Article

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

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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.

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... 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). carbon atom in the position 2. D-mannose is the 'C-2 epimer' of glucose (14,15). ...
... A total of 7 studies were identified (6)(7)(8)(9)(10)(11)(12). Their primary methodological characteristics are presented in Table II. ...
... In the other studies D-mannose was given alongside several other compounds, including cranberry extract, Morinda citrifolia fruit extract, pomegranate extract, fructo-oligosaccharides, lactobacilli, and N-acetylcysteine. Four studies evaluated the changes in symptoms in the short term (7-15 days) (8,(10)(11)(12), one after 30 days (7), one after 60 days (9) and one after 24 weeks (6). ...
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Several studies, reviews and meta-analyses have documented that D-mannose use lowers the risk of recurrent urinary tract infections (UTI), but its role in the treatment of UTI/cystitis-related symptoms is unclear. In particular, no systematic review has analyzed the role of treatment with D-mannose in acute UTI/cystitis. In this paper, we systematically reviewed the published data on the effect of D-mannose, alone or in association with other compounds, on the typical symptoms of UTI/cystitis. PubMed/Medline and EMBASE databases were searched, from 1990 to January 2022, using combinations of the following keywords: 'urinary tract infections', 'cystalgia', 'recurrent next urinary tract infection', 'cystitis', 'mannose', 'mannoside', 'D-mannose', 'bacteriuria', 'pyuria', 'pyelocystitis' with the appropriate Boolean modifiers (Limits: Human, English, full article). Studies were selected for the systematic review if they were clinical studies and reported original data, the number of patients using D-mannose alone or in association with other treatments, and the number of patients with symptoms of UTI/cystitis at trial entry and after the follow-up period. A total of seven studies were identified. D-mannose was given alone in two studies, and was associated with cranberry extract, Morinda citrifolia fruit extract, pomegranate extract, fructo-oligosaccharides, lactobacilli, and N-acetylcysteine in the others. All studies reported that symptoms decreased after treatment with D-mannose. Despite the limitations of the studies, the consistent results observed among all studies give support to the general findings that D-mannose may be useful in the treatment of UTI/cystitis symptoms.
... As a result, researchers are investigating alternative therapies. 45 Combining cranberry extract with D-mannose may be an effective method for managing acute UTIs. In a pilot study with 93 healthy, non-pregnant women, participants received either a recommended antibiotic alone or with cranberry extract plus D-mannose, followed by a clinical examination on day 7. ...
... This suggests that cranberry extract in combination with D-mannose is promising for managing acute UTIs, especially in resistant cases. 45 In addition, utilizing a combination of non-antibiotic methods may lead to improved results compared to the use of a single treatment approach. A recent small-scale trial involving 33 premenopausal women demonstrated that the administration of d-Mannose, cranberry extract, and lactobacilli in powder form effectively managed symptoms of acute uncomplicated cystitis and UTI. ...
... Ongoing and optimized clinical trials continue to focus on the potential of mannose in UTI prevention and treatment (Konesan et al., 2022). Radulescu et al. (2020) highlighted that a combined treatment of cranberry extract and D-mannose might bolster the sensitivity of uropathogens to antibiotics during acute UTI treatment (Radulescu et al., 2020). Moreover, postcystoscopy administration of D-mannose and Saccharomyces boulardii was found to markedly decrease UTI incidence, mitigate the severity of lower urinary tract symptoms (LUTS), and reduce localized discomfort (Quattrone et al., 2023). ...
... Ongoing and optimized clinical trials continue to focus on the potential of mannose in UTI prevention and treatment (Konesan et al., 2022). Radulescu et al. (2020) highlighted that a combined treatment of cranberry extract and D-mannose might bolster the sensitivity of uropathogens to antibiotics during acute UTI treatment (Radulescu et al., 2020). Moreover, postcystoscopy administration of D-mannose and Saccharomyces boulardii was found to markedly decrease UTI incidence, mitigate the severity of lower urinary tract symptoms (LUTS), and reduce localized discomfort (Quattrone et al., 2023). ...
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Mannose, a different isomer of the hydroxyl group at the C-2 position of glucose, shares the same transport carrier protein with glucose to enter cells and participate in the regulation of glucose metabolism. It affects cell growth, differentiation, and function and plays an active role in tumor immunity and inflammatory processes. This paper provides theoretical support for expanding the clinical applications of mannose by exploring its constitution, metabolic pathways, and role in regulating immune cell function and treating immunology-related diseases.
... 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. ...
... 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. ...
Article
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Urinary tract infections (UTIs) are one of the most prevalent bacterial diseases worldwide. Despite the efficacy of antibiotics targeted against UTI, the recurrence rates remain significant among the patients. Furthermore, the development of antibiotic resistance is a major concern and creates a demand for alternative treatment options. D-mannose, a monosaccharide naturally found in fruits, is commonly marketed as a dietary supplement for reducing the risk for UTIs. Research suggests that supplemented D-mannose could be a promising alternative or complementary remedy especially as a prophylaxis for recurrent UTIs. When excreted in urine, D-mannose potentially inhibits Escherichia coli , the main causative organism of UTIs, from attaching to urothelium and causing infection. In this review, we provide an overview of UTIs, E. coli pathogenesis and D-mannose and outline the existing clinical evidence of D-mannose in reducing the risk of UTI and its recurrence. Furthermore, we discuss the potential effect mechanisms of D-mannose against uropathogenic E.coli .
... Авторы проанализировали подгруппы больных с резистентностью к выбранному антибиотику. Ожидаемо, что частота излеченности в подгруппе, получавшей только триметоприм+сульфаметоксазол, была низкой (37,5%), а в группе, где антибиотик назначался совместно с экстрактом клюквы и D-маннозой, процент вылеченных пациенток составлял около 90%, и был схож с результатами в группе, где отмечалась чувствительность к использованному антибактериальному препарату [47]. ...
Article
Introduction. Prevention of urinary tract infections (UTI) is an urgent problem due to their high prevalence. Regular use of antibiotics, especially when recurrent urinary tract infections occur, contributes to the formation of resistant strains of microorganisms and the development of antibiotic cross-resistance. Thus, the relevance of finding alternative approaches for the treatment and prevention of such diseases is increasing. Materials and methods. Literature review from eLibrary.ru and PubMed revealed insufficient study of the use of D-mannose and proanthocyanidins of cranberry. Results. D-mannose is a simple sugar that has structural similarity to the mannose residues of uroplakin-1a, which coats the surface of urothelial umbrella epithelial cells. D-mannose is able to saturate FimH-adhesins, which prevents E. coli attachment mediated by FimH and type 1 fimbriae through a competitive inhibition mechanism, and excrete pathogens with urine. Cranberry consumption also inhibits bacterial adhesion. Although roanthocyanidins contained in cranberries do not have their own antibacterial activity, they prevent the attachment of uropathogenic E. coli by blocking the P-type fimbriae. Knowledge of the mechanisms of action of D-mannose and proanthocyanidins of cranberry, which exert their anti-adhesive effect by interacting with different types of fimbriae, suggests that the combination of these substances can bring much greater benefit and maximally block the adhesion of pathogenic bacteria. Conclusion. The published results of clinical studies have confirmed the efficacy of prescribing D-mannose and cranberry proanthocyanidins for the prevention of UTIs, but further reliably designed clinical trials of the combined use of different prophylactic methods to control urinary tract infection are needed.
... Some studies have shown a relationship between smoking and seroma (30)(31)(32). Our patient was a heavy smoker, which might have been a contributing factor. ...
... The study enrolled a total of 926 hospitalized subjects, with 343 (37.0%) men and 583 (63.0%) women, indicating a higher incidence of UTIs in women, which is consistent with previous studies (5,32,33). UTIs were much more common in women than in men due to certain anatomical and physiological characteristics, such as a shorter urethra, the proximity of the urethral opening to the anus, changes during menopause, pregnancy and other factors, with this difference increasing with age (34,35). The analysis of sex distribution revealed noteworthy differences in the prevalence of bacterial pathogens between male and female groups. ...
... In the present study, H&E staining revealed a large zone of infiltrating inflammatory cells in renal tissue from rats in the TS group. D-mannose is widely regarded as a treatment for UTIs [35,73,74]. Here, we found that UTI symptoms were reduced in the TS + Man group based on histological staining of renal and urethral tissue, as well as inflammatory cell counts. ...
