Objective: To compare maternal infection rates, neonatal sepsis rates, and bacterial resistance patterns in cases of neonatal sepsis for three antibiotic protocols for women with preterm premature rupture of membranes (PROM).
Methods: From January 1, 1988 to February 28, 1998, women with preterm PROM not requiring immediate delivery were treated according to one of three antibiotic protocols. During three distinct periods, patients received no antibiotics, intravenous ampicillin for 48 hours followed by oral amoxicillin, or intravenous ticarcillin-clavulanic acid for 48 hours followed by oral amoxicillin-clavulanic acid. Rates of chorioamnionitis, endometritis, and neonatal sepsis were compared, as were antimicrobial resistance patterns. Statistical analysis was done using χ2 analysis, Fisher exact test, and the log-likelihood ratio test. The Bonferroni correction was used for multiple comparisons.
Results: During the three periods, preterm PROM was diagnosed in 1695 women. The incidence of endometritis was lower during the third (5.3%) compared with the first (15.1%, P < .001) and second (11.6%, P < .001) protocols. Chorioamnionitis rates were 13.6%, 12.7%, and 15.6% (P = .34) for the first, second, and third periods, respectively, and neonatal sepsis rates were 2.2%, 0.6%, and 1.1% (P = .08), respectively. Neonatal sepsis with gram-negative (P = .02) and ampicillin-resistant (P = .04) organisms was more likely when mothers received antepartum ampicillin or ticarcillin-clavulanic acid.
Conclusion: Antibiotic therapy for patients with preterm PROM was associated with a decrease in the rate of endometritis and a trend toward less neonatal sepsis but an increase in the proportion of gram-negative and ampicillin-resistant organisms causing neonatal sepsis.
Preterm premature rupture of membranes (PROM) complicates more than 130,000 pregnancies in the United States every year and is associated with at least one third of preterm births.1 Although the latency period is inversely proportional to gestational age, 70–80% of women with preterm PROM, overall, will deliver within 1 week of membrane rupture.2 Infant morbidity in these cases is related primarily to gestational age at delivery. However, neonatal sepsis remains an important cause of morbidity and mortality at all gestational ages.
When remote from term, the fetus of a patient with preterm PROM can benefit from expectant treatment. Adjunctive treatments to reduce neonatal morbidity in this setting include tocolysis and maternal administration of corticosteroids and antibiotics. Whereas tocolysis and corticosteroid therapy are controversial, several trials of antibiotic therapy have shown prolongation of the latency period,3–12 reduction in neonatal morbidity,5,6,9,10,12,13 and decreased incidence of maternal infection.6,9,12–15
Although those trials show a benefit of antibiotic therapy, the optimal drug or combination of drugs, route of administration, and duration of therapy are yet to be determined. Because of the variety of potential pathogens colonizing the vagina (and possibly the amnion after membrane rupture), broad-spectrum antibiotics offer some theoretic advantages over more narrow-spectrum agents. A potential pitfall of broad-spectrum agents is the emergence of resistant organisms in gravidas and their neonates. To investigate this phenomenon, we reviewed the records of women treated at Shands Hospital at the University of Florida. We compared maternal infection rates, neonatal sepsis rates, and bacterial resistance rates associated with three antibiotic protocols for women with preterm PROM.
Antibiotic therapy for patients with expectantly treated preterm premature rupture of membranes was associated with a higher proportion of gram-negative and ampicillin-resistant organisms causing neonatal sepsis and fewer cases of puerperal endometritis.
Department of Obstetrics and Gynecology, University of Florida, Gainesville, Florida; and the Department of Obstetrics and Gynecology, University of Texas Medical Branch, Galveston, Texas.
Reprints are not available.
Received September 27, 1999. Received in revised form January 11, 2000. Accepted January 20, 2000.