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Clinical characteristics and outcomes of community-onset acute pyelonephritis caused by Escherichia coli in elderly patients
European Geriatric Medicine 5 (2014) 78–81
Available online at
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Research paper
Clinical characteristics and outcomes of community-onset acute pyelonephritis caused by Escherichia coli in elderly patients S.-J. Kang a, S.-I. Jung a,*, Y.M. Wi b, M.O. Jang a, H.-C. Jang a, K.-H. Park a, D.R. Chung c, K.R. Peck c, J.-H. Song c a b c
Department of Internal Medicine, Chonnam National University Medical School, Gwangju, South Korea Division of Infectious Diseases, Samsung Changwon Hospital, Sungkyunkwan University School of Medicine, Changwon-si, Gyeongsangnam-do, South Korea Division of Infectious Diseases, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, South Korea
A R T I C L E I N F O
A B S T R A C T
Article history: Received 9 August 2013 Accepted 19 November 2013 Available online 12 December 2013
Purpose: To evaluate clinical characteristics and outcomes of community-onset acute pyelonephritis (APN) caused by Escherichia coli in elderly patients. Patients/methods: Cases of adult patients with community-onset APN caused by E. coli were collected from 10 referral centres in Korea from November 2006 to August 2007. Demographic, clinical and microbiological data were analysed. Results: Diabetes mellitus (38% vs 23%, P = 0.036), chills (83% vs 66%, P = 0.015), gastrointestinal symptoms (55% vs 34%, P = 0.008), altered mental status on admission (21% vs 9%, P = 0.032), acute renal failure (17% vs 3%, P = 0.004) and concomitant bacteraemia (34% vs 17%, P = 0.015) were more frequently observed in patients aged 65 years compared with those aged < 65 years. The overall intergroup mortality rates did not differ. However, diabetes mellitus (OR = 3.54, 95% CI = 1.40–9.00, P = 0.008) and age of 65 years (OR = 2.34, 95% CI = 1.05–5.19, P = 0.037) were significantly related to a longer duration of hospital stay ( 5 days). Conclusion: Elderly patients with APN have a higher frequency of atypical manifestations, such as gastrointestinal symptoms, altered mental status and longer durations of hospital stays. Age was independently associated with longer duration of hospital stays among patients with APN. Careful diagnosis and appropriate treatment are crucial in the management of elderly patients with APN. ß 2013 Elsevier Masson SAS and European Union Geriatric Medicine Society. All rights reserved.
Keywords: Acute pyelonephritis Escherichia coli Elderly Atypical manifestation Outcome
During the latter half of the 20th century, the average life expectancy in developed countries has rapidly increased. In 1900, 5.1% of the Korean population was aged 65 years, and currently 11.4% of the Korean population is aged 65 years, which is estimated to increase to 37.4% by the year 2050 [1]. Providing care for this ageing population presents a major challenge for 21st century medicine. Geriatric infectious diseases, in particular, have become an increasingly important issue. Infectious diseases in the elderly are not only more frequent and severe but also have clinical presentations that are distinct from the younger population [2–4]. In the elderly, urinary tract infection (UTI) is the most common bacterial infection, manifesting as the most common cause of fever in patients hospitalised for acute febrile disease [5] and as the most frequent source of bacteraemia [6]. Although most UTIs are mild and managed in outpatient departments, upper UTIs, such as acute pyelonephritis (APN), can be devastating, resulting in sepsis and
* Corresponding author. Department of Infectious Disease, Chonnam National University Medical school, 671, Jebong Ro, Donggu, Gwangju 501-757, Korea. Tel.: +82 62 220 6296; fax: +82 62 225 8578. E-mail addresses: [email protected], [email protected] (S.-I. Jung).
death (1%–5%) [7–9]. UTIs in elderly patients frequently present with atypical manifestations, such as gastrointestinal symptoms or respiratory symptoms, which tend to direct the clinician’s attention away from considering UTI as the source of infection, and often lead to a delay in the diagnosis of UTIs [10]. Moreover, among patients with bacteraemia, the adverse impact of inappropriate empirical antibiotic therapy on patient outcome is greater in the elderly than in younger patients [11]. Therefore, early and prompt diagnosis of UTIs and appropriate treatment are critical in improving the outcomes of UTIs in elderly patients. Several previous studies have dealt with the clinical manifestations, outcomes and etiologic organisms of UTIs in elderly patients [2–4,12]. However, most studies have focused on the elderly group and have compared the results with historical control groups. Few studies have directly compared UTIs in the elderly with those in younger patients. Furthermore, it is difficult to assess whether the differences in clinical manifestations and outcomes were due to different clinical settings or etiologic organisms. In this study, we analysed the clinical characteristics and outcomes of communityonset APN caused by E. coli in patients aged 65 and compared the results with those in younger patients.
1878-7649/$ – see front matter ß 2013 Elsevier Masson SAS and European Union Geriatric Medicine Society. All rights reserved. http://dx.doi.org/10.1016/j.eurger.2013.11.006
S.-J. Kang et al. / European Geriatric Medicine 5 (2014) 78–81
1. Methods
79
to treatment, with no relapse within 14 days of completing antimicrobial therapy.