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Background Astronauts undergo significant microgravity-induced bone loss during space missions, which has become one of the three major medical problems hindering human's long-term space flight. A risk-free and antiresorptive drug is urgently needed to prevent bone loss during space missions. D-mannose is a natural C-2 epimer of D-glucose and is abundant in cranberries. This study aimed to investigate the protective effects and potential mechanisms of D-mannose against bone loss under weightlessness. Methods The hind legs of tail-suspended (TS) rats were used to mimic weightlessness on Earth. Rats were administered D-mannose intragastrically. The osteoclastogenic and osteogenic capacity of D-mannose in vitro and in vivo was analyzed by micro-computed tomography, biomechanical assessment, bone histology, serum markers of bone metabolism, cell proliferation assay, quantitative polymerase chain reaction, and western blotting. RNA-seq transcriptomic analysis was performed to detect the underlying mechanisms of D-mannose in bone protection. Results The TS rats showed lower bone mineral density (BMD) and poorer bone morphological indices. D-mannose could improve BMD in TS rats. D-mannose inhibited osteoclast proliferation and fusion in vitro, without apparent effects on osteoblasts. RNA-seq transcriptomic analysis showed that D-mannose administration significantly inhibited the cell fusion molecule dendritic cell-specific transmembrane protein (DC-STAMP) and two indispensable transcription factors for osteoclast fusion (c-Fos and nuclear factor of activated T cells 1 [NFATc1]). Finally, TS rats tended to experience dysuria-related urinary tract infections (UTIs), which were suppressed by treatment with D-mannose. Conclusion D-mannose protected against bone loss and UTIs in rats under weightlessness. The bone protective effects of D-mannose were mediated by inhibiting osteoclast cell fusion. Our findings provide a potential strategy to protect against bone loss and UTIs during space missions.
Article
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OBJECTIVE: This study was designed to determine the effect of cranberry extract used in patients with single urinary tract infections. METHODS: Patients with simple-type urinary tract infections were divided into two groups. Treatment with fosfomycin or cranberry tablet was started. On days 1, 3, and 7 of the treatment, whether there was a decrease in the complaints was evaluated with a Likert-type scale. The recovery status of urinary tract infections and the well-being of patients were compared via antibiotic and cranberry groups. RESULTS: After the treatment, the leukocyte levels of the cranberry users were at the same level as those of the other group, and the rate of well-being and the portion of patients that reported to be “very well” on days 3 and 7 in the cranberry group was significantly higher compared with the fosfomycin group (p<0.05). CONCLUSION: Considering the results of this study, it was determined that the patient's complaints decreased from day 3 and their well-being increased with the use of cranberry only. Specifically, on day 7, the well-being of the cranberry group was higher than that of the fosfomycin group. For this reason, cranberry is a favorable alternative to antibiotics in uncomplicated and simple urinary tract infections.
Article
Background: Cranberries (particularly in the form of cranberry juice) have been used widely for several decades for the prevention and treatment of urinary tract infections (UTIs). The aim of this review is to assess the effectiveness of cranberries in treating such infections. Objectives: To assess the effectiveness of cranberries for the treatment of UTIs. Search methods: We searched the Cochrane Kidney and Transplant Register of Studies up to 1 August 2023 through contact with the Information Specialist using search terms relevant to this review. Studies in the Register are identified through searches of CENTRAL, MEDLINE, and EMBASE, conference proceedings, the International Clinical Trials Registry Portal (ICTRP) Search Portal and ClinicalTrials.gov. Selection criteria: All randomised controlled trials (RCTs) or quasi-RCTs of cranberry juice or cranberry products for the treatment of UTIs. Studies of men, women or children were to be included. Data collection and analysis: Titles and abstracts of studies that were potentially relevant to the review were screened and studies that were clearly ineligible were discarded. Further information was sought from the authors where papers contained insufficient information to make a decision about eligibility. Main results: No studies were found that fulfilled all of our inclusion criteria. Seven studies were excluded because they were the wrong study design, mixed interventions or did not report any relevant outcomes. One study is ongoing; however, its current status is unknown. Authors' conclusions: After a thorough search, no RCTs which assessed the effectiveness of cranberry juice for the treatment of UTIs were found. Therefore, at the present time, there is no good quality evidence to suggest that it is effective for the treatment of UTIs. Well-designed parallel-group, double-blind studies comparing cranberry juice and other cranberry products versus placebo to assess the effectiveness of cranberry juice in treating UTIs are needed. Outcomes should include a reduction in symptoms, sterilisation of the urine, side effects and adherence to therapy. The dosage (amount and concentration) and duration of therapy should also be assessed. Consumers and clinicians will welcome the evidence from these studies.
Article
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Background: Cranberries contain proanthocyanidins (PACs), which inhibit the adherence of p-fimbriated Escherichia coli to the urothelial cells lining the bladder. Cranberry products have been used widely for several decades to prevent urinary tract infections (UTIs). This is the fifth update of a review first published in 1998 and updated in 2003, 2004, 2008, and 2012. Objectives: To assess the effectiveness of cranberry products in preventing UTIs in susceptible populations. Search methods: We searched the Cochrane Kidney and Transplant Specialised Register up to 13 March 2023 through contact with the Information Specialist using search terms relevant to this review. Studies in the Register are identified through searches of CENTRAL, MEDLINE, and EMBASE, conference proceedings, the International Clinical Trials Registry Platform (ICTRP) Search Portal and ClinicalTrials.gov. Selection criteria: All randomised controlled trials (RCTs) or quasi-RCTs of cranberry products compared with placebo, no specific treatment or other intervention (antibiotics, probiotics) for the prevention of UTIs were included. Data collection and analysis: At least two authors independently assessed and extracted data. Information was collected on methods, participants, interventions and outcomes (incidence of symptomatic UTIs, positive culture results, side effects, adherence to therapy). Risk ratios (RR) with 95% confidence intervals (CI) were calculated where appropriate. Study quality was assessed using the Cochrane risk of bias assessment tool. Confidence in the evidence was assessed using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach. Main results: For this update, 26 new studies were added, bringing the total number of included studies to 50 (8857 randomised participants). The risk of bias for sequence generation and allocation concealment was low for 29 and 28 studies, respectively. Thirty-six studies were at low risk of performance bias, and 23 studies were at low risk of detection bias. Twenty-seven, 41, and 17 studies were at low risk of attrition bias, reporting bias and other bias, respectively. Forty-five studies compared cranberry products with placebo, water or no specific treatment in six different groups of participants. Twenty-six of these 45 studies could be meta-analysed for the outcome of symptomatic, culture-verified UTIs. In moderate certainty evidence, cranberry products reduced the risk of UTIs (6211 participants: RR 0.70, 95% CI 0.58 to 0.84; I² = 69%). When studies were divided into groups according to the treatment indication, cranberry products probably reduced the risk of symptomatic, culture-verified UTIs in women with recurrent UTIs (8 studies, 1555 participants: RR 0.74, 95% CI 0.55 to 0.99; I² = 54%), in children (5 studies, 504 participants: RR 0.46, 95% CI 0.32 to 0.68; I² = 21%) and in people with a susceptibility to UTIs due to an intervention (6 studies, 1434 participants: RR 0.47, 95% CI 0.37 to 0.61; I² = 0%). However, there may be little or no benefit in elderly institutionalised men and women (3 studies, 1489 participants: RR 0.93, 95% CI 0.67 to 1.30; I² = 9%; moderate certainty evidence), pregnant women (3 studies, 765 participants: RR 1.06, 95% CI 0.75 to 1.50; I² = 3%; moderate certainty evidence), or adults with neuromuscular bladder dysfunction with incomplete bladder emptying (3 studies, 464 participants: RR 0.97, 95% CI 0.78 to 1.19; I² = 0%; low certainty evidence). Other comparisons were cranberry products with probiotics (three studies) or antibiotics (six studies), cranberry tablets with cranberry liquid (one study), and different doses of PACs (two studies). Compared to antibiotics, cranberry products may make little or no difference to the risk of symptomatic, culture-verified UTIs (2 studies, 385 participants: RR 1.03, 95% CI 0.80 to 1.33; I² = 0%) or the risk of clinical symptoms without culture (2 studies, 336 participants: RR 1.30, 95% CI 0.79 to 2.14; I² = 68%). Compared to probiotics, cranberry products may reduce the risk of symptomatic, culture-verified UTIs (3 studies, 215 participants: RR 0.39, 95% CI 0.27 to 0.56; I = 0%). It is unclear whether efficacy differs between cranberry juice and tablets or between different doses of PACs, as the certainty of the evidence was very low. The number of participants with gastrointestinal side effects probably does not differ between those taking cranberry products and those receiving a placebo or no specific treatment (10 studies, 2166 participants: RR 1.33, 95% CI 1.00 to 1.77; I² = 0%; moderate certainty evidence). There was no clear relationship between compliance with therapy and the risk for repeat UTIs. No difference in the risk for UTIs could be demonstrated between low, moderate and high doses of PACs. Authors' conclusions: This update adds a further 26 studies, taking the total number of studies to 50 with 8857 participants. These data support the use of cranberry products to reduce the risk of symptomatic, culture-verified UTIs in women with recurrent UTIs, in children, and in people susceptible to UTIs following interventions. The evidence currently available does not support its use in the elderly, patients with bladder emptying problems, or pregnant women.
