cefazolin (Ancef, Kefzol)

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^[1]^[2]^[3]^[4]^[5]^[6]^[7]^[8]

Introduction

Tradenames: Ancef, Kefzol. 1st generation cephalosporin.

Indications

treatment of serious infections caused by susceptible gram positive & gram negative organisms
surgical prophylaxis against Staphylococci
- administered 60 minutes prior to procedure
- repeated during procedures lasting more than 4 hours
prophylaxis for bacterial endocarditis^[6]

Contraindications

cefazolin allergy is rare in persons reporting penicillin allergy^[7]

pregnancy category = b

safety in lactation = ?

Dosage

0.5-1.5 g IV/IM 6-8 hours

Children: 25-50 mg/kg/day divided every 6-8 hours.

Severe infections: 100 mg/kg/day.

Pharmacokinetics

time to peak serum concentration: 5 min (IV), 0.5-2 h (IM)
elimination 1/2 life 1.5-2.5 hours (40-70 hours ESRD)
80-100% eliminated unchanged in the urine
dosage adjustment with renal failure (see below)
protein binding 74-86%
distributed to most tissues
does not achieve therapeutic levels in CNS
removed by hemodialysis Dosage adjustment with renal failure:

Creatinine clearance	dose
> 50 mL/min	1 g IV/IM every 8 hours
10-49 mL/min	1 g 1V/IM every 12 hours
< 9 mL/min	0.5 g IV/IM every 12 hours
post dialysis	0.5-1 g IV/IM

elimination via kidney

1/2life = 1.8 hours

protein binding = 75-86 %

elimination by hemodialysis = +

elimination by peritoneal dialysis = -

Antimicrobial activity

Notable lack of activity against enterococcus, MRSA & anaerobes.

Adverse effects

not common (1-10%)
- diarrhea
uncommon (< 1%)
- CNS irritation, seizures, abdominal cramps, fever, rash, eosinophilia, decreased prothrombin, urticaria, leukopenia, pseudomembranous colitis, thrombocytopenia, transient increase in serum alkaline phosphatase & transaminases, cholestatic jaundice, pain at site of injection, superinfection
other
- hypersensitivity reactions
  - lack of cross-reactivity between cefazolin & penicillin^[8]
  - cefazolin has no cross reactivity with any cephalosporin available in the U.S.^[8]
- blood dyscrasias (rare)
- headache
- direct Coomb's test may be positive

drug adverse effects of cephalosporins

Drug interactions

probenecid increases the 1/2 life of cefazolin

Laboratory

specimen:
- serum
- keep specimen on ice-water
- centrifuge at 4 degrees C
- remove cells as soon as possible
- freeze at -70 degrees C until assayed
methods: HPLC, MB

Mechanism of action

inhibition of bacterial cell wall synthesis.

More general terms

cephalosporin, 1st generation

References

↑ The Pharmacological Basis of Therapeutics, 9th ed. Gilman et al, eds. Permagon Press/McGraw Hill, 1996
↑ Harrison's Principles of Internal Medicine, 13th ed. Companion Handbook. Isselbacher et al (eds), McGraw-Hill Inc. NY, 1995, pg 161
↑ Sanford Guide to antimicrobial therapy 1997, 2001
↑ Drug Information & Medication Formulary, Veterans Affairs, Central California Health Care System, 1st ed., Ravnan et al eds, 1998
↑ Clinical Guide to Laboratory Tests, 3rd ed. Teitz ed., W.B. Saunders, 1995
↑ ^6.0 ^6.1 Deprecated Reference
↑ ^7.0 ^7.1 Sousa-Pinto B et al. Assessment of the frequency of dual allergy to penicillins and cefazolin: A systematic review and meta-analysis. JAMA Surg 2021 Mar 17; e210021 PMID: https://www.ncbi.nlm.nih.gov/pubmed/33729459 https://jamanetwork.com/journals/jamasurgery/article-abstract/2777647
↑ ^8.0 ^8.1 ^8.2 Goh GS, Shohat N, Austin MS et al. A simple algorithmic approach allows the safe use of cephalosporin in "penicillin-allergic" patients without the need for allergy testing. J Bone Joint Surg Am 2021 Dec 15; 103:2261. PMID: https://www.ncbi.nlm.nih.gov/pubmed/34644269 https://journals.lww.com/jbjsjournal/Abstract/2021/12150/A_Simple_Algorithmic_Approach_Allows_the_Safe_Use.2.aspx

Database

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