, cefotaxime	Broad Gram-negative, meningitis penetration, CAP, gonorrhoea
3rd (anti-pseudomonal)	Ceftazidime	Adds Pseudomonas cover, weaker Gram-positive
4th	Cefepime	Broad Gram-positive and Gram-negative incl. Pseudomonas -- severe/nosocomial infection
5th (anti-MRSA)	Ceftaroline	Only cephalosporin with MRSA activity; not anti-pseudomonal

Ceftriaxone is the main exception to renal dosing: predominantly biliary/faecal excretion -- no renal dose adjustment needed (unlike almost all other cephalosporins, which are renally cleared and require adjustment)
Trap: reflexively dose-reducing ceftriaxone in renal impairment -- unnecessary and can underdose
Choosing generation by need: cefazolin for surgical prophylaxis/simple skin infection; ceftriaxone for CAP/meningitis/sepsis of unknown source; cefepime for febrile neutropenia/nosocomial pseudomonal risk; ceftaroline for MRSA when vancomycin/other options limited

Ceftazidime and cefepime both cover Pseudomonas but cefepime retains better Gram-positive activity -- relevant when the organism is unknown
Ceftaroline is the cephalosporin exception to "cephalosporins don't cover MRSA" -- do not assume any other agent in the class covers it
Renal excretion generalisation feeds directly into TDM/dose-adjustment questions across the class -- ceftriaxone is the named exception to remember

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