Similar Neutrophil-Driven Inflammatory and Antibacterial Responses in Elderly Patients with Symptomatic and Asymptomatic Bacteriuria

Abstract

bDifferential diagnosis of asymptomatic bacteriuria (ASB) and urinary tract infection (UTI) is based on the presence of diverse symptoms, including fever (>38.5°C), rigors, malaise, lethargy, flank pain, hematuria, suprapubic discomfort, dysuria, and urgent or frequent urination. There is consensus in the medical community that ASB warrants antibiotic treatment only for patients undergoing urological procedures that lead to mucosal bleeding, catheterized individuals whose ASB persists for more than 48 h after catheter removal, and pregnant women. Pyuria is associated with UTI and implicates host immune responses via release of antibacterial effectors and phagocytosis of pathogens by neutrophils. Such responses are not sufficiently described for ASB. Metaproteomic methods were used here to identify the pathogens and evaluate molecular evidence of distinct immune responses in cases of ASB compared to UTI in elderly patients who were hospitalized upon injury. Neutrophil-driven inflammatory responses to invading bacteria were not discernible in most patients diagnosed with ASB compared to those with UTI. In contrast, proteomic urine analysis for trauma patients with no evidence of bacteriuria, including those who suffered mucosal injuries via urethral catheterization, rarely showed evidence of neutrophil infiltration. The same enzymes contributing to the synthesis of leukotrienes LTB 4 and LTC 4 , mediators of inflammation and pain, were found in the UTI and ASB cohorts. These data support the notion that the pathways mediating inflammation and pain in most elderly patients with ASB are not quantitatively different from those seen in most elderly patients with UTI and warrant larger clinical studies to assess whether a common antibiotic treatment strategy for elderly ASB and UTI patients is justified. U ncomplicated urinary tract infections (UTI) affect the health of approximately 150 million people worldwide and 7 million people in the United States annually; the majority of those affected are women (1). Ascending to the kidneys, UTIs lead to pyelonephritis, which is estimated to have an incidence of 12 cases per 10,000 women in the United States (2). Catheter-associated urinary tract infection (CAUTI), in particular, that seen following long-term catheterization, is characterized by biofilm formation on luminal and external urethral catheter surfaces and frequently causes nosocomial infections. CAUTIs are complicated UTIs because the rate of recurrence is higher and the effectiveness of short-term antibiotic treatment is decreased (3, 4). The incidence of CAUTIs, especially of CAUTIs contracted by elderly patients in long-term care centers and hospitals and by patients with spinal cord injuries and neurogenic bladders (3, 4), is estimated to be 0.9 to 1.5 million cases per year in the United States (1, 3). The infections are deemed potentially preventable complications of hospitalization by the Center of Medicare and Medicaid Services, and the associated costs are no longer reimbursed (3). Escherichia coli causes ...

Microbial metagenome of urinary tract infection

“…Next generation sequencing techniques create the possibility of investigating the microbial metagenome associated with infection and inflammation of the urinary tract. Metaproteomic methods have enabled a deeper characterization of the inflammatory response towards uropathogens in cases of UTI and asymptomatic bacteriuria [5,6]. Several studies have characterized the urinary microbiome by 16S rRNA sequencing to study adults with a cumulative number of 253 subjects investigated across these studies (UTI, n=50; other urinary manifestations, n=154; sexually transmitted diseases, n=20; renal transplant samples, n=60) [4,[7][8][9][10][11][12][13][14][15][16][17][18][19].…”

“…Eukarya. The median (range) number of species identified per individual was 2 (1)(2)(3)(4)(5)(6)(7)(8) Candida species both colonize and cause invasive disease in the urinary tract [24]. The identification of the lipophilic fungi Malassezia is not unexpected as these fungi predominate in most skin sites in healthy adults [25].…”

Diagnosis of urinary tract infection in older persons in the emergency department: To pee or not to pee, that is the question

“…12 ASB is associated with pyuria to no less an extent than in UTI. 16 Table 1 describes the prevalence of ASB in older people.…”

Nutritional Immunity and Antibiotic Drug Treatments Influence Microbial Composition but Fail to Eliminate Urethral Catheter Biofilms in Recurrently Catheterized Patients

“…Pyuria is known to occur in patients with indwelling catheters independent of the symptomology (7). Our recent work revealed neutrophil and complement system activation at similar levels in patients diagnosed with CAASB and CAUTI after catheterization at a single timepoint (28). Here, we publish the first comprehensive analyses of catheter biofilms associated with recurrent catheterization of patients.…”