Double-blind, placebo-controlled trial of piperacillin prophylaxis in preterm membrane rupture Charles 1. Lockwood, MD, Kathleen Costigan, RN, MPH, Alessandro Ghidini, MD, Rosemary Wein, RN, David Chien, MS, Barry L. Brown, MD, Manuel Alvarez, MD, and Curtis L. Cetrulo, MD New York, New York, and Boston, Massachusetts OBJECTIVE: We attempted to test whether antibiotic therapy prolongs pregnancy in preterm premature rupture of membranes, because preterm premature rupture of membranes is frequently associated with chorionic-decidual infection. STUDY DESIGN: Women with preterm premature rupture of membranes and a singleton gestation at 24 to 34 completed weeks were randomized to receive either piperacillin 3 gm or placebo intravenously every 6 hours for 72 hours and were managed conservatively until spontaneous delivery, chorioamnionitis, or fetal distress. RESULTS: Between January 1987 and January 1992, a total of 75 patients were randomized to receive piperacillin (n = 38) or placebo (n = 37). There were no differences between the piperacillin group and the placebo group in mean gestational age at randomization (30.2 ± 3 vs 30.3 ± 2.9 weeks). However, a greater number of patients had pregnancy prolonged beyond 7 days (42.1 % vs 10.8%, P = 0.005) and the mean latency period was significantly prolonged (11.4 ± 18.8 vs 6.1 ± 13.6 days, p = 0.001) in the piperacillin group compared with the control groups. CONCLUSIONS: Use of intravenous piperacillin for 72 hours in preterm premature rupture of membranes significantly prolongs the latency period between membrane rupture and delivery. (AM J OBSTET GYNECOL 1993;169:970-6.) Key words: Fetal membrane, premature rupture, antibiotic, randomized clinical trial Preterm premature rupture of membranes has an incidence of 3% to 9% but accounts for more than half of all spontaneous preterm deliveries and is a leading cause of perinatal mortality and morbidity in the United States.' A recent review of published studies demonstrates that the prevalance of subclincial infec- tion of the amniotic cavity in cases of preterm prema- ture rupture of membranes without contractile uterine activity is 29%.2 Moreover, 75% of patients with preterm premature rupture of membranes who are not in labor on admission but subsequently begin spontaneous labor have a positive amniotic fluid culture." The microorgan- isms isolated from the amniotic fluid in preterm pre- mature rupture of membranes include both aerobes (gram positive and negative) and anerobes, as well as polymicrobial infections in nearly one third of the cases." There is evidence that ascending genital tract infections may lead to chorionic-decidual inflamamtion, From the Department of Obstetrics, Gynecology and Reproductive Medicine, Mount Sinai School of Medicine, and the Department of Obstetrics and Gynecology, Tufts University School of Medicine. Supported by a grant from Lederle Laboratories. Presented at the Thirteenth Annual Meeting of the Society of Peri- natal Obstetricians, San Francisco, California, February 8-13,1993. Reprints not available. Copyright © 1993 by Moshy-Year Book, Inc. 0002-9378/93 $1.00 + .20 6/6/48973 970 with expression of extracellular matrix-degrading pro- teinases capable of compromisng membrane integrity and causing cervical changes:- 6 Such inflammation also causes decidual activation with release of cytokines and prostaglandins, leading to contractile uterine activity." Recent randomized clinical trials have shown that pro- phylactic administration of a variety of antibiotics (ampicillin, mezlocillin, erythromycin, or combinations of multiple antibiotics) in asymptomatic women with preterm premature rupture of membranes can signifi- cantly lengthen the interval between membrane rupture and labor (latency period).7'2 During the same period we undertook a prospective, double-blind, placebo- controlled clinical trial of piperacillin sodium (Pipracil, Lederle) in patients with preterm premature rupture of membranes. Given the broad range of microorganisms associated with preterm premature rupture of mem- branes, we chose an extended-spectrum, [3-lactamase- susceptible penicillin with an activity against the anaer- obic and aerobic organisms isolated in pelvic and gen- ital infections in women.'" Transplacental passage of piperacillin is prompt, I", and no untoward effects on the fetus have been reported. Material and methods Between January 1987 and January 1992, patients admitted to the Departments of Obstetrics and Gyne-