Anti-infective
PREGNANCY RECOMMENDATION: Limited Human Data—Animal Data Suggest Low Risk
BREASTFEEDING RECOMMENDATION: Limited Human Data—Probably Compatible
PREGNANCY SUMMARY
Although the human data are very limited, the tazobactam–piperacillin combination appears to be relatively safe in pregnancy. No fetal harm in animals was observed at doses very close to those used in humans. Moreover, there is substantial experience with penicillins in human pregnancy that has shown this class of anti-infectives to be safe for the embryo–fetus. Because tazobactam is a derivative of the penicillin nucleus, it also probably is safe in pregnancy.
FETAL RISK SUMMARY
Tazobactam, a β-lactamase inhibitor, is combined with piperacillin to increase its antibacterial spectrum. It is not available as a single agent. Structurally, tazobactam is a derivative of the penicillin nucleus and is metabolized to an inactive metabolite. The plasma half-life ranges from 0.7 to 1.2 hours. Only 30% of tazobactam (and none of the metabolite) is bound to plasma proteins.
Reproduction studies with tazobactam have been conducted in mice and rats. No evidence of fetal harm was observed in these species at doses ≤6 and 14 times, respectively, the human dose based on BSA (HD). In rats, no effects on fertility were observed with doses 3 or fewer times the HD.
Consistent with its molecular weight (about 322) and its low protein binding, tazobactam crosses the human placenta. A 1998 report described the pharmacokinetics of piperacillin–tazobactam in six women with gestations of 25–32 weeks (2). Because of the increase in renal clearance and other factors, a marked decrease in maternal serum concentrations of both agents was observed. In one of the women (samples were inadequate in the other five), the fetal:maternal serum ratio of tazobactam was 2 approximately 3 hours after a dose. In two other women, low concentrations of tazobactam, 2.3 and 3.7 mcg/mL, respectively, were measured in the amniotic fluid and, in two others, low concentrations in fetal urine, 8.2 and 12.4 mcg/mL, respectively.
BREASTFEEDING SUMMARY
Although specific details were lacking, the manufacturer states that tazobactam is excreted into breast milk in low concentrations (1). This is consistent with its molecular weight (about 322) and low protein binding (30%). Piperacillin also is excreted into milk (see Piperacillin). The effects of this low exposure on a nursing infant probably are not clinically significant, but 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. Zosyn. Wyeth Pharmaceuticals, 2004.
2.Bourget P, Sertin A, Lesne-Hulin A, Fernandez H, Ville Y, Van Peborgh P. Influence of pregnancy on the pharmacokinetic behaviour and the transplacental transfer of the piperacillin-tazobactam combination. Eur J Obstet Gynecol Reprod Biol 1998;76:21–7.