Management of RECURRENT URINARY TRACT INFECTION OVERVIEW Challenge of Recurrent UTI What is Recurrent UTI Risks prevention Management of recurrent UTI Cranberry & D-mannose Tablets Composition Clinical Studies Indication Dosage & Administration Contraindications Warnings & Precautions Adverse Events Take Home Massages FAQs

1. Management of RECURRENT
URINARY TRACT INFECTION
Dr. Sharda Jain
Dr. Jyoti Agarwal
Dr. Jyoti Bhaskar

2. Our Team
dedicated for giving knowledge & skill to doctors

3. OVERVIEW
• Challenge of Recurrent UTI
• What is Recurrent UTI
• Risks
• prevention
• Management of recurrent UTI
• Cranberry & D-mannose Tablets
 Composition
 Clinical Studies
 Indication
 Dosage & Administration
 Contraindications
 Warnings & Precautions
 Adverse Events
Take Home Massages
• FAQs

4. Complicated & recurrent UTI
As many as 50 percent of women who suffer an
uncomplicated acute bacterial episode of
cystitis will have another infection within a
year.
Up to 5 percent have recurring symptoms soon
after treatment. When symptoms develop in
such women, the likelihood that a true
infection is present in greater than 80
percent.

5. 1. Prim Care Clin Office Pract 2013; 40: 687–706
2. Urological Science 2014; 25: 1-8
Recurrence poses significant clinical challenges
and has a major impact on quality of life.2
Even after treatment,
women frequently suffer
from recurrent infection
with the same or different
microrganisms.1

6. Recurrent UTI
• Recurrent UTI is defined as 2 episodes in
the last 6 months or 3 episodes of UTI in
the last 12 months.1
• Recurrent UTI occurs in 20-40% of
women.2
1. Urological Science 2014; 25: 1-8
2. Indian J. Community Med 2012; 37(1): 39-44

7. Risk Factorsof Recurrent UTI
• Sexual intercourse
• Use of spermicide
• A mother with a history of UTI
• History of UTI during childhood
EAU Guidelines on Urological Infections 2015

8. Risk Factorsof Recurrent UTI
• Atrophic urethritis and
vaginitis (postmenopausal)
•Anormalities of urinary tract
(indwelling catheter, neuropathic
bladder, vesico-ureteric reflux(VUR),
outflow obstruction, anatomical
anomalies)

9. Risk Factorsof Recurrent UTI
•Incomplete bladder
emptying (dysfuctional
urination)
•History of urinary tract
surgery
•Immune compromise-eg,HIV

10. Evaluation of Recurrent UTI
•MSU culture (GOLD STANDARS)
•A clean catch urine sample is the
recommended method for urine
collection
•A midstream urine bacterial count
1x10 CFU/L considered positive,
but here 1x10 CFU/L can be taken
as positive
5
2

11. Evaluation of Recurrent UTI
•USG, CT SCAN-for anatomical abnormality
•Excretory urography and cystoscopy
•Further evaluation of urinary tract is
recommende if supicion arises about
complicating factors such as structural or
fuctional abnormalities of the
geniotourinary tract, the isolation of
Proteus species in urine
5
2

12. Prevention of Recurrent UTI
•Maintain hydration
•Frequent voiding
•Life style modification
•Practice correct toilet habits (wiping front to back)
•Avoid hygiene products

13. Prevention of Recurrent UTI
•Consider a trial of cranberry juice 2 to 3 glasses per day
If related to sexual intercourse:
•Topical vaginal oestrogen may help postmenopausal
women
Change the contraceptive method if a diaphragm or
spermicide is being used Advice voiding after intercourse
Using a lubricant

14. Women Suffering from Recurrent UTI have a
negative impact on patient quality of life…

15. STUDY DESIGN:
The short form (SF) health
survey, a 36-Item questionnaire
was administered to 47 women
with a diagnosed UTI and
compared with a control
population of 71 women.
Significantly lower SF-36 quality-of-life
questionnaire score was observed in women
suffering with UTI.
Am Board Fam Pract 2000; 13: 392-397
Recurrent UTI