1.1. Study design and patient selection 1.3. Statistical analysis We performed a multicentre surveillance study for UTI from November 2006 to August 2007 at 10 tertiary hospitals in South Korea [13]. From this registry’s database, a post-hoc analysis was conducted on all consecutive cases of microbiologically documented community-onset APN caused by E. coli in adult patients (age, 18 years). We compared data from patients with community-onset E. coli APN that were aged 65 years with those aged < 65 years to determine the impact of ageing on clinical manifestations, outcomes and antibiotic resistance. This study was approved by the Institutional Review Boards of all the 10 participating hospitals. Demographic, clinical and microbiological data were analysed. Data collected included age, sex, underlying disease, clinical manifestations and outcomes. The presence of the following comorbid conditions was also documented: neutropenia, renal transplantation, history of urinary calculi, recurrent UTIs, intermittent urinary catheterisations and indwelling urinary catheters. Because this study was observational, patient management and antimicrobial treatment regimens were chosen by the patients’ physicians without any guidelines or intervention from the study protocol or study investigators. Species identification was performed using a standard identification card, and antimicrobial susceptibility testing was performed at each hospital that participated in the study using the automated system by the modified broth microdilution or disk diffusion method, following the recommendations from the Clinical and Laboratory Standards Institute [14]. 1.2. Definitions APN caused by E. coli was defined by the presence of E. coli [ 105 colony forming units (CFU)/mL in voided urine, 103 CFU/ mL in nonvoided urine] in the urine and/or blood culture with simultaneous presence of pyelonephritis-related symptoms/ signs, such as fever, nausea, vomiting, costovertebral angle (CVA) tenderness or flank pain and pyuria ( 10 leukocyte per high-power field in the centrifuged specimen) [15]. Communityonset APN was defined on the basis of its diagnosis within the first 48 h of hospitalisation. Neutropenia was defined as an absolute neutrophil count of < 500 cells/mm3. Recurrent UTI was defined as 2 infections in six months or 3 infections in one year. A catheter that was maintained for > 7 days prior to the onset of APN was defined as a chronic indwelling urinary catheter, and that inserted for < 7 days before APN onset was defined as a short-term indwelling urinary catheter. Acute renal failure was defined as: absolute increase in serum creatinine concentration by 0.3 mg/ dL from baseline; percentage increase in serum creatinine concentration of 50% within 48 h; presence of oliguria, with a urine output of < 0.5 mL/kg/h for >6 h.
Septic shock was defined as sepsis with one or more signs of organ dysfunction with a systemic mean blood pressure of < 60 mm Hg despite adequate fluid resuscitation. Microbiologic eradication was defined as the elimination of E. coli in the urine culture with no relapse in bacteriuria within 14 days following the completion of antimicrobial therapy. Successful treatment was defined as the resolution of clinical symptoms/signs present prior
Student’s t-test was used to compare continuous variables. Chi2 or Fisher exact test was used to compare categorical variables. To identify factors associated with longer duration of hospital stays, a logistic regression model was used. Variables with P < 0.10 in the univariate analysis were candidates for multivariate analysis. The odds ratio (OR) and 95% confidential intervals (CIs) were calculated. All P-values were two-tailed, and the value of P < 0.5 was considered statistically significant. Data analysis was performed using PASW Statistics 17.0 (IBM SPSS, Chicago, IL, USA).
2. Results Among the 510 adult patients with a urinary tract infection, 289 patients were diagnosed with APN and 179 of these were caused by E. coli. Of the 179 patients, 20 were excluded from the analysis because their APN was considered as a nosocomial infection. Finally, a total of 159 patients [median age, 58 years (range: 18– 88 years); 92.5% were female; age 65 years, 71 patients (44.7%); age < 65 years, 88 patients (55.3%)] with community-onset APN caused by E. coli were analysed. Baseline characteristics of patients with community-onset APN due to E. coli are listed in Table 1. Diabetes mellitus was more common in patients aged 65 years than in those aged < 65 years (38.0% vs 22.7%, P = 0.036). Although no statistical significance was observed between the two groups, patients aged 65 years had a trend towards a more frequent history of hospital admission in the previous 6 months (21.1% vs 10.2%, P = 0.056). The frequencies of neurogenic bladders and the use of urinary catheters did not differ between the two groups. Clinical features and outcomes are presented in Table 2. The most common symptom was fever (90.6%), followed by chills (73.6%), CVA tenderness (53.5%), gastrointestinal symptoms Table 1 Baseline characteristics of patients with community-onset acute pyelonephritis due to Escherichia colia.