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Defining urinary tract infection (UTI) is complex, as numerous clinical and diagnostic parameters are involved. In this systematic review we aimed to gain insight into how UTI is defined across current studies. We included 47 studies, published between January 2019 and May 2022, investigating therapeutic or prophylactic interventions in adult patients with UTI. Signs and symptoms, pyuria and a positive urine culture were required in 85%, 28% and 55% of study definitions, respectively. Five studies (11%) required all three categories for the diagnosis of UTI. Thresholds for significant bacteriuria varied from 103 to 105 colony-forming units/mL. None of the 12 studies including acute cystitis and 2/12 (17%) defining acute pyelonephritis used identical definitions. Complicated UTI was defined by both host factors and systemic involvement in 9/14 (64%) studies. In conclusion, UTI definitions are heterogeneous across recent studies, highlighting the need for a consensus-based, research reference standard for UTI.
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Background: Cranberries contain proanthocyanidins (PACs), which inhibit the adherence of p-fimbriated Escherichia coli to the urothelial cells lining the bladder. Cranberry products have been used widely for several decades to prevent urinary tract infections (UTIs). This is the fifth update of a review first published in 1998 and updated in 2003, 2004, 2008, and 2012. Objectives: To assess the effectiveness of cranberry products in preventing UTIs in susceptible populations. Search methods: We searched the Cochrane Kidney and Transplant Specialised Register up to 13 March 2023 through contact with the Information Specialist using search terms relevant to this review. Studies in the Register are identified through searches of CENTRAL, MEDLINE, and EMBASE, conference proceedings, the International Clinical Trials Register Search Portal (ICTRP) and ClinicalTrials.gov. Selection criteria: All randomised controlled trials (RCTs) or quasi-RCTs of cranberry products compared with placebo, no specific treatment or other intervention (antibiotics, probiotics) for the prevention of UTIs were included. Data collection and analysis: Two authors independently assessed and extracted data. Information was collected on methods, participants, interventions and outcomes (incidence of symptomatic UTIs, positive culture results, side effects, adherence to therapy). Risk ratios (RR) with 95% confidence intervals (CI) were calculated where appropriate. Study quality was assessed using the Cochrane risk of bias assessment tool. Confidence in the evidence was assessed using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach. Main results: For this update 26 new studies were added, bringing the total number of included studies to 50 (8857 randomised participants). The risk of bias for sequence generation and allocation concealment was low for 29 and 28 studies, respectively. Thirty-six studies were at low risk of performance bias, and 23 studies were at low risk of detection bias. Twenty-seven, 41, and 17 studies were at low risk of attrition bias, reporting bias and other bias, respectively. Forty-five studies compared cranberry products with placebo or no specific treatment in six different groups of participants. Twenty-six of these 45 studies could be meta-analysed for the outcome of symptomatic, culture-verified UTIs. In moderate certainty evidence, cranberry products reduced the risk of UTIs (6211 participants: RR 0.70, 95% CI 0.58 to 0.84; I² = 69%). When studies were divided into groups according to the treatment indication, cranberry products probably reduced the risk of symptomatic, culture-verified UTIs in women with recurrent UTIs (8 studies, 1555 participants: RR 0.74, 95% CI 0.55 to 0.99; I² = 54%), in children (5 studies, 504 participants: RR 0.46, 95% CI 0.32 to 0.68; I² = 21%) and in people with a susceptibility to UTIs due to an intervention (6 studies, 1434 participants: RR 0.47, 95% CI 0.37 to 0.61; I² = 0%). However, in low certainty evidence, there may be little or no benefit in elderly institutionalised men and women (3 studies, 1489 participants: RR 0.93, 95% CI 0.67 to 1.30; I² = 9%), pregnant women (3 studies, 765 participants: RR 1.06, 95% CI 0.75 to 1.50; I² = 3%), or adults with neuromuscular bladder dysfunction with incomplete bladder emptying (3 studies, 464 participants: RR 0.97, 95% CI 0.78 to 1.19; I² = 0%). Other comparisons were cranberry products with probiotics (three studies) or antibiotics (six studies), cranberry tablets with cranberry liquid (one study), and different doses of PACs (two studies). Compared to antibiotics, cranberry products may make little or no difference to the risk of symptomatic, culture-verified UTIs (2 studies, 385 participants: RR 1.03, 95% CI 0.80 to 1.33; I² = 0%) or the risk of clinical symptoms without culture (2 studies, 336 participants: RR 1.30, 95% CI 0.79 to 2.14; I² = 68%). Compared to probiotics, cranberry products may reduce the risk of symptomatic, culture-verified UTIs (3 studies, 215 participants: RR 0.39, 95% CI 0.27 to 0.56; I = 0%). It is unclear whether efficacy differs between cranberry juice and tablets or between different doses of PACs as the certainty of the evidence was very low. The number of participants with gastrointestinal side effects probably does not differ between those taking cranberry products and those receiving placebo or no specific treatment (10 studies, 2166 participants: RR 1.33, 95% CI 1.00 to 1.77; I² = 0%; moderate certainty evidence). There was no clear relationship between compliance with therapy and the risk for repeat UTIs. No difference in the risk for UTIs could be demonstrated between low, moderate and high doses of PACs. Authors' conclusions: This update adds a further 26 studies taking the total number of studies to 50 with 8857 participants. These data support the use of cranberry products to reduce the risk of symptomatic, culture-verified UTIs in women with recurrent UTIs, in children, and in people susceptible to UTIs following interventions. The evidence currently available does not support its use in the elderly, patients with bladder emptying problems, or pregnant women.
Chapter
Urinary tract infections (UTIs) are economically and medically challenging around the world. As a natural alternative, cranberries have been documented and well established to treat UTIs. In this chapter, the possible mechanism(s) of actions for cranberries are discussed in multiple studies.
Article
Background: Urinary tract infections (UTIs) are very common, affecting more than 7 million people worldwide. Whilst many people may only experience a single episode in their lifetime and are generally responsive to standard antibiotics, a significant proportion of adults and children (approximately 15% to 25%) are chronic symptomatic UTI sufferers. Certain population groups are at greater risk than others, such as immunosuppressed and people with chronic kidney disease. D-mannose is a sugar part of normal human metabolism found within most diets. The mechanism of action is to prevent bacterial adherence to the uroepithelial cells. The D-mannose-based inhibitors can block uropathogenic Escherichia coli adhesion and invasion of the uroepithelial cells. The bacteria are then understood to essentially be eliminated by urination. Early pilot studies on animals and humans have trialled concentrated forms of D-mannose (tablets or sachets) in doses ranging from 200 mg up to 2 to 3 g and found possible efficacy in reducing UTI symptoms or recurrence. Although the anti-adhesive effects of D-mannose have been well-established, only recently have we seen a small number of pilot studies and small clinical trials conducted. Objectives: To assess the benefits and harms of D-mannose for preventing and treating UTIs in adults and children. Search methods: We searched the Cochrane Kidney and Transplant Register of Studies up to 22 February 2022 through contact with the Information Specialist using search terms relevant to this review. Studies in the Register are identified through searches of CENTRAL, MEDLINE, and EMBASE, conference proceedings, the International Clinical Trials Register (ICTRP) Search Portal and ClinicalTrials.gov. Selection criteria: We included RCTs measuring and reporting the effect of D-mannose, in any combination and any formulation, to prevent or treat UTIs in adults and children, females and males, in any setting (including perioperative). Authors independently assessed the retrieved titles and abstracts and, where necessary, the full text to determine which satisfied the inclusion criteria. Data collection and analysis: Data extraction was independently carried out by two authors using a standard data extraction form. Methodological quality of the included studies was assessed using the Cochrane risk of bias tool. Data entry was carried out by one author and cross-checked by another author. The certainty of the evidence was assessed using the GRADE approach. Main results: We included seven RCTs (719 participants) in adult females and males who had either acute cystitis or a history of recurrent (at least two episodes in six months or three episodes in 12 months) UTIs (symptomatic or asymptomatic). Two were prevention studies, four were prevention and treatment studies (two perioperative and one in people with multiple sclerosis), and one was a treatment study. Time periods ranged from 15 days to six months. No two studies were comparable (by dose or treatments), and we could not undertake meta-analyses. Individual studies reported no clear evidence to determine whether D-mannose is more or less effective in preventing or treating UTIs. D-mannose (2 g) had uncertain effects on symptomatic and bacteriuria-confirmed UTIs when compared to no treatment (1 study, 205 participants; very low certainty evidence) and antibiotics (nitrofurantoin 50 mg) (1 study, 206 participants; very low certainty evidence). D-mannose, in combination with herbal supplements, had uncertain effects on symptomatic and bacteria-confirmed UTI and pain when compared to no treatment (1 study, 40 participants; very low certainty evidence). D-mannose 500 mg plus supplements (N-acetylcysteine and Morinda citrifolia fruit extract) had uncertain effects on symptomatic and bacteriuria-confirmed UTIs when compared to an antibiotic (prulifloxacin 400 mg) (1 study, 75 participants; very low certainty evidence). Adverse events were very few and poorly reported; none were serious (mostly diarrhoea and vaginal burning). Overall, the quality of the evidence is poor. Most studies were judged to have unclear or high risk of bias across most domains. Data was sparse and addressed very few outcomes. The GRADE evaluation was rated as very low certainty evidence due to very serious limitations in the study design or execution (high risk of bias across all studies) and sparse data (single study data and small sample sizes). Authors' conclusions: There is currently little to no evidence to support or refute the use of D-mannose to prevent or treat UTIs in all populations. This review highlights the severe lack of high-quality RCTs testing the efficacy of D-mannose for UTIs in any population. Despite UTIs being one of the most common adult infections (affecting 50% of women at least once in their lifetime) and the growing global antimicrobial resistance, we found very few studies that adequately test this alternative treatment. Future research in this field requires, in the first instance, a single adequately powered RCT comparing D-mannose with placebo.
