Urinary tract infections (UTIs) are among the most common community bacterial infections and remain a leading source of bloodstream infections in adults (1, 2). Community-acquired bacteremia of urinary origin contributes substantially to global morbidity and mortality (3, 4). The presence of bacteremia in UTI generally signals more severe disease and is associated with higher risks of sepsis, septic shock, and intensive care requirements (1). Whether bacteremia independently worsens prognosis in UTIs remains a matter of debate. In generally healthy populations, available data suggest that bacteremia does not meaningfully alter clinical outcomes (5). In contrast, studies in adults with complicated UTIs have yielded inconsistent results: some report higher rates of serious complications among bacteremic cases, whereas others find no significant differences in hard outcomes such as mortality (1, 6). This inconsistency highlights the need to clarify the independent effect of bacteremia on disease severity and prognosis across distinct patient subgroups. Identifying risk factors for bacteremia in community-acquired UTIs (CA-UTIs) is therefore critical for early recognition and targeted management of high-risk patients. Prior work highlights several clinical predictors, particularly markers of systemic inflammation and severity, including high fever (≥ 39°C), hemodynamic instability, and elevated infection biomarkers such as procalcitonin, which have each been associated with bloodstream invasion in UTI (7, 8). Advanced age is a consistently identified risk factor for bacteremia, mainly attributable to the higher burden of comorbidities and the increased frequency of atypical clinical presentations in older adults (9). Additionally, male sex, structural urinary tract abnormalities, and recent exposure to healthcare settings may further increase the risk of developing bacteremia (10). From a microbiological perspective, Escherichia coli, a Gram-negative bacillus within Enterobacterales, remains the predominant etiologic agent in both uncomplicated and bacteremic urinary tract infections (11). In complicated infections, however, the etiologic spectrum broadens, and other Gram-negative bacilli, Gram-positive organisms, and yeasts are also commonly implicated (12). Given the rising antimicrobial resistance among community-acquired uropathogens and our study’s inclusive approach to all urinary tract infection–causing organisms, we aim to comprehensively assess both host and microbiological determinants.

Although UTIs are highly prevalent, detailed data on community-acquired bacteremic UTIs in adults remain limited. The existing literature has primarily focused on specific subpopulations, leaving broader epidemiological and clinical insights incomplete. There is an ongoing need for community-based studies to identify patients at the highest risk for bacteremia and to clarify its impact on key clinical outcomes, including sepsis severity, intensive care unit (ICU) admission, and mortality. To address this knowledge gap, we conducted a comparative analysis of adult patients treated at our institution with community-acquired bacteremic versus non-bacteremic UTIs. Our primary objective was to delineate the clinical and biological determinants of concomitant bacteremia in adults hospitalized with community-acquired urinary tract infection and to quantify its independent association with short-term clinical outcomes. Secondary objectives were to compare the clinical course of bacteremic versus non-bacteremic CA-UTI and to derive a simple bedside risk score based on admission variables to support early risk stratification at presentation.

Our findings may contribute to a better understanding of bacteremic UTIs in community settings and could help with timely recognition of higher-risk patients and the development of targeted management strategies.

In this study, we identified a distinct high-risk phenotype for bacteremic CA-UTI characterized by male sex, specific comorbidities, fulminant symptom onset, and a profound systemic inflammatory response. Although bacteremia was present in one-third of our cohort, consistent with the 24–33% prevalence reported in comparable tertiary care settings (1, 18), our findings provide a more nuanced perspective on the role of age. Unlike population-based surveillance studies that depict a linear correlation between advancing age and bacteremia risk (2, 6), age did not emerge as an independent predictor in our multivariate model. This divergence highlights a critical distinction in hospitalized cohorts: age likely functions as a proxy for accumulated frailty and immune senescence rather than as an independent driver of bloodstream invasion. In our study, the specific nature of the underlying pathology (e.g., diabetes, malignancy) outweighed chronological age, suggesting that biological reserve is a more accurate determinant of invasiveness than demographic age alone.