Median age (range), years Female Underlying disease Diabetes mellitus Congestive heart failure Ischemic heart disease Chronic lung disease Liver cirrhosis Solid cancer Neutropenia Cerebrovascular disease Other neurologic diseases Chronic kidney disease Renal transplant recipient Neurogenic bladder Urinary calculi Recurrent UTI History of admission within 6 months Prior antibiotics Urinary catheterization Clean intermittent Short-term indwelling Chronic indwelling
Age < 65 years n = 88
Age 65 years n = 71
47 (18–64) 81 (92.0)
72 (65–88) 66 (93.0)
0.829
20 2 0 2 2 6 0 1 1 7 6 2 5 7 9
27 4 5 4 0 5 1 5 6 4 1 3 7 3 15
(38.0) (5.6) (7.0) (5.6) (0.0) (7.0) (1.4) (7.0) (8.5) (5.6) (1.4) (4.2) (9.9) (4.2) (21.1)
0.036 0.408 0.016 0.408 0.503 1.000 0.447 0.090 0.045 0.756 0.132 0.657 0.322 0.514 0.056
31 (35.2)
26 (36.6)
0.856
0 (0.0) 4 (4.5) 2 (2.3)
3 (4.2) 5 (7.0) 0 (0.0)
0.087 0.514 0.503
(22.7) (2.3) (0.0) (2.3) (2.3) (6.8) (0.0) (1.1) (1.1) (8.0) (6.8) (2.3) (5.7) (8.0) (10.2)
UTI: urinary tract infection. a Data are the number (%) of patients, unless otherwise indicated.
P-value
S.-J. Kang et al. / European Geriatric Medicine 5 (2014) 78–81
80
Table 2 Clinical features and outcome of community-onset acute pyelonephritis due to Escherichia coli in patients aged < 65 years versus 65 yearsa.
Symptoms and signs Fever Chill Urgency Frequency Voiding difficulty Dysuria Suprapubic tenderness Gastrointestinal symptom Flank pain Abdominal pain Pleuritic chest pain CVA tenderness Altered mentality Concomitant bacteremia Acute renal failure Septic shock Appropriate empirical antibiotics Appropriate definitive antibiotics Clinical outcome Median length of hospital stay, days (Interquartile range) Microbiologic eradication Successful treatment 14-day mortality
Age < 65 years n = 88
Age 65 years n = 71
P-value
78 58 23 33 28 35 4 30 33 12 2 45 8 15 3 3 70/83
66 59 13 34 23 26 4 39 24 6 1 40 15 24 12 7 53/66
(93.0) (83.1) (18.3) (47.9) (32.4) (36.6) (5.6) (54.9) (33.8) (8.5) (1.4) (56.3) (21.1) (33.8) (16.9) (9.9) (80.3)
0.354 0.015 0.241 0.187 0.938 0.684 1.000 0.008 0.629 0.305 1.000 0.513 0.032 0.015 0.004 0.112 0.519
60/64 (93.8)
0.700
7 (4-11)
0.009
30 (42.3) 55 (77.5) 3 (4.2)
0.068 0.385 0.657
(88.6) (65.9) (26.1) (37.5) (31.8) (39.8) (4.5) (34.1) (37.5) (13.6) (2.3) (51.1) (9.1) (17.0) (3.4) (3.4) (84.3)
78/81 (96.3)
5 (1-8)
50 (56.8) 73 (83.0) 2 (2.3)
CVA: costovertebral angle. a Data are the number (%) of patients, unless otherwise indicated.
(43.4%) and urinary frequency (42.1%). Concomitant bacteraemia and acute renal failure were present in 39 (24.5%) and 15 (9.4%) patients, respectively. Compared with patients aged < 65 years, chills (83.1% vs 65.9%, P = 0.015), gastrointestinal symptoms (54.9% vs 34.1%, P = 0.008) and altered mental status on admission (21.1% vs 9.1%, P = 0.032) were more frequently observed in patients aged 65 years. Acute renal failure (16.9% vs 3.4%, P = 0.004) and concomitant bacteraemia (33.8% vs 17.0%, P = 0.015) were more common in patients aged 65 years. Overall, the mortality rate was not significantly different between patients aged 65 years and those aged < 65 years (4.2% vs 2.3%, P = 0.657). There was a trend towards a decrease in successful treatment and microbiologic eradication in patients aged 65 years, but there was no statistical significance (77.5% vs 83.0%, P = 0.385; 42.3% vs 56.8%, P = 0.068). Inappropriate empirical or definitive antibiotic treatments were not related to the length of hospital stay. However, patients aged 65 years had longer duration of hospital stays than those aged < 65 years (median, 7.0 days; interquartile range (IQR), 4–11 days vs median 5 days; IQR of 1–8 days; P = 0.009). In the multivariate analysis, diabetes mellitus (OR = 5.34, 95% CI = 1.76–16.2, P = 0.003) and an age of 65 years (OR = 3.640, 95% CI = 1.43–9.27, P = 0.007) were significantly related to longer duration of hospital stays ( 5 days). The proportions of isolates with antimicrobial-resistant E. coli are summarised in Table 3. The overall resistance rates were 7.9% (11/139) for cefotaxime, 2.9% (4/139) for ceftazidime, 27.3% (38/ 139) for ciprofloxacin, 23.7% (33/139) for gentamicin, 8.7% (12/ 138) for piperacillin/tazobactam and 33.1% (46/139) for trimethoprime/sulfamethoxazole. Fourteen isolates, including six isolates from patients aged 65 years, were extended spectrum beta lactamase (ESBL) producing isolates. All isolates were susceptible to imipenem. The resistance rates to ciprofloxacin among E. coli isolated from patients aged 65 years had a trend towards higher resistance than those isolated from patients aged < 65 years, but
Table 3 Antibiotic resistance of Escherichia coli isolates causing community-onset acute pyelonephritis in patients aged < 65 years versus 65 yearsa.
