Deliberately induced E. coli 83972 bacteriuria protected patients with incomplete bladder emptying who are prone to urinary tract infection from recurrent urinary tract infection as demonstrated by the delay in time to urinary tract infection and the decrease in number of urinary tract infection episodes.

No abstract

Objectives: To study urinary interleukin-6, interleukin-8 and pyuria during episodes of asymptomatic bacteriuria and symptomatic urinary tract infection in the institutionalized elderly, and to investigate the role of interleukin-6 as a biomarker for differential diagnosis. Methods: Levels of interleukin-6, interleukin-8 and pyuria were assessed in 35 older adults with asymptomatic bacteriuria and symptomatic urinary tract infection to define possible diagnostic thresholds. In a two-phase intervention study, the antibiotic treatment for urinary tract infection before and after introduction of urinary interleukin-6 as a biomarker was then assessed. Results: Asymptomatic bacteriuria patients had no or low levels of interleukin-6, and low levels of interleukin-8 and pyuria. Women had lower interleukin-6 and interleukin-8 than men (P = 0.05). Interleukin-6 was the only marker showing significant increases during urinary tract infection episodes in patients with both asymptomatic bacteriuria and urinary tract infection, in pooled (P = 0.042) and in paired intra-individual (P = 0.017) comparisons. In the intervention study lectures, the increased use of urine cultures and the introduction of interleukin-6 as a biomarker reduced antibiotic treatments by 20%. Antibiotic-treated urinary tract infection episodes had increased interleukin-6 as compared with urinary tract infection episodes not treated (P = 0.02), and as compared with asymptomatic bacteriuria patients (P < 0.0001). The sensitivity and specificity of interleukin-6 (cut-off 25 pg/mL) differentiating asymptomatic bacteriuria from urinary tract infection was 57% and 80%, respectively. Conclusions: Urinary interleukin-6 shows promise as a biomarker to detect the transition from asymptomatic bacteriuria to symptomatic urinary tract infection in older adults. Further larger studies with robust methodology are warranted to determine whether development for near to patient testing would be worthwhile.

The severity of urinary tract infection (UTI) reflects the quality and magnitude of the host response. While strong local and systemic innate immune activation occurs in patients with acute pyelonephritis, the response to asymptomatic bacteriuria (ABU) is low. The immune response repertoire in ABU has not been characterized, due to the inherent problem to distinguish bacterial differences from host-determined variation. In this study, we investigated the host response to ABU and genetic variants affecting innate immune signaling and UTI susceptibility. Patients were subjected to therapeutic urinary tract inoculation with E. coli 83972 to ensure that they were exposed to the same E. coli strain. The innate immune response repertoire was characterized in urine samples, collected from each patient before and after inoculation with bacteria or PBS, if during the placebo arm of the study. Long-term E. coli 83972 ABU was established in 23 participants, who were followed for up to twelve months and the innate immune response was quantified in 233 urine samples. Neutrophil numbers increased in all but two patients and in an extended urine cytokine/chemokine analysis (31 proteins), the chemoattractants IL-8 and GRO-α, RANTES, Eotaxin-1 and MCP-1, the T cell chemoattractant and antibacterial peptide IP-10, inflammatory regulators IL-1-α and sIL-1RA and the T lymphocyte/dendritic cell product sIL-2Rα were detected and variably increased, compared to sterile samples. IL-6, which is associated with symptomatic UTI, remained low and numerous specific immune mediators were not detected. The patients were also genotyped for UTI-associated IRF3 and TLR4 promoter polymorphisms. Patients with ABU associated TLR4 polymorphisms had low neutrophil numbers, IL-6, IP-10, MCP-1 and sIL-2Rα concentrations. Patients with the ABU-associated IRF3 genotype had lower neutrophils, IL-6 and MCP-1 responses than the remaining group. The results suggest that the host-specific, low immune response to ABU mainly includes innate immune mediators and that host genetics directly influence the magnitude of this response.

Triggered interleukin-6 correlated to urinary tract infection symptom severity and demonstrated a promising differential diagnostic capacity to discriminate urinary tract infection from asymptomatic bacteriuria. Future studies should explore interleukin-6 as a biomarker of urinary tract infection severity and assess the treatment indication in nonfebrile urinary tract infections.