Blood Neutrophil-to-Lymphocyte Ratio and Urine IL-8 Levels Predict the Type of Bacterial Urinary Tract Infection in Type 2 Diabetes Mellitus Patients

BACKGROUND: Extended-spectrum ß-lactamase (ESBL)-producing Escherichia coli (E. coli) and Klebsiella pneumoniae (K. pneumoniae) are the most common uropathogens causing UTI (urinary tract infection) in type 2 diabetes mellitus (T2DM). Circulatory inflammatory markers such as C-reactive protein (CRP) and neutrophil-to-lymphocyte ratio (NLR) are usually dysregulated during UTI. However, the differential regulation of these inflammatory signatures during E. coli and K. pneumoniae UTI in T2DM has not been determined. METHODS: A case–control study on 466 patients was performed to investigate the inflammatory signatures indicative of ESBL-E. coli and K. pneumoniae UTIs in T2DM. Serum CRP levels and blood NLR for these patients were determined and associated with E. coli and K. pneumoniae ESBL uropathogen using multivariate logistic regression analysis. Urinary interleukin 8 (IL-8) levels were also assessed and associated with these two UTI uropathogens in T2DM. The association of the two ESBL-uropathogens with the survival outcomes of T2DM patients was also analyzed using Cox-proportional hazard model. RESULTS: T2DM patients with ESBL-E. coli UTI had lower serum CRP levels (median, CRP mg/dL 33.7 vs 39.8, respectively; P=0.023) and higher blood NLR (median, NLR 3.2 vs 2.6, respectively; P=0.010) compared to those with K. pneumoniae UTIs (P<0.001). Moreover, in T2DM, the urinary IL-8 levels was higher in ESBL-E. coli compared to those with K. pneumoniae UTIs (P<0.0001). After adjusting for confounders, including age, gender, serum albumin, hemoglobulin, leukocytes, and platelet counts, T2DM patients with blood NLR ≥ 3.5 were at higher risk for ESBL-E. coli UTIs than ESBL-K. pneumoniae UTIs (odds ratio [OR], 3.61, 95% confidence interval, Cl, 1.49–8.73; P=0.004). Moreover, T2DM patients with ESBL-E. coli UTIs had higher all-cause mortality (hazard ratio [HR], 4.09; 95%, 1.14–14.59) than those with K. pneumoniae UTIs. CONCLUSION: Serum CRP levels, blood NLR, and IL-8 urinary levels differentiate ESBL-E. coli from K. pneumoniae UTIs in T2DM.