Ampicillin Gentamicin Ceftazidime Cefotaxime Aztreonam Ciprofloxacin Piperacillin/tazobactam Trimethoprime/ sulfamethoxazole Imipenem
Age < 65 years n = 80
Age 65 years n = 59
P-value
57 17 3 6 3 19 8 24
41 16 1 5 5 19 4 22
0.822 0.422 0.637 1.000 0.284 0.269 0.558 0.367
(71.3) (21.3) (3.8) (7.5) (3.8) (23.8) (10.0) (30.0)
0 (0.0)
(69.5) (27.1) (1.7) (8.5) (8.5) (32.2) (6.8) (37.3)
0 (0.0)
–
Intermediate resistance was also considered as resistance. Minimal inhibitory concentration (MIC, ug/mL) interpretative standards were followed the performance standards for antimicrobial susceptibility testing: seventeenth information supplement M100-S16. For each antibiotics, the criteria for susceptible, intermediates, resistance were ampicillin 8, 16, 32, gentamicin 4, 8, 16, ceftazidime 8, 16, 32, cefotaxime 8, 16–32, 64, aztreonam 8, 16, 32, ciprofloxacin 1, 2, 4, piperacillin-tazobactam 16/4, 32/4–64/4, 128/4, trimethoprime/sulfamethoxazole 2/38, –, 4/76, imipenem 4, 8, 16. a Data are the number (%) of patients, unless otherwise indicated.
this difference was not statistically significant (32.2% vs 23.8%, P = 0.269). The antibiotic resistance rate to other kinds of antibiotics did not significantly differ between the two groups.
3. Discussion In the present study, the clinical presentation of APN in elderly patients was observed to markedly differ from that of younger patients. Atypical presentations, such as altered mental status and gastrointestinal symptoms, were more common in the elderly patients than in younger patients, which is consistent with other infectious diseases in the elderly [2–4,12]. Furthermore, at the time of admission, the severity of the disease, which is reflected by concomitant bacteraemia and acute kidney injury, was higher among elderly patients than among younger patients. Gleckman et al. [16] suggested that APN in the elderly leads to a higher incidence of bacteraemia than that in younger patients. However, only elderly patients with APN were assessed in this study, and the results were compared to those in younger patients from a separate previous report [17]. The study’s findings indicated that elderly patients required longer duration of hospital stays compared with younger patients, although the mortality rate did not differ between the two groups. Differences relating to age groups in UTIs have been previously described, but these findings may be exaggerated, for instance, in the context of clinical manifestations and outcomes in the elderly [18]. The present study was confined to patients with community-onset APN caused by E. coli to investigate the impact of ageing on infection by reducing confounding factors, such as co-morbidities and etiologic agents. The mortality rate from APN in elderly patients was similar to that found in younger patients. In this study, the overall mortality rate for APN was 3.1%, which corresponds to the results found in previous studies [15,19]. It was difficult to demonstrate any differences in the mortality rate between elderly and younger patients because of the low mortality rate associated with APN. These findings are consistent with those of previous studies, which showed the elderly are not associated with higher mortality rates for UTI compared to the younger patients, while most other common infections are associated with at least a two-fold or higher death rate in the elderly population [5,20]. However, APN in elderly patients is related to poorer outcomes compared to that in younger individuals. In this study, elderly patients had longer duration of
S.-J. Kang et al. / European Geriatric Medicine 5 (2014) 78–81
hospital stays than younger patients. In addition, diabetes mellitus and age of 65 years were independent risk factors for prolonged hospitalisation ( 5 days). There was a tendency for fever to persist longer in elderly patients, even though no statistical significance was observed. Furthermore, the proportion of clinically successful treatments and microbiologic eradication had a tendency to decrease in those aged 65 years. These results are consistent with previous studies showing that most infectious diseases in the elderly have poorer outcomes than those in younger patients [4,21]. Several factors most likely contribute to poor outcomes in the elderly. One of the most important factors is that the number of co-morbidities increases according to age [21]. In this study, for patients aged 65 years, diabetes mellitus and a history of admission within the previous 6 months were more common than in those aged < 65 years. Further study on the contributing factors related to poor outcomes should be undertaken. Antibiotic susceptibility did not differ across the different age groups of patients with APN. In a previous study, quinolone resistance and ESBL production were 26.7% and 8.9%, respectively, among E. coli isolates from patients with community-onset APN at a referral centre in Korea. The levels detected in our study are consistent with these findings [15]. We hypothesised that antibiotic susceptibility of E. coli in elderly patients may be different from that in younger patients. Although patients aged 65 years had a trend towards higher resistance to ciprofloxacin, there was no statistical difference in E. coli isolate antibiotic resistance in terms of the patients’ age. These findings suggest that antibiotic resistance is affected more by the underlying conditions, such as risk factors for health care-associated infection, than by aging itself [15]. Our study has some limitations. First, we conducted this study primarily in large referral centres. Thus, many of our patients had serious underlying illnesses and severe clinical manifestations. Our findings may not be representative of other general elderly populations, particularly those in community hospitals. Second, this observational study was performed from August 2006 to September 2007 and the results may therefore no longer reflect the current status. Changing trends in both medical practice and antimicrobial resistance of uropathogens emphasise the need to update