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

OBJECTIVE: We wanted to determine the optimal dose of intravenous penicilli n (PCN) in the third trimester of pregnancy for the prophylaxis of group B Streptococcus. STUDY DESIGN: Healthy women in the third trimester with a singleton pregnan cy were recruited. Eligibility included no previous penicillin or cephalosp orin allergy and no history of renal disease. We obtained a baseline 24-hou r 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 wer e obtained through the second catheter at 1, 5, 15, 30, 60, 90, 120, 150, 1 80, 210, and 240 minutes. Serum was stored at -80 degreesC until assays wer e performed. Reverse-phase highperformance liquid chromatography was used t o determine serum concentrations. RESULTS: 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 mug/mL (range, 34-132) and was reached within 5 minutes. Average serum PCN concentration was 12 mug/mL (ra nge, 9-25) after 4 hours of urine collection. CONCLUSION: The C-max was 67 mug/mL (670 x minimum inhibitory concentration ). One million units of intravenous PCN G exceeds MIC in the treatment of G BS. The dosing interval should be 4 hours to ensure anti-GBS activity in al l patients. More frequent dosing does not increase activity. Current recomm endations for GBS prophylaxis which use PCN G should be modified pending fu ture studies of neonatal PCN concentrations.