Research Paper presentation

1. Escherichia coli 83972 Bacteriuria Protects Against Recurrent
Lower Urinary Tract Infections in Patients With Incomplete
Bladder Emptying
Sundén, F., Håkansson, L., Ljunggren, E., & Wullt, B. (2010). Escherichia coli
83972 bacteriuria protects against recurrent lower urinary tract infections
in patients with incomplete bladder emptying.
The Journal of urology, 184(1), 179-185.
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2. Introduction
• Urinary tract infection (UTI), as the name suggests is an infection
affecting the part of urinary tract.
• It is one of the most common infectious diseases in humans, and there
are part of susceptible individuals experiencing recurrent UTI episodes.
• UTIs are mostly caused by E.coli, may be other virulent bacteria or
fungus.
• UTIs are treated by prescribing antibiotics which is significantly
effective, but rapid building up of resistance in gram-negative
uropathogens is a cause of concern. Thus, demanding alternate
therapeutic approach.
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3. • This study, has thrown light on bacterial interference as alternate.
• Bacterial interference is a phenomenon in which bacteria of low virulence
inhibits symptomatic infections (UTI) by competing for nutrients or by
producing toxic metabolites.
• For this study, strains from Asymptomatic bacteriuria (ABU) was used to
prevent the more virulent E. coli strains from causing ascending infection.
• Now, Bacteriuria is presence of bacteria in urine.
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4. • Asymptomatic bacteriuria is the condition in which a patient carries a single
species of bacteria in the concentration more than 105 cfu/ml of urine. But the
patient shows no symptom as the bacteria being avirulent.
• When patient has the symptoms it is know to have caused urinary tract
infection(UTI)
• Study on pediatric population have shown that eradication of ABU increased
the chances of symptomatic UTI.
• Based on this observation a protocol to deliberately establish bacteriuria of the
lower urinary tract was created as an alternative to conventional therapy in
patients with recurrent complicated UTIs.
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5. E.coli 83972
• E.coli 83972 was originally isolated from a girl with long-term ABU,
this strain was used in this study for inoculation.
• It lacks expressed virulence factors as well as a defined O:K:H
serotype.
• Sensitive to all common antibiotics used for UTI
• Carries a small plasmid (1.2 kilobase), enabling identification through
plasmid test.
• Early colonization studies identified incomplete bladder emptying as a
prerequisite for E. coli 83972 establishment.
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6. • This clinical trial investigated if E. coli 83972 bacteriuria protects against
symptomatic infections in patients prone to UTI with incomplete bladder
emptying.
• In phase 1 of the study compared the time to the first UTI in the same
patients with and without E.coli 83972 bacteriuria.
• In phase 2 we compared the number of UTIs in the same patients during
approximately 12 months with and 12 months without E.coli 83972
bacteriuria.
• Patients with incomplete bladder emptying and with recurrent lower UTIs
were invited to participate in the study.
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7. Method Of Study
Table:1 (Criteria for study participation)
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8. Table 2: (Patient characteristics and UTI episodes before study)
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9. PHASE 1
• Phase 1 was a blinded, randomized and placebo controlled crossover study.
• Patients were inoculated with E. coli 83972 or with saline according to the
randomization.
• The outcome measure was the time to the first UTI after establishment of E. coli
83972 compared with the time to the first UTI after placebo or failed E. coli
83972 inoculation.
• Crossover was after the first UTI report or after approximately 12 months if no
UTI was reported.
• Patients who did not establish E. coli 83972 bacteriuria during phase 1 were
excluded from the study .
• Patients who had spent less than approximately 12 months in either of the study
arms during phase 1 were given additional saline or E. coli 83972 inoculations
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10. Figure 1: (Participant’s Flow Chart)
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11.  There were 23 UTI reports from the 20 patients who fulfilled the phase 1
protocol.
 8 patients reporting UTI from both study arms.
 1 only after established E. coli 83972 bacteriuria.
 6 only after saline or failed E. coli 83972 inoculation.
 Median time to UTI was significantly longer after E. coli 83972
establishment compared to after saline or failed E. coli 83972 inoculation
(11.3 vs 5.7 months, sign test p _ 0.0129)
Bacteriuria Delays UTI Recurrence
Result For Phase 1
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12. 12
Figure 2 (Kaplan-Meier estimate of
study phase 1)

13. PHASE 2
• All patients who fulfilled phase 1 proceeded to phase 2, which was
blinded, observational and placebo controlled.
• The outcome measure was the total number of UTIs during an optimal
period of 12 months with E. coli 83972 bacteriuria vs 12 months without
E. coli 83972 bacteriuria.
• A minimum of 3 months in both study arms was required for evaluation in
this phase.
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14. Table 2: (In Phase 2 the number of self reported UTIs)
Result For Phase 2
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15. • Evaluation was performed when the patients had spent 202 months (mean
10.1 per patient) with E. coli 83972 bacteriuria and 168 months (mean 8.4 per
patient) without E. coli 83972 bacteriuria.
• The number of reported UTIs was significantly lower in the same patients
with vs without E. coli 83972 bacteriuria (13 and 35 UTI reports, respectively,
paired t test p _ 0.009, CI 0.31–1.89)
• Bacteriuria Reduces Number of UTI Episodes
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16. Analysis of Symptom-Free Periods and Reported Minor Episodes
• Patient symptom scores in conjunction with the monthly urine sampling
were compared between the study arms.
• The scoring from asymptomatic periods did not differ between patients
with or without established E. coli 83972 bacteriuria.
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17. 17
Figure 3 (Mean monthly scoring from patients with RES and those with SP, with and without Ecoli 83972 bacteriuria)

18. • The frequency of minor symptoms was halved in patients with established
E. coli 83972 bacteriuria compared to those without established E. coli
83972, but this difference was not statistically significant (paired t test p _
0.13)
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20. Discussion
• A total of 20 patients completed the study, and fulfilled the criteria for
evaluation in phases 1 and 2.
• There were no significant side effects reported in patients with established E.
coli 9372 bacteriuria and no febrile UTI episodes reported in either of the
study arms.
• Patients with incomplete bladder emptying and UTI susceptibility were shown
to benefit from the deliberate establishment of bacteriuria with the ABU
isolate E. coli 83972 in this study.
• It has previously been shown that eradication of spontaneously developed
ABU increases the risk of a subsequent symptomatic UTI episode.
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21. • Here this concept is carried further by showing that deliberate bacteriuria
with a model ABU strain can be established, that it carries a protective effect
similar to that of naturally selected strains and that individuals prone to UTI
benefit from this approach.
• This study shows that the E. coli 83972 bacteriuria approach is safe, as
reflected by the absence of serious side effects such as pyelonephritis.
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22. Conclusion
• Patients with dysfunctional voiding and recurrent UTI can benefit from the
protective effect of spontaneous ABU
• But if this does not occur protective ABU may be induced by deliberate
inoculation with E. coli 83972.
• Due to increasing microbial multiresistance driven by the antibiotic use,
alternative therapies including the E. coli 83972 bacteriuria approach might
become more widely used in the future.
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23. Thank You!!
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