studies on ageing populations. Third, because of the observational nature of this study, some variables were not accurately collected. In some patients, data on previous UTIs episodes or previous antibiotic use were unavailable, which may have influenced the results of this study. Despite these limitations, we believe that the findings of this investigation provide distinct clinical characteristics and outcomes of community-onset APN in elderly patients that will allow appropriate treatment of these populations. In conclusion, elderly patients with community-onset APN caused by E. coli have a higher frequency of atypical manifestations, such as gastrointestinal symptoms, altered mental status and poorer outcomes, including longer duration of hospital stays. Ageing directly affects atypical clinical manifestations and poor outcomes caused by infectious diseases. Careful diagnosis and prompt appropriate treatment are crucial in managing elderly patients with APN. Disclosure of interest The authors declare that they have no conflicts of interest concerning this article. Acknowledgements This study was supported in part by grants from the Chonnam National University Hospital Research Institute of Clinical Med-
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icine (CRI08062-1) and the Korea Centers for Disease Control and Prevention (2007-E00037-00). The funder had no role in the study design, data collection and analysis, decision to publish, or preparation of the manuscript. The authors would like to thank all participating investigators including Jae-Hoon Song, Kyong Ran Peck, and Doo Ryeon Chung (Samsung Medical Center, Sungkyunkwan University School of Medicine, Suwon, South Korea); Joon-Sup Yeom (Kangbuk Samsung Hospital, Sungkyunkwan University School of Medicine, Seoul, South Korea); Yu Mi Wi (Samsung Changwon Hospital, Sungkyunkwan University School of Medicine, Changwon, South Korea); Hyun Kyun Ki and Hae Suk Cheong (Konkuk University Hospital, Seoul, South Korea); Jun Seong Son (Kyunghee University Hospital at Gangdong, Seoul, South Korea); Yeon-Sook Kim (Chungnam National University Hospital, Daejeon, South Korea); Sook-In Jung, Seung-ji Kang, and Kyung Hwa Park (Chonnam National University Hospital, Gwangju, South Korea); Shin-Woo Kim and Hyun-Ha Chang (Kyungpook National University Hospital, Daegu, South Korea); Ki Tae Kwon (Daegu Fatima Hospital, Daegu, South Korea); and Sang Taek Heo (Jeju National University Hospital, Jeju, South Korea). References [1] Korean Statistical Information Service Online (KOSIS): http://kosis.kr/statisticsList/statisticsList_01List.jsp?vwcd=MT_ZTITLE&parentId=A.[Accessed June 3, 2013]. [2] Norman DC, Toledo SD. Infections in elderly persons. An altered clinical presentation. Clin Geriatr Med 1992;8:713–9. [3] Chassagne P, Peridol MB, Doucet J, Trivalle C, Me´nard JF, Manchon ND, et al. Is presentation of bacteremia in the elderly the same as in younger patients? Am J Med 1996;100:65–70. [4] Cooper GS, Shlaes DM, Salata RA. Intraabdominal infection: differences in presentation and outcome between younger patients and the elderly. Clin Infect Dis 1994;19:146–8. [5] Tal S, Guller V, Levi S, Bardenstein R, Berger D, Gurevich I, et al. Profile and prognosis of febrile elderly patients with bacteremic urinary tract infection. J Infect 2005;50:296–305. [6] Lark RL, Saint S, Chenoweth C, Zemencuk JK, Lipsky BA, Plorde JJ. Four-year prospective evaluation of community-acquired bacteremia: epidemiology, microbiology, and patient outcome. Diagn Microbiol Infect Dis 2001;41:15–22. [7] Al-Hasan MN, Eckel-Passow JE, Baddour LM. Bacteremia complicating Gramnegative urinary tract infections: a population-based study. J Infect 2010;60:278–85. [8] Jerkeman M, Braconier JH. Bacteremic and non-bacteremic febrile urinary tract infection – review of 168 hospital-treated patients. Infection 1992;20:143–5. [9] Lee SS, Kim Y, Chung DR. Impact of discordant empirical therapy on outcome of community-acquired bacteremic acute pyelonephritis. J Infect 2011;62:159–64. [10] Barkham TM, Martin FC, Eykyn SJ. Delay in the diagnosis of bacteraemic urinary tract infection in elderly patients. Age Ageing 1996;25:130–2. [11] Lee CC, Chang CM, Hong MY, Hsu HC, Ko WC. Different impact of the appropriateness of empirical antibiotics for bacteremia among younger adults and the elderly in the ED. Am J Emerg Med 2013;31:282–90. [12] Jarrett PG, Rockwood K, Carver D, Stolee P, Cosway S. Illness presentation in elderly patients. Arch Intern Med 1995;155:1060–4. [13] Korea Centers for Disease Control Prevention. Result report on KCDC research – antimicrobial resistance and molecular epidemiology of clinical isolates from patients with urinary tract infection or bacteremia in Korea; 2007;e00027. [14] Performance standards for antimicrobial susceptibility testing. Sixteenth Informational Supplement. Clin. Lab. Stand. Insitutue; 2006, M100-S16. [15] Ha YE, Kang CI, Joo EJ, Park SY, Kang SJ, Wi YM, et al. Clinical implications of healthcare-associated infection in patients with community-onset acute pyelonephritis. Scand J Infect Dis 2011;43:587–95. [16] Gleckman R, Blagg N, Hibert D, Hall A, Crowley M, Pritchard A, et al. Acute pyelonephritis in the elderly. South Med J 1982;75:551–4. [17] McMurdock J, Speirs CF, Geddes AM, et al. Treatment of recurrent urinary tract infection. In: O’Grady FO, Brumfitt W, editors. Urinary Tract Infection. London: Oxford Press; 1968. p. 227–34. [18] Kang SC, Tsao HM, Liu CT, Perng CL, Hwang SJ. The characteristics of acute pyelonephritis in geriatric patients: experiences in rural northeastern Taiwan. Tohoku J Exp Med 2008;214:61–7. [19] Aguilar-Duran S, Horcajada JP, Sorlı´ L, Montero M, Salvado´ M, Grau S, et al. Community-onset healthcare-related urinary tract infections: comparison with community and hospital-acquired urinary tract infections. J Infect 2012;64:478–83. [20] Ackermann RJ, Monroe PW. Bacteremic urinary tract infection in older people. J Am Geriatr Soc 1996;44:927–33. [21] Gavazzi G, Krause KH. Ageing and infection. Lancet Infect Dis 2002;2:659–66.