A key finding of our analysis is that bacteremic patients presented with a significantly shorter duration of symptoms than non-bacteremic cases. Rather than reflecting mild disease, this inverse relationship likely indicates failure of early mucosal containment and a more aggressive host–pathogen interaction. In contrast to the more gradual course of localized cystitis, bacteremic cases appear to follow a more rapidly progressive trajectory, with escalation from lower urinary tract symptoms to high fever and hemodynamic compromise, prompting earlier presentation to the emergency department (1, 24). This pattern is biologically plausible: a blunted or delayed innate immune response at the uroepithelial surface may permit rapid bacterial proliferation and translocation into the bloodstream, particularly in the presence of virulence factors that enhance adhesion, immune evasion, and serum resistance. The association of this phenotype with male sex further supports a mechanistic link. Although females generally have a higher incidence of uncomplicated UTI, males in our cohort demonstrated a substantially higher propensity for bacteremic progression. This is consistent with the concept that urinary tract infections in males are intrinsically complicated due to anatomical factors, including prostatic hypertrophy and urinary retention, which promote bacterial persistence and impair adequate urinary washout (10). Moreover, translational data suggest that males may mount less robust and slower local mucosal immune responses than females, thereby facilitating a quicker hematogenous spread despite shorter symptom duration (10, 25). Taken together, our data suggest that brief symptom duration in the presence of systemic features should be interpreted as a potential marker of a more invasive course rather than as a reassuring feature of mild disease.

Our model confirms that bacteremia risk is driven by the severity of host compromise. The persistence of DM as a robust independent risk factor (aOR 3.43, 95% CI 1.85–6.38) warrants specific attention. This association likely extends beyond simple hyperglycemia; it reflects a complex interplay of diabetic cystopathy (urinary stasis) and distinct immune defects, particularly impaired neutrophil chemotaxis and phagocytosis, which facilitate the breach of the uroepithelial barrier (26, 27). Similarly, the strong association with solid-organ malignancy and recent healthcare exposure points to a “vulnerable host” phenotype. In these patients, the urinary tract frequently serves as a portal of entry for opportunistic pathogens, underscoring the need for heightened vigilance in oncologic patients presenting with even subtle urinary symptoms (28, 29). Notably, the comorbidity profile of our cohort, characterized by diabetes, chronic kidney disease, dementia, and solid-organ malignancy, is highly consistent with that reported in contemporary CA-UTI and bacteremic sepsis cohorts from other tertiary-care hospitals. (30, 31). This heterogeneity supports the external validity of our findings and suggests that, despite the single-center design, our results are likely to be generalizable to similar inpatient populations in settings with a comparable case mix and antimicrobial resistance ecology.

In addition, our study highlights the intersection between antimicrobial resistance and clinical severity. A history of ESBL/CRO colonization or infection within the previous year was a strong predictor of bacteremia (aOR 2.88, 95% CI 1.18–7.03). Notably, the distribution of urinary pathogens and their antimicrobial resistance profiles were broadly comparable between bacteremic and non-bacteremic CA-UTI cases in our cohort. This finding suggests that a history of prior ESBL/CRO infection may represent a broader phenotype encompassing host vulnerability and prior healthcare exposure, rather than merely indicating increased antimicrobial resistance at the index episode. This observation suggests that resistance is not only a therapeutic challenge but may also signal an increased risk of invasive disease. Patients with prior healthcare exposure and resistant colonization are more likely to receive inappropriate initial empirical therapy and may harbor pathogens with enhanced virulence potential (32, 33). The coexistence of delayed effective treatment and host vulnerability may facilitate progression from localized infection to bacteremia. These findings support the incorporation of prior colonization history into risk stratification algorithms at triage. In our cohort, ESBL-producing uropathogens accounted for 16% of isolates, which places our setting within the intermediate range reported for community-acquired UTIs worldwide. Contemporary data indicate that ESBL-producing E. coli in CA-UTIs ranges from approximately 3–48% across regions, with reported rates of 6.3% in uncomplicated and 17.4% in complicated infections in Türkiye (34), 3.3% in community-onset infections and up to 12.1% among nursing-home residents in France (35, 36), and 37.2% in Chinese cohorts (37); in the United States, 36.8% of ESBL-positive E. coli infections now originate in the community, and more than half occur in patients without traditional healthcare-associated risk factors (38). This suggests that our setting does not represent an extreme-resistance hotspot and that the results are likely to apply to populations with similar or moderately lower ESBL burdens, while still aligning with the worldwide trend of increasing ESBL prevalence.

We demonstrate the utility of integrating physiological scores with inflammatory biomarkers for early risk stratification. The strong independent association of qSOFA ≥ 2 with bacteremia suggests that this simple bedside tool effectively captures the threshold of sepsis-defining organ dysfunction (39). In addition, both elevated CRP (> 100 mg/L) and PCT (≥ 0.5 ng/mL) were independently associated with bacteremia, supporting their role as markers of a higher systemic inflammatory and infectious burden. PCT is generally regarded as more specific than CRP for systemic bacterial infections and sepsis, particularly in distinguishing bacterial from viral or non-infectious inflammatory states, and our findings are broadly consistent with this literature (40–43). However, we did not formally compare the discriminatory performance of CRP and PCT, and our data should therefore not be interpreted as demonstrating diagnostic superiority of one biomarker over the other. Clinically, a markedly elevated PCT level in a patient with UTI symptoms may justifiably raise the index of suspicion for bacteremia and prompt closer monitoring and timely escalation of therapy. In contrast, low PCT values could support more conservative antibiotic strategies in carefully selected patients.

The clinical impact of bacteremia in our cohort extended beyond the acute phase, resulting in increased utilization of healthcare resources. Bacteremic patients had an approximately threefold higher rate of ICU admission and a longer length of stay. The higher rate of 7-day clinical failure in this group reflects the difficulty of eradicating invasive infections, particularly when complicated by the resistance patterns discussed above. These findings suggest that the bacteremic subgroup disproportionately drives the economic and operational cost of CA-UTI. Therefore, early identification using the risk factors we identified (male sex, DM, qSOFA, PCT) could facilitate earlier aggressive interventions (e.g., source control, targeted antibiotics), potentially mitigating these downstream costs and improving clinical success rates (19, 44).

From a prognostic perspective, two complementary observations emerged. In the overall CA-UTI cohort, both bacteremia and qSOFA ≥ 2 were independently associated with 30-day mortality, with qSOFA exerting a more substantial relative effect, highlighting the central role of acute organ dysfunction. This pattern is consistent with findings from severe sepsis cohorts, in which short-term survival correlates more closely with the extent of organ failure than with microbiological parameters alone (45–47). In contrast, within the subset of patients with bacteremic CA-UTI, qSOFA ≥ 2 remained the only independent predictor of death. In contrast, age and comorbidity burden did not retain statistical significance in the exploratory multivariable model. Taken together, these data suggest that, while bacteremia identifies a higher-risk group at the time of presentation, the short-term prognosis is primarily determined by the severity of organ dysfunction that has occurred with bacteremia. Clinically, this supports a risk-stratification strategy that considers both bacteremia and qSOFA, but prioritizes early recognition and aggressive management of organ dysfunction in patients with elevated qSOFA scores.

Our study has limitations inherent to its single-center, retrospective design, which precludes causal inference and remains vulnerable to selection bias and residual confounding despite multivariable adjustment. Because we focused on hospitalized adults and excluded mild outpatient CA-UTI, the observed prevalence of bacteremia, sepsis, and short-term adverse outcomes may be higher than in unselected community cohorts. In addition, center-specific antimicrobial resistance ecology and care pathways in Türkiye may limit generalizability to settings with different patient populations, diagnostic practices, and ecological profiles. Although the sample size was adequate for the primary endpoints, the mortality analyses were likely underpowered to detect smaller effect sizes within subgroups, such as the borderline association observed with impaired functional status. Moreover, the overall number of deaths was modest, with 22 events in the full cohort and 11 deaths in the bacteremic subgroup, resulting in a low events-per-variable ratio. This increases the risk of overfitting and may yield potentially unstable adjusted estimates in Tables 4, 5. These findings should therefore be interpreted cautiously as exploratory and hypothesis-generating. Several predictors were operationalized using clinically motivated binary thresholds to facilitate bedside interpretability and risk-score construction. However, dichotomization can reduce statistical power and obscure dose–response or non-linear relationships, and sensitivity analyses using continuous or spline-based specifications were not performed. Finally, the eight-item bacteremia risk score was derived and evaluated within the same cohort without resampling-based internal validation, such as bootstrapping or cross-validation. Consequently, its apparent discrimination may be optimistic, and the reported AUROC should be interpreted as derivation-sample performance that may overestimate true performance in independent populations. Future multicenter studies should externally validate discrimination and calibration, assess clinical utility, and evaluate transportability across diverse healthcare systems and epidemiological contexts.

In conclusion, our data convey three complementary take-home messages. First, chronological age alone is a poor discriminator of risk in hospitalized adults with CA-UTI; instead, specific vulnerability markers—including diabetes, higher comorbidity burden, prior ESBL/CRO colonization or infection, and acute physiological derangement—more accurately define the phenotype prone to bacteremic progression. Second, in the overall cohort, both bacteremia and a qSOFA score of 2 or higher were independently associated with 30-day mortality. Among patients with bacteremic CA-UTI, mortality risk was primarily stratified by the severity of organ dysfunction (qSOFA ≥ 2). Third, we derived a simple additive eight-item risk score based on readily available clinical variables that predicted bacteremia with good internal discrimination (AUROC 0.83 for the whole model and 0.80 for the simplified score); however, this score should be regarded as exploratory and requires external validation in independent cohorts before it can be adopted for routine triage decisions. Taken together, these findings support a pragmatic approach in which clinicians prioritize comorbidity profile, history of resistant colonization, and early markers of organ dysfunction over age alone or blood culture status when triaging and managing adults hospitalized with CA-UTI.