Introduction: Urinary tract infections are the most common bacterial infections in the older population.

Aim: This study aims to determine the impact of the isolated pathogen from urine culture on the estimated survival time of elderly male patients.

Materials and methods: We conducted a retrospective cross-sectional study to evaluate the male patients with pathogenic growth in their urine culture tests. We included in the study only male patients aged 80 years or over with positive urine culture tests for pathogenic growth. Urine samples were collected from either first clean-catch midstream urine or from the urinary catheters. Bacterial growth of ≥10⁵ colony-forming units/mL (CFU/mL) in the culture was considered significant. For comparison of the survival time, five groups were created according to the pathogens identified in the urine culture.

Results: Between February 2014 and December 2020, there were 1133 patients that met the study criteria. The most common pathogen was Escherichia coli with a rate of 29.5%. The median overall survival time was 4 months. The longest and shortest median overall survival times for the E. coli group and the fungi group were 17.4 months and 0.4 months, respectively (p<0.001). While being in the ICU is the most important risk factor for mortality in this elderly cohort, the statistical analysis showed that being infected with fungi carries a 1.57-fold increased risk of mortality compared with the E. coli infection (p<0.001).

Conclusions: The aging of the population requires evaluation of the diseases that are frequently encountered in advanced age. Our study showed that the causative pathogen of the urinary tract infection might have an impact on overall survival time in the senior population.

elderly, urinary tract infection, urine culture, survival

Urinary tract infection (UTI) is the most common bacterial infection in the elderly population, and E. coli is the most common pathogen in community-dwelling people older than 65 years.^[1] Female sex, sexual activity, family history, impaired urinary flow, immunosuppression, and age are the known risk factors for UTIs.^[2] On the other hand, the incidence of sepsis and mortality increases with age, and the severity of UTI is high in males.^[3–5]

The population is aging, and the related problems are growing. In developed countries, this particular group will have a higher proportion of the population soon. In addition, certain measures will be needed to meet their requirements. Consequently, the United Nations took a decision to take action, and the ten years from 2021 to 2030 were declared the United Nations Decade of Healthy Ageing.^[6] In the aging male, considerable causes of frailty are impaired urine flow and UTIs. Different risk factors such as urinary incontinence, cognitive impairment, chronic catheter, diabetes mellitus, and the prostatic disease can contribute to the development of UTIs in older males due to aging.^[7] Besides the comorbidities, UTIs could be the primary cause of mortality in elderly patients.^[8]

Although there are many reports on urinary tract infections, studies investigating the effect of the causative pathogen on survival in aging men are limited. In this study, we retrospectively reviewed the association between isolated pathogens in urine culture and overall mortality rates in male patients aged ≥80 years.

A retrospective, cross-sectional study was conducted of the urine cultures carried out by our microbiology department between February 2014 and December 2020. The inclusion criteria of the study were male patients at least 80 years old with urine cultures performed at our laboratory who must have pathogenic growth in their culture results. We excluded cases if there was an anaerobic bacterial infection, polymicrobial growth, growth with non-pathogenic microorganisms, or no growth in urine culture. Demographic features of the patients were collected from hospital records.

Urine samples were obtained from either first clean-catch midstream urine using a sterile wide-mouth container or urinary catheters. A standard loopful of each urine sample (10 μL) was dispensed onto a chromogenic medium and incubated at 37°C for 24 hours. Bacterial growth ≥10⁵ CFU/mL was considered significant. A clinical microbiologist evaluated the plates and categorized them according to the Gram stain or as yeast. The bacterial identification and susceptibility tests were performed with the Phoenix automated system (NJ, USA).