Available online at
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Research paper
Clinical characteristics and outcomes of community-onset acute pyelonephritis caused by Escherichia coli in elderly patients S.-J. Kang a, S.-I. Jung a,*, Y.M. Wi b, M.O. Jang a, H.-C. Jang a, K.-H. Park a, D.R. Chung c, K.R. Peck c, J.-H. Song c a b c
Department of Internal Medicine, Chonnam National University Medical School, Gwangju, South Korea Division of Infectious Diseases, Samsung Changwon Hospital, Sungkyunkwan University School of Medicine, Changwon-si, Gyeongsangnam-do, South Korea Division of Infectious Diseases, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, South Korea
A R T I C L E I N F O
A B S T R A C T
Article history: Received 9 August 2013 Accepted 19 November 2013 Available online 12 December 2013
Purpose: To evaluate clinical characteristics and outcomes of community-onset acute pyelonephritis (APN) caused by Escherichia coli in elderly patients. Patients/methods: Cases of adult patients with community-onset APN caused by E. coli were collected from 10 referral centres in Korea from November 2006 to August 2007. Demographic, clinical and microbiological data were analysed. Results: Diabetes mellitus (38% vs 23%, P = 0.036), chills (83% vs 66%, P = 0.015), gastrointestinal symptoms (55% vs 34%, P = 0.008), altered mental status on admission (21% vs 9%, P = 0.032), acute renal failure (17% vs 3%, P = 0.004) and concomitant bacteraemia (34% vs 17%, P = 0.015) were more frequently observed in patients aged 65 years compared with those aged < 65 years. The overall intergroup mortality rates did not differ. However, diabetes mellitus (OR = 3.54, 95% CI = 1.40–9.00, P = 0.008) and age of 65 years (OR = 2.34, 95% CI = 1.05–5.19, P = 0.037) were significantly related to a longer duration of hospital stay ( 5 days). Conclusion: Elderly patients with APN have a higher frequency of atypical manifestations, such as gastrointestinal symptoms, altered mental status and longer durations of hospital stays. Age was independently associated with longer duration of hospital stays among patients with APN. Careful diagnosis and appropriate treatment are crucial in the management of elderly patients with APN. ß 2013 Elsevier Masson SAS and European Union Geriatric Medicine Society. All rights reserved.
Keywords: Acute pyelonephritis Escherichia coli Elderly Atypical manifestation Outcome
During the latter half of the 20th century, the average life expectancy in developed countries has rapidly increased. In 1900, 5.1% of the Korean population was aged 65 years, and currently 11.4% of the Korean population is aged 65 years, which is estimated to increase to 37.4% by the year 2050 [1]. Providing care for this ageing population presents a major challenge for 21st century medicine. Geriatric infectious diseases, in particular, have become an increasingly important issue. Infectious diseases in the elderly are not only more frequent and severe but also have clinical presentations that are distinct from the younger population [2–4]. In the elderly, urinary tract infection (UTI) is the most common bacterial infection, manifesting as the most common cause of fever in patients hospitalised for acute febrile disease [5] and as the most frequent source of bacteraemia [6]. Although most UTIs are mild and managed in outpatient departments, upper UTIs, such as acute pyelonephritis (APN), can be devastating, resulting in sepsis and
* Corresponding author. Department of Infectious Disease, Chonnam National University Medical school, 671, Jebong Ro, Donggu, Gwangju 501-757, Korea. Tel.: +82 62 220 6296; fax: +82 62 225 8578. E-mail addresses: [email protected], [email protected] (S.-I. Jung).
death (1%–5%) [7–9]. UTIs in elderly patients frequently present with atypical manifestations, such as gastrointestinal symptoms or respiratory symptoms, which tend to direct the clinician’s attention away from considering UTI as the source of infection, and often lead to a delay in the diagnosis of UTIs [10]. Moreover, among patients with bacteraemia, the adverse impact of inappropriate empirical antibiotic therapy on patient outcome is greater in the elderly than in younger patients [11]. Therefore, early and prompt diagnosis of UTIs and appropriate treatment are critical in improving the outcomes of UTIs in elderly patients. Several previous studies have dealt with the clinical manifestations, outcomes and etiologic organisms of UTIs in elderly patients [2–4,12]. However, most studies have focused on the elderly group and have compared the results with historical control groups. Few studies have directly compared UTIs in the elderly with those in younger patients. Furthermore, it is difficult to assess whether the differences in clinical manifestations and outcomes were due to different clinical settings or etiologic organisms. In this study, we analysed the clinical characteristics and outcomes of communityonset APN caused by E. coli in patients aged 65 and compared the results with those in younger patients.
