Randomized clinical trial of antibiotic therapy for antenatal pyelonephritis. Outpatient treatment of pyelonephritis in pregnancy: a randomized controlled trial. Treatment of lower urinary tract infection in pregnancy. A randomized trial of three antibiotic regimens for the treatment of pyelonephritis in pregnancy. Pyelonephritis in pregnancy: a prospective randomized trial to prevent recurrent disease evaluating suppressive therapy with nitrofurantoin and close surveillance. Randomized trial of antibiotics in addition to tocolytic therapy to treat preterm labor. Antibiotic treatment in preterm labor and intact membranes: a randomized, double-blinded, placebo-controlled trial. Outpatient treatment of acute pyelonephritis in pregnancy after 24 weeks. Antibiotic treatment of preterm labor with intact membranes: a multicenter, randomized, double-blinded, placebo-controlled trial.
The aim of this study was to prospectively evaluate the efficacy of a therapeutic course of intravenous antibiotics followed by oral antibiotics vs. intravenous antibiotics alone to prevent recurrent urinary tract infection.
                Pyelonephritis was documented by strict criteria in 67 pregnant women who were then treated with appropriate intravenous antibiotics until afebrile and asymptomatic for 48 h. Women were then randomized to completion of a 10-day course of oral nitrofurantoin 100 mg qid or no further antibiotic therapy. Urine cultures (UC) were obtained 2 and 6 weeks after discharge, and at delivery. A positive UC or readmission for pyelonephritis was considered endpoints for participation in the study. Antibiotic suppression was not used.
                Readmission for pyelonephritis prior to the 2-week follow-up visit occurred in 2/36 (5.6%) women randomized to the oral therapy group compared to 4/31 (12.9%) in the no oral treatment group (P = 0.29). At the 2-week follow-up visit, 6/31 (19.4%) women had a positive UC in the oral therapy compared to 8/26 (30.1%) in the no oral treatment group but this difference was not statistically significant (P = 0.31).
                Completion of 10 days of antibiotic therapy with oral medication does not significantly reduce the risk of recurrent pyelonephritis immediately post-parenteral treatment. Women in the no oral treatment group had a non-significant increase in positive UC at the 2-week follow-up visit. The high rates of recurrent urinary tract infection during pregnancy in both groups underscore the need for regular UC and for the possible role of oral antibiotic suppression. To compare the safety and efficacy of outpatient and inpatient treatment of pyelonephritis in pregnancy.
                We performed a randomized controlled trial of pregnant women with pyelonephritis before 24 weeks' estimated gestational age, comparing inpatient and outpatient treatment. Sixty inpatients received cefazolin intravenously until afebrile for 48 hours, and 60 outpatients received two injections of ceftriaxone intramuscularly. All patients completed a 10-day course of oral cephalexin. We performed a urine culture 5-14 days after completion of therapy.
                The two groups were similar with respect to age, parity, temperature, estimated gestational age, initial white blood cell count, and incidence of bacteremia. Escherichia coli was the major uropathogen isolated (86% of cultures, 95 of 111). Twelve percent (13 of 111) of bacteria were resistant to cefazolin. Eleven outpatients and 12 inpatients had positive urine cultures after therapy (relative risk 0.9, 95% confidence interval 0.4-1.9). Three patients in each group had recurrent pyelonephritis. We switched six inpatients to gentamicin because of a worsening clinical picture (two) or a prolonged febrile course (four); no outpatients required a change in antibiotic (Fisher exact test, P = .03). One preterm delivery occurred in an inpatient with recurrent pyelonephritis.
                Outpatient antibiotic therapy is effective and safe in selected pregnant women with pyelonephritis. Urinary tract infection (UTI) is a common complication of pregnancy. Approximately 20--40% of women with asymptomatic bacteriuria will develop pyelonephritis during pregnancy. All pregnant women, therefore, should have their urine cultured at their first visit to the clinic. In a clinical study comparing single-dose treatment with 3 g fosfomycin trometamol versus a 3-day course of 400 mg ceftibuten orally, the inclusion criteria were acute symptomatic lower UTI (acute cystitis), significant bacteriuria (> or =10(3) CFU/ml), pyuria and confirmed pregnancy. Excluded were patients with asymptomatic bacteriuria or acute pyelonephritis. Predisposing factors comprised a history of recurrent UTI, diabetes mellitus, analgesic nephropathy, hyperuricaemia or Fanconi's syndrome. Escherichia coli was the most frequently isolated pathogen in both groups. Therapeutic success (clinical cure and bacteriological eradication of uropathogens) was achieved in 95.2% of the patients treated with fosfomycin-trometamol versus 90.0% of those treated with ceftibuten (P, non-significant). The treatment of acute cystitis in pregnant women using a single-dose of fosfomycin trometamol was equally effective as the 3-day course of oral ceftibuten. Both regimens were well tolerated with only minor adverse effects. Long-term chemoprophylaxis should be suggested in patients with recurrent UTI or following acute pyelonephritis during pregnancy. To compare the effectiveness of three antibiotic regimens for the treatment of acute pyelonephritis in pregnancy.
