The full, clinically endorsed recommendation should be obtained from Lareb.  

Rationale for drug selection  

Cefazolin is widely used for perioperative prophylaxis in pregnancy, including caesarean sections. Due to pregnancy-induced changes in the pharmacokinetics of cefazolin, dose adjustments may be necessary to maintain effective antibiotic concentrations during pregnancy.

Pharmacokinetics of cefazolin in pregnancy 

Cefazolin is renally cleared with minimal metabolism in the liver. Pregnancy increases glomerular filtration which can lower drug concentrations in the blood and body tissues. Therefore, the time the drug remains above the minimum level required to effectively treat the infection (MIC), which often originate in the adipose tissue, may be reduced. Placental transfer occurs, with foetal levels reaching about 18–45% of the maternal concentration. Population-pharmacokinetic and maternal PBPK models, investigated the pharmacokinetics in pregnancy, but also the effect of body weight on cefazolin distribution. These models indicated that pregnant women weighing over 80kg may need higher dosing compared to pregnant women weighing under 80kg, to provide adipose concentrations above the target MIC.

Benefits and risks with the proposed drug adjustments 

The expected benefits and associated risk of a higher dosing of cefazolin during pregnancy.

In short 

Cefazolin is prescribed as perioperative prophylaxis in pregnancy. Pregnancy increases cefazolin clearance and thereby may reduce adipose tissue exposure. Therefore, dose adjustments may be necessary to maintain effective antibiotic concentrations. Based on the weighing of benefits and risks, the working committee derived an appropriate dose adjustments. Consult Lareb for the model-informed dosing recommendations.