16. There is a need to prevent rUTI
by reducing morbidity for
better QoL.

17. Management of Recurrent UTIs
Management of recurrent UTI includes:
1. Counselling and Behavioural
Modifications
2. Antimicrobial Prophylaxis
3. Non-antimicrobial Prophylaxis
EAU Guidelines on Urological Infections 2015

18. Management of Recurrent UTIs
1. Counselling and Behavioural Modifications
Measures such as increase fluid intake, postcoital
urination, wiping from front to back after
defecation may help to reduce the risk of UTI.1
Drawback:
Insufficient evidence2
1. EAU Guidelines on Urological Infections 2015
2. Rev Urol. 2013; 15(2): 41-48

19. Management of Recurrent UTIs
• Continuous prophylaxis: daily for 3 – 6
months is the main stay of treatment
• Postcoital prophylaxis: single postcoital dose1
1. EAU Guidelines on Urological Infections
2015
2. Urological Science 2014; 25: 1-8
3. Clinical Nursing Research 2014; 23(1):
54-79
4. Clin Infect Dis 2004; 38(10): 1413-1419
Prophylaxis of antibioticsis in table 1 and 2.
choice of antibiotic based upon the susceptibility
patterns of strains causing the patent's previous UTIs
and any history of drug allergies

22. Drawbacks:
•Optimal duration of prophylaxis is not yet known2
•Increasing antimicrobial resistance 3
•Risk of adverse reactions4
1. EAU Guidelines on Urological Infections
2015
2. Urological Science 2014; 25: 1-8
3. Clinical Nursing Research 2014; 23(1):
54-79
4. Clin Infect Dis 2004; 38(10): 1413-1419
Management of Recurrent UTIs
2. Antimicrobial Prophylaxis
Single-dose therapy is effective but still not popular than 3-day
regimens. Nitrofurantoin regimens are usually 7 days.
TREATMENT COURSES longer than 3 days result in almost twice the
number of adverse events & not more effective in treating
uncomplicated cystitis , are more costly , & have higher rates of non
compliance.

23. Management of Recurrent UTIs
3. Non-antimicrobial Prophylaxis
Trend towards increased use of non-antimicrobial based
approach such as cranberry, D-mannose etc.1
Advantages:
• Safe and effective in reducing rUTI2
• Addition of non-antimicrobial agent to lifestyle
modifications may provide better clinical outcomes3
• Efficacy of non-antimicrobial agent is comparable to
antibiotic4
• Can be safely used as an adjunct to antimicrobial
prophylaxis in UTIs5
1. Drugs 2009; 69 (7): 775-807
2. Phytomedicine 2007;14: 237-241
3. Eur Rev Med Pharmacol Sci. 2015; 19(1): 77-80
4. World J Urol. 2014; 32(1): 79-84
5. Clinical Nursing Research 2014; 23(1): 54-79

24. EAU Guidelines 2015 Recommendations

25. A novel approach to reducing the risk of
recurrent UTI, probiotics may protect the
vagina from colonization by
uropathogens through variety of
mechanisms.
PROBIOTICS

26. Cranberry
Or
Cranberry and D – Mannose Tables
SIMPLY a REVOLUTION
is Created by

27. Composition
Each tablet contains:
Cranberry Extract (25% Proanthocyanidins)……300 mg
D-mannose……………………………………………………..600 mg

28. Cranberry
• Cranberry is a plant from the
family Ericaceae and is known as
Vaccinium macrocarpon.
• Cranberries are composed of 88%
water and a complex mixture of
organic acids, vitamin C,
flavonoids, anthocyanidins,
catechins and triterpinoids.
Drugs 2009; 69 (7): 775-807

