PIPERACILLIN

Fetal Risk Summary

Piperacillin, a piperazine derivative of ampicillin, is a broad-spectrum penicillin (see also Ampicillin). Animal reproduction studies in mice and rats at doses up to four times the human dose have shown no evidence of impaired fertility or fetal harm (1).

No reports linking the use of piperacillin with congenital defects in humans have been located. Piperacillin has been used between 24 and 35 weeks' gestation in women with premature rupture of the membranes to delay delivery (2). No adverse maternal or fetal effects were observed.

Piperacillin rapidly crosses the placenta to the fetus (3). Three women, between 22 and 33 weeks' gestation, were administered a single 4-g IV dose of the antibiotic immediately before intrauterine exchange transfusion for Rh isoimmunization. The mean concentrations of piperacillin in fetal serum was 20 ± 12 µg/mL, in maternal serum 121 ± 50 µg/mL (fetal:maternal ratio 0.17), and in amniotic fluid 0.9 ± 0.4 µg/mL.

The pharmacokinetics of piperacillin during pregnancy have been reported (4). Women were administered a 4-g IV dose just before cesarean section. The mean venous cord concentration was 9.7 µg/mL, representing a mean fetal:maternal ratio of 0.27. As with other penicillins, an increased clearance of the antibiotic was observed during pregnancy.

Breast Feeding Summary

Piperacillin is excreted in small amounts in human breast milk (1). Although concentrations are low, three potential problems exist for the nursing infant: modification of bowel flora, direct effects on the infant, and interference with the interpretation of culture results if a fever workup is required.

References

1. Product information. Pipracil. Lederle Laboratories, 2000.
2. Lockwood CJ, Costigan K, Ghidini A, Wein R, Cetrulo C, Alvarez M, Berkowitz RL. Double-blind, placebo-controlled trial of piperacillin sodium in preterm membrane rupture. Am J Obstet Gynecol 1993;168:378 (Abstract).
3. Brown CEL, Christmas JT, Bawdon RE. Placental transfer of cefazolin and piperacillin in pregnancies remote from term complicated by Rh isoimmunization. Am J Obstet Gynecol 1990;163:938–43.
4. Heikkilä A, Erkkola R. Pharmacokinetics of piperacillin during pregnancy. J Antimicrob Chemother 1991;28:419–23.