Lactobacillus Reuteri for Treatment of Uncomplicated UTI in Pregnant Women

Study Overview
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Brief Summary
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Prevalence of uro-genital infections during pregnancy move between 7% to 12% in developed countries, meanwhile in developing countries this figure moved between 14% and until 55%, such is the case of Mexico. Meanwhile use of antibiotics for 3 to 7 days had established as a standard of care, the use of non-antibiotic therapy, such as cranberry powder or probiotics for prevention/treatment of this conditions is scarce. Randomized controlled trial aimed to evaluate the safety and efficacy of probiotic vs. antibiotics to treat pregnant women with uncomplicated cystitis or asymptomatic bacteriuria

Detailed Description
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Randomized controlled trial, aimed to evaluate the efficacy of Lactobacillus reuteri DSM 16666/ATCC 55845 & Lactobacillus reuteri DSM 17938 for the treatment of pregnant women with asymptomatic bacteriuria or uncomplicated acute cystitis. As primary outcome we will evaluate the number of cases with clinical (symptoms severity) or bacteriological cure in pregnant women with uncomplicated cystitis or asymptomatic bacteriuria after 7 days treatment with probiotics vs. placebo. As secondary outcome we will evaluate a) rate of recurrence cases in each group; b) time to relapse; c) frequency of pyelonephritis; d) birth weight and head circumference; d) number of cases of preterm babies (less than 36 weeks of gestation); e) frequency of antibiotic as rescue treatment; f) frequency of adverse related events in each arm and g) frequency of preeclampsia. Women on active group will receive a combination of at least 5*10^8 CFU of Lactobacillus reuteri DSM 16666/ATCC 55845 & Lactobacillus reuteri DSM 17938, PAC-A and Zinc. Women in control group will receive o Amoxicillin + clavulanic acid (500 mg twice daily) for seven days in patients with negative nitrites in dipstick or oral nitrofurantoin (200mg twice per day) ror patients with positive dipstick.

Official Title
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Randomized Clinical Trial on the Safety and Efficacy of Lactobacillus Reuteri DSM 16666/ATCC 55845 & Lactobacillus Reuteri DSM 17938 for Treatment of Pregnant Women With Asymptomatic Bacteriuria or Uncomplicated Acute Cystitis

Conditions
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Urinary Tract Infection in Pregnancy

Intervention / Treatment
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* Dietary Supplement: Probiotics
* Drug: Antibiotics


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Healthy women on the second or third trimester of pregnancy with positive urine culture according to the operational definition with or without symptoms Age 18 to 40 years Verbal and Written Informed Consent for participation in the study Exclusion Criteria: Pathologic pregnancy (different for UTI) No supplementation of probiotics 2 weeks before study start or during the study period. Antibiotic therapy within last 2 weeks before randomization Known allergies towards the ingredients of the experimental product Inability to comprehend the study protocol Systemic diseases Multiple pregnancy

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 40 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: Randomized controlled trial, double blind allocation concealment, parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Probiotic<br>5*10^8 CFU of Lactobacillus reuteri DSM 16666/ATCC 55845 & Lactobacillus reuteri DSM 17938, PAC-A and Zinc | Dietary Supplement: Probiotics<br>* The Probiotic group will receive Sachet 1 - contains an instant cranberry drink, consisting of xylitol, monosodium citrate, cranberry aroma, cranberry extract, grape-skin extract, xanthan gum, acesulfame potassium and zinc gluconate and Sachet 2 - contains a total of 5*10^8 CFU of Lactobacillus reuteri DSM 16666/ATCC 55845 & Lactobacillus reuteri DSM 17938, mixed with maltodextrin. Both Sachets should be administered Day 1-14, twice per day This group will also receive for Placebo for Antibiotic treatment day 1-7, twice per day<br>|
| Active Comparator: Antibiotic<br>Amoxicillin + clavulanic acid (500 mg twice daily) for seven days in patients with negative nitrites in dipstick or oral nitrofurantoin (200mg twice per day) for patients with positive nitrates in dipstick | Drug: Antibiotics<br>* Patient in this group will receive for 7 days Amoxicillin + clavulanic acid (500 mg twice daily) for seven days in patients with negative nitrites in dipstick or oral nitrofurantoin (200mg twice per day) for patients with positive nitrates in dipstick. This group will also receive for placebo for probiotics 2 sachets for 14 days<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Clinical and/or Bacteriological cure | Number of cases with improvement of symptoms severity and/or urinary culture during the first seven days of treatment | 14 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Recurrence rate | Rate of recurrence cases during the rest of pregnancy | 6 months | 
| Time to relapse | Time occurred since the finish of treatment until new UTI occurred | 6 months | 
| Frequency of pyelonephritis | Number of cases of pyelonephritis in each branch | 6 months | 
| Frequency of preterm babies | Number of children at delivery with <36wekks of gestation | 6 months | 
| Antibiotic rescue | Use of antibiotics for the treatment of pyelonephritis | 6 months | 
| Adverse events | Frequency of adverse events in each branch | 14 days |