Yale University School of Medicine Thesis Award Recipients — 2010

The 2002 CDC guidelines recommend a minimum of four hours of intrapartum penicillin G prophylaxis to assure a neonate is adequately prophylaxed against group B streptococcus (GBS). We examined the validity of this duration through the relationship between duration of prophylaxis and fetal serum penicillin G levels among fetuses exposed to less than four hours of prophylaxis compared to longer durations. We also investigated if clinicians were altering management to achieve four hours of prophylaxis. Ninety-eight laboring GBS positive women carrying singleton gestations >37 weeks received penicillin G according to the CDC protocol. Umbilical cord blood samples were collected at delivery and penicillin G levels measured by high-performance liquid chromatography. Intra and inter-assay coefficient of variation were <3 percent. Seventy of 96 eligible clinicians (72.9 percent) completed our survey. Fetuses exposed to less than four hours prophylaxis had higher penicillin G levels than those exposed to greater than four hours (p = 0.003). In multivariable linear regression analysis, fetal penicillin G levels were determined by time of exposure, time since last dose, dosage, and number of doses, but not maternal BMI. Penicillin G levels increased linearly until one hour (R2 = .40) and then decreased rapidly according to a power-decay model (R2 = .67). All sub-groups analyzed were above the minimum inhibitory concentration (MIC) for GBS (0.1μg/mL)(p < 0.002). Individual samples were 10-179 fold above the MIC. In our survey, only 22.9 percent of clinicians reported not altering their management of labor in GBS positive pregnancies that achieved less than four hours of prophylaxis. These alterations included “laboring down” or delaying pushing; turning off or decreasing an oxytocin infusion; or delaying or avoiding artificial rupture of membranes. Short durations of prophylaxis achieved levels significantly above the MIC, suggesting a benefit even in precipitous labors. The designation of infants exposed to less than four hours of prophylaxis as particularly at risk for GBS sepsis may be pharmacokinetically inaccurate. However, clinicians report delaying labor to achieve four hours. The 2002 CDC guidelines are being interpreted differently in the clinical setting than the authors may have intended. The effects and consequences of this interpretation are unknown.