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The aim of our study was evaluation of prevalence of uncomplicated and complicated urinary tract infections (UTIs) among patients with UTIs associated with Gram-negative bacteria and analysis of prognostic risk factors in complicated UTIs. Weretrospectivelyanalyzed the medical records of inpatients with diagnosis of UTI based on clinical, biological and microbiological assay. Susceptibility tests for different antimicrobial categories were performed. Risk factors in complicated UTIs were correlated with pathogens' susceptibility. A total of 96 eligible patients were analyzed. Complicated UTIs were identified in 66.67% cases. The most frequent uropathogens isolated were E.coli and Klebsiella species. Exrtrarenal factors and nephropathic disease were the most common factors associatedwith an increased prevalence of multi-drug resistant isolates. Knowledge of the spectrum of the possible pathogens and local resistance patterns are very important for the antibacterial treatment outcome.
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Urinary tract infections (UTI) commonly occur in older adults and can lead to more severe, life-threatening infections. Physiological factors that change with age are thought to contribute to the increased frequency of UTI recurrence in older adults. Unfortunately, there are limited methods to prevent UTI in older adults, and utilization of antimicrobial agents for prevention can have many negative consequences. Methenamine has been proposed as a useful drug for the prevention of UTI as it works as a urinary antiseptic, safely producing formaldehyde to prevent bacterial growth while avoiding bacterial resistance. The objective of this review is to evaluate the existing literature and discuss the use of methenamine in older adults for prevention of UTI. A PubMed search was conducted to identify studies evaluating the effectiveness of methenamine to prevent UTI in older adults, and 10 publications were selected based on relevant criteria. Based on the literature, methenamine appears to be a safe and effective option to prevent UTI in older adults with recurrent UTI, genitourinary surgical procedures, and potentially long-term catheterization. Studies have not evaluated the safety of methenamine in patients with impaired renal function or CrCl <30 ml/min. When selecting a treatment approach to preventing UTI in older adults with adequate renal function, clinicians may consider methenamine as a viable option.
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Antibiotic resistance is spreading at an alarming rate among pathogenic bacteria in both medicine and agriculture. Interfering with the intrinsic resistance mechanisms displayed by pathogenic bacteria has the potential to make antibiotics more effective and decrease the spread of acquired antibiotic resistance. Here, it is demonstrated that cranberry proanthocyanidin (cPAC) prevents the evolution of resistance to tetracycline in Escherichia coli and Pseudomonas aeruginosa, rescues antibiotic efficacy against antibiotic‐exposed cells, and represses biofilm formation. It is shown that cPAC has a potentiating effect, both in vitro and in vivo, on a broad range of antibiotic classes against pathogenic E. coli, Proteus mirabilis, and P. aeruginosa. Evidence that cPAC acts by repressing two antibiotic resistance mechanisms, selective membrane permeability and multidrug efflux pumps, is presented. Failure of cPAC to potentiate antibiotics against efflux pump‐defective mutants demonstrates that efflux interference is essential for potentiation. The use of cPAC to potentiate antibiotics and mitigate the development of resistance could improve treatment outcomes and help combat the growing threat of antibiotic resistance.
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Urinary tract infections (UTIs) are the most common outpatient infections, with a lifetime incidence of 50−60% in adult women. This is a narrative review aimed at acting as an introduction to the epidemiology and burden of UTIs. This review is based on relevant literature according to the experience and expertise of the authors. The prevalence of UTI increases with age, and in women aged over 65 is approximately double the rate seen in the female population overall. Etiology in this age group varies by health status with factors such as catheterization affecting the likelihood of infection and the pathogens most likely to be responsible. In younger women, increased sexual activity is a major risk factor for UTIs and recurrence within 6 months is common. In the female population overall, more serious infections such as pyelonephritis are less frequent but are associated with a significant burden of care due to the risk of hospitalization. Healthcare-associated UTIs (HAUTIs) are the most common form of healthcare-acquired infection. Large global surveys indicate that the nature of pathogens varies between the community and hospital setting. In addition, the pathogens responsible for HAUTIs vary according to region making adequate local data key to infection control. UTIs create a significant societal and personal burden, with a substantial number of medical visits in the United States every year being related to UTIs. European data indicate that recurrent infections are related to increased absenteeism and physician visits. In addition, quality of life measures are significantly impacted in women suffering from recurrent UTIs. Data suggest that nonantimicrobial prophylactic strategies offer an opportunity to reduce both the rate of UTIs and the personal burden experience by patients.
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Objectives: We aimed to update the 2010 evidence- and consensus-based national clinical guideline on the diagnosis and management of uncomplicated urinary tract infections (UTIs) in adult patients. Materials and methods: An interdisciplinary group consisting of 17 representatives of 12 medical societies and a patient representative was formed. Systematic literature searches were conducted in MEDLINE, -EMBASE, and the Cochrane Library to identify literature published in 2010-2015. Results: We provide 75 recommendations and 68 statements in the updated evidence- and consensus-based national clinical guideline. The diagnostics part covers practical recommendations on cystitis and pyelonephritis for each defined patient group. Clinical examinations, as well as laboratory testing and microbiological pathogen assessment, are addressed. Conclusion: In accordance with the global antibiotic stewardship initiative and considering new insights in scientific research, we updated our German clinical UTI guideline to promote a responsible antibiotic use and to give clear hands-on recommendations for the diagnosis and management of UTIs in adults in Germany for healthcare providers and patients.
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Urinary tract infections (UTIs) are an economic burden for public health. The increasing prevalence of resistant bacteria which cause UTIs may be related to the inappropriate prescription of antibiotics. The aim of this preliminary study was to evaluate whether three different combinations of plant extracts plus d-mannose are effective in preventing the recurrence of UTIs. Three groups of patients received three combinations of plant extracts in conjunction with d-mannose. These were: berberine, arbutin and birch (group A); berberine, arbutin, birch and forskolin (group B); and proanthocyanidins (group C). The clinical recurrence of cystitis at the end of treatment and during follow-up was determined by comparison with baseline measurements using the microbiological assessment of urine samples, vaginal swabs and vaginal smear slides. Patients in groups A and B had a lower incidence of episodes of recurrent cystitis during treatment and follow-up, samples with a significantly lower median bacterial load and a reduction of the grade of lactobacillary flora compared to patients in group C.
