Recurrent urinary tract infections (UTIs) in children can occur frequently even in those with normal anatomy, with up to 30% experiencing reinfections. The pathogenesis involves either repeated ascending infections or persistent infections, often linked to E. coli strains identical to initial infections, and may be influenced by deficiencies in host defense mechanisms. Factors such as genetic polymorphisms in toll-like receptors and issues with urothelial barriers contribute to recurrent UTIs, highlighting complex interactions between bacterial factors and immune responses.

1. By Kourosh Alizadeh

2. Although most UTIs can be effectively
treated by antibiotics, UTI recurrence is
a common problem and sometimes may
be very troublesome.

3. UTI can recur easily in an
immunocompetent child with
anatomically normal urinary tracts.

4. Recurrent UTI: three febrile UTIs in six
months or four total UTIs in one year.
8 to 30 percent of children with UTI
experience on or more reinfections.
Recurrent episodes of pyelonephritis can
lead to renal scarring.

5. Routine surveillance cultures
should not be performed.
In asymptomatic children after
their first UTI.
Am Ac Peds. March 18, 2014

6. Antimicrobial prophylaxis has been
suggested in children without VUR
who have frequent recurrent UTIs
and it may reduce the
Risk of recurrent UTI.
N Engl J Med.2009;361(18):174

7. There are two possible pathways in the
pathogenesis of recurrent UTI;
Frequent repeat ascending infections
and chronic/persistent infections in the
bladder.

8. Each pathway also might result
from two possible mechanisms;
Bacterial factors and deficiencies in
host defense.

9. Adhesion is particularly important
When infection occurs in an
anatomically normal urinary tract
Am J Kidney Dis.1991;17(1):1.
Curr Opin Urol.2002;12(1):33.
Cell Microbiol. 2002;4(5):257

10. Most recurrent UTIs were caused
by an E. coli strain which was
identical to the primary infecting
strain.
Dan Med Bull. 2011 Apr; 58(4):B4187.
J Clin Microbiol. 2012 Dec; 50(12):4002-7.

11. Patients with frequent recurrent
UTIs might just be infected by a
special strain of E. coli.
J Infect. 2007 Jul; 55(1):8-18.
Virulence. 2011 Nov-Dec; 2(6):528-37.

12. E. coli with DNA papG coding for a
P-fimbriae was significantly
associated with recurrent UTIs.

13. Another possible mechanism for
frequent recurrent UTIs is the survival of
bacteria in the bladder through
progression of intracellular bacterial
communities (IBCs)

14. Early studies showed that E. coli could
replicate intracellularly, form a loose
collection of bacteria, and then escape
into the bladder lumen.
EMBO J. 2000 Jun 15; 19(12):2803-12.
Infect Immun. 2001 Jul; 69(7):4572-9.

15. IBCs in the bladder could form 4–16 h
after bacterial infection, and then
develop a persistent quiescent
intracellular reservoir 2 weeks later.
Proc Natl Acad Sci U S A. 2006 Sep 19; 103(38):14170-5.

16. These IBCs could be quiescent for
extended periods despite
antibacterial therapy, and then re-
emerge to cause recurrent UTI.

17. A recent study revealed that bacteria
in the IBCs, can utilize a galactoside for
metabolism and oxidative stress
resistance.
MBio. 2016;7:e00104–16.

18. Since studies propose that most
recurrent UTIs are caused by E.
coli strains which are identical to the
primary infection, IBCs and a quiescent
intracellular reservoir might play
important roles in the pathogenesis of
recurrent UTIs.

19. It is well known that patients with
immunodeficiency tend to have
frequent, recurrent, and severe
UTIs.
Br J Haematol. 2009;145:709–27

20. However, recurrent UTIs in some
immunocompetent patients might
also be caused by host defense
deficiencies.

21. The innate immune response in the
bladder, such as toll-like receptors (TLRs),
can recognize pathogens and induce a
robust inflammatory immune response.

22. TLRs are essential for the
activation of immune responses
and may be associated with
recurrent UTI.

23. Patients with specific TLR
polymorphisms may have deficiency of
pathogen recognition in the bladder,
which then leads to higher prevalence
of recurrent UTIs.
[PLoS One. 2009;4:e5990].

24. Polymorphism of TLR2 G2258A, is
associated with an increased risk of
bacteriuria. alsoTLR5 C1174T, is
associated with an increased risk of
recurrent UTI.
[PLoS One. 2009;4:e5990].

25. On the contrary, TLR polymorphism
including TLR4 A896G and TLR1
G1805T might have potential roles
in protection from recurrent UTI.
[PLoS One. 2009;4:e5990]

26. The urothelium can secrete pro-
inflammatory cytokines and protective
glycoprotein plaaques such as uroplakin
and Tamm–Horsfall protein (THP) on the
bladder surface as anatomical barriers.
[Nat Rev Immunol. 2015;15:655–63,
Kidney Int. 2009;75:1153–65].

27. The urothelium's antibacterial
adherence mechanism is fundamental
in host defense, and it had been proven
to be less potent in patients with
recurrent UTI.
[J Urol. 1988;140:157–9]

28. Uroplakins are the essential
structural components of the
urothelium and a deficiency
compromises the urothelial
permeability barrier.
[Kidney Int. 2009;75:1153–65]

29. Decreased or entirely absent
uroplakin expression in the
urothelium has been found in
patients with recurrent UTI.
[J Urol. 2011;186:2359–64.]

30. also, animal studies showed that
urinary THP has the potential to
prevent bacteria from interacting or
aggregating in the urothelium.
[Kidney Int. 2004;65:791–7,Am J Physiol
Renal Physiol. 2004;286:F795–802.]