Treatment of lower urinary tract infection in pregnancy. [Acute cystourethritis during pregnancy]. Randomized clinical trial of antibiotic therapy for antenatal pyelonephritis. Antibiotic treatment in preterm labor and intact membranes: a randomized, double-blinded, placebo-controlled trial. Single-dose versus six-day therapy with sulfamethizole for asymptomatic bacteriuria during pregnancy. A prospective randomised study. Antibiotic treatment of preterm labor with intact membranes: a multicenter, randomized, double-blinded, placebo-controlled trial.
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. A prospective study was carried out in 103/863 obstetric patients with cystitis characterized by urinary urgency and frequency, dysuria, pyuria and suprapubic discomfort in the absence of systemic symptoms such as fever and costovertebral angle tenderness. The association of symptomatic lower urinary tract infection with low-count bacteriuria (10(2)-10(5) UFC/mL of urine) was present in all the patients. The incidence of cystourethritis was about 12%, most of the infections occurred at the first trimester. To learn whether a multiple-dose of nitrofurantoin or ampicillin is safe and effective therapy for acute uncomplicated urinary tract infections, 103 symptomatic pregnant women were randomly grouped to receive oral nitrofurantoin (100 mg t.i.d.) or ampicillin (500 mg t.i.d.) for five days. Seventeen patient were excluded since they did not return for follow-up. Escherichia coli was isolated in 67% of infections. Overall cure varied from 87% to 89%, without any great differences between the regimens. Nine patients had asymptomatic bacteriuria in the course of pregnancy, four developed acute pyelonephritis and one of them had abnormal intravenous pyelogram. 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. 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. Single-dose versus conventional six-day therapy with sulfamethizole for asymptomatic urinary tract infection in pregnant women was investigated in a prospective, randomised open study. During a nine-month period 4,274 pregnant women were screened for significant bacteriuria, which was found in 123 (2.9%), of whom only five had symptoms of urinary tract infection. Seventy-nine of the patients had a second urine culture performed, revealing significant counts of the same bacteria in only 41. These 41 patients were randomly allocated to one of the two treatment groups. Control urine cultures one week and 4-6 weeks after start of treatment revealed the same cure rates of approximately 50% in both groups. Single-dose treatment is not inferior to conventional therapy; future study is needed to find the best single-dose regimen. 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.
Although antibiotic treatment is effective for the cure of urinary tract infections, there are insufficient data to recommend any specific drug regimen for treatment of symptomatic urinary tract infections during pregnancy. All the antibiotics studied were shown to be very effective in decreasing the incidence of the different outcomes. Complications were very rare. All included trials had very small sample sizes to reliably detect important differences between treatments. Future studies should evaluate the most promising antibiotics, in terms of class, timing, dose, acceptability, maternal and neonatal outcomes and costs.