Adjunctive clindamycin therapy for preterm labor: results of a double-blind, placebo-controlled trial. Ampicillin and metronidazole treatment in preterm labour: a multicentre, randomised controlled trial. Randomized trial of antibiotics in addition to tocolytic therapy to treat preterm labor. Antibiotic treatment of preterm labor with intact membranes: a multicenter, randomized, double-blinded, placebo-controlled trial. A randomized, prospective study of adjunctive ceftizoxime in preterm labor. Ampicillin-metronidazole treatment in idiopathic preterm labour: a randomised controlled multicentre trial. Broad-spectrum antibiotics for spontaneous preterm labour: the ORACLE II randomised trial. ORACLE Collaborative Group. A randomized, blinded, placebo-controlled trial of antibiotics in idiopathic preterm labor. Antibiotic treatment in preterm labor and intact membranes: a randomized, double-blinded, placebo-controlled trial. Combination antibiotics and indomethacin in idiopathic preterm labor: a randomized double-blind clinical trial.
A double-blind, placebo-controlled, randomized trial was conducted to evaluate the efficacy, safety, and tolerance of a course of clindamycin (administered for 3 days intravenously and 4 days orally) among hospitalized women with preterm labor at less than or equal to 34 weeks' gestation who were treated with tocolytics. One hundred three woman-perinate pairs were analyzed. Univariate analysis demonstrated that pregnancies were continued longer in women treated with clindamycin than in women who received placebo (clindamycin-treated group, 35 days; placebo-treated group, 25 days; p = 0.02). Survival analysis showed that pregnancy continued at least 35.5 days in 50% of clindamycin-treated women versus 20 days for control women (p = 0.03). Obstetric and microbiologic parameters associated with treatment outcomes were also sought. Women with bacterial vaginosis more often delivered preterm (p = 0.03; relative risk, 1.4; 95% confidence interval, 1.04 to 2.0). Among women with bacterial vaginosis, trends for increased duration of pregnancy (clindamycin-treated group, 36 days; placebo-treated group, 19 days), increased birth weight (clindamycin-treated group, 2634 gm; placebo-treated group, 2256 gm), and increased mean gestational age at delivery (clindamycin-treated group, 35 weeks; placebo-treated group, 34 weeks) were associated with clindamycin treatment. Women with either group B streptococcus, Chlamydia trachomatis, Trichomonas vaginalis, or Staphylococcus aureus were more likely to have preterm premature rupture of membranes (p = 0.01). Clindamycin treatment of these women reduced the incidence of preterm premature rupture of membranes to that of uninfected subjects. Stratification by gestational age at enrollment showed clindamycin treatment to be associated with an increased interval to delivery only among mothers enrolled before 33 weeks' gestation (clindamycin-treated group, 40 days; placebo-treated group, 28 days; p less than 0.05). Treatment with clindamycin appeared safe and well tolerated, with benefits limited to women who were less than or equal to 32 weeks' gestation. To ascertain whether adjuvant ampicillin and metronidazole given to women in preterm labour with intact membranes would prolong pregnancy and decrease the perinatal mortality and morbidity.
                A multicentre, prospective, randomised controlled trial.
                Three perinatal centres serving an indigent population.
                Eighty-one women in active preterm labour with otherwise uncomplicated singleton pregnancies between 26 and 34 weeks gestation or an ultrasound fetal weight estimate of 800 g to 1500 g.
                The study group received ampicillin and metronidazole for five days. The control group received no antibiotics. In all women contractions were suppressed with hexoprenaline and indomethacin for 24 h, and betamethasone was given for fetal lung maturity.
                Days gained and perinatal mortality and morbidity.
                The study (n = 43) and control groups (n = 38) were comparable at entry. In those receiving ampicillin and metronidazole the pregnancy was significantly prolonged (median 15 days versus 2.5 days, P = 0.04) with significantly more women still pregnant after seven days (63% versus 37%, P = 0.03, OR 0.34 95% CI 0.13-0.94). Significantly more infants in the control group developed necrotising enterocolitis than in the study group (5 versus 0, P = 0.02).
                Adjuvant ampicillin and metronidazole in the management of women in preterm labour with intact membranes significantly prolonged the pregnancy and decreased neonatal morbidity. The objective of this study was to assess whether antibiotic therapy plus tocolysis given to women in preterm labor would prolong pregnancy compared with tocolysis alone.
                A randomized, double-blind trial of intravenous mezlocillin and oral erythromycin therapy vs. placebo was used in addition to tocolysis among women in preterm labor < or =34 weeks gestation with intact membranes. Amniocentesis was performed, and chorioamnionic membranes were examined histologically and cultured for microorganisms after delivery.