1878-7649/$ – see front matter ß 2013 Elsevier Masson SAS and European Union Geriatric Medicine Society. All rights reserved. http://dx.doi.org/10.1016/j.eurger.2013.11.006
S.-J. Kang et al. / European Geriatric Medicine 5 (2014) 78–81
1. Methods
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to treatment, with no relapse within 14 days of completing antimicrobial therapy.
1.1. Study design and patient selection 1.3. Statistical analysis We performed a multicentre surveillance study for UTI from November 2006 to August 2007 at 10 tertiary hospitals in South Korea [13]. From this registry’s database, a post-hoc analysis was conducted on all consecutive cases of microbiologically documented community-onset APN caused by E. coli in adult patients (age, 18 years). We compared data from patients with community-onset E. coli APN that were aged 65 years with those aged < 65 years to determine the impact of ageing on clinical manifestations, outcomes and antibiotic resistance. This study was approved by the Institutional Review Boards of all the 10 participating hospitals. Demographic, clinical and microbiological data were analysed. Data collected included age, sex, underlying disease, clinical manifestations and outcomes. The presence of the following comorbid conditions was also documented: neutropenia, renal transplantation, history of urinary calculi, recurrent UTIs, intermittent urinary catheterisations and indwelling urinary catheters. Because this study was observational, patient management and antimicrobial treatment regimens were chosen by the patients’ physicians without any guidelines or intervention from the study protocol or study investigators. Species identification was performed using a standard identification card, and antimicrobial susceptibility testing was performed at each hospital that participated in the study using the automated system by the modified broth microdilution or disk diffusion method, following the recommendations from the Clinical and Laboratory Standards Institute [14]. 1.2. Definitions APN caused by E. coli was defined by the presence of E. coli [ 105 colony forming units (CFU)/mL in voided urine, 103 CFU/ mL in nonvoided urine] in the urine and/or blood culture with simultaneous presence of pyelonephritis-related symptoms/ signs, such as fever, nausea, vomiting, costovertebral angle (CVA) tenderness or flank pain and pyuria ( 10 leukocyte per high-power field in the centrifuged specimen) [15]. Communityonset APN was defined on the basis of its diagnosis within the first 48 h of hospitalisation. Neutropenia was defined as an absolute neutrophil count of < 500 cells/mm3. Recurrent UTI was defined as 2 infections in six months or 3 infections in one year. A catheter that was maintained for > 7 days prior to the onset of APN was defined as a chronic indwelling urinary catheter, and that inserted for < 7 days before APN onset was defined as a short-term indwelling urinary catheter. Acute renal failure was defined as: absolute increase in serum creatinine concentration by 0.3 mg/ dL from baseline; percentage increase in serum creatinine concentration of 50% within 48 h; presence of oliguria, with a urine output of < 0.5 mL/kg/h for >6 h.
Septic shock was defined as sepsis with one or more signs of organ dysfunction with a systemic mean blood pressure of < 60 mm Hg despite adequate fluid resuscitation. Microbiologic eradication was defined as the elimination of E. coli in the urine culture with no relapse in bacteriuria within 14 days following the completion of antimicrobial therapy. Successful treatment was defined as the resolution of clinical symptoms/signs present prior
Student’s t-test was used to compare continuous variables. Chi2 or Fisher exact test was used to compare categorical variables. To identify factors associated with longer duration of hospital stays, a logistic regression model was used. Variables with P < 0.10 in the univariate analysis were candidates for multivariate analysis. The odds ratio (OR) and 95% confidential intervals (CIs) were calculated. All P-values were two-tailed, and the value of P < 0.5 was considered statistically significant. Data analysis was performed using PASW Statistics 17.0 (IBM SPSS, Chicago, IL, USA).
2. Results Among the 510 adult patients with a urinary tract infection, 289 patients were diagnosed with APN and 179 of these were caused by E. coli. Of the 179 patients, 20 were excluded from the analysis because their APN was considered as a nosocomial infection. Finally, a total of 159 patients [median age, 58 years (range: 18– 88 years); 92.5% were female; age 65 years, 71 patients (44.7%); age < 65 years, 88 patients (55.3%)] with community-onset APN caused by E. coli were analysed. Baseline characteristics of patients with community-onset APN due to E. coli are listed in Table 1. Diabetes mellitus was more common in patients aged 65 years than in those aged < 65 years (38.0% vs 22.7%, P = 0.036). Although no statistical significance was observed between the two groups, patients aged 65 years had a trend towards a more frequent history of hospital admission in the previous 6 months (21.1% vs 10.2%, P = 0.056). The frequencies of neurogenic bladders and the use of urinary catheters did not differ between the two groups. Clinical features and outcomes are presented in Table 2. The most common symptom was fever (90.6%), followed by chills (73.6%), CVA tenderness (53.5%), gastrointestinal symptoms Table 1 Baseline characteristics of patients with community-onset acute pyelonephritis due to Escherichia colia.