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Clinical Presentations and Epidemiology of Urinary Tract Infections, Page 1 of 2 Abstract Urinary tract infection (UTI) is one of the most common bacterial infections, and the incidence in women is much higher than in men. The diagnosis of a UTI can be made based on a combination of symptoms and a positive urine analysis or culture. Most UTIs are uncomplicated UTIs, defined as cystitis in a woman who is not pregnant, is not immunocompromised, has no anatomical and functional abnormalities of the urogenital tract, and does not exhibit signs of tissue invasion and systemic infection. All UTIs that are not uncomplicated are considered to be complicated UTIs. Differentiation between uncomplicated and complicated UTIs has implications for therapy because the risks of complications or treatment failure are increased for patients with a complicated UTI. Asymptomatic bacteriuria (ASB) is defined as the presence of a positive urine culture collected from a patient without symptoms of a UTI. Concerning the complicated UTI, it is possible to make a differentiation between UTI with systemic symptoms (febrile UTI) and UTI in a host, which carries an increased risk to develop complications of this UTI. Febrile UTIs are urosepsis, pyelonephritis, and prostatitis. A complicated host is defined as one that has an increased risk for complications, to which the following groups belong: men, pregnant women, immunocompromised patients, or those who have an anatomical or functional abnormality of the urogenital tract (e.g., spinal cord-injury patients, renal stones, urinary catheter).
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Infection with Clostridium difficile has become increasingly more frequent in recent years, being currently one of the most common aetiology of diarrheal disease. The aim of our work was to broaden the current knowledge of the Clostridium difficile digestive infections in patients admitted to the Infectious Diseases Hospital from Iasi City, Romania. We have studied 166 patients with Clostridium difficile enterolactis, hospitalized between 01.01.2014 - 31.03 2015. We have found an increasing trend in the number of cases between December 2014 and March 2015, particularly among immunocompromised patients, 48% of cases occurred in patients with previous surgery area and 57% came from medical services. Investigation of the used groups of antibiotics revealed that the highest risk is the use of fluoroquinolones, followed by cephalosporins. Relapses were found in 28.67% cases, and treatment was performed with Metronidazole (66.26%), Vancomycin (5.42%) and Vancomycin + Metronidazole (28.31%). Analysis of cases is a warning on unjustified and irrational use of antibiotics and the danger of nosocomial infections. © 2016, Romanian Society for Pharmaceutical Sciences. All rights reserved.
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Unlabelled: The currently available treatment for uncomplicated urinary tract infections includes only antibiotics and chemotherapeutic agents. Experience in the management of acute uncomplicated infections using non-antibiotic products is very limited. The aim of this observation was to study to what extent the response to Cystostop Rapid would be more rapid and more effective compared to antibiotic therapy in patients with acute uncomplicated urinary bladder infections. The secondary objective was to determine the time to improvement of cystitis symptoms following the start of treatment, as well as the duration of patients' disablement. A total of 158 female subjects were included, assessed microbiologically, and evaluated for incidence and severity of symptoms, before the start of treatment and after completion of treatment. A visual analogue scale was used for patient self-assessment of the severity of symptoms, the improvement of symptoms, as well as the time to improvement of symptoms. Results: 158 females, eligible according to the inclusion criteria of the study, were allocated to one of the two groups according to time of enrollment: Group A included 86 subjects: assigned to Cystostop Rapid for 3 days and administered according to the manufacturer's recommended regimen; and Group B included 72 women: assigned to ciprofloxacin 500 mg twice daily for 3 days according to the Product Registration File with the BDA. The clinical and microbiological effectiveness of Cystostop Rapid was comparable to that of ciprofloxacin, providing a two-fold more rapid improvement of cystitis symptoms, at a mean time to improvement of 24 hours (p < 0.02) versus 46 hours for ciprofloxacin. Clinical improvement within 48 hours of Cystostop Rapid regimen occurred in 97% (p < 0.02) of patients, vs. 65.3% of patients on ciprofloxacin. Improvement of symptoms within 12 hours was reported in 36% of patients on Cystostop Rapid vs. 5.5% of patients in the ciprofloxacin group (p < 0.02). No adverse events or intolerability to the therapy were reported throughout the course of the study.
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Urinary tract infections (UTIs) are a severe public health problem and are caused by a range of pathogens, but most commonly by Escherichia coli, Klebsiella pneumoniae, Proteus mirabilis, Enterococcus faecalis and Staphylococcus saprophyticus. High recurrence rates and increasing antimicrobial resistance among uropathogens threaten to greatly increase the economic burden of these infections. In this Review, we discuss how basic science studies are elucidating the molecular details of the crosstalk that occurs at the host–pathogen interface, as well as the consequences of these interactions for the pathophysiology of UTIs. We also describe current efforts to translate this knowledge into new clinical treatments for UTIs.
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Recurrent urinary tract infections (RUTI) are prevalent and pose significant clinical challenges. Although the term RUTI has long been vaguely defined, a consensus definition has emerged in recent years. The exact etiology behind RUTI remains under debate, with valid arguments for both ascending reinfections as well as persistent infection inside the bladder. These persistent infections exist in the form of quiescent intracellular reservoirs in the mouse model and may represent a novel concept to explain UTI recurrence in humans. Manageable risk factors such as behavioral patterns alongside nonmanageable risk factors including genetic susceptibility are growing fields of investigation. Acute UTI have been studied through two model bacterial strains: Escherichia coli UTI89 and CFT073. However, the clinical relevance to RUTI of these two strains has not been firmly established. Current treatment strategies for RUTI are limited and remain dominated by antibiotic usage despite variable efficacy. The majority of studies in humans have focused on younger groups of women with little information available about the postmenopausal population despite a heightened risk of RUTI in this age group.
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Cranberries have been used widely for several decades for the prevention and treatment of urinary tract infections (UTIs). This is the third update of our review first published in 1998 and updated in 2004 and 2008. To assess the effectiveness of cranberry products in preventing UTIs in susceptible populations. Search methods: We searched MEDLINE, EMBASE, the Cochrane Central Register of Controlled Trials (CENTRAL in The Cochrane Library) and the Internet. We contacted companies involved with the promotion and distribution of cranberry preparations and checked reference lists of review articles and relevant studies. Date of search: July 2012. Selection criteria: All randomised controlled trials (RCTs) or quasi-RCTs of cranberry products for the prevention of UTIs. Data collection and analysis: Two authors independently assessed and extracted data. Information was collected on methods, participants, interventions and outcomes (incidence of symptomatic UTIs, positive culture results, side effects, adherence to therapy). Risk ratios (RR) were calculated where appropriate, otherwise a narrative synthesis was undertaken. Quality was assessed using the Cochrane risk of bias assessment tool. This updated review includes a total of 24 studies (six cross-over studies, 11 parallel group studies with two arms; five with three arms, and two studies with a factorial design) with a total of 4473 participants. Ten studies were included in the 2008 update, and 14 studies have been added to this update. Thirteen studies (2380 participants) evaluated only cranberry juice/concentrate; nine studies (1032 participants) evaluated only cranberry tablets/capsules; one study compared cranberry juice and tablets; and one study compared cranberry capsules and tablets. The comparison/control arms were placebo, no treatment, water, methenamine hippurate, antibiotics, or lactobacillus. Eleven studies were not included in the meta-analyses because either the design was a cross-over study and data were not reported separately for the first phase, or there was a lack of relevant data. Data included in the meta-analyses showed that, compared with placebo, water or not treatment, cranberry products did not significantly reduce the occurrence of symptomatic UTI overall (RR 0.86, 95% CI 0.71 to 1.04) or for any the subgroups: women with recurrent UTIs (RR 0.74, 95% CI 0.42 to 1.31); older people (RR 0.75, 95% CI 0.39 to 1.44); pregnant women (RR 1.04, 95% CI 0.97 to 1.17); children with recurrent UTI (RR 0.48, 95% CI 0.19 to 1.22); cancer patients (RR 1.15 95% CI 0.75 to 1.77); or people with neuropathic bladder or spinal injury (RR 0.95, 95% CI: 0.75 to 1.20). Overall heterogeneity was moderate (I² = 55%). The effectiveness of cranberry was not significantly different to antibiotics for women (RR 1.31, 95% CI 0.85, 2.02) and children (RR 0.69 95% CI 0.32 to 1.51). There was no significant difference between gastrointestinal adverse effects from cranberry product compared to those of placebo/no treatment (RR 0.83, 95% CI 0.31 to 2.27). Many studies reported low compliance and high withdrawal/dropout problems which they attributed to palatability/acceptability of the products, primarily the cranberry juice. Most studies of other cranberry products (tablets and capsules) did not report how much of the 'active' ingredient the product contained, and therefore the products may not have had enough potency to be effective. Prior to the current update it appeared there was some evidence that cranberry juice may decrease the number of symptomatic UTIs over a 12 month period, particularly for women with recurrent UTIs. The addition of 14 further studies suggests that cranberry juice is less effective than previously indicated. Although some of small studies demonstrated a small benefit for women with recurrent UTIs, there were no statistically significant differences when the results of a much larger study were included. Cranberry products were not significantly different to antibiotics for preventing UTIs in three small studies. Given the large number of dropouts/withdrawals from studies (mainly attributed to the acceptability of consuming cranberry products particularly juice, over long periods), and the evidence that the benefit for preventing UTI is small, cranberry juice cannot currently be recommended for the prevention of UTIs. Other preparations (such as powders) need to be quantified using standardised methods to ensure the potency, and contain enough of the 'active' ingredient, before being evaluated in clinical studies or recommended for use.
