Deliberate Establishment of Asymptomatic Bacteriuria-A Novel Strategy to Prevent Recurrent UTI - PubMed (original) (raw)

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Deliberate Establishment of Asymptomatic Bacteriuria-A Novel Strategy to Prevent Recurrent UTI

Björn Wullt et al. Pathogens. 2016.

Abstract

We have established a novel strategy to reduce the risk for recurrent urinary tract infection (UTI), where rapidly increasing antibiotic resistance poses a major threat. Epidemiologic studies have demonstrated that asymptomatic bacteriuria (ABU) protects the host against symptomatic infections with more virulent strains. To mimic this protective effect, we deliberately establish ABU in UTI-prone patients, who are refractory to conventional therapy. The patients are inoculated with Escherichia coli (E. coli) 83972, now widely used as a prototype ABU strain. Therapeutic efficacy has been demonstrated in a placebo-controlled trial, supporting the feasibility of using E. coli 83972 as a tool to prevent recurrent UTI and, potentially, to outcompete antibiotic-resistant strains from the human urinary tract. In addition, the human inoculation protocol offers unique opportunities to study host-parasite interaction in vivo in the human urinary tract. Here, we review the clinical evidence for protection using this approach as well as some molecular insights into the pathogenesis of UTI that have been gained during these studies.

Keywords: asymptomatic bacteriuria (ABU); therapeutic efficacy; virulence.

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Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1

Figure 1

The human therapeutic inoculation protocol. Antibiotics are administered to sterilize the urine. After an antibiotic-free interval, the patient is catheterized, the bladder is emptied, and 30 mL E. coli 83972 (105 CFU/mL) are injected. If bacteriuria is not established, the procedure may be repeated daily for maximally three days. Published with permission from Cellular Microbiology [35].

Figure 2

Figure 2

Protection by E. coli 83972 bacteriuria compared to the placebo arm of the study. Risk for symptomatic UTI in 20 patients, who were randomized to blinded E. coli 83972 inoculations or placebo. After 12 months of observation, a cross-over was performed. The median time to the first symptomatic UTI was longer in patients with E. coli 83972 bacteriuria (median 11.3 vs. 5.7 months, sign test p = 0.0129). Published with permission from the Journal of Urology [16].

References

    1. Wullt B., Bergsten G., Fischer H., Godaly G., Karpman D., Leijonhufvud I., Lundstedt A.C., Samuelsson P., Samuelsson M., Svensson M.L., et al. The host response to urinary tract infection. Infect. Dis. Clin. North Am. 2003;17:279–301. doi: 10.1016/S0891-5520(03)00028-X. -DOI -PubMed
    1. Kass E.H. Asymptomatic infections of the urinary tract. Trans. Assoc. Am. Physicians. 1956;69:56–64. -PubMed
    1. Lindberg U. Asymptomatic bacteriuria in schoolgirls. V. The clinical course and response to treatment. Acta Paediatr. Scand. 1975;64:718–724. doi: 10.1111/j.1651-2227.1975.tb03910.x. -DOI -PubMed
    1. Stenqvist K., Sandberg T., Lidin-Janson G., Orskov F., Orskov I., Svanborg-Eden C. Virulence factors of Escherichia coli in urinary isolates from pregnant women. J. Infect. Dis. 1987;156:870–877. doi: 10.1093/infdis/156.6.870. -DOI -PubMed
    1. Nordenstam G., Sundh V., Lincoln K., Svanborg A., Eden C.S. Bacteriuria in representative population samples of persons aged 72–79 years. Am. J. Epidemiol. 1989;130:1176–1186. -PubMed

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