Safety, tolerability and pharmacokinetics of subcutaneous cefazolin as an alternative to intravenous administration.

Background: Subcutaneous (SC) administration of antibiotics is a practical alternative to IV administration. Cefazolin is widely used for skin and soft tissue infections and other complex infections by IV administration.

Methods: In this prospective, cross-over self-controlled study, a single dose of SC cefazolin was administered to 15 stable inpatients established on IV cefazolin as part of their management plan. The equivalent dose of cefazolin was diluted in 50 mL of normal saline via gravity feed over 30 min. Venous blood samples were collected at baseline and 0.5, 1, 2, 4 and 8 h following both the SC and IV doses. Antibiotic concentrations were measured using UPLC-MS/MS. Pharmacokinetic data were analysed using a non-linear mixed-effects modelling approach. Pain scores and infusion site reactions (oedema/erythema) were evaluated.

Results: SC cefazolin was well tolerated. The bioavailability of SC administration was 74.8% (95% CI 66.7%-81.7%). Slower absorption from SC tissue was associated with a BMI of ≥30. Lower peak, and higher trough concentrations were observed with SC administration. Although lower bioavailability was observed with SC administration, the PTA for unbound drug concentrations greater than the MIC for more than 90% of the time between doses was higher for SC compared with IV administration at MICs between 0.25 and 4 mg/L. Simulated SC doses of 3 g twice daily had similar PTA to standard IV dosing of 2 g three times daily. A simulated 6 g continuous 24 h infusion of SC cefazolin had a favourable pharmacokinetic profile.

Conclusion: SC cefazolin appears to be well tolerated, with an improved pharmacokinetic profile compared with IV administration. Either 3 g twice daily, or 6 g as a 24 h SC infusion could be considered for future evaluation.