The document discusses recurrent urinary tract infections (UTIs), characterized by two or more infections in six months or three in a year, caused either by reinfection or relapse of persistent infection. It details various risk factors, including behavioral and host factors, as well as possible microbiological causes, diagnostic techniques, clinical presentations, and management strategies for acute cystitis and pyelonephritis. Additionally, it reviews preventive measures, including behavioral modifications, dietary changes like cranberry juice, and antimicrobial prophylaxis.

1. RECURRENT UTI

2. Dr. Niranjan Chavan
MD, FCPS, DGO, DFP, MICOG, DICOG, FICOG
Professor and Unit Chief, L.T.M.M.C & L.T.M.G.H
Chairperson, FOGSI Oncology and TT Committee (2012-2014)
Treasurer, MOGS (2017- 2018)
Chair and Convener, FOGSI Cell- Violence against Doctors (2015-2016)
Chief Editor, AFG Times (2015-2017)
Editorial Board, European Journal of Gynecologic Oncology
Editor of FOGSI FOCUS, MOGS, AFG & IAGE Newsletters
Member, Managing Committee, IAGE (2013-2017)
Member , Oncology Committee, AOFOG (2013 -2015)
Recipient of 6 National & International Awards
Author of 15 Research Papers and 19 Scientific Chapters
Course Co-Ordinator, of 11 batches, of MUHS recognized Certificate Course of
Basic Infertility Management Including Endoscopy (BIMIE) at LTMGH

3. INTRODUCTION
• Recurrent urinary tract infection (UTI) refers
to ≥2 infections in six months or ≥3 infections
in one year.
• Recurrence can be due to reinfection or a
relapse of persistent foci of infection.
• Most recurrent UTIs are thought to
represent reinfection with the same
organism.
* Cochrane Database Syst Rev. 2015;

4. INTRODUCTION
• Relapses is symptomatic recurrent UTIs
with the same organism following adequate
therapy.
• Reinfection is recurrent UTIs with
previously isolated bacteria after treatment
and with a negative intervening urine
culture, or caused by a second bacterial
isolate.
American College of Obstetricians and Gynecologists. ACOG Practice Bulletin No. 91: Treatment
of urinary tract infections in nonpregnant women. Obstet Gynecol. 2008;111(3):785–794

5. EPIDEMIOLOGY
• In postmenopausal women the prevalence
rate for having one episode of UTI in a
given year varies from 8% to 10%.
• In reproductive age, the six-month risk of a
second UTI is 26.6 percent; the risk of a
third UTI, 2.7 percent.
* Cochrane Database Syst Rev. 2015;

6. WHAT ARE THE RISK FACTORS
PREDISPOSING TO RECURRENCE?

7. BEHAVIOURAL RISK FACTORS OF
RECURRENCE
• Frequent intercourse: strongest risk factor: >
9 times increases the risk 10 times.
• Spermicidal use
• Use of vaginal diaphragm
• New sex partner in the past year
• Age at first UTI ≥ 15 years

8. BEHAVIOURAL RISK FACTORS OF
RECURRENCE
• There is no proven association between recurrent
UTIs 1. Pre- or postcoital voiding patterns
2. Frequency of urination
3. Wiping patterns, douching
4. Use of tight undergarments
5. Delayed voiding habits.
Scholes D, et al. Risk factors for recurrent urinary tract infection in young women. J Infect Dis.
2000;182(4):1177–1182.

9. HOST RISK FACTORS FOR RECURRENCE
Factors causing immunosuppression
• Chronic renal insufficiency
• Diabetes mellitus
• Immunosuppressant medications
• Renal transplant
• HIV AIDS

10. HOST RISK FACTORS FOR RECURRENCE
Nosocomial factors and instrumentation
• Exposure to antibiotic-resistant bacteria
• Indwelling urinary catheter
• Intermittent catheterization
• Nephrostomy tube
• Ureteral stent

11. HOST RISK FACTORS FOR RECURRENCE
• Mechanical and physiologic factors affecting bladder
emptying:
• Incontinence
• Cystocele
• Postvoiding residual urine
• Increased Postvoid residual urinary volume (i.e., more
than about 50 mL) is an independent risk factor for
recurrent UTIs in postmenopausal women.*
Stern JA, et al. Residual urine in an elderly female population: novel implications for oral estrogen
replacement and impact on recurrent urinary tract infection. J Urol. 2004;171(2 pt 1):768–770.