29. D-Mannose
• D-mannose is a simple sugar
structurally related to glucose.
• It is found in several fruits such as
peaches, apples and oranges and is
also produced in the body.
• It has an important role in human
metabolism, especially in the
glycosylation of certain proteins.
J Clin Urol 2014; 7(3): 208-213
World J Urol. 2014; 32(1): 79-84

30. Attachment of Bacteria to Uroepithelium
• E.coli has hair-like protruding fimbria on their surface.
• Fimbria produces 2 adhesins [mannose sensitive (type 1) and mannose
resistant (type P)]
• Through these adhesins, bacteria attaches to the specific receptors on
uroepithelial cells.
Fimbria
Adhesins

31. Mechanism of Action of Cranberry
Proanthocyanidins A from cranberry inhibits the
mannose-resistant adhesins (P-fimbriae) of
uropathogenic E.coli.
Drugs 2009; 69 (7): 775-80

32. Mechanism of Action of D-Mannose
type 1 pili
D-mannose
M-receptor
D-mannose binds to the type 1 pili of bacteria
blocking their adhesion to uroepithelial cells.
World J Urol. 2014; 32(1): 79-84

33. Spectrum of Activity
In vitro studies have shown
inhibition of adherence for
following uropathogens:
• Escherichia coli
• Enterococcus faecalis
• Staphylococcus aureus
• Klebsiella pneumoniae
• Proteus mirabilis
CLINICS 2012; 67(6): 661-667
J Clin Urol 2014; 7(3): 208-213
World J Urol. 2014; 32(1): 79-84

34. Indication
Prophylaxis of
Recurrent UTI (Cystitis)

35. Unique
features
1. Cranberry is
safe and
efficacious in
preventing rUTIs
in women.
2. Addition of
cranberry extract
to lifestyle
advice results in
better clinical
outcomes.
3. Cranberry
reduces
incidence of UTIs
in elderly
patients who are
at higher risk of
UTI.
4. Cranberry
prevents
recurrent
postcoital UTIs
and improves
QoL.
5. D-mannose
prophylaxis is as
effective as
nitrofurantoin
for preventing
rUTIs in women.
1. Phytomedicine 2007;14: 237-241
2. Eur Rev Med Pharmacol Sci. 2015; 19(1): 77-80
3. J Am Geriatr Soc 2014; 62:103-110
4. BMC Urology 2013, 13: 28
5. World J Urol. 2014; 32(1): 79-84

36. Cranberry is Safe and Efficacious in
Preventing Recurrent UTIs in Women
AIM
• The objective of this study was to examine
the ability of a concentrated cranberry
preparation to prevent UTIs in women with
a history of recurrent infections.
Phytomedicine 2007;14: 237-241

37. STUDY DESIGN
• Randomized, cross-over study
• N=60 women aged 22 - 54 years who had an acute symptomatic UTI and three
or more UTIs during the preceding 12 months documented with culture of
midstream urine specimen
• They were randomized to receive:
 Group A: A 5-day regimen of trimethoprim/sulfamethoxazole 160 mg/800
mg twice a day, followed by a single dose at bedtime for 1 week each
month in the following 23 weeks
 Group B: A regimen of oral D-mannose 1 g three times a day, every 8 hours
for 2 weeks, and subsequently 1 g twice a day for 22 weeks.
• Cross-over was done at 24 weeks and patients in group A switched to group B
and vice versa.
• Outcomes:
 Primary outcome: Time to recurrence of UTI after antibiotic treatment and
with D-mannose treatment.
 Secondary outcome: Evaluation of bladder pain (VASp), urinary urgency
(VASu) on VAS scale during the episodes of UTI.
J Clin Urol 2014; 7(3): 208–213

38. CONCLUSION
Journal of Clinical Urology 2014; 7(3): 208–213
• D-mannose appeared to be safe and effective
treatment choice for acute and recurrent UTIs in
adult women.
• A statistically significant difference was seen in
the proportion of women remaining infection free
during an average course of 24-week treatment,
both for treatment of acute episodes and as a safe
and preventative therapy of UTI recurrences
compared with targeted antibiotic treatment.