                Clinical characteristics including gestational age at enrollment, frequency of contractions, cervical Bishop's score, and white blood cell count on admission were similar in the 2 groups. Antibiotic therapy was well tolerated. No significant differences in the interval to delivery, birth weight, and neonatal outcomes were observed between the 2 groups. Women in the antibiotic group had a significantly lower incidence of postpartum infections compared with women in the placebo group. Patients with evidence of upper genital tract infection in either group had a significantly shorter interval to delivery, lower gestational age at delivery, lower mean birth weight, and increased neonatal hospitalization time.
                Lack of an antibiotic effect on the gestational age at delivery may be due to the low prevalence of upper genital tract infection among unselected women in preterm labor, to advanced preterm labor unresponsive to antibiotic therapy, or to an inability of antibiotics given alone to inhibit the cytokine response. Further work is needed to identify markers of upper genital tract infection among women in preterm labor and to evaluate other potential therapeutic interventions. Although an association between subclinical intrauterine infection and preterm birth is well established, there is conflicting evidence regarding the benefits of antibiotic administration to women in preterm labor with intact membranes. We attempted to determine the effect of ampicillin-amoxicillin and erythromycin treatment on prolongation of pregnancy, the rate of preterm birth, and neonatal morbidity in patients with preterm labor and intact membranes.
                A multicenter, randomized, double-blinded, placebo-controlled trial was designed and implemented by the Maternal-Fetal Medicine Units Network of the National Institute of Child Health and Human Development. Two hundred seventy-seven women with singleton pregnancies and preterm labor with intact membranes (24 to 34 weeks) were randomly allocated to receive either antibiotics or placebos.
                Of the 2373 patients screened for participation in this study in six medical centers, 277 women were enrolled (n = 133 for antibiotics group vs n = 144 for placebo group). In each study group, 60% of patients completed all the study medications. The overall prevalence of microbial invasion of the amniotic cavity was 5.8% (14/239). No significant difference between the antibiotic group and the placebo group was found in maternal outcomes, including duration of randomization-to-delivery interval, frequency of preterm delivery (< 37 weeks), frequency of preterm premature rupture of membranes, clinical chorioamnionitis, endometritis, and number of subsequent admissions for preterm labor. Similarly, no significant difference in neonatal outcomes could be detected between the two groups including respiratory distress syndrome, bronchopulmonary dysplasia, intraventricular hemorrhage, sepsis, and admission and duration of newborn intensive special care unit hospitalization.
                The results of this study do not support the routine use of antibiotic administration to women in preterm labor with intact membranes. Our purpose was to determine the effect of ceftizoxime in the prolongation of pregnancies receiving tocolysis for preterm labor.
                A prospective, randomized, double-blinded, placebo-controlled trial was conducted in patients with preterm labor between 24 and 35 weeks' gestation. A total of 545 patients with intact membranes and without chorioamnionitis who were receiving magnesium sulfate were screened. Exclusions were for advanced cervical dilatation, penicillin allergy, current antibiotic therapy, and failure to give informed consent. Of these, 117 consecutive, eligible, consenting patients were randomized to receive either 2 gm of ceftizoxime or a placebo every 8 hours. The primary end point was prolongation of gestation. Statistical comparisons were performed by use of unpaired two-tailed t tests and chi 2 analysis.
                Of the 58 ceftizoxime and 59 placebo patients, there was no difference in the interval to delivery (34.5 +/- 21.1 days vs 34.6 +/- 24.5 days, p = 0.99) and no difference in the rate of delivery before 37 weeks' gestation (60% in the ceftizoxime group vs 58% in the placebo group, p = 0.91). Subanalyses of 61 subjects who received nine or more doses and who were group B streptococci negative, 69 patients at < or = 32 weeks on presentation, and 22 sets of twins all showed no differences in delivery interval or rate of delivery at < 37 weeks. The sample size of this study was sufficient to detect a 9-day difference in prolongation of pregnancy (alpha = 0.05, beta = 0.2).
                Ceftizoxime had no effect on interval to delivery or duration of pregnancy in women treated for preterm labor. To determine whether treatment with ampicillin and metronidazole in women with threatened idiopathic preterm labour will prolong the gestation and reduce maternal and neonatal infectious morbidity.
                Randomised controlled double-blind trial.
                Six obstetric departments in the Copenhagen area.
                One hundred and twelve women with singleton pregnancies, with threatened idiopathic preterm labour and intact amniotic membranes at 26 to 34 weeks of gestation.
                Random allocation to eight days intravenous and oral treatment with ampicillin and metronidazole, or placebo.
                Number of days from admission to delivery, gestational age at delivery, rates of preterm delivery, low birthweight, maternal infections and neonatal infections.
                Treatment with ampicillin and metronidazole was associated with a significant prolongation of pregnancy (admission to delivery 47.5 days versus 27 days, P < 0.05), higher gestational age at delivery (37 weeks versus 34 weeks, P < 0.05), decreased incidence of preterm birth (42% versus 65%, P < 0.05), and lower rate of admission to neonatal intensive care unit (40% versus 63%, P < 0.05), when compared with placebo treatment. Antibiotic treatment had no significant effects on infectious morbidity.