12. RISK FACTORS RELATED TO INFECTION
FOR RECURRENCE
• The strongest predictors of recurrence were
characteristics of the infection itself: the
presence of haematuria and urgency in 1st
UTI.
• In a Finnish study of women ages 17 to 82
who had E. coli cystitis, 44 percent had a
recurrence within one year.
Ikäheimo R, Siitonen A, Heiskanen T, Kärkkäinen U, Kuosmanen P, Lipponen P, Mäkelä PH. Recurrence of
urinary tract infection in a primary care setting: analysis of a 1-year follow-up of 179 women. Clin Infect Dis.
1996 Jan;22(1):91-9.

13. OESTROGEN AND RECURRENT UTI
• Estrogen loss in postmenopausal women leads to
1. Decreasing glycogen
2. Thinning of the epithelium, and
3. Alkalization of the vagina.
4. Vaginal pH rises after menopause and vaginal
Lactobacillus decrease, allowing gram negative bacteria
to grow and act as uropathogen.
• All these changes change vaginal flora and predispose to UTI.
Oestrogens for preventing recurrent urinary tract infection in postmenopausal women, Cochrane
database 2008

14. WHAT IS THE CAUSE OF RECURRENCE IN
LOW COUNT BACTERIURIA OR EVEN
NEGATIVE CULTURES?
• Answer lies in
Intracellular Bacterial
Colonies forming
BIOFILM

15. BIOFILMS
• Uropathogenic E Coli (UPEC) like E. coli CFT073,
UTI89, and 536 invades urothelial cells lining the
urinary bladder which forms intracellular bacterial
communities (IBCs) or BIOFILM.
• This infection remains undetected in normal urine
cultures and causes recurrence.
• These culture negative infections presents as
unexplained dysuria and urgency and are termed as
INTERSTITIAL CYSTITIS/ BLADDER PAIN
SYNDROME.

17. MICROBIOLOGY
• Escherichia coli is the predominant
uropathogen (80 percent) isolated in acute
community-acquired uncomplicated UTIs.
• Coagulase-negative Staphylococcus (up to
15%)
• Klebsiella pneumoniae (∼8%)
• S. aureus (up to 8%)
Ronald A. The etiology of urinary tract infection: traditional and emerging pathogens. Am J Med.
2002;113(suppl 1A):14S–19S.

18. MICROBIOLOGY
• Group B streptococci (GBS) (2–7%).
• Pseudomonas infections are relatively more
common in patients with chronic catheterization.
• Proteus mirabilis is a common uropathogen in
patients with indwelling catheters, spinal cord
injuries, or structural abnormalities of the
urinary tract
Ronald A. The etiology of urinary tract infection: traditional and emerging pathogens. Am J Med.
2002;113(suppl 1A):14S–19S.

19. DIAGNOSIS
• Urine routine and microscopy.
• Leukocyte esterase-nitrite dipstick are when the
prevalence is 2 percent or less.
• Dipstick culture technique
• Urine culture sensitivity.(Gold Standard)

20. Leukocyte esterase-nitrite dipstick

21. DIAGNOSIS
• There are no specific guidelines or indications for imaging
studies in women who have recurrent UTIs.
• Indications for ultrasonography or computed tomography
(CT) include
1. Recurrent noncoital UTIs
2. Persistent haematuria associated with UTIs
3. Acute pyelonephritis
4. Evidence of renal insufficiency.
Neal DE Jr. Complicated urinary tract infections. Urol Clin North Am. 2008;35(1):13–22.

22. POSSIBLE BIOMARKERS
Serum biomarker Urine biomarker
Granulocyte colony-stimulating factor↑ NGF↓
Macrophage colony-stimulating factor↑ NGAL↓
IL5↑ IL8↑
IgG, IgM, and IgA↑
PSA↓
Vitamin D↓

23. SERUM BIOMARKERS
• Serum antibodies were the first possible biomarkers found in
recurrent UTI.
• The levels of serum antibody immunoglobulin (Ig) G, IgM, and
IgA in the study patients were significantly higher than those in
healthy controls.
• Serum hormone granulocyte colony-stimulating factor (CSF) and
interleukin-5 (IL-5) at onset were significantly higher in the mice
with redevelopment of cystitis than those without reinfection .
Hannan TJ, Mysorekar IU, Hung CS, Isaacson-Schmid ML, Hultgren SJ. Early severe inflammatory
responses to uropathogenic E. coli predispose to chronic and recurrent urinary tract infection. PLoS
Pathog. 2010 Aug 12;6(8):e1001042. doi:10.1371/journal.ppat.1001042

24. SERUM BIOMARKERS
• Macrophage CSF was found to be significantly elevated in
patients who subsequently developed recurrent UTI.
• Mean serum levels of Vitamin D among premenopausal
women with recurrent UTI were significantly lower than
those of controls.
• Deficiency of serum Vitamin D also might be a biomarker
for recurrent UTI.
Jhang J-F, Kuo H-C. Recent advances in recurrent urinary tract infection from pathogenesis and
biomarkers to prevention. Tzu-Chi Medical Journal. 2017;29(3):131-137.
doi:10.4103/tcmj.tcmj_53_17.

25. URINARY BIOMARKERS
• Nerve growth factor (NGF) is a small protein
that induces survival and differentiation of
neurons .
• Urinary NGF levels were significantly
increased in women with overactive bladder
and were considered a possible biomarker.
Jhang J-F, Kuo H-C. Recent advances in recurrent urinary tract infection from pathogenesis and
biomarkers to prevention. Tzu-Chi Medical Journal. 2017;29(3):131-137.
doi:10.4103/tcmj.tcmj_53_17.

26. CLINICAL PRESENTATION

27. CLINICAL PRESENTATION
• The most common form recurrent UTI is
recurrent or persistent Asymptomatic
Bacteriuria.
• However, it may also present as Acute
Cystitis or Acute Pyelonephritis after an
untreated primary Asymptomatic
Bacteriuria.

28. ASYMPTOMATIC BACTERIURIA
According to recommendations developed by the IDSA
(Infectious Diseases Society of America), significant
bacteriuria in asymptomatic women is defined as
• Bacterial monoculture in the quantity of ≥
105 colony-forming units (CFU) per ml in two
consecutive mid-stream clean-catch urine specimens
• Or ≥ 102 CFU/ml in urine collected from single
urinary bladder catheterization
• AYMPTOMATIC

29. ASYMPTOMATIC BACTERIURIA:
SIGNIFICANCE
• If asymptomatic bacteriuria is not
treated, approximately 40 percent of
infected women will develop
symptomatic infection.

30. SYMPTOMS OF ACUTE CYSTITIS
• Dysuria
• Frequency
• Urgency
• Suprapubic pain in the absence of systemic illness
• Haematuria
• Lower urinary tract symptoms with pyuria
accompanied by a sterile urine culture may be from
urethritis caused by Chlamydia trachomatis.

31. ACUTE PYELONEPHRITIS
• Abrupt onset with fever, shaking chills
• Aching pain in one or both lumbar regions
• Anorexia
• Nausea, and vomiting
• Tenderness elicited at costovertebral angles

32. MICROORGANISM IN ACUTE
PYELONEPHRITIS
• E coli 70 to 80 %,
• Klebsiella pneumoniae 3 to 5 %
• Enterobacter or Proteus 3 to 5%
• Gram-positive organisms, including
group B Streptococcus and S
aureus10%

33. ACUTE PYELONEPHRITIS: DIAGNOSIS
• The diagnostic gold standard in pyelonephritis
is renal biopsy but this is impractical in clinical
practice.
• A combination of symptoms, full blood count,
inflammatory markers, renal function tests,
blood culture, urine culture and sensitivity
testing are used.

34. ACUTE PYELONEPHRITIS: MEDICAL
COMPLICATIONS
• Endotoxin-induced alveolar injury are
manifest in up to 10 %of women and may
result in frank pulmonary oedema. It may be
severe enough to cause ARDS (Acute
Respiratory Distress Syndrome)
• Endotoxin also causes Haemolysis, also
causes Anaemia 23%.
• Bacteraemia is demonstrated in 15 to 20 %.
• Transient renal dysfunction (2%).

35. MANAGEMENT

36. ASYMPTOMATIC BACTERIURIA:
TREATMENT

37. ACUTE CYSTITIS: MANAGEMENT
• Increasing oral fluid intake
• Nitrofurantoin 100mg BD for 7 days
• Urine alkalinising agents
• Cranberry juice also act as Urine alkaliser and is
used to treat urinary infection and inhibit the
symptoms.

38. ACUTE PYELONEPHRITIS: MANAGEMENT
• Hospitalize patient.
• Obtain urine and blood cultures.
• Evaluate hemogram, serum creatinine, and
electrolytes.
• Monitor vital signs frequently, including urinary
output— consider indwelling catheter.
• Establish urinary output ≥ 50 mL/hr with
intravenous crystalloid solution.

39. ACUTE PYELONEPHRITIS: MANAGEMENT
• Administer intravenous antimicrobial therapy
• Obtain chest radiograph if there is dyspnea or
tachypnea
• Repeat hematology and chemistry studies in 48 hours
• Change to oral antimicrobials when afebrile Discharge
when afebrile 24 hours,
• Consider antimicrobial therapy for 7 to 10 days
• Repeat urine culture 1 to 2 weeks after antimicrobial
therapy completed

40. ACUTE PYELONEPHRITIS: MANAGEMENT
* Nicolle LE, Bradley S, Colgan R, Rice JC, Schaeffer A, Hooton TM, Infectious Diseases Society of
America., American Society of Nephrology. 2005, reaffirmed 2015

41. NEWER ANTIBIOTICS
• Fosfomycin (Monurol) is a new antibiotic that is taken
as a single dose.
• It is a broad-spectrum antibiotic produced by
certain Streptomyces species, and has bactericidal
action
• Administered as a single dose of 3 gram sachet.
• Category B drug.
• Better compliance, Cost Rs 280/sachet

42. WHAT IF ACUTE PYELONEPHRITIS
DOES NOT RESPOND TO TREATMENT?

43. PERSISTENT ACUTE PYELONEPHRITIS
INFECTION
• Generally, intravenous hydration and
antimicrobial therapy are followed by stepwise
defervescence of approximately 1°F per day.
• With persistent spiking fever or lack of clinical
improvement by 48 to 72 hours, Urinary tract
obstruction or another complication, it is
considered to be PERSISTENT INFECTION.*
* Williams Obstetrics, 24th Edition, p.2214 (Chapter 53)

44. CAUSES OF PERSISTENT INFECTION
• Urinary tract obstruction
• Abnormal ureteral or pyelocaliceal
dilatation
• Intrarenal or perinephric abscess
• Nephrolithiasis

45. MANAGEMENT OF PERSISTENT
INFECTION
• USG KUB, or one-shot intravenous pyelogram
or MRI may be used to detect the cause of
persistent infection.
• Obstruction relief is important, and one
method is cystoscopic placement of a double-J
ureteral stent.
• Percutaneous nephrostomy
• Surgical removal of stones.

46. PREVENTION OF
RECURRENCE

47. PREVENTION OF RECURRENCE
• Behavioral modifications and avoidance of risk
factors,
• Nonantimicrobial measures like cranberry juice,
probiotics and hormone replacement in
postmenopausal women.
• Antimicrobial prophylaxis.

48. PROPHYLAXIS WITH CRANBERRY JUICE
• Drinking cranberry juice might be the most well-
known means of prevention of recurrent UTI.
• It has been shown to inhibit the adherence of P-
fimbriated E. coli to urothelium, and could decrease the
virulence in bacterial cystitis.
• Early randomized controlled trials showed that
cranberry juice decreased the number of symptomatic
relapses over a 12-month period in women with
recurrent UTIs. *
* Jepson RG, et al. Cranberries for preventing urinary tract infections. Cochrane
Database Syst Rev. 2008;(1):CD001321.

49. PROPHYLAXIS WITH PROBIOTICS
• Since the urogenital flora of healthy premenopausal women
is dominated by Lactobacilli, it has been suggested that
restoration of the unhealthy urogenital flora from
uropathogens with Lactobacilli may protect against UTI.
• Promising result has been with intravaginal Lactobacillus
crispatus daily for 5 days and then once weekly for 10
weeks.
• No efficacy seen with oral lactobacillus.

50. HORMONE REPLACEMENT PROPHYLAXIS
Oestrogens for preventing recurrent urinary tract
infection in postmenopausal women, Cochrane database
2008 concluded that,
• Intravaginal estrogen therapy in the form vaginal
creams, ring pessary significantly reduces the risk of
recurrent UTI in postmenopausal women.
• Oral estrogen has not effective to prevent recurrence.
• Vaginal irritation is the main adverse effect and might
occur in up to 20% of women.
Oestrogens for preventing recurrent urinary tract infection in postmenopausal women, Cochrane
database 2008

51. IMMUNOACTIVE AGENT PROPHYLAXIS
• One of the possible pathogeneses in recurrent
UTI is adaptive immune response
dysfunction, especially in defects of pathogen
recognition.
• Thus, using a vaccine to strengthen active
acquired immunity against uropathogens
might be a reasonable prevention of UTI
recurrence.

52. IMMUNOACTIVE AGENT PROPHYLAXIS
• Vaginal vaccine significantly reduces the risk of recurrence of
UTI. It significantly increases vaginal and urinary IgG and
IgA .
• A recent meta-analysis published in 2013 enrolled four clinical
trials of an oral vaccine (OM-89), and showed that it
significantly decreased the rate of UTI recurrence.
• European Association of Urology Guidelines 2015,
recommends use of OM-89 for immunoprophylaxis in female
patients with recurrent uncomplicated UTI.
Uehling DT, Hopkins WJ, Elkahwaji JE, Schmidt DM, Leverson GE.Phase 2 clinical trial of a vaginal
mucosal vaccine for urinary tract infections. J Urol 2003;170:867-9.

53. ANTIMICROBIAL PROPHYLAXIS
• It should be used after nonantimicrobial agents
have failed.
• Antimicrobial prophylaxis for preventing UTI
recurrence can be given continuously for long
periods of time (3–6 months), or as a single
postcoital dose.
• A Cochrane review found that postcoital
prophylaxis was just as effective as low-dose
continuous antibiotic prophylaxis in the
prevention of a recurrent UTI .
* Cochrane Database Syst Rev. 2015;

54. ANTIMICROBIAL PROPHYLAXIS
• Continuous prophylaxis for 6 or 12 months
significantly reduced the rate of UTIs during the
prophylaxis period, with no difference between the
two treatment groups after cessation of prophylaxis.
• Postcoital prophylaxis involves taking a dose of
antibiotics within 2 h of intercourse.
• It requires smaller amounts of antibiotics than
continuous prophylaxis and is associated with fewer
side effects .
* Cochrane Database Syst Rev. 2015;

55. ANTIMICROBIAL PROPHYLAXIS
DOSES
Antimicrobial agents Continuous
prophylaxis (daily
dose) (mg)
Postcoital prophylaxis
(one-time dose) (mg)
Cephalexin 125-250 250
Ciprofloxacin 125 125
Nitrofurantoin 50-100 50-100
Trimethoprim/sulfameth
oxazole
40/200 40/200-80/400
Norfloxacin 200 200

56. CONCLUSION
• Recurrent UTI might be one of the most common problems
in urology clinics.
• Treating UTI might not be difficult, but preventing UTI
recurrence sometimes might be very troublesome for both
patients and doctors.
• Recent research has revealed many novel concepts in
recurrent UTI, including the pathogenesis, risk factors,
biomarkers, and prevention.

57. CONCLUSION
• Nowadays, recurrent UTI may be considered a distinct
disease, and patients with recurrent UTI should be
managed aggressively.
• Further basic science studies are needed to elucidate
details in the pathogenesis, and RCTs are also necessary
to clarify the efficacy of the current management.

58. REFERNCES
• Williams Obstetrics, 24th Edition
• Hooton TM. Urinary tract infections and asymptomatic bacteriuria in pregnancy; 2011. UpToDate.com; updated.
• Smaill FM, Vazquez JC. Antibiotics for asymptomatic bacteriuria in pregnancy. Cochrane Database Syst Rev 2015;
:CD000490.
• Greentop Guidelines no 36, 2012, Preventtion of early onset Gropu b Streptococcus infection in neonates.
• Farkash E, Wientraub AY, Sergienko R, et al. Acute antepartum pyelonephritis in pregnancy: a critical analysis of
risk factors and outcomes. Eur J Obstet Gynecol Reprod Biol. 2012;162:24–7.
• 3. Gravett MG, Martin ET, Bernson JD, et al. Serious and life-threatening pregnancy-related infections:
opportunities to reduce the global burden. Plos Med. 2012;9:e1001324.
• Bolton M, Horvath DJ, Li B, et al. Intrauterine growth restriction is a direct consequence of localized maternal
uropathogenic Escherichia coli cystitis. Plos ONE. 2012;7:1–9.
• Jolley JA, Wing DA. Pyelonephritis in pregnancy: an update on treatment options for optimal
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