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Background: Recurrent urinary tract infections (UTIs) are a common problem among women. However, comparative effectiveness strategies for managing recurrent UTIs are lacking. Methods: We performed a systematic literature review of management of women experiencing ≥3 UTIs per year. We then developed a Markov chain Monte Carlo model of recurrent UTI for each management strategy with ≥2 adequate trials published. We simulated a cohort that experienced 3 UTIs/year and a secondary cohort that experienced 8 UTIs/year. Model outcomes were treatment efficacy, patient and payer cost, and health-related quality of life. Results: Five strategies had ≥2 clinical trials published: (1) daily antibiotic (nitrofurantoin) prophylaxis; (2) daily estrogen prophylaxis; (3) daily cranberry prophylaxis; (4) acupuncture prophylaxis; and (5) symptomatic self-treatment. In the 3 UTIs/year model, nitrofurantoin prophylaxis was most effective, reducing the UTI rate to 0.4 UTIs/year, and the most expensive to the payer ($821/year). All other strategies resulted in payer cost savings but were less efficacious. Symptomatic self-treatment was the only strategy that resulted in patient cost savings, and was the most favorable strategy in term of cost per quality-adjusted life-year (QALY) gained. Conclusions: Daily antibiotic use is the most effective strategy for recurrent UTI prevention compared to daily cranberry pills, daily estrogen therapy, and acupuncture. Cost savings to payers and patients were seen for most regimens, and improvement in QALYs were seen with all. Our findings provide clinically meaningful data to guide the physician-patient partnership in determining a preferred method of prevention for this common clinical problem.
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Unlabelled: The increasing frequency of extended-spectrum beta-lactamases (ESBLs) producing Enterobacteriaceae among nosocomial and community-acquired infections is an important problem for both microbiologists and clinicians, because of the difficulty in correctly detecting, reporting and treating such infections. Results: In the Clinical Hospital of Infectious Diseases Iaşi the most frequent etiological agents of urinary tract infections were: E. coli - 64%, Klebsiella spp. 11% and Enterococcus spp - 5%. The resistance rate of E. coli and Klebsiella spp. was 41% and 60%, respectively to amoxicillin-clavulanic acid, 29.6% and 72.5%, respectively to third generation cephalosporins, 26% and 24%, respectively to ciprofloxacin. The most active antimicrobial agents against cephalosporins resistant strains of E. coli and Klebsiella spp were carbapenems (susceptibility rate 99% and 94%, respectively) and colimycin (susceptibility rate 89% and 83%, respectively).
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To determine the efficacy of the consumption of cranberry juice versus placebo with regard to the presence of in vitro bacterial anti-adherence activity in the urine of healthy volunteers. Twenty healthy volunteers, 10 men and 10 women, were included. The study was a double-blind, randomized, placebo-controlled, and cross-over study. In addition to normal diet, each volunteer received at dinner a single dose of 750 ml of a total drink composed of: (1) 250 ml of the placebo and 500 ml of mineral water, or (2) 750 ml of the placebo, or (3) 250 ml of the cranberry juice and 500 ml of mineral water, or (4) 750 ml of the cranberry juice. Each volunteer took the four regimens successively in a randomly order, with a washout period of at least 6 days between every change in regimen. The first urine of the morning following cranberry or placebo consumption was collected and used to support bacterial growth. Six uropathogenic Escherichia coli strains (all expressing type 1 pili; three positive for the gene marker for P-fimbriae papC and three negative for papC), previously isolated from patients with symptomatic urinary tract infections, were grown in urine samples and tested for their ability to adhere to the T24 bladder cell line in vitro. There were no significant differences in the pH or specific gravity between the urine samples collected after cranberry or placebo consumption. We observed a dose dependent significant decrease in bacterial adherence associated with cranberry consumption. Adherence inhibition was observed independently from the presence of genes encoding type P pili and antibiotic resistance phenotypes. Cranberry juice consumption provides significant anti-adherence activity against different E. coli uropathogenic strains in the urine compared with placebo.
Article
Introduction: UTI (urinary tract infections) represent a central pathology for a urological service. Antibiotic resistance is growing at a steady and alarming rate worldwide and especially in Romania. Method and materials: We have analyzed all the patients that were admitted to our clinic for continuous hospitalization between January 2015 and October 2015. All patients undergone urine culture and all cultures positive had an antibiogram worked up. We have selected all patients that had antibiotic resistance to at least an antibiotic. Results: From 1745 patients admitted for continuous hospitalization, we had 180 positive urine cultures at admission from which 125 had at least an antibiotic resistance. Conclusions: Antibiotic resistance is a serious phenomenon, with potential lethal complications, which we encounter daily in urological practice.
Article
Purpose: This document seeks to establish guidance for the evaluation and management of women with recurrent urinary tract infections (rUTI) to prevent inappropriate use of antibiotics, decrease the risk of antibiotic resistance, reduce adverse effects of antibiotic use, provide guidance on antibiotic and non-antibiotic strategies for prevention, and improve clinical outcomes and quality of life by reducing recurrence of urinary tract infection (UTI) events. Materials & methods: The systematic review utilized to inform this guideline was conducted by a methodology team at the Pacific Northwest Evidence-based Practice Center. A research librarian conducted searches in Ovid MEDLINE (1946 to January Week 1 2018), Cochrane Central Register of Controlled Trials (through December 2017) and Embase (through January 16, 2018). An update literature search was conducted on September 20, 2018. Results: When sufficient evidence existed, the body of evidence was assigned a strength rating of A (high), B (moderate), or C (low). Such evidence-based statements are provided as Strong, Moderate, or Conditional Recommendations. In instances of insufficient evidence, additional guidance is provided as Clinical Principles and Expert Opinions. Conclusions: Our ability to diagnose, treat, and manage rUTI long-term has evolved due to additional insights into the pathophysiology of rUTI, a new appreciation for the adverse effects of repetitive antimicrobial therapy, rising rates of bacterial antimicrobial resistance (AMR), and better reporting of the natural history and clinical outcomes of acute cystitis and rUTI. As new data continue to emerge in this space, this document will undergo review to ensure continued accuracy.
Article
Objectives: The aim of this study was to systematically review the various definitions of recurrent urinary tract infection (RUTI) recommended by experts and specialty societies cited in biomedical literature. Methods: A systematic review of RUTI in women was conducted using MEDLINE, EMBASE, and PubMed between 1966 and 2016 according to the Preferred Reporting Items for Systematic Review and Meta-Analyses Statement. Twenty-five publications were selected for inclusion in this analysis. Results: From review of included publications, 14 definitions of RUTI were obtained. Each source was searched for a textual definition of RUTI as well as presence or absence of specific key elements including urinary symptoms, colony forming unit count, bacterial species, number of UTIs per year, interval time between infections and a negative intervening culture. All data were reviewed by 2 separate investigators. The definition of RUTI was found highly variable in the literature. The tallying of key elements in included definitions suggests that a minimum RUTI definition should include urinary symptoms, urine culture colony forming unit/mL threshold, differentiation of bacterial persistence versus reinfection by bacterial species, and number of UTIs per year. Conclusions: This review of major RUTI definition recommendations by expert individuals and specialty societies underlines the lack of uniformity and the need for a more robust and generally agreeable RUTI definition for use in clinical and academic practice.
Article
In our paper we intended to realize an analysis of the economic crisis's effects on the Romanian pharmaceutical market for the first six months of 2010; we also tried to provide some possible solutions to the challenges that pharmaceutical companies have to face. In order to escape the current economic turn down managers from the pharmaceutical industry need to recognize the importance of motivation and the involvement of employees; also, leaders' intellectual capability and creativity determine the organizations' potential; innovative thinking attracts other talent that further stimulates creativity and enhances the organizations' ability to compete.
