Duration of intrapartum prophylaxis and concentration of penicillin G in fetal serum at delivery.
OBJECTIVE
Intrapartum penicillin G prophylaxis aims to prevent early-onset group B streptococci (GBS) sepsis by interrupting vertical transmission. We examined the relationship between duration of prophylaxis and fetal serum penicillin G levels among fetuses exposed to fewer than 4 hours of prophylaxis compared with longer durations.


METHODS
In this prospective cohort study, 98 laboring GBS-positive women carrying singleton gestations at 37 weeks or greater were administered 5 million units of intravenous penicillin G followed by 2.5 million units every 4 hours until delivery. Umbilical cord blood samples were collected at delivery, and penicillin G levels were measured by high-performance liquid chromatography. Intraassay and interassay coefficients of variation were less than 3%.


RESULTS
Fetuses exposed to fewer than 4 hours of prophylaxis had higher penicillin G levels than those exposed to greater than 4 hours (P=.003). In multivariable linear regression analysis, fetal penicillin G levels were determined by duration of exposure, time since last dose, dosage, and number of doses, but not maternal body mass index. Penicillin G levels increased linearly until 1 hour (R(2)=.40) and then decreased rapidly according to a power-decay model (R(2)=.67). All subgroups analyzed were above the minimal inhibitory concentration (MIC) for GBS (0.1 micrograms/mL)(P<.002). Individual samples were 10-179-fold above the MIC. In patients receiving maintenance dosing, penicillin G did not accumulate in the cord blood and returned to baseline after each 4-hour interval.


CONCLUSIONS
Short durations of prophylaxis achieved levels significantly above the MIC, suggesting a benefit even in precipitous labors. The designation of infants exposed to fewer than 4 hours of prophylaxis as particularly at risk for GBS sepsis may be pharmacokinetically inaccurate.
Barber
Emma L
EL
Department of Obstetrics, Gynecology, and Reproductive Sciences, Yale University School of Medicine, New Haven, Connecticut, USA.
Zhao
Guomao
G
Buhimschi
Irina A
IA
Illuzzi
Jessica L
JL
D000328:Adult; D019072:Antibiotic Prophylaxis / Q000379:methods; D005260:Female; D005312:Fetal Blood / Q000737:chemistry*; D005333:Fetus / Q000502:physiology; D006801:Humans; D016014:Linear Models; D010400:Penicillin G / Q000008:administration & dosage* / Q000097:blood* / Q000493:pharmacokinetics; D011446:Prospective Studies; D013290:Streptococcal Infections / Q000097:blood / Q000517:prevention & control*; D013292:Streptococcus agalactiae
D010400:Penicillin G