Ampicillin for neonatal group B streptococcal prophylaxis: How rapidly can bactericidal concentrations be achieved?,☆☆,

Presented at the Sixteenth Annual Meeting of the Society of Perinatal Obstetricians, Kamuela, Hawaii, February 4-10, 1996.
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Abstract

OBJECTIVE: Our purpose was to determine how rapidly bactericidal concentrations of ampicillin against group B streptococci are achieved in amniotic fluid and cord blood after a 2 gm maternal infusion. STUDY DESIGN: Ampicillin was administered at varying time intervals between 3 and 67 minutes before elective cesarean delivery in 40 women. Samples of amniotic fluid were obtained by amniocentesis just before the uterine incision was made. Umbilical and maternal blood were obtained at the time of delivery. Ampicillin concentrations were measured by high-pressure liquid chromatography. RESULTS: The mean concentrations of ampicillin measured in maternal and umbilical cord sera all exceeded the minimum bactericidal concentrations reported for group B streptococci (0.25 to 2.0 μg/ml) and were achieved as soon as 5 minutes after ampicillin infusion. Similarly, bactericidal levels of ampicillin in the amniotic fluid could be detected as early as 5 minutes. However, such concentrations of ampicillin in the amniotic fluid were achieved in only 85% of the pregnancies studied. CONCLUSIONS: Bactericidal levels of ampicillin against group B streptococci can usually be achieved rapidly in both fetal blood and amniotic fluid after a standard 2 gm intravenous dose given to the mother for neonatal prophylaxis. (Am J Obstet Gynecol 1996;175:974-6.)

Section snippets

MATERIAL AND METHODS

Ampicillin was administered at arbitrarily determined time intervals before delivery in term parturients who were not in labor and who were undergoing elective cesarean delivery. The study protocol was approved by the Institutional Review Board of the University of Texas Southwestern Medical Center at Dallas, and informed written consent was obtained from each participant. Women who had ruptured membranes, signs of infection, or an allergy to penicillin were excluded. A standard 2 gm dose of

RESULTS

Between June 16, 1995, and September 19, 1995, 40 women consented to participate in this investigation. The women ranged in age from 18 to 40 years (27 ± 6 years [mean ± SD]). The gestational age at delivery was 39 ± 1 week (mean ± SD). The majority of patients received regional anesthetics (n = 34) and the remainder received general anesthetics (n = 6). The umbilical artery pH was 7.26 ± 0.06 (mean ± SD), and all infants were born in good condition. No infant had neonatal sepsis.

The time

COMMENT

After an intravenous infusion of 2 gm of ampicillin, concentrations well in excess of the minimum bactericidal concentration reported for group B streptococci3, 4 were achieved within 3 minutes in all maternal and umbilical cord blood samples. In contrast, bactericidal concentrations were not achieved in the amniotic fluid in 15% of the pregnancies studied. We speculate that the variability observed in amniotic fluid ampicillin levels may reflect whether ampicillin excretion by fetal

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    However, despite adequate bactericidal levels in fetal cord blood, 15% of their mothers will have amniotic fluid antibiotic concentrations below the minimal inhibitory concentration for GBS.7 Cases of neonatal GBS sepsis that occur with short durations of maternal antibiotic prophylaxis (ie, <4 hours) may either be the result of the following: (1) fetal exposure to GBS in utero prior to antibiotic administration when tissue injury by GBS may not be quickly reversible or (2) inadequate time for antibiotics to decrease vaginal GBS colony counts.6,7 Most published medical literature on intrapartum antibiotic prophylaxis for GBS suggest a 4 hour time threshold for antibiotic exposure.

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    Other diverse strategies to reduce maternal colonization and vertical transmission have been studied; but, none could prove effective for prevention of GBS EOD [13,109]. Currently, intravenous administration of penicillin G, being the first choice, or ampicillin, at least 4 hours before delivery, have proven effective for prevention of GBS vertical transmission and are recommended [2,13,41,110], but shorter duration might still provide some protection [111,112]. The dosages of penicillin or ampicillin used for IAP are aimed at achieving adequate levels in the foetal circulation and amniotic fluid rapidly [113,114].

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From the Department of Obstetrics and Gynecology, University of Texas Southwestern Medical Center.

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Reprint requests: Steven L. Bloom, MD, Department of Obstetrics and Gynecology, University of Texas Southwestern Medical Center, 5323 Harry Hines Blvd., Dallas, TX 75235-9032.

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