Article
Purpose of review Both in the community and hospital setting, urinary tract infections (UTIs) are common. Initial appropriate empirical treatment requires a good knowledge of epidemiological data. In this review, the most recent global epidemiological data of UTIs have been summarized. Recent findings Community-associated UTI (CAUTI) prevalence is 0.7% and the main risk factors are age, history of UTI, sexual activity and diabetes. The most common pathogen is Escherichia coli and resistance rates to common antibiotics depend very much on the geographical location. The lowest observed resistance was for fosfomycin (range: 0-2.9%), nitrofurantoin (range: 0-4.4%) and mecillinam (range: 0-4%). Healthcare-associated UTI (HAUTI) frequency among HCAIs is 12.9 (confidence interval: 10.2-16%), 19.6 and 24% in the United States, Europe and developing countries, respectively. In urology departments, the prevalence is 5.1%. Resistance to almost all antibiotics in HAUTIs is above 20% and there is a significant geographical variation. Community onset HAUTIs bacterial spectrum is similar to hospital onset HAUTIs and different from CAUTIs. Summary It is challenging to provide with an exact frequency of UTIs. Both CAUTI and HAUTI frequency, pathogen spectrum and resistance rates vary according to geographical setting.
Article
Background: Urinary tract infections (UTIs) are the most common bacterial infection in women. Most UTIs are acute uncomplicated cystitis caused by Escherichia coli (86%). This study was undertaken to assess the effectiveness of an association of a cranberry dry extract, D-mannose, a gelling complex composed of the exopolysaccharides produced by Streptococcus thermophilus ST10 (DSM 25246) and tara gum, as well as the 2 microorganisms Lactobacillus plantarum LP01 (LMG P-21021) and Lactobacillus paracasei LPC09 (DSM 24243) in women affected by acute uncomplicated cystitis. Materials and methods: Thirty-three premenopausal, nonpregnant women diagnosed with acute uncomplicated cystitis were enrolled in a pilot prospective study and completed the treatment protocol. Subjects were instructed to take 2 doses per day during the first month, and then to continue with 1 sachet per day until the sixtieth day. Nitrites and leukocyte esterase on urine dipstick testing were used as indicators of cystitis, with analysis performed at enrollment, after 30 and 60 days, and after 1 month of follow-up. Typical UTI symptoms, namely dysuria, frequent voiding of small volumes, urinary urgency, suprapubic pain, and gross hematuria were scored 0 to 3 and evaluated at each visit. Results: Positive results for the presence of nitrites and leukocyte esterase were found in 14 and 20 subjects after 30 days and in 9 and 14 women after 60 days, respectively (P<0.001). At the end of the follow-up period, positive results for nitrites and leukocyte esterase were recorded in only 4 and 3 of 24 and 19 subjects (16.7%, P=0.103; 15.8%, P=0.325, respectively), with negative results after 60 days. Typical symptoms of cystitis, specifically dysuria, frequent voiding, urgency, and suprapubic pain were significantly improved as well. No significant differences were recorded in the incidence and severity of hematuria at any visit. Conclusion: The long-term ability of an association of cranberry, D-mannose, an innovative gelling complex, and the 2 microorganisms tested to significantly improve the uncomfortable symptoms reported by women with acute cystitis has been suggested.
Article
Recurrence after urinary tract infection (rUTI) is common in adult women. The majority of recurrences are believed to be reinfection from extraurinary sources such as the rectum or vagina. However, uropathogenic Escherichia coli are now known to invade urothelial cells and form quiescent intracellular bacterial reservoirs. Management of women with frequent symptomatic rUTI can be particularly vexing for both patients and their treating physicians. This review addresses available and promising management strategies for rUTI in healthy adult women.
Article
Urinary tract infections (UTIs) represent a common and quite costly medical problem, primarily affecting the female population which may be due to a shorter urethra. The bacterium Escherichia coli are mainly responsible for most uncomplicated UTIs. Cranberry antibacterial effects have widely been studied in vitro, and laboratory and clinical studies have also been performed to elucidate the mechanisms of cranberry actions and the clinical benefits of cranberry consumption against UTIs. The present review aimed to summarize the proposed mechanisms of cranberry actions against UTIs and the clinical trials that evaluated the efficacy of supplementing cranberry products in different subpopulations. Taking into consideration the existing data, cranberry consumption may prevent bacterial adherence to uroepithelial cells which reduces the development of UTI. Cranberry consumption could also decreasing UTI related symptoms by suppressing inflammatory cascades as an immunologic response to bacteria invasion. The existing clinical trials suggest that the beneficial effects of cranberry against UTIs seem to be prophylactic by preventing the development of infections; however, they exert low effectiveness in populations at increased risk for contracting UTIs. Additional well-designed, double-blind, placebo-controlled clinical trials that use standardized cranberry products are strongly justified in order to determine the efficiency of cranberry on the prevention of UTIs in susceptible populations.
Article
The ARESC (Antimicrobial Resistance Epidemiological Survey on Cystitis) study is an international survey to investigate the prevalence and susceptibility of pathogens causing cystitis. Female patients (n=4264) aged 18-65 years with symptoms of uncomplicated cystitis were consecutively enrolled in nine European countries as well as Brazil during 2003-2006. Pathogens were identified and their susceptibility to nine antimicrobials was determined. Escherichia coli accounted for 76.7% of isolates. Among E. coli, 10.3% of the isolates were resistant to at last three different classes of antimicrobial agents. Resistance was most common to ampicillin (48.3%), trimethoprim/sulfamethoxazole (29.4%) and nalidixic acid (18.6%). Fosfomycin, mecillinam and nitrofurantoin were the most active drugs (98.1%, 95.8% and 95.2% susceptible strains, respectively) followed by ciprofloxacin, amoxicillin/clavulanic acid and cefuroxime (91.7%, 82.5% and 82.4%, respectively). Resistance to ciprofloxacin was >10% in Brazil, Spain, Italy and Russia. Overall, Proteus mirabilis were more susceptible to beta-lactams and less susceptible to non-beta-lactams than E. coli, whereas Klebsiella pneumoniae strains, which are intrinsically resistant to ampicillin, were less susceptible to mecillinam (88.8%), fosfomycin (87.9%), cefuroxime (78.6%) and nitrofurantoin (17.7%). Resistance was rare in Staphylococcus saprophyticus, with the exception of ampicillin (36.4%) and trimethoprim/sulfamethoxazole (10.2%). In Italy, Spain, Brazil and Russia, the countries most affected by antimicrobial resistance, extended-spectrum beta-lactamase (ESBL) enzymes (mainly CTX-M type) were detected in 48 strains (39 E. coli, 6 K. pneumoniae and 3 P. mirabilis). Despite wide intercountry variability in bacterial susceptibility rates to the other antimicrobials tested, fosfomycin and mecillinam have preserved their in vitro activity in all countries investigated against the most common uropathogens.
Article
Urinary tract infection (UTI) refers to the presence of clinical signs and symptoms arising from the genitourinary tract plus the presence of one or more micro-organisms in the urine exceeding a threshold value for significance (ranges from 102 to 103 colony-forming units/mL). Infections are localized to the bladder (cystitis), renal parenchyma (pyelonephritis) or prostate (acute or chronic bacterial prostatitis). Single UTI episodes are very common, especially in adult women where there is a 50-fold predominance compared with adult men. In addition, recurrent UTIs are also common, occurring in up to one-third of women after first-episode UTIs. Recurrences requiring intervention are usually defined as two or more episodes over 6 months or three or more episodes over 1 year (this definition applies only to young women with acute uncomplicated UTIs). A cornerstone of prevention of UTI recurrence has been the use of low-dose once-daily or post-coital antimicrobials; however, much interest has surrounded non-antimicrobial-based approaches undergoing investigation such as use of probiotics, vaccines, oligosaccharide inhibitors of bacterial adherence and colonization, and bacterial interference with immunoreactive extracts of Escherichia coli. Local (intravaginal) estrogen therapy has had mixed results to date. Cranberry products in a variety of formulations have also undergone extensive evaluation over several decades in the management of UTIs. At present, there is no evidence that cranberry can be used to treat UTIs. Hence, the focus has been on its use as a preventative strategy. Cranberry has been effective in vitro and in vivo in animals for the prevention of UTI. Cranberry appears to work by inhibiting the adhesion of type I and P-fimbriated uropathogens (e.g. uropathogenic E. coli) to the uroepithelium, thus impairing colonization and subsequent infection. The isolation of the component(s) of cranberry with this activity has been a daunting task, considering the hundreds of compounds found in the fruit and its juice derivatives. Reasonable evidence suggests that the anthocyanidin/proanthocyanidin moieties are potent antiadhesion compounds. However, problems still exist with standardization of cranberry products, which makes it extremely difficult to compare products or extrapolate results. Unfortunately, most clinical trials have had design deficiencies and none have evaluated specific key cranberry-derived compounds considered likely to be active moieties (e.g. proanthocyanidins). In general, the preventive efficacy of cranberry has been variable and modest at best. Meta-analyses have established that recurrence rates over 1 year are reduced approximately 35% in young to middle-aged women. The efficacy of cranberry in other groups (i.e. elderly, paediatric patients, those with neurogenic bladder, those with chronic indwelling urinary catheters) is questionable. Withdrawal rates have been quite high (up to 55%), suggesting that these products may not be acceptable over long periods. Adverse events include gastrointestinal intolerance, weight gain (due to the excessive calorie load) and drug-cranberry interactions (due to the inhibitory effect of flavonoids on cytochrome P450-mediated drug metabolism). The findings of the Cochrane Collaboration support the potential use of cranberry products in the prophylaxis of recurrent UTIs in young and middle-aged women. However, in light of the heterogeneity of clinical study designs and the lack of consensus regarding the dosage regimen and formulation to use, cranberry products cannot be recommended for the prophylaxis of recurrent UTIs at this time.
