Optimal dosing of penicillin G in the third trimester of pregnancy for prophylaxis against group B Streptococcus

We wanted to determine the optimal dose of intravenous penicillin (PCN) in the third trimester of pregnancy for the prophylaxis of group B Streptococcus.

Healthy women in the third trimester with a singleton pregnancy were recruited. Eligibility included no previous penicillin or cephalosporin allergy and no history of renal disease. We obtained a baseline 24-hour urine collection for total protein concentration and creatinine clearance. Two intravenous catheters were placed, and 1 million units of penicillin G (PCN G) sodium was infused through one catheter. Serial blood samples were obtained through the second catheter at 1, 5, 15, 30, 60, 90, 120, 150, 180, 210, and 240 minutes. Serum was stored at -80 degrees C until assays were performed. Reverse-phase high-performance liquid chromatography was used to determine serum concentrations.

Fifteen patients met the requirements for eligibility. The average 24-hour urine sample for total protein concentration was 187 mg/dL (range, 11-252), and creatinine clearance was 191 mL/min (range, 137-245). Average maximum serum concentration (C(max)) was 67 microg/mL (range, 34-132) and was reached within 5 minutes. Average serum PCN concentration was 12 microg/mL (range, 9-25) after 4 hours of urine collection.

The C(max) was 67 microg/mL (670 x minimum inhibitory concentration). One million units of intravenous PCN G exceeds MIC in the treatment of GBS. The dosing interval should be 4 hours to ensure anti-GBS activity in all patients. More frequent dosing does not increase activity. Current recommendations for GBS prophylaxis which use PCN G should be modified pending future studies of neonatal PCN concentrations.