S-HYDRACYST

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Hooton TM, et al. "Effect of Increased Daily Water Intake in Premenopausal Women With Recurrent Urinary Tract Infections". JAMA Internal Medicine. 2018. 178(11):1509-1515.
PubMedFull textClinicalTrials.gov

Clinical Question

In premenopausal women who experience 3 urinary tract infections per year, does increasing water intake to more than 1.5L per day decrease the number of recurrent urinary tract infections?

Bottom Line

In women who drink less than 1.5L of water per day, increasing that amount decreased the number of urinary tract infections over a 12 month period.

Major Points

Acute uncomplicated cystitis can affect half of the female population over their lifetime. While self-limiting, the vast majority will report pain, discomfort, and a decrease in quality of life. Commonly antimicrobials are prescribed to treat this infection and in the modern era of growing antimicrobial resistance, finding interventions to limit their utilization and saving this precious resource for the future or my more serious infections. Prior to this trial, the common teaching for women with recurrent UTI was to increase their water intake.

The 2018 S-HYDRACYST trial, sponsored by makers of bottle water, included 140 healthy, premenopausal women with normal weight and low fluid intake. Participants were randomized to an additional 1.5L of bottled water to their usual fluid intake (n=70) or control (n=70). For their primary outcome, they observed 1.7 episodes of cystitis in the water group compared to 3.2 in the control (P<0.001). The amount of antimicrobials utilized was significantly lower, 1.9 vs. 3.6 (P<0.001). There was also a non-surprising increase in the number of voids and volume of urine produced.

This trial, conducted at a single site, had a number of limitations including be sponsored by makers of bottled water. It was also open-label, but blinding would have been exceptionally challenging given the intervention. Finally, the outcome was self-reported but they did attempt to confirm with culture as much as possible. The effect seen in this trial may be associated with the increase in voiding and output, decreasing the bacterial burden within the bladder. Overall, this trial showed that a simple intervention of increasing water intake in a population with low water intake may decrease the utilization of antimicrobials, and may be made more accessible by utilizing tap water instead of bottled.

Guidelines

As of September 2019, no guidelines have been published that reflect the results of this trial.

Design

  • Randomized, open-label, controlled study
  • N=140
    • Water supplementation group (n=70)
    • Control (n=70)
  • Setting: Bulgaria
  • Enrollment: 2013-2016
  • Follow-up: 12 months
  • Analysis: intention-to-treat
  • Primary Outcome: Number of cystitis episodes over 12 months

Population

Inclusion Criteria

  • ≥18 years old
  • Good general health
  • No current UTI symptoms
  • ≥3 symptomatic episodes of cystitis in the past year resulting in a documented visit to a clinician
  • ≥1 episode culture confirmed
  • Self-reported water consumption <1.5 L of fluid daily
  • Eats ≥3 meals/day
  • Internet access to receive information about hydration
  • Able to communicate

Exclusion Criteria

  • Current symptoms of UTI or recent use of antibiotics or supplements
  • Recent complicated UTI dx (e.g., pyelonephritis) in the past 12 months or multiple-antibiotic resistant strains previously
  • Interstitial cystitis, kidney stones, urinary tract abnormalities
  • Chronic diarrhea or constipation requiring medical treatment
  • Obesity or low BMI (outside of range 18.5-30 kg/m2)
  • Symptomatic vulvovaginitis
  • Pregnant, lactating, or planning to become pregnant in the following 12 months
  • Menopause or perimenopausal
  • Anticoagulant medication use
  • GFR <60 mL/min/1.73 m2

Baseline Characteristics

Among all participants.

  • Demographics: Age 36 years
  • Anthropometrics: BMI 23 kg/m2
  • Physiologic parameters: 92% sexually active in past month
  • UTI details:
    • UTIs in the past year: 3.3
    • ≥3 UTIs in past year: 72%
    • ≥4 UTI in past year: 28%
    • Causative organism: 78% Escherichia coli, 10% Klebsiella species, 4% Proteus
  • Fluid details:
    • Daily fluid intake: 1.1 L
    • 24h urine output: 0.9 L
      • 24h urine osmolality: 724 mOsm/kg
      • No. voids/day: 6

Interventions

  • Randomized to a group:
    • Water supplementation group - Given three 500 mL water bottles to drink daily in addition to usual fluid intake for 12 months.
    • Control - No additional water given.

Outcomes

Comparisons are water supplementation group vs. control. "Difference" is difference in means.

Primary Outcomes

Mean cystitis episodes over 12 months
1.7 vs. 3.2 (difference 1.5, 95% CI 1.2-1.8; P<0.001)
Total episodes in 12 mo: 111 vs. 216
93% of the water supplementation group had ≤2 UTI episodes while 88% of the control group had ≥3 episodes. See Figure 2 on page 1512 for a histogram of the number of episodes.

Secondary Outcomes

Mean number of antimicrobial courses prescribed
1.9 vs. 3.6 (difference 1.7, 95% CI 1.3-2.1; P<0.001)
Mean time interval between cystitis episodes
142.8 days vs. 84.4 days (difference 58.4, 95% CI 39.4-77.4; P<0.001)
Median time to first cystitis episode
148 days vs. 94 days (hazard ratio 0.51, 95% CI 0.36-0.74; P<0.001)
Mean increase in 24-hour urine volume
1.3L vs. 0.1L, P<0.001

Adverse Events

Not separate between groups No serious ADR reported, 9% reported headache, 6% reported GI symptoms

Criticisms

  • Open label design (attempted mitigation via monthly phone follow-up, measured urine volume/osmolality, cultured confirmed UTI)
  • Single site, limiting generalizability
  • Self-reported primary outcome
  • Study sponsor sells intervention

Funding

  • Danone Research, seller of the bottled water used in the study

Further Reading