Vitamin ‘C1’ – cefazolin, cephalexin and cephalothin unpacked

These so-called first generation cephalosporins (C1) remain important agents for skin, soft tissue and urinary tract infections due to susceptible organisms and for surgical prophylaxis.  Increases in community acquired MRSA in some regions may lead to a different empiric choice for skin/soft tissue infection (e.g. doxycycline or trimethoprim+sulphamethoxazole).  Local cumulative antibiograms should also be examined to determine whether Gram negative resistance in urinary isolates precludes use of cephalexin for empiric treatment of UTI.

Cefazolin structure with central betalactam double ring



  • Gram positive: excellent action against methicillin-susceptible Staphylococcus aureus (1) (first line is usually dicloxacillin or flucloxacillin), pyogenic streptococci (e.g. Streptococcus (group A) pyogenes).
  • Gram negative:  Cefazolin and cephalexin have better action against common Gram negatives such as E. coli and Proteus mirabilis compared with cephalothin.

Clinical utility

These agents are useful for skin, soft tissue and urinary tract infections due to susceptible organisms and for surgical prophylaxis.  There is also evidence of microbiological and clinical activity documented against methicillin-resistant coagulase negative staphylococci that cause neonatal infection(2) and peritonitis associated with peritoneal dialysis(3).

  • NOT used for meningitis (penetration to cerebrospinal fluid is very poor)
  • NOT active against MRSA, nor enterococci
  • NOT active against Bacteroides species and related Gram negative anaerobes

Avoid for treatment of pneumonia/otitis media and sinusitis owing to poor activity against the Streptococcus pneumoniae strains that have reduced susceptibility to penicillin (there is a relatively much higher reduction in susceptibility against cefazolin/cephalexin in such strains) (4).

Surgical Prophylaxis

Also see HNELHD_CG_14_35_Surgical_Antibiotic_Prophylaxis Guideline.

Cefazolin is the primary agent used for prophylaxis in view of its long half life and combined Gram positive/ Gram negative activity. Larger patients (>80kg) require 2 grams IV and Therapeutic Guidelines (Aust), Edition 15 recommends this dose regardless of weight for adults. An even greater increase in dose for morbidly obese patients is prudent.  Dose should be repeated intraoperatively if surgery lasts longer than 3 hours. The paediatric dose is 30mg/kg up to 2 grams IV. Patients colonised with MRSA require addition of teicoplanin (see Guideline).

Cephalothin is no longer in use across HNELHD.  It displays excellent action against methicillin-susceptible S. aureus but has a very short half-life, necessitating frequent dosing in bacteraemic infection.

Leave a Reply

Fill in your details below or click an icon to log in: Logo

You are commenting using your account. Log Out /  Change )

Twitter picture

You are commenting using your Twitter account. Log Out /  Change )

Facebook photo

You are commenting using your Facebook account. Log Out /  Change )

Connecting to %s

%d bloggers like this: