Recurrent UTI in females by Prof.Dr. Sherine Ragy Ain Shams University Urology dpt. see: uronotes2012.blogspot.com

1. RECURRENT UTI (RUTI)
IN FEMALES
BY
PROFESSOR DR.
Shereen Ragy

2. Epidemiology of Recurrent UTI in females (1)
 Urinary tract infections (UTIs) are the most common
bacterial infections
 Additionally, UTI is the most common cause of
nosocomial infection.
 Women make up a significant proportion of UTI
sufferers with annual incidence of 12.1%.
 Peak incidence of UTI in women occurs between the
ages of 20 to 24 years.
 20-30% of women who have a UTI will have a
Recurrent UTI.
McLaughlin et al., 2004

3. Epidemiology of Recurrent UTI in females (2)
 Recurrent UTIs result in significant discomfort for
women and have a high impact on ambulatory health
care costs as a result of outpatient visits, diagnostic
tests and prescriptions.
 RUTI is more common in post-menopausal females
due to residual urine after voiding, which is often
associated with bladder or uterine prolapse.
 In addition, the lack of estrogen causes marked
changes in the vaginal microflora, including a loss of
lactobacilli and increased colonization by E. coli .

4. Definition of Recurrent UTI in females
● UTI is diagnosed in women by presence of at least
100,000 colony forming units (cfu)/mL in a pure
culture of voided clean-catch urine.
● Recurrent UTIs are caused by either re-emergence of
bacteria from a site within the urinary tract (bacterial
persistence) or new infections from bacteria outside
the urinary tract (reinfection).
 Recurrent urinary tract infection (RUTI) is defined as
three episodes of culture-confirmed UTI in the last 12
months or two episodes in the last 6 months.
EAU Guidelines 2009

5. Pathogenesis of UTI
 The interaction between bacterial virulence and host
defense factors can ultimately result in UTI.
 More virulent bacteria are necessary to infect healthy hosts
with a normal urinary tract, whereas less virulent bacteria
may easily infect compromised hosts.
 The cause of UTIs in women is usually colonization of the
vagina and then the urethra with bacteria from the
intestinal tract.
Anderson et al., 2003

6. 1- Bacterial Virulence in pathogenesis of UTI
 The initial step in pathogenesis of UTI is bacterial
adherence to the urothelium by pilli.
 Pili are filamentous adhesive organelles produced by
all UPEC (uropathogenic strains of Escherichia coli )
that present significant virulence factors .
 Bacterial colonization follows and causes a host
inflammatory response, which includes neutrophil
influx followed by apoptosis and exfoliation of the
bladder’s epithelial cells in an effort to rid the bladder
of bacteria.
Anderson et al., 2003

7. Bacterial adherence
Adhesins on pili (fimbriae) attach to specific epithelial cell receptors
(Wein et al., 2007)

8. Pathogens cultured in uncomplicated UTI
 Escherichia coli……………………………. 70 – 95%
 Staphylococcus Saprophyticus………. 5 – 20%
(in pre-menopausal women)
 Klebsiella.
 Enterococcus faecalis.
 Proteus Mirabilis.
E.coli

9. 2- Host Risk Factors in pathogenesis of UTI
 Host factors include genetic, anatomic, functional, and
behavioral factors that affect the host’s susceptibility to
uropathogens and its ability to overcome them.
Host Risk Factors in pathogenesis of UTI
Anderson et al., 2003

10. Risk factors of RUTI differ in
pre- and post- menopausal
 In sexually active pre-menopausal risk factors are:
 frequency of sexual intercourse.
 spermicide use.
 age of first UTI (less than 15 years of age indicates a greater
risk of RUTI).
 history of UTI in the mother (due to genetic factors and/or
long-term environmental exposures).
 In post-menopausal risk factors are:
 vesical prolapse.
 incontinence.
 post-voiding residual urine.
Raz et al., 2000

11. Management of recurrent UTI
(Wein et al., 2007)

12. Initial Evaluation of females with RUTIs
 Most women with recurrent UTI’s do not have
anatomic abnormalities and do not need X-rays.
 Assesment should include:
History and physical examination that includes a
pelvic examination.
pelvic ultrasound for retained urine.
Urine culture documenting that UTI is the cause of
symptoms (typically, frequency, dysuria & hematuria).
Howes DS, 2009

13. Specialized Evaluation of females with RUTIs
 Women with RUTI who should undergo further
evaluation include women who also have:
 1) Congenital abnormalities –either a CT scan or
IVP should be done.
 2) Prior pelvic surgery –
 a renal US should be done to check for kidney obstruction
(hydronephrosis) caused by a ureter caught in scarring, a stitch
or clip during prior surgery.
 cystoscopy to check the bladder for stitches which can form a
nidus for stone or infection.
(continued)

14. Specialized Evaluation of females with RUTIs
(continued)
 3) UTI’s with Klebsiella, Pseudomonas or Proteus
bacteria – a KUB is done.
These bacteria have urease splitting enzymes that alkalinize
urine & may cause formation of struvite (infection) stones.
 4) History of kidney stones – check non-contrast CT
for stones, evidence of urinary obstruction.
 5) Pyelonephritis – diagnosed by positive urine
culture, back pain and high fever.
Howes DS, 2009

15. Differential Diagnosis of Recurrent UTI
 Not all women with the symptoms of frequency,
dysuria & hematuria have UTI.
 In the case of Recurrent UTI, especially with
negative culture; a urological and gynaecological
evaluation should be performed in order to exclude a
bladder cancer, obstructive problems, detrusor
failure, vaginal infections, genital infection,
interstitial cystitis or neurological disease.
Howes DS, 2009

16. Complications of Recurrent UTI
 Serious complications of recurrent UTI include the
following:
Acute papillary necrosis with potential ureteric
obstruction.
Overwhelming sepsis syndrome with septic shock
due to loss of vasomotor tone, capillary leak, and
impaired myocardial performance.
Perinephric abscess.
Howes DS, 2009

17. Treatment of recurrent UTI
 Primary treatment for recurrent UTI should be tailored
according to the culture and senstivity results.
 Commonly used antimicrobials that act on gram negative
uropathic organisms include:
 Trimethoprim (TMP) and Co-trimoxazole (TMP-SMX).
 Fluroquinolones (ciprofloxacin, enoxacin, levofloxacin,
lomefloxacin, norfloxacin, ofloxacin).
 Nitrofurantoin.
 Beta-lactams penicillins (amoxycillin, ampicillin-like
compounds, cefadroxil, cefuroxime, cefpodoxime).
● Duration of treatment of 7 to 10 days increases rate of
eradication and minimize resistance to drugs.
EAU Guidelines 2009

18. Doses of recommended drugs for treatment of RUTI
EAU Guidelines 2009

19. Prevention of Recurrent UTI
 Approaches proposed for the prevention of RUTI,
include:
 Non-pharmacological therapies.
 Local Estrogen for post-menopausal females.
 Antimicrobial prophylaxis therapy: given regularly
or postcoital prophylaxis in sexually active women.
 Immunoactive prophylaxis.

20. I- Non-pharmacological prophylactic therapy
 Non-pharmacological therapy for prophylaxis
against recurrent UTI has doubtful role & include:
 Adequate fluid intake.
 Voiding after sexual intercourse.
 Ingestion of cranberry juice.
 Eating yogurt (contain active lactobacillus cultures).
 Vaginal application of lactobacilli.
 Avoiding constipation.
Osset et al., 2001

21. II- Prophylactic antimicrobial therapy
 Women with recurrent UTI’s may be treated with,
Continous prophylactic antimicrobial therapy OR
Post-coital antimicrobial therapy OR
Self-start antimicrobial therapy.

22. A- Continous prophylactic antimicrobial therapy
 One effective approach for the management of
recurrent UTI is the prevention of infection through
the use of long-term, prophylactic antimicrobials
taken on a regular basis at bedtime.
 With respect to antibiotic prophylaxis, it is not
known which antibiotic schedule is best or the
optimal duration of prophylaxis, the incidence of
adverse events, or the recurrence of infections after
stopped prophylaxis or treatment compliance.
Albert et al., 2004

23. EAU Guidelines 2009 on
Antimicrobial prophylaxis of RUTI in females
EAU Guidelines 2009

24. Choice of antibiotic
 Trimethoprim, co-trimoxazole or nitrofurantoin can
still be considered as the standard regimen.
 In cases of ‘breakthrough’ infection due to resistant
pathogens, low doses of fluoroquinolones may also
be used.
 During pregnancy, an oral first-generation
cephalosporin is recommended.

25. B- Post-intercourse antimicrobial therapy
 Post-intercourse therapy: is an alternative
prophylactic approach for women in whom episodes
of infection are associated with sexual intercourse.
 The same antimicrobials can be used in the same
doses as recommended for continuous prophylaxis.
 Self-start therapy: may be suitable for management
in well-informed, young women, in whom the rate of
recurrent episodes is not too common.
 This is, however, strictly speaking, not prophylaxis
but early treatment.
Gupta et al., 2001

26. C- Self-start antimicrobial therapy
 ‘‘Self-start’’ therapy had emerged in an effort to
decrease overall antibiotic usage.
 It relies on the patient to make the clinical diagnosis
of UTI, which is not difficult for these patients.
 It presumes past episodes had been confirmed to be
infections by culture.
 Patients are given a prescription for an appropriate
urinary antibiotic (nitrofurantoins, TMP-SMX or
cephalexin), which they take for 2 or 3 days at the
first symptom of infection.
Wein et al., 2007

27. Efficacy & Side effects of Prophylactic therapy (1)
 Generally, the number of patients with recurrent
UTIs decreased by eightfold after prophylaxis.
 The UTI episodes per patient-year is reduced by 95%
during antimicrobial prophylaxis.
 However, Prophylaxis does not appear to modify the
natural history of a recurrent UTI or exert a long-
term effect on the baseline infection rate.

28. Efficacy & Side effects of Prophylactic therapy (2)
 When prophylactic therapy is discontinued, (even
after extended periods), approximately 60% of
women will become re-infected within 3-4 months.
 Side effects of prophylactic antimicrobials include
vaginal and oral candidiasis and gastrointestinal
symptoms.
Howes DS, 2009

29. Recurrent UTI during pregnancy
 Women with bacteria in the urine during pregnancy
should be placed on low dose prophylactic antibiotics
until delivery (e.g, Keflex or amoxacillin) for
prophylaxis.
 Other options for patients who are allergic to
penicillins include nitrofurantoin or co-trimoxazole.
 Women with bacteria in their urine who do not have
symptoms and who are not pregnant do not need to
be treated with antibiotics.

30. Immuno-active prophylaxis (1)
A- Oral administration (Uro-vaxom)
 Properties
Uro-Vaxom is an extract of Escherichia coli, a germ responsible for the
majority of urinary infections. It stimulates the immune system in order
to increase the body’s natural defences against a wide spectrum of
urinary pathogens. Uro-Vaxom prevents recurrent urinary tract
infections, in particular cystitis.
 Effects
Uro-Vaxom is an immunostimulating agent.
In animals, a protective effect against experimental infections, a
stimulation of macrophages, B-lymphocytes and immunocompetent
cells in the Peyer's patches, as well as an increase in IgA level in
intestinal secretions have been reported.
In humans, Uro-Vaxom stimulates T-lymphocytes, induces production
of endogenous interferon and increases sIgA level in urine.

31. Immuno-active prophylaxis (2)
 Composition
Active principle: 1 capsule contains: 6 mg of lyophilized bacterial lysates
of E. coli.
 Mechanism of action

32. Immuno-active prophylaxis (3)
 Indications
Immunotherapy. Prevention of recurrent lower urinary tract infections.
Comedication in the treatment of acute urinary tract infections.
 Dosage and administration
Preventive treatment and/or consolidation therapy: 1 capsule daily on
an empty stomach, for 3 consecutive months.
Treatment during acute episodes: 1 capsule daily on an empty stomach
as comedication to conventional antimicrobial therapy, until
disappearance of the symptoms but for at least 10 consecutive days.
 Shelf life
Stored in its original package, Uro-Vaxom has a shelf life of 5 years.

33. Immuno-active prophylaxis (4)
 Adverseeffects
The overall incidence of adverse effects in clinical trials lies around 4 %.
Gastrointestinal troubles (diarrhea, nausea, abdominal pain),
dermatologic reactions (pruritus, exanthema), as well as generalized
problems (slight fever) are the most frequent complaints reported.
 Limitations for use
Known hypersensitivity towards the constituents of Uro-Vaxom.
The efficacy and safety of Uro-Vaxom have not been established in
children below 4 years.
Uro-Vaxom is presumed to be safe and unlikely to produce a sedative
effect.

Pregnancy and lactation
Reproduction studies in animals have not demonstrated any risk to the
fetus, but controlled studies in pregnant or breast-feeding women are
not available.

34. Immuno-active prophylaxis (5)
B- Injectable administration
 Immunoactive prophylaxis is also available as
intramuscular and intravaginal immunization with
heat-killed uropathogenic bacteria.
EAU Guidelines 2009

35. Inpatient Care for RUTI
 The necessity for admission is based on host factors,
age, risk of complicated infection, and likelihood of
morbidity with failed outpatient treatment.
I- All patients with complicated UTI including:
 Structural abnormalities (eg, calculi, tract anomalies,
indwelling catheter, obstruction).
 Metabolic disease (eg, diabetes, renal insufficiency)
 Impaired host defenses (eg, HIV, current
chemotherapy, underlying active cancer).
Howes DS, 2009

36. Inpatient Care for RUTI (continued)
II- Some patients with uncomplicated
pyelonephritis also should be admitted:
 Patients unable to maintain adequate oral hydration
or have evidence of vasomotor instability or
unresponding fever despite antipyretic therapy.
 Patients with debilitating pain or dehydration that
cannot be corrected promptly in the outpatient.
 Patients with inadequate home care or resources to
fill prescriptions or comply with the medical
regimen.

37. Take home message
 Recurrent UTIs are a major issue for many women
because they are common, costly, and cause considerable
morbidity.
 Patients with Recurrent UTI should be properly
investigated by lab and radiological techniques to
exclude complicated causes or gynecological problems.
 Prophylactic therapy proved efficacy with decrease rate
of recurrence, minimal side effects and drug resistance
but without alteration of natural history of disease.