39. Common Side Effects
Most commonly reported side effects
are:
Mild gastrointestinal upset such as:
• Gastric reflux
• Vomiting
• Nausea
• Frequent bowel moments Drugs 2009; 69 (7): 775-807
CLINICS 2012; 67(6): 661-667
World J Urol. 2014; 32(1): 79-84
Clinical Nursing Research 2014; 23(1): 54-79

40. TAKE HOME MESSAGES
• UTI is the common infection occurring in young women. The
most common presentation in young non-pregnant women is
acute uncomplicated cystitis.
• Recurrent UTI is a common phenomenon in adult women.
• Recurrent UTI can be managed by behavioural modifications,
non-antimicrobial prophylaxis and antimicrobial prophylaxis.

41. TAKE HOME MESSAGES
•EAU guidelines recommend that antimicrobial prophylaxis
should be considered only after behavioural modifications
have been attempted and when non-antimicrobial
prophylaxis have been unsuccessful.
• Cranberry and D-mannose prevent adhesion of
uropathogens to uroepithelium.
•Clinical studies on cranberry and D-mannose have
reported that, both reduces the rate of recurrent UTI in
women.

42. TAKE HOME MESSAGES
• The data on the use of cranberry in pregnancy and
diabetic patients is insufficient and hence its
usage should be avoided in these population.
• Prophylaxis with D-mannose is as effective as
nitrofurantoin in preventing recurrent UTI in
women.
• Most commonly reported adverse reactions are
gastrointestinal upset such as nausea, vomiting
and frequent bowel moments.

43. TAKE HOME MESSAGES
• Unique features of combination of cranberry & D-mannose
includes:
1. Cranberry is safe and effective in preventing rUTIs in
women.
2. Addition of cranberry to lifestyle modifications results in
better clinical outcomes.
3. Cranberry reduces incidence of UTIs in elderly patients
who are at higher risk of UTI.
4. Cranberry prevents recurrent poistcoital UTIs and
improves QoL.
5. D-mannose is as effective as nitrofurantoin for preventing
rUTIs in women.

44. FAQs

45. 1. Why not hibiscus with Fosamycin
• Hibiscus flower contains biologically active components such
as alkaloids, flavonoids, phenolics, biterenoids and methanol
that are responsible for antibacterial activity.1
• The in vitro antibacterial activity of hibiscus flower petals was
carried out and it has shown to inhibit pathogens such as E.
coli, B. subtilis, P. aeruginosa, S. aureus etc.2
• This plant has been reported to have antihypertensive,
hepatoprotective, anticancer and antioxidant properties.3
• However, the data on hibiscus in preventing UTI is
inconclusive.
1. J Med Food 2011; 14(9): 950-956
2. Asian Pacific Journal of Tropical Biomedicine 2012; 399-
403
3. Natural Product Radiance 2009; 8(1): 77-83

46. 2. What is the duration of cranberry &D-
mannose combination for prophylaxis of
rUTI?
• The long-term efficacy and safety data on cranberry is
available for 1 year in preventing rUTI.
• The long-term efficacy and safety data on D-mannose is
available for 6 months in preventing rUTI.
• However, there is no clear data available for the
duration up to which these products can be taken for
preventing rUTI.

47. 3. What is the rational regarding dosage
of cranberry & D –mannose combination?
• Recommended dose of cranberry extract ranges between 600
- 1200 mg per day and there is data to suggest that, efficacy
improves in a dose-dependent manner.
• The recent study on D-mannose as well as EAU guidelines
mentions that, 2 gm of D-mannose is as efficacious as
nitrofurontoin 50 mg in preventing rUTI in women.
• Hence we can recommend the dose for Cranfit up to one
tablet thrice daily (Cranberry 900 mg/day & D-mannose 1.8
gm/day).
1 tablet contains 25% PAC = 75 mg
3 tablets = 225 mg of PAC/day

48. Thank You
Stay healthy, keep smiling
don’t
ignore U.T.I.
