Presence of urinary symptoms in bacteremic urinary tract infection: a retrospective cohort study of Escherichia coli bacteremia

Expert consensus and stewardship interventions emphasize treatment of bacteriuria based on urinary symptoms [1‐4]. However, clinicians often diagnose and treat elderly patients for urinary tract infection (UTI) when they have only non-specific symptoms such as delirium based on the belief that elderly patients with UTI may present without localizing symptoms [5‐7]. This raises uncertainty as to what constitutes symptoms of UTI, what is asymptomatic bacteriuria, and whether it warrants treatment. Hereafter, we use the term asymptomatic bacteriuria to signify bacteriuria without any urinary symptoms.

Bacteriuria with bacteremia is a true infection requiring treatment, so it can be used to guide diagnostic criteria for UTI. Diagnostic criteria for UTI should capture all bacteremic UTI (bUTI), because it is associated with a higher mortality rate [8, 9]. Prior studies suggested that elderly patients with bUTI often do not have urinary symptoms [10‐12], which is recognized by Centre of Disease Control as “asymptomatic bacteremic urinary tract infection” [13]. However, prior studies do not provide alternative clinical features to reliably capture bUTI [10‐12].

Approximately 20–30% of patients presenting to emergency department with febrile or complicated UTI or pyelonephritis have bacteremia [14‐16]. Escherichia coli is the most important pathogen for UTI and accounts for over 70% of all cases [17, 18]. In patients admitted to hospital with E coli bacteriuria who had a blood culture done, approximately 15% of patients had E coli bacteremia [19].

In total, 462 patients with E. coli bacteremia and a known infectious source were included in the analysis (Fig. 1). Of the 462 patients, 284 (61.5%) patients had a bUTI and 178 (38.5%) patients had a non-urinary source (Table 1). Baseline characteristics of patients with E coli bacteremia and an unclear source are described in Additional file 1: Table S1.

Urinary frequency had the highest positive likelihood ratio (PLR) of 7.6 (95% CI 3.1–18.7) for ruling in urinary source (Table 2). Other urinary symptoms and signs have PLR ranging from 1.4 to 4.4 and negative likelihood ratio (NLR) ranging from 0.81 to 0.99. On clinical assessment, no urinary symptoms and signs had a NLR of 0.56 (95% CI 0.48–0.66). Negative leukocytes and nitrites on urinalysis had the lowest NLR of 0.18 (95% CI 0.11–0.28) for ruling out a urinary source.

Of the 284 patients with bUTI, 123 (43.3%) had no urinary symptoms (Table 3). Fever and/or urinary symptoms were present in 244 (85.9%) patients with bUTI. In the univariate analysis, potential significant predictors of bUTI without urinary symptoms included age, dementia, benign prostate hypertrophy, prior UTI, nephrolithiasis, delirium, sepsis by qSOFA criteria, and hypotensive shock (Additional file 1: Table S2). In the final multivariable model, significant predictors included only age, delirium and prior UTI (Table 4, Additional file 1: Table S3). With increasing age, the proportion of patients with delirium and bUTI without urinary symptoms also increased (Additional file 1: Table S4).

We used a comparison group of non-urinary source E. coli bacteremia patients. The majority of these patients had intra-abdominal or hepato-biliary infection, similar to prior studies [27, 28]. Patients with a non-urinary source had similar outcomes including mortality compared to patients with urinary source. We believe this is an appropriate comparison group as it simulates a common scenario whereby a patient presents with sepsis or E. coli bacteremia of unknown source, and the clinician must evaluate and determine the source of infection.

Our finding of a significant proportion of bUTI presenting without urinary symptoms in elderly patients is consistent with prior studies on bUTI [11, 12] and non-bacteremic UTI [29]. Although our study found urinary frequency to be useful for ruling in UTI, it demonstrated little diagnostic utility in a systematic review of observational studies [29]. This may be due to the wide variation in the case definition of UTI that includes asymptomatic bacteriuria without true infection. The usefulness of urinalysis in ruling out UTI in our study was similarly found in prior studies with a reported high sensitivity [30] and negative predictive value [31].

