Table 1.

Summary of studies included in the review

	Year of study	Type of study	Inclusion criteria	Exclusion criteria	Sample size	Method	Strength	Limitation
Kranjcec, et al.[21]	2013	Randomized controlled trial	Age over 18 years, positive history of recurrent cystitis	Pregnant, breastfeeding, trying to conceive, past symptoms of upper UTI and symptoms of SIRS, history of urinary tract anomalies, interstitial cystitis or diabetes, taking hormone therapy, contraception had previously received antibiotic prophylaxis	n=308; 103 in D-mannose group; 103 in nitrofurantoin group; 102 in placebo group	D-mannose group received 2 g of D-mannose powder diluted in 200 ml of water once daily in the evening for 6 months; nitrofurantoin group received 50 mg of nitrofurantoin once daily in the evening for 6 months; placebo group did not receive anything for 6 months	Analysis for projected UTI recurrence rate of 30% in no prophylaxis group was done	It was not blinded and the total number of recurrences per patient could not be calculated since we did not re-enter the patients into the study after the antibiotic treatment of recurrent infection
McMurdo, et al.[22]	2008	Randomized controlled trial	Community-dwelling women aged ≥45 years with at least two antibiotic-treated UTIs or episodes of cystitis in the previous 12 months	Previous urological surgery, stones or anatomical abnormalities of the urinary tract, urinary catheter, diabetes mellitus, immunocompromised, pyelonephritis, severe renal blood dyscrasia, symptomatic UTI at baseline, resident in institutional care, on long-term antibiotic therapy, on warfarin therapy, regular cranberry consumers, childbearing potential	n=137; 69 in cranberry group; 68 in TMP-SMX group	Cranberry group received 200 capsules containing 500mg of cranberry extract for 6 months; TMP-SMX group received 200 capsules containing 100mg of trimethoprim for 6 months	The target of 120 participants for the trial was met, as well as the primary and secondary outcomes. Therefore, there is good internal validity	Did not have a placebo group
Beerepoot et al.[23]	2011	Randomized controlled trial, double-blind, double-dummy	Premenopausal women, 18 years of age or older, with a medical history of at least three symptomatic UTIs in the year preceding enrolment	Symptoms of a UTI, use of antibiotics or cranberry in the previous two weeks, relevant interactions with existing medication or contraindications for TMP-SMX or cranberries, pregnancy, breastfeeding and history of renal transplantation	n=221; 110 in TMP-SMX group; 111 in cranberry group	TMP-SMX group took one tablet with 480 mg TMP-SMX at night and one placebo capsule twice daily for 12 months; cranberry group took one capsule with 500 mg cranberry extract twice daily and one placebo tablet at night for 12 months	Relatively long intervention period of 12 months; inclusion of a washout period after the discontinuation of the study medication; thorough microbiologic testing and rigorous analyses were performed; effect of long-term (antibiotic) prophylaxis on the indigenous flora was assessed	Only premenopausal women were included in this study; target of 280 participants was not reached; high resistance rates at baseline and the relatively high background incidence of UTIs in the study population might have influenced the success rates; high withdrawal rates (≤58%); did not confirm that all women took the cranberry prophylaxis (antibacterial activity is present in the urine of TMP-SMX group)
Raz, et al.[24]	2003	Randomized trial, double-blind, double dummy	Postmenopausal women who had a history of recurrent UTI	History of any usage of HRT in the previous year, known malignancy patients, patients with vaginal bleeding, active or recent thromboembolic disease, usage of indwelling catheter, known urinary retention, long-term recipient of antibiotic treatment for the past 3 months	n=171; 86 in estriol group ; 85 in NM group	Estriol group received an estriol-containing vaginal pessary daily for 2 weeks and then once every two weeks for 9 months together with oral placebo capsules each night during the same period; NM group received a capsule of NM nightly for 9 months together with a placebo vaginal pessary daily for two weeks, followed by a placebo pessary every two weeks for the remainder of the 9-month period	Result showed that women who received NM had fewer episodes of bacteriuria as compared to those using estriol containing pessaries as compared to other papers	Do not understand estrogen’s ability to restore the population of lactobacilli and reduce pH
Barbosa-Cesnik, et al.[15]	2011	Prospective, randomized, Double-blind, placebo-controlled trial	Women 18-40 years of ages, had more than three urinary symptoms, would be in Ann Arbor for the next 6 months	Antibiotic treatment over the last 48 h, hospitalization, or catheterization within the previous two weeks, kidney stones, diabetes, pregnancy or cranberry allergy, and a negative urine culture result	n=319; 155 in cranberry group; 164 in placebo group	Cranberry juice group were given 8oz of 27% low-calorie cranberry juice cocktail twice per day for 6 months; placebo group were given eight oz of placebo juice twice per day for 6 months	This study is double-blinded and randomized; recurrence rate is lower than expected right before the study was done; study juice was delivered to participant’s home every one to two weeks starting on the day of enrollment to promote compliance	No validated test for a biological marker of cranberry juice consumption, and blinded assessments of potential tests did not distinguish between groups, compliance was assessed based on self-report; smaller sample study size than expected (expecting 200 in each group); low compliance rate (many patients dropped out during the study)
Ruxer et al.[25]	2006	Randomized controlled trial	Type 2 diabetic women presenting with dysuric symptoms, not taking any antibacterials within 1 month before inclusion, aged 50-70 years old, suffering from at least three recurrent episodes of urinary tract infection in the past year, diagnosed with significant bacteriuria and whose pathogen cultured from the urine was sensitive to both Nitrofurantoin and Fosfomycin	Serum creatinine above 1.5 mg/dl, alanine aminotransferase and aspartate aminotransferase levels of more than twice the upper limit of normal, bilirubin exceeding 1.3 mg/dl, sonographic changes in the hepatic and renal parenchyma and nephrolithiasis, women with a history of renal or hepatic disorders, late diabetic complications, hematopoietic system disorders, and alcoholism	n=50; 25 in fosfomycin group; 25 to nitrofurantoin group	Fosfomycin group received fosfomycin granules dissolved in a glass of boiled water and were given 2 h after dinner and voiding, every thirty days for 6 months; Nitrofurantoin group received nitrofurantoin capsules 100 mg every 12 h (at breakfast and dinner time) for the first seven days followed by 100 mg once daily at dinner time for 6 months	Study revealed only one case of adverse reactions associated with NF, namely vertigo; high treatment compliance, only three patients dropped out of study during the duration of six months	Small sample size (50 women)

The heterogeneity of the studies is illustrated by differing sample size and different regimes used in the treatment of rURI. Compliance to therapy was only 45% in Beerepoot’s study. NM=Nitrofurantoin macrocrystal, UTI=Urinary tract infection, SIRS=Systemic inflammatory response syndrome, TMP-SMX=Trimethoprim-sulfamethoxazole