                One hundred seventy-nine pregnant women earlier than 24 weeks' gestation who had acute pyelonephritis were randomized to 1) intravenous (i.v.) ampicillin and gentamicin, 2) i.v. cefazolin, or 3) intramuscular ceftriaxone. All participants then completed 10-day courses of oral cephalexin after primary treatment. A urine culture was performed on admission and 5-14 days after completion of therapy. Surveillance for persistent or recurrent infection and obstetric complications continued until delivery. On the basis of a two-sided hypothesis test and with alpha = .025, 60 subjects were needed in each group for statistical power greater than 80% to detect a difference between ceftriaxone and other antibiotics if hospital length of stay differed by 1 or more days.
                The treatment groups were similar in age, parity, temperature, gestational age, and initial white blood cell count. There were no statistically significant differences in length of hospitalization, hours until becoming afebrile, days until resolution of costovertebral angle tenderness, or infecting organism. There were no statistically significant differences in birth outcomes between the three groups. The average (standard deviation) age at delivery was 38.8 +/- 3.6 weeks. The average birth weight was 3274 +/- 523 g. Eleven (6.9%) of 159 subjects delivered prematurely. Escherichia coli was the most common uropathogen isolated (137 of 179, 76.5%). Blood cultures were positive for organisms in 15 cases (8.4%). At follow-up examination within 2 weeks of initial therapy, eight (5.0%) of 159 subjects had urine cultures positive for organisms. Ten women (6.3%) had cultures positive for organisms later in their antepartum course, and 10 other participants (6.3%) developed recurrent pyelonephritis.
                There are no significant differences in clinical response to antimicrobial therapy or birth outcomes among subjects treated with ampicillin and gentamicin, cefazolin, or ceftriaxone for acute pyelonephritis in pregnancy before 24 weeks' gestation. It has been advocated that if a patient develops acute pyelonephritis during pregnancy, she should receive suppressive therapy for the remainder of the gestation to prevent a recurrence of the disease. We have prospectively evaluated 200 patients following an acute episode of pyelonephritis during pregnancy. All patients were followed in a special clinic. Half the patients received nitrofurantoin as suppressive therapy. Recurrent pyelonephritis occurred in 7% of the patients receiving suppressive therapy versus 8% of those patients receiving close surveillance in the clinic. The results cast doubt upon the need for suppressive therapy and instead dramatized the beneficial effects of close surveillance with cultures. The data also suggest, at least in a high-risk population, that patients with gram-negative bacilluria of less than 10(5) colonies/ml may have a substantial risk of developing symptomatic recurrences. Prompt treatment of even low levels of gram-negative bacilluria should be considered in patients at risk for recurrent disease. 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 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. To compare outpatient to inpatient management of acute pyelonephritis in pregnancy beyond 24 weeks' gestation.
                Ninety-two gravidas past 24 weeks' gestation, randomized to outpatient or inpatient therapy, received two 1-g doses of intramuscular ceftriaxone at 24-hour intervals while hospitalized, then were discharged and reevaluated within 48-72 hours or remained hospitalized until afebrile for 48 hours. Subjects received oral cephalexin after initial treatment. Urine cultures were done on admission and 5-14 days after therapy. Surveillance continued until delivery. We anticipated that 15% of outpatients and 0.01% of inpatients would require changes in antibiotic therapy.
                Twenty-one percent of women evaluated were excluded. Thirteen of 46 (28%) outpatients' hospitalization exceeded 24 hours. Six outpatients (13.0%) and one inpatient did not respond to initial therapy and were treatment failures (relative risk [RR] 1.82, 95% confidence interval [CI] 1.00, 3.31). Within 2 weeks of initial therapy, seven of 81 (8.6%) subjects had positive urine cultures, four outpatients versus three inpatients (P > .999). Eleven of 84 (13.1%) deliveries for which birth data were available occurred preterm (six of 41 outpatients versus five of 43 inpatients) (RR 1.14, 95% CI 0.61, 2.11).
                There were no significant differences in clinical responses or birth outcomes of inpatients or outpatients treated for acute pyelonephritis after 24 weeks' gestation if they completed their assigned protocols. Thirty percent of outpatients were unable to, and most women with acute pyelonephritis in the third trimester were not candidates for outpatient therapy. 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.
Antibiotic treatment is effective in reducing the risk of pyelonephritis in pregnancy. A reduction in low birthweight is consistent with current theories about the role of infection in adverse pregnancy outcomes, but this association should be interpreted with caution given the poor quality of the included studies.