There are several reasons why an elderly patient with delirium and a UTI may have no urinary symptoms. Frail adults may have atypical presentation of infections [6, 32]. Even if such patients experience UTI symptoms, they may not be able to describe or demonstrate them due to cognitive dysfunction [6]. While clinical evaluation for typical urinary symptoms and signs were not sensitive to capture all bUTI, sepsis by SIRS criteria came close. The qSOFA components such as altered mental status and tachypnea tend to be non-specific for infection in elderly patients [33, 34]. This may lead to overtreatment and missed diagnosis of delirium causes other than infection [8]. In our study, qSOFA was not sensitive for bUTI, being positive in only 38.7% of all bUTI patients and 46.3% of bUTI patients without urinary symptoms. In contrast, SIRS criteria have been shown previously to be sensitive in identifying bacteremia in all patients [35] including elderly patients in particular [33]. Therefore, physicians may continue to use SIRS criteria for decisions on when to draw blood cultures, especially in elderly patients.

This study has several strengths. It included a large population of 284 bUTI cases compared to prior studies that ranged from 61 to 191 patients [10‐12]. It was conducted across academic and community hospitals, which increases its generalizability. Also, by limiting inclusion to those patients with bacteremia, it allows characterization of UTI without urinary symptoms and largely eliminates the inclusion of asymptomatic bacteriuria without true infection.

Our study has limitations that merit discussion. First, there are the inherent limitations from a retrospective chart review. However, the data collection was rigorous and a second auditor had performed sample data checking to ensure completeness and quality. The clinical assessment of patients for urinary symptoms and signs were not standardized and may vary between clinicians. Almost all patients in our study had sepsis as per SIRS or qSOFA criteria, and had a blood culture drawn at presentation. Therefore, all patients should have undergone a systematic evaluation for possible infectious foci including UTI. As well, the non-standardized approach reflects real world settings. Second, there may be ascertainment bias. The study could only capture patients in whom blood cultures were drawn. Physicians may be more likely to order blood cultures for patients in whom the symptoms are non-specific or the infectious source is uncertain. The study also likely selected sicker patients with higher suspicion for bacteremia. This could lead to overestimation of the diagnostic properties but does not affect our most important findings: that UTI is the most common cause of E. coli bacteremia, and most elderly or delirious patients had bUTI without urinary symptoms. Third, our study captured bUTI by E. coli only, so it would be an extrapolation to all bUTI. Nonetheless, E coli is the most common and important pathogen responsible for approximately 70% of pyelonephritis [17]. Fourth, UTI presentation may be different and unique in patients with spinal cord injury or disease. Unfortunately, our study did not collect information on spinal cord injury or disease. It is likely that many of these patients would have been captured in the variable of chronic indwelling Foley catheter.

These findings offer insight in the clinical presentation of E coli bUTI. Urinary symptoms are useful to diagnose UTI. However, elderly and/or delirious patients may have a bUTI despite having no urinary symptoms or signs elicited on history or exam. For these cases, in addition to symptoms and signs, SIRS criteria and positive urinalysis without any other clear infectious source may be important clues to a bUTI that require antibiotic therapy. Our study should be interpreted with caution and not be extrapolated to E coli bacteriuria without bacteremia. This is outside the scope of our study. Thus, our study does not address which patients are at risk for bUTI. This should be explored in future studies.

Our study adds to the evidence that UTI without urinary symptoms is common and important in elderly and/or delirious patients. We hope that this study can contribute towards a meaningful update of the concept of UTI symptoms. Emphasis on urinary symptoms without consideration of other aspects of the patient’s presentation is potentially harmful and may miss bUTI. A more holistic approach would consider other clinical factors including age, delirium and sepsis by SIRS criteria. This approach may help increase the chance of antibiotics being given to those who truly need it.