D-mannose

ChEBI · EMBL-EBI ↗ · Källdatum saknas · Källans villkor

A mannose with D-configuration.

Gail Hayward; Sam Mort; Alastair D Hay; Michael Moore; Nicholas P B Thomas; Johanna Cook; Jared Robinson; Nicola Williams; Nicola Maeder; Rebecca Edeson; Marloes Franssen; Jenna Grabey; Margaret Glogowska; Yaling Yang; Julie Allen; Christopher C Butler ↗ · 8 apr. 2024 · Källans villkor

Women were identified either by responding to an advertisement in their surgery, on presentation to their primary care clinician, or by participating primary care centers through records search followed by a written invitation to participate. We recruited from 99 primary care centers based in 10 of 15 regions of England and 4 of 7 health boards in Wales. Practice locations spanned the full range of the Index of Multiple Deprivation deciles, with 40% based in deciles 1 to 5. The trial team or recruiting site established eligibility and took informed consent via a conversation either face to face or by telephone using an online form. Women were eligible if they were 18 years or older, willing and able to give informed consent for participation and comply with study procedures, and had presented to ambulatory care with symptoms consistent with a UTI and/or resulting in a UTI-specific antibiotic prescription 3 or more times in the past year or 2 or more times in the past 6 months. Women were ineligible if they were pregnant, lactating, or planning pregnancy during the study; had formal diagnosis of interstitial cystitis or overactive bladder syndrome; were a nursing home resident; catheterized, including intermittent self-catheterization; using Uromune (Inmunotek); or had previously participated in this study or had participated in a research study involving an investigational medicinal product in the past 12 weeks. Women were also ineligible if they had started prophylactic antibiotics in the past 3 months and were unwilling to discontinue or intended to start them during the next 6 months or were currently using d-mannose and unwilling to discontinue it.

Gail Hayward; Sam Mort; Alastair D Hay; Michael Moore; Nicholas P B Thomas; Johanna Cook; Jared Robinson; Nicola Williams; Nicola Maeder; Rebecca Edeson; Marloes Franssen; Jenna Grabey; Margaret Glogowska; Yaling Yang; Julie Allen; Christopher C Butler ↗ · 8 apr. 2024 · Källans villkor

Eligible, consenting participants were randomized in equal allocation between d-mannose and placebo using a secure, web-based randomization system (Sortition). Block randomization was implemented with varying block sizes. Randomization was stratified by primary care center. Participants, clinicians, and members of the trial team responsible for recruitment/follow-up/monitoring of participants were blinded to group assignment. To conceal allocation, bottles of d-mannose and fructose (placebo) looked identical and were randomly assigned a number that was used in the randomization process.

Gail Hayward; Sam Mort; Alastair D Hay; Michael Moore; Nicholas P B Thomas; Johanna Cook; Jared Robinson; Nicola Williams; Nicola Maeder; Rebecca Edeson; Marloes Franssen; Jenna Grabey; Margaret Glogowska; Yaling Yang; Julie Allen; Christopher C Butler ↗ · 8 apr. 2024 · Källans villkor

Participants were randomized to either take a daily scoop amounting to approximately 2 g of d-mannose powder or a similar, daily scoop of fructose powder.

Gail Hayward; Sam Mort; Alastair D Hay; Michael Moore; Nicholas P B Thomas; Johanna Cook; Jared Robinson; Nicola Williams; Nicola Maeder; Rebecca Edeson; Marloes Franssen; Jenna Grabey; Margaret Glogowska; Yaling Yang; Julie Allen; Christopher C Butler ↗ · 8 apr. 2024 · Källans villkor

Between March 28, 2019, and January 31, 2020, 598 women were randomized to d-mannose (n = 303) or placebo (n = 295).

Gail Hayward; Sam Mort; Alastair D Hay; Michael Moore; Nicholas P B Thomas; Johanna Cook; Jared Robinson; Nicola Williams; Nicola Maeder; Rebecca Edeson; Marloes Franssen; Jenna Grabey; Margaret Glogowska; Yaling Yang; Julie Allen; Christopher C Butler ↗ · 8 apr. 2024 · Källans villkor

The primary outcome was the proportion of women experiencing at least 1 further episode of clinically suspected UTI for which they contacted ambulatory care (including primary care, emergency departments, hospitals, ambulance services, and out-of-hours primary care) within 6 months of randomization established via primary care record review. This outcome was chosen after discussion with women with lived experience of rUTI as the most important indicator of symptom burden, which prophylaxis would aim to avoid. In primary care, microbiological confirmation is not generally relied on for guiding initial antibiotic prescribing and in up to one-third of cases will be inconclusive.20