Article
At the interface between the innate and adaptive immune systems lies the high-output isoform of nitric oxide synthase (NOS2 or iNOS). This remarkable molecular machine requires at least 17 binding reactions to assemble a functional dimer. Sustained catalysis results from the ability of NOS2 to attach calmodulin without dependence on elevated Ca2+. Expression of NOS2 in macrophages is controlled by cytokines and microbial products, primarily by transcriptional induction. NOS2 has been documented in macrophages from human, horse, cow, goat, sheep, rat, mouse, and chicken. Human NOS2 is most readily observed in monocytes or macrophages from patients with infectious or inflammatory diseases. Sustained production of NO endows macrophages with cytostatic or cytotoxic activity against viruses, bacteria, fungi, protozoa, helminths, and tumor cells. The antimicrobial and cytotoxic actions of NO are enhanced by other macrophage products such as acid, glutathione, cysteine, hydrogen peroxide, or superoxide. Although the high-output NO pathway probably evolved to protect the host from infection, suppressive effects on lymphocyte proliferation and damage to other normal host cells confer upon NOS2 the same protective/destructive duality inherent in every other major component of the immune response.
Article
The first step in the colonization of the human urinary tract by pathogenic Escherichia coli is the mannose-sensitive binding of FimH, the adhesin present at the tip of type 1 pili, to the bladder epithelium. We elucidated crystallographically the interactions of FimH with D-mannose. The unique site binding pocket occupied by D-mannose was probed using site-directed mutagenesis. All but one of the mutants examined had greatly diminished mannose-binding activity and had also lost the ability to bind human bladder cells. The binding activity of the mono-saccharide D-mannose was delineated from this of mannotriose (Man(alpha 1-3)[Man(alpha 1-6)]Man) by generating mutants that abolished D-mannose binding but retained mannotriose binding activity. Our structure/function analysis demonstrated that the binding of the monosaccharide alpha-D-mannose is the primary bladder cell receptor for uropathogenic E. coli and that this event requires a highly conserved FimH binding pocket. The residues in the FimH mannose-binding pocket were sequenced and found to be invariant in over 200 uropathogenic strains of E. coli. Only enterohaemorrhagic E. coli (EHEC) possess a sequence variation within the mannose-binding pocket of FimH, suggesting a naturally occurring mechanism of attenuation in EHEC bacteria that would prevent them from being targeted to the urinary tract.
Article
“Collateral damage” is a term used to refer to ecological adverse effects of antibiotic therapy; namely, the selection of drug-resistant organisms and the unwanted development of colonization or infection with multidrug-resistant organisms. The risk of such damage can be assessed for different antibiotic classes by a variety of epidemiologic studies. Cephalosporin use has been linked to subsequent infection with vancomycin-resistant enterococci, extended-spectrum β-lactamase—producing Klebsiella pneumoniae, β-lactam—resistant Acinetobacter species, and Clostridium difficile. Quinolone use has been linked to infection with methicillin-resistant Staphylococcus aureus and with increasing quinolone resistance in gram-negative bacilli, such as Pseudomonas aeruginosa. Neither third-generation cephalosporins nor quinolones appear suitable for sustained use in hospitals as “workhorse” antibiotic therapy.
Article
Urinary tract infections (UTIs) have plagued mankind long before bacteria were recognized as the causative agents of disease and before urology became an established medical specialty. To our knowledge a comprehensive review of the recorded medical history of UTI from its first description in ancient Egyptian papyri through today has not been attempted until now. Numerous resources were used to collect the information described in this review. Older textbooks from the school of medicine library at our institution were used to collect information on UTI in ancient times. Medical texts from the 19th century contains information regarding the treatment of UTI during that era. Early volumes of the Journal of Urology from the beginning of the 20th century are rich with information on the first attempts at chemotherapy for UTI. MEDLINE searches were used to collect appropriate information after 1969. The Ebers papyrus from ancient Egypt recommended herbal treatments to ameliorate urinary symptoms without providing insight into pathological mechanisms. Hippocrates believed that disease was caused by disharmony of the 4 humors and accordingly diagnosed urinary disorders. Roman medicine further expanded the conservative approach (bed rest, diet, narcotics and herbs) advocated by Greek physicians, while also improving invasive techniques (surgical lithotomy for stones and catheterization for retention). The Arabian physician Aetius refined uroscopy and created a detailed classification and interpretation of urinary disease based on this technique. During the Middle Ages no major advances occurred, although existing therapies were refined and treatments for gonococcal urethritis were well described. The early 19th century provided vivid and detailed descriptions of UTIs without the knowledge that they were caused by microorganisms. Management included hospitalization, bed rest, attention to diet, plasters, narcotics, herbal enemas and douches, judicious bleeding (direct bleeding, cupping and leeches), and surgery for stones, abscess and retention. The discovery of microorganisms as the etiological agents of infectious diseases in general and inflammation associated with urinary diseases in particular provided an impetus for physicians critically to examine management approaches and develop evidence based strategies for UTI treatment. Various antibacterial agents, such as hexamine, mercurochrome and others (hexylresorcinol, methylene blue, pyridium, acriflavin and mandelic acid), showed promise in laboratory studies but their efficacy in clinical investigations was disappointing. Treatments for UTI until the discovery of antibiotics were largely palliative because the bacterial origin of UTI was not recognized and no specific antimicrobial therapies were available.
Article
This study evaluated the antibacterial efficacy of the consumption of cranberry capsules vs. placebo in the urine of healthy volunteers. A first double-blind, randomised, crossover trial involved eight volunteers who had followed three regimens, with or without cranberry, with a wash-out period of at least 6 days between each regimen. Twelve hours after consumption of cranberry or placebo hard capsules, the first urine of the morning was collected. Different Escherichia coli strains were cultured in the urine samples. Urinary antibacterial adhesion activity was measured in vitro using the human T24 epithelial cell-line, and in vivo using the Caenorhabditis elegans killing model. With the in-vitro model, 108 mg of cranberry induced a significant reduction in bacterial adherence to T24 cells as compared with placebo (p <0.001). A significant dose-dependent decrease in bacterial adherence in vitro was noted after the consumption of 108 and 36 mg of cranberry (p <0.001). The in-vivo model confirmed that E. coli strains had a reduced ability to kill C. elegans after growth in the urine of patients who consumed cranberry capsules. Overall, these in-vivo and in-vitro studies suggested that consumption of cranberry juice represents an interesting new strategy to prevent recurrent urinary tract infection.
Major trends in the microbial etiology of urinary tract infection
  • I F Mihai
  • G Lacatusu
  • F Filip-Ciubotaru
  • C Dorobat
  • C Romanescu
  • C Manciuc
Mihai IF, Lacatusu G, Filip-Ciubotaru F, Dorobat C, Romanescu C and Manciuc C: Major trends in the microbial etiology of urinary tract infection. GARJM 8: 35-37, 2019.
Cranberry for the prevention and treatment of non-nomplicated urinary tract infections
  • P Gopalakrishna
  • D Bonnie
Gopalakrishna P, Bonnie D, Richard Z and Lacie D: Cranberry for the prevention and treatment of non-nomplicated urinary tract infections. SOJ Pharm Sci 6: 1-9, 2018.