Prospective cohort study of microbial and inflammatory events immediately preceding Escherichia coli recurrent urinary tract infection in women

Abstract

Background: A prospective cohort study was conducted to characterize the temporal sequence of microbial and inflammatory events immediately preceding Escherichia coli recurrent urinary tract infection (rUTI).

Methods: Women with acute cystitis and a history of UTI within the previous year self-collected periurethral and urine samples daily and recorded measurements of urine leukocyte esterase, symptoms, and sexual intercourse daily for 3 months. rUTI strains were characterized by pulsed-field gel electrophoresis and genomic virulence profiling. Urinary cytokine levels were measured.

Results: There were 38 E. coli rUTIs in 29 of 104 women. The prevalence of periurethral rUTI strain carriage increased from 46% to 90% during the 14 days immediately preceding rUTI, with similar increases in same-strain bacteriuria (from 7% to 69%), leukocyte esterase (from 31% to 64%), and symptoms (from 3% to 43%), most notably 2-3 days before rUTI (P<.05 for all comparisons). Intercourse with periurethral carriage of the rUTI strain also increased before rUTI (P=.008). Recurrent UTIs preceded by bacteriuria, pyuria, and symptoms were caused by strains less likely to have P fimbriae than other rUTI strains (P=.002).

Conclusions: Among women with frequent rUTIs, the prevalences of periurethral rUTI strain carriage, bacteriuria, pyuria, and intercourse dramatically increase over the days preceding rUTI. A better understanding of the pathogenesis of rUTI will lead to better prevention strategies.

Figure 1

Point prevalence of the recurrent urinary tract infection (rUTI) strain during the 14 days before Escherichia coli rUTI (n = 38) for any growth in the periurethra (P < .001 for day −14 vs day −1) (A); ≥1 × 10³ colony-forming units (CFUs)/mL in urine (P < .001 for day −14 vs day −1; asterisks denote ≥1 × 10⁵ CFUs/mL) (B); trace levels of urine leukocyte esterase or more (P = .04 for day −14 vs day −1) (C); dysuria, frequency, or urgency (P < .001 for day −14 vs day −1) (D); and the combination of bacteriuria, pyuria, and urinary symptoms (preclinical UTI; P = .004 for day −14 vs day −1) (E). Data are the percentage of women with the indicated characteristic on the days before E. coli rUTI. P values were determined by the McNemar test.

Figure 2

A, Point prevalence of sexual intercourse either with (black) or without (gray) periurethral carriage of the recurrent urinary tract infection (rUTI) strain during the 14 days before Escherichia coli rUTI (P = .008 for intercourse with periurethral carriage for day −14 vs day −1). B, Cumulative prevalence of sexual intercourse either with (black) or without (gray) periurethral carriage of the rUTI strain during the 5 days before E. coli rUTI. Data are the percentage of women with the indicated characteristic on the days before E. coli rUTI. P values were determined by the McNemar test.

Figure 3

Concentrations of interleukin 6 (IL-6) (A) and interleukin 8 (IL-8) (B) in the urine during the 3 days before Escherichia coli recurrent urinary tract infection (rUTI) (n = 18). Individual (white circles) and median (black circles) concentrations are shown. P = .008 and P = .03 for changes in median concentrations from day −3 to the day of rUTI for IL-6 and IL-8, respectively. P values were determined by the sign test.