Gail Hayward; Sam Mort; Alastair D Hay; Michael Moore; Nicholas P B Thomas; Johanna Cook; Jared Robinson; Nicola Williams; Nicola Maeder; Rebecca Edeson; Marloes Franssen; Jenna Grabey; Margaret Glogowska; Yaling Yang; Julie Allen; Christopher C Butler ↗ · 8 apr. 2024 · Källans villkor

Of 294 women in the d-mannose group and 289 in the placebo group, 150 (51.0%) and 161 (55.7%) had a further episode of clinically suspected UTI, respectively, for which they contacted ambulatory care (relative risk [RR], 0.92; 95% CI, 0.80-1.05; P = .22; and unadjusted risk difference, −5%; 95% CI, −13% to 3%; P = .26; Table 2).

Gail Hayward; Sam Mort; Alastair D Hay; Michael Moore; Nicholas P B Thomas; Johanna Cook; Jared Robinson; Nicola Williams; Nicola Maeder; Rebecca Edeson; Marloes Franssen; Jenna Grabey; Margaret Glogowska; Yaling Yang; Julie Allen; Christopher C Butler ↗ · 8 apr. 2024 · Källans villkor

Table 2. Frequency of Women Experiencing at Least 1 Further Episode of a Clinically Suspected Urinary Tract Infection (UTI) for Which They Contacted Ambulatory Care by Randomized Group≥1 Further episode of a clinically suspected UTINo. (%)P valued-Mannose (n = 303)Placebo (n = 295)Yes150 (51.0)161 (55.7)NANo144 (49.0)128 (44.3)NAMissing96NAUnadjusted risk difference (95% CI)−0.05 (−0.13 to 0.03).26Adjusted relative risk (95% CI)a0.92 (0.80 to 1.05).22Abbreviation: NA, not applicable. a Log-Poisson generalized linear mixed-effects model with robust standard errors of the proportion of women experiencing at least 1 further episode of a clinically suspected UTI modeled against randomized arm as a fixed effect and site as a random effect. The level of statistical significance is P = .05.

Gail Hayward; Sam Mort; Alastair D Hay; Michael Moore; Nicholas P B Thomas; Johanna Cook; Jared Robinson; Nicola Williams; Nicola Maeder; Rebecca Edeson; Marloes Franssen; Jenna Grabey; Margaret Glogowska; Yaling Yang; Julie Allen; Christopher C Butler ↗ · 8 apr. 2024 · Källans villkor

Limitations include possible underdosing, although the dose was the same as in 2 previous trials that found benefit.16,25 Although the patient advisory panel favored a powder over capsule form, it is possible that capsules might have resulted in a more consistent dose per day.

Gail Hayward; Sam Mort; Alastair D Hay; Michael Moore; Nicholas P B Thomas; Johanna Cook; Jared Robinson; Nicola Williams; Nicola Maeder; Rebecca Edeson; Marloes Franssen; Jenna Grabey; Margaret Glogowska; Yaling Yang; Julie Allen; Christopher C Butler ↗ · 8 apr. 2024 · Källans villkor

d-Mannose is a relatively expensive food supplement that is sold directly to the public in the US and UK. It should not be used to prevent rUTI in a primary care setting. However, the present results are not necessarily generalizable to secondary care populations who may be more severely affected. There has recently been interest in other approaches to block the binding of the Escherichia coli type 1 pili. Synthetic mannosides, which have a much higher affinity for the FimH adhesin, have shown promise in mouse models.27,28 A phase 1 trial of a vaccine against the FimH adhesin recently demonstrated safety and immunogenicity.29

Gail Hayward; Sam Mort; Alastair D Hay; Michael Moore; Nicholas P B Thomas; Johanna Cook; Jared Robinson; Nicola Williams; Nicola Maeder; Rebecca Edeson; Marloes Franssen; Jenna Grabey; Margaret Glogowska; Yaling Yang; Julie Allen; Christopher C Butler ↗ · 8 apr. 2024 · Källans villkor

In this randomized clinical trial, daily d-mannose did not reduce the proportion of women with rUTI in primary care who experienced a subsequent clinically suspected UTI. Daily d-mannose should not be recommended to prevent future episodes of clinically suspected UTI in women with rUTI in primary care.