What are the recommended cefazolin dosing regimens for adult surgical prophylaxis, treatment of infections, patients with impaired renal function (creatinine clearance <30 mL/min), and pediatric patients older than 1 month, and what are suitable alternatives for cephalosporin‑allergic patients?

Cefazolin Dosing

For adult surgical prophylaxis and most infections, administer cefazolin 1-2 g IV every 8 hours; for penicillin-allergic patients (non-anaphylactoid type) requiring endocarditis treatment, use 6 g per 24 hours IV divided into 3 equal doses; in pediatric patients >1 month, give 100 mg/kg/24h IV in 3 divided doses; and in patients with severe renal impairment (CrCl <30 mL/min), reduce dosing frequency to every 12-24 hours based on creatinine clearance.

Adult Dosing for Surgical Prophylaxis and General Infections

Standard Dosing (Normal Renal Function)

• Administer cefazolin 1-2 g IV as a single pre-operative dose for surgical prophylaxis 1
• The standard 1 g IV bolus achieves peak serum concentrations of approximately 185 mcg/mL and provides at least 6 hours of intra-operative protection 1
• For treatment of staphylococcal endocarditis in penicillin-allergic patients (non-anaphylactoid type), give 6 g per 24 hours IV divided into 3 equally divided doses (2 g every 8 hours) for 6 weeks 2

Weight-Based Dosing Controversy in Obesity

• Do not use weight-based dosing (e.g., 3 g doses) in obese patients for surgical prophylaxis, as cefazolin is hydrophilic and does not penetrate adipose tissue regardless of dose 1
• Higher doses result in proportionately higher serum concentrations but do not increase adipose tissue concentrations, which is not a valid target tissue for clean-contaminated surgical site infection prophylaxis 1
• Avoid intra-operative re-dosing for procedures lasting 6 hours or less, as standard 1-2 g dosing provides adequate duration of coverage 1

Renal Dose Adjustments

Moderate to Severe Renal Impairment

• In patients with creatinine clearance <50 mL/min, significantly extend dosing intervals 3, 4
• A linear correlation exists between elimination rate-constants and creatinine clearance (Ke = 0.022 + 0.0028 CrCl), allowing calculation of individualized maintenance doses 4
• For patients with CrCl <50 mL/min, postoperative dosing intervals should be extended to every 12-24 hours rather than every 6-8 hours 3
• Only 7.4% of patients with CrCl <49 mL/min had free cefazolin concentrations <4 μg/mL at 24 hours post-operation, compared to 54.3% of patients with normal renal function 3

Critical Safety Consideration

• Failure to adjust cefazolin dosing in renal dysfunction can lead to drug accumulation, encephalopathy, and seizures 5
• A case report documented a fatal outcome in an 87-year-old patient with renal dysfunction who received cefazolin 2 g IV every 4 hours (instead of the recommended every 12 hours), resulting in tonic-clonic seizures and death 5
• Neurotoxicity risk is potentiated by older age, pre-existing CNS conditions, and renal failure 5

Pediatric Dosing (>1 Month of Age)

Standard Pediatric Regimen

• For staphylococcal endocarditis in penicillin-allergic children (non-anaphylactoid type), administer cefazolin 100 mg/kg per 24 hours IV divided into 3 equally divided doses 2
• Pediatric dose should not exceed that of a normal adult 2
• Duration of therapy is 6 weeks for endocarditis 2

Surgical Prophylaxis in Pediatric Patients

• Cefazolin is the preferred antibiotic for perioperative prophylaxis in children, including those with non-severe penicillin-class allergies 6
• A quality improvement initiative demonstrated that 90% of eligible pediatric patients with penicillin allergies safely received cefazolin for surgical prophylaxis without severe allergic reactions 6

Penicillin-Allergic Patients

Non-Anaphylactoid Allergy

• Cefazolin is safe and appropriate for patients with non-anaphylactoid (non-IgE-mediated) penicillin allergies 2, 6
• Use the standard dosing regimens outlined above 2

Anaphylactoid Allergy

• Cephalosporins including cefazolin should be avoided in patients with anaphylactoid-type hypersensitivity to beta-lactams 2
• Vancomycin should be used as an alternative in these cases: 30 mg/kg per 24 hours IV in 2 equally divided doses, adjusted to achieve 1-hour serum concentration of 30-45 μg/mL and trough concentration of 10-15 μg/mL 2

Key Clinical Pitfalls

Avoid Excessive Dosing

• Do not administer cefazolin more frequently than every 8 hours in patients with normal renal function, as this provides no additional benefit and increases toxicity risk 5, 1
• The time-dependent killing kinetics of cefazolin mean that concentrations above the MIC provide adequate bacterial killing without need for higher concentrations 1

Monitor Renal Function Closely

• Always calculate creatinine clearance before dosing and adjust intervals accordingly in patients with CrCl <50 mL/min 5, 3, 4
• Consider therapeutic drug monitoring in high-risk patients (elderly, pre-existing CNS disease, renal impairment) to prevent neurotoxicity 5

Reassess Penicillin Allergy History

• Clarify the type of penicillin reaction (anaphylactoid vs. non-anaphylactoid) before automatically avoiding cefazolin 2, 6
• Most reported penicillin allergies are non-severe and do not contraindicate cefazolin use 6