                Treatment with ampicillin and metronidazole in women with threatened idiopathic preterm labour significantly prolonged the gestation, but had no effects on maternal and neonatal infectious morbidity. Preterm birth after spontaneous preterm labour is associated with death, neonatal disease, and long-term disability. Previous small trials of antibiotics for spontaneous preterm labour have reported inconclusive results. We did a randomised multicentre trial to resolve this issue.
                6295 women in spontaneous preterm labour with intact membranes and without evidence of clinical infection were randomly assigned 250 mg erythromycin (n=1611), 325 mg co-amoxiclav (250 mg amoxicillin and 125 mg clavulanic acid; n=1550), both (n=1565), or placebo (n=1569) four times daily for 10 days or until delivery, whichever occurred earlier. The primary outcome measure was a composite of neonatal death, chronic lung disease, or major cerebral abnormality on ultrasonography before discharge from hospital. Analysis was by intention to treat.
                None of the trial antibiotics was associated with a lower rate of the composite primary outcome than placebo (erythromycin 90 [5.6%], co-amoxiclav 76 [5.0%], both antibiotics 91 [5.9%], vs placebo 78 [5.0%]). However, antibiotic prescription was associated with a lower occurrence of maternal infection.
                This trial provides evidence that antibiotics should not be routinely prescribed for women in spontaneous preterm labour without evidence of clinical infection. Because subclinical genital tract infection may play a major role in preterm birth, the efficacy of adjunctive antibiotic therapy in combination with standard parenteral tocolysis was examined in a randomized, blinded study of patients with idiopathic preterm labor. Labor was documented by three contractions in 20 minutes, cervical dilation of 1 cm or more, and the need for parenteral tocolysis. Enrollment was restricted to patients with intact membranes and without known causes for preterm labor. One hundred three patients at 24-34 weeks' gestation were randomized to intravenous ampicillin plus oral erythromycin or corresponding placebos. Compared with the placebo group, the adjunctive antibiotic group had a similar frequency of preterm birth (38 versus 44%), time to delivery (34 versus 34 days), birth weight (2847 versus 2855 g), and episodes of recurrent labor requiring parenteral tocolysis (0.43 versus 0.49). In our population, we found no benefit to the adjunctive use of ampicillin plus erythromycin. Significant differences in genital microflora between our patients and those of other studies may explain our results. Although an association between microbial invasion of amniotic cavity and preterm birth has been extensively demonstrated, there is conflicting evidence regarding the benefits of antibiotic therapy in patients with preterm labor and intact membranes. We attempted to assess the efficacy of amoxicillin and erythromycin on pregnancy outcome in those patients. A randomized, double-blinded, placebo-controlled trial was designed and implemented. A total of 196 patients with singleton pregnancies and preterm labor with intact membranes (22-36 weeks) were randomly allocated to receive either antibiotics or placebo, plus adjunctive parenteral tocolysis, and 173 patients (antibiotics group n = 83 vs. placebo group n = 90) completed the treatment. The overall prevalence of microbial invasion of the amniotic cavity was 5.2% (9/173). No significant difference between both groups was found in maternal outcomes, including duration of randomization-to-delivery interval, frequency of preterm delivery, and frequency of clinical chorioamnionitis and endometritis. Rate of cesarean section was significantly higher in the placebo group (28% vs. 12%). Regarding neonatal outcome, no significant difference was detected between both groups in neonatal death, respiratory distress syndrome, proven sepsis, and birthweight. Suspected sepsis was significantly more frequent in the placebo group (6/90 vs. 0/78). The results of this trial indicate that amoxicillin and erythromycin do not prolong pregnancy in patients with preterm labor and intact membranes. A significant reduction in the rate of cesarean section was observed in patients receiving antibiotics. A significant reduction in the rate of neonatal suspected sepsis was also demonstrated. Subclinical infection may play a role in the failure of magnesium sulfate tocolysis. Using a double-blind randomized study design, we administered a combination of ampicillin-sulbactam and indomethacin or corresponding placebos to patients in preterm labor who were receiving intravenous magnesium sulfate tocolysis. The mean gestational age at enrollment was 30.1 weeks, and mean cervical dilatation was 2.15 cm. No differences were noted between placebo (n = 43) and study patients (n = 43) in gestational age at delivery, term deliveries, days gained, or neonatal outcome. Preterm delivery (less than 36 weeks) occurred in 61% of the total population. The likelihood of a beta error was 0.07 to 0.23 on the basis of outcome analysis. In our population adjunctive ampicillin-sulbactam with indomethacin did not improve the success of magnesium sulfate tocolysis.