We created 5 groups: E. coli, Klebsiella, Enterococcus, fungi, and Others (including Acinetobacter, Citrobacter, Enterobacter, Proteus, Pseudomonas, Serratia, Staphylococcus, and Streptococcus species) in terms of the isolated pathogen from the urine culture. Risk factors such as the presence of a urethral catheter, hospitalization status, admission to the intensive care unit, having 3 or more comorbidities (hypertension, diabetes mellitus, benign prostate hyperplasia, having any cancer, chronic kidney disease, chronic obstructive pulmonary disease, ischemic heart disease, cerebrovascular event, congestive heart disease, atrial fibrillation, Alzheimer disease, Parkinson disease, anemia, dementia, urethral stricture), and the exitus status was also recorded. For calculation of the estimated survival, we accepted the last positive urine culture date as the starting of the follow-up and the last pathogen in the urine culture was the causative pathogen. All patients received an appropriate antibiotic treatment according to the antibiotic susceptibility test.

A total of 1133 men over 80 years old meeting our inclusion criteria were included in the study. The mean age of the patients was 85.8±4.3 years (range, 80–102). The number of pathogens across the groups and the mean age of the patients in terms of the isolated pathogen are presented in Table 1. According to the statistical analysis, there was no difference between groups in terms of age (p=0.10). The most prevalent pathogen was E. coli with a 29.5% rate followed by Enterococcus with a 21% rate.

The institutionalized and ICU patient rate was 40.6% and 18.4%, respectively. E. coli and fungi were the common pathogens in the institutionalized and ICU patients with a rate of 25.3% and 46.9%, respectively (p<0.001). Of the 1133 patients, 26.9% had a urethral catheter. E. coli was the most prevalent microorganism with a rate of 25.2% in catheterized patients (p=0.03). On the other hand, the rate of patients with 3 or more comorbidities was 23.6%, and Enterococcus had the highest rate (28.1%) in this group of patients. The overall mortality rate was 73% and the common pathogens in this group were E. coli, fungi, and Enterococcus with a rate of 24.7%, 23.9%, and 21.4 %, respectively (p<0.001) (Table 2).

The overall median survival time was 4 months in this elderly cohort according to the Kaplan-Meier survival analysis. The highest median survival time was considered in the E. coli group with 17.4 months and the lowest time was in the fungi group with 0.4 months (Table 3). The log rank test showed that the median survival times between groups were statistically significant (p<0.001) (Fig. 1). In univariate Cox regression analysis, the pathogen group, catheterization status, and department of the patient had a statistically significant effect on survival. Therefore, these variables were included in the final multivariate Cox regression analysis. Due to the E. coli group and non-institutionalized patients having the highest median survival time in univariate analysis and lack of control group, we designated the E. coli group and non-institutionalized patients as the reference groups in multivariate analysis. According to the multivariate Cox regression analysis, being in an ICU unit carried the highest risk for mortality (HR:5.3, p<0.001, 95% CI 4.25–6.72). Regarding the urinary pathogen, being infected by fungi had the highest risk for mortality (HR:1.57, p<0.001, 95% CI 1.25–1.97). However, the Klebsiella spp. and Enterococcus spp. groups did not show a statistically significant difference despite the elevated risk for mortality compared with the E. coli group (Table 3).

Figure 1.

The overall survival rate of patients according to the pathogen group.

This study, including a large cohort of male patients aged ≥80 years and over, has shown that isolated pathogens from urine culture have an effect on the overall mortality in this cohort. The common pathogen in the cohort was E. coli; moreover, the overall survival time was better in patients infected with E. coli. On the other hand, the worst-case scenario for these patients was a fungal infection with an almost 1.57-fold increase in overall mortality risk. The median survival time after a fungal infection in male patients aged ≥80 years were calculated at 0.4 months.

