Combination of cranberry extract and D-mannose�-�possible enhancer of uropathogen sensitivity to antibiotics in acute therapy of urinary tract infections: Results of a pilot study

Abstract

Uncomplicated lower urinary tract infections are extremely common in women. Antibiotic treatment for acute episodes and for recurrence prophylaxis has its drawbacks and alternative therapies are sought in order to reduce the antimicrobial resistance phenomenon and the intestinal dismicrobism expansion. There are few studies on the effect of combination of cranberry extract with D-mannose in acute urinary tract infection management. In a pilot, randomized study 93 non-pregnant, otherwise healthy women, were enrolled with mean age of 39.77±10.36, diagnosed with uncomplicated lower urinary tract infection. Medical history, clinical examination, urine culture and a list of complaints were noted at the baseline visit. In a first phase of the study, treatment with either guideline recommended antibiotic alone or in association with the investigated product (cranberry extract plus D-mannose) was prescribed and all patients were clinically examined at day 7. All ameliorated and cured patients received in a second phase of the study, in a double-blind manner, prophylaxis with the investigated product or placebo for another 21 days, then a second clinical examination and a check of the list of complaints were performed. The cure rates were higher at day 7 when investigated product was added to antibiotic (91.6 vs. 84.4%). In resistant strains, a significantly higher cure rate was shown when the investigated product was added to antibiotic prescribed (88.8 vs. 37.5%, P<0.0001). The effect of cranberry extract plus D-mannose combination in acute urinary tract infection episodes seems to be promising. The significant cure rate registered in the patients with antibiotic-resistant urine cultures may be explained by a beneficial influence of the product on the antimicrobial sensitivity. Further studies are needed on this subject.

Role of D-mannose in urinary tract infections – a narrative review

“…Further, 14 of the 18 studies reported on prophylaxis in the management of rUTI. Of these 14 studies, 13 reported on reductions in rUTI, one study [ 82 ] did not report a difference in recurrence compared to the antibiotic control. Thus, D-mannose may help to improve clinical/symptomatic recovery rate from UTI - sometimes even faster than some of the used antibiotics – and/or may especially have potential as a prophylactic by decreasing the risk for rUTIs.…”

“…n = 80 Acute preventive Group A: antibiotic Prulifloxacine 400 mg/day for 5 days (n = 40), Group B: D-mannose 500 mg, N-acetylcysteine 100 mg and Morinda citrifolia fruit extract 300 mg, twice a day for 7 days (n = 40) D-mannose and NAC therapy resulted similar results to the antibiotic therapy in preventing UTIs in patients submitted to urodynamic examination. Considered as usable alternative treatment No AEs Panchev 2012 [ 81 ] Article in Bulgarian Multicenter, comparative, observational study Female patients with acute uncomplicated urinary bladder infections (Age not reported) n = 158 Acute: Group 1: Product containing D-mannose 1000 mg, standardized dry birch leaf extract 50 mg, standardized dry cranberry extract 50 mg according to manufacturer’s instructions ( n = 86) Group 2: Ciprofloxacin 500 mg twice daily for 3 days (n = 72) Better effectiveness related to symptoms and clinical outcomes with the product compared to antibiotic was reported No AEs Rădulescu 2020 [ 82 ] a pilot, randomized study non-pregnant, healthy women with uncomplicated lower UTI Age range 18–60 years n = 93 First phase/Acute: 1) Antibiotic (TMP-SMX) ( n = 45) or 2) Antibiotic + D-mannose (1000 mg) + cranberry (400 mg) (Uro-Care with CranActin®)( n = 48) for 7 days Second phase/ prophylaxis: For cured participants either 1) D-mannose + cranberry ( n = 47) or 2) placebo ( n = 46) for 21 days Higher cure rate after acute phase in the combined group especially in the resistant strains. No significant differences between the active and the placebo in the second phase of the study No AEs related to IP usage specified Russo 2020 [ 83 ] A prospective, randomized, no-placebo, controlled study ~ 67.2 years old postmenopausal women undergoing surgery for cystocele n = 40 Active: cranberry, D-mannose, Boswellia, Curcuma and Noxamicine VR (Kistinox ActVR) twice a day for 2 weeks starting from surgery (n = 20) Control: only surgery (n = 20) Symptom relief was reported in the active group compared to control.…”

“…At 48 h, 97% of the IP group had improved symptoms, whereas only 65.3% in the antibiotic group. A pilot study by Radulesku et al , [ 82 ] showed that cure rate in acute UTI was higher when combining 7 days antibiotic treatment with an oral IP containing D-mannose and cranberry (84.44% in the antibiotic alone and 91.66% in the antibiotic + IP) – though not reaching statistically significant difference between the groups. When looking at only the patients with antibiotic resistant strains, the cure rate was significantly better in the combined group.…”

Systematic review of the effect of D‑mannose with or without other drugs in the treatment of symptoms of urinary tract infections/cystitis (Review)

“…A total of 7 studies were identified (6)(7)(8)(9)(10)(11)(12). Their primary methodological characteristics are presented in Table II.…”

“…Recent guidelines from the main international associations, such as the American and Canadian Urological Associations, and the Society of Urodynamics, Female Pelvic Medicine and Urogenital Reconstruction (3), and the recent scientific literature (4,5) have underlined the importance of limited antibiotic use and of new research on molecules that interact with bacterial load or virulence mechanisms of uropathogens for the treatment of UTI. Among these molecules, several studies have identified D-mannose (6)(7)(8)(9)(10)(11)(12), which is characterized by a non-pharmacological, non-metabolic, non-bacteriostatic or bactericidal, but biomechanical mechanism of action and does not affect antibiotic resistance (13).…”