The aging population and related issues are growing across the world. As a result, the United Nations (UN) declared the ten years between 2021 and 2030 as the United Nations Decade of Healthy Ageing.^[6] According to a UN report, the number of people aged ≥80 increased almost 3-fold between 1990 and 2019, from 54 million to 143 million, globally. The calculated projections also proved the increase for 2050 that the ≥80-year-old population will rise to 426 million.^[9] One of the key areas for the action indicated by the UN report is to improve evidence of clinical data interested in the elder population.^[10] With the motivation of the United Nations Decade of Healthy Ageing plan, we retrospectively evaluated the urine cultures of male patients ≥80 years old which is a growing problem for urological service providers. Our results highlighted the fact that the different pathogens might affect the overall survival of aging males.

In elderly patients, altered physiology in the urinary tract, immobility, use of urinary catheters, hospitalization, and age-related deficiencies are responsible for urinary bacterial outgrowth and can lead to bacteremia, hospitalization, urosepsis, and even death.^{[7, 11]} It has been shown that the male sex is an independent risk factor associated with mortality in older patients with UTIs.^[12] Also, in men without urinary catheters, the UTI is a rare condition amongst men younger than 60 years. However, the incidence increases considerably in men over 60 years old.^{[13, 14]} According to literature, the incidence of UTI in men younger than 55 years is 0.9 to 2.4 cases per 1000 men, which increases to 7.7 cases per 1000 men when the patient’s age is 85 years or above.^{[15, 16]} In older men, the common cause of bacteremia is UTI; however, it is rarely responsible for the death.^[17] Our initial hypothesis was that the pathogens causing a UTI in male patients aged ≥80 years would affect the survival time of the patients due to frailty. The mean age of our cohort was 85.8 years and there was no statistical difference between groups in terms of age. The commonly isolated pathogen was E. coli as usual. However, the estimated survival was better in the E. coli group with a median of 17.4 months than in the other groups. Our results were unable to suggest a cause-and-effect connection between the variables.

The catheterized patients rate was 26.9% at the time of collecting the urine for a culture test. In the presence of a urinary catheter, despite E. coli being the common pathogen that was isolated, the second common pathogen was fungi, with 24.9% of all catheterized patients. This rate was calculated at 3.7% in community-acquired urinary tract infection patients without catheterization. Also, ICU patients had the highest fungal infection rate. Fungal infections can easily be lethal, especially in older patients. Older patients with a urinary catheter have an increased mortality risk according to Gong et al.^[18] In our cohort, the fungal infection group had the lowest estimated survival time, and had a 1.57-fold increased mortality risk compared to the E. coli infected patients. All other infection groups had worse survival outcomes compared to the E. coli group.

In elderly patients, comorbidities should be considered in the management of infections.^[7] In this study group, 23.6% of the patients had at least 3 or more comorbidities. Interestingly, the Enterococcus group had the highest proportion of pathogens in patients with 3 or more comorbidities. The distribution of the pathogens in different clinical variables is shown in Table 2.

There are several limitations to our study. The retrospective design without a control group is limiting the interpretation of the results. Also, some patients at this age could be transferred to ICU several times during the hospitalization, but we assigned them according to the urine sampling time. The grouping of the pathogens was decided with the frequency of the pathogens with the consideration of microbiology taxonomy. However, our grouping is not a universal system. There could be an interference in the survival time for patients registered in 2020 due to the coronavirus pandemics. Since the follow-up time was accepted as the duration after the last UTI to death or the last registry at our hospital, our results were consistent to offer perspective.

There is limited data in the literature about the aging male population and the effect of UTIs on several outcomes such as cost or survival. In this study, we presented our results about the effect of isolated pathogens from urine culture on survival in a large cohort with a broad timespan. In the face of the fact that society is aging rapidly, further studies are needed to investigate UTIs in the senior population.

Study concept and design: C.B.; data acquisition: C.B., A.T.A., V.S., A.B., and Ç.A.; data analysis: C.B., Ç.A., and A.Ö.; drafting of manuscript: C.B. and E.C.P.; critical revision of the manuscript: Ç.A., E.C.P., and A.Ö.

The authors have no support to report.

The authors have no funding to report.

The authors have declared that no competing interests exist.