Median age (range), years Female Underlying disease Diabetes mellitus Congestive heart failure Ischemic heart disease Chronic lung disease Liver cirrhosis Solid cancer Neutropenia Cerebrovascular disease Other neurologic diseases Chronic kidney disease Renal transplant recipient Neurogenic bladder Urinary calculi Recurrent UTI History of admission within 6 months Prior antibiotics Urinary catheterization Clean intermittent Short-term indwelling Chronic indwelling
Age < 65 years n = 88
Age 65 years n = 71
47 (18–64) 81 (92.0)
72 (65–88) 66 (93.0)
0.829
20 2 0 2 2 6 0 1 1 7 6 2 5 7 9
27 4 5 4 0 5 1 5 6 4 1 3 7 3 15
(38.0) (5.6) (7.0) (5.6) (0.0) (7.0) (1.4) (7.0) (8.5) (5.6) (1.4) (4.2) (9.9) (4.2) (21.1)
0.036 0.408 0.016 0.408 0.503 1.000 0.447 0.090 0.045 0.756 0.132 0.657 0.322 0.514 0.056
31 (35.2)
26 (36.6)
0.856
0 (0.0) 4 (4.5) 2 (2.3)
3 (4.2) 5 (7.0) 0 (0.0)
0.087 0.514 0.503
(22.7) (2.3) (0.0) (2.3) (2.3) (6.8) (0.0) (1.1) (1.1) (8.0) (6.8) (2.3) (5.7) (8.0) (10.2)
UTI: urinary tract infection. a Data are the number (%) of patients, unless otherwise indicated.
P-value
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Table 2 Clinical features and outcome of community-onset acute pyelonephritis due to Escherichia coli in patients aged < 65 years versus 65 yearsa.
Symptoms and signs Fever Chill Urgency Frequency Voiding difficulty Dysuria Suprapubic tenderness Gastrointestinal symptom Flank pain Abdominal pain Pleuritic chest pain CVA tenderness Altered mentality Concomitant bacteremia Acute renal failure Septic shock Appropriate empirical antibiotics Appropriate definitive antibiotics Clinical outcome Median length of hospital stay, days (Interquartile range) Microbiologic eradication Successful treatment 14-day mortality
Age < 65 years n = 88
Age 65 years n = 71
P-value
78 58 23 33 28 35 4 30 33 12 2 45 8 15 3 3 70/83
66 59 13 34 23 26 4 39 24 6 1 40 15 24 12 7 53/66
(93.0) (83.1) (18.3) (47.9) (32.4) (36.6) (5.6) (54.9) (33.8) (8.5) (1.4) (56.3) (21.1) (33.8) (16.9) (9.9) (80.3)
0.354 0.015 0.241 0.187 0.938 0.684 1.000 0.008 0.629 0.305 1.000 0.513 0.032 0.015 0.004 0.112 0.519
60/64 (93.8)
0.700
7 (4-11)
0.009
30 (42.3) 55 (77.5) 3 (4.2)
0.068 0.385 0.657
(88.6) (65.9) (26.1) (37.5) (31.8) (39.8) (4.5) (34.1) (37.5) (13.6) (2.3) (51.1) (9.1) (17.0) (3.4) (3.4) (84.3)
78/81 (96.3)
5 (1-8)
50 (56.8) 73 (83.0) 2 (2.3)
CVA: costovertebral angle. a Data are the number (%) of patients, unless otherwise indicated.
(43.4%) and urinary frequency (42.1%). Concomitant bacteraemia and acute renal failure were present in 39 (24.5%) and 15 (9.4%) patients, respectively. Compared with patients aged < 65 years, chills (83.1% vs 65.9%, P = 0.015), gastrointestinal symptoms (54.9% vs 34.1%, P = 0.008) and altered mental status on admission (21.1% vs 9.1%, P = 0.032) were more frequently observed in patients aged 65 years. Acute renal failure (16.9% vs 3.4%, P = 0.004) and concomitant bacteraemia (33.8% vs 17.0%, P = 0.015) were more common in patients aged 65 years. Overall, the mortality rate was not significantly different between patients aged 65 years and those aged < 65 years (4.2% vs 2.3%, P = 0.657). There was a trend towards a decrease in successful treatment and microbiologic eradication in patients aged 65 years, but there was no statistical significance (77.5% vs 83.0%, P = 0.385; 42.3% vs 56.8%, P = 0.068). Inappropriate empirical or definitive antibiotic treatments were not related to the length of hospital stay. However, patients aged 65 years had longer duration of hospital stays than those aged < 65 years (median, 7.0 days; interquartile range (IQR), 4–11 days vs median 5 days; IQR of 1–8 days; P = 0.009). In the multivariate analysis, diabetes mellitus (OR = 5.34, 95% CI = 1.76–16.2, P = 0.003) and an age of 65 years (OR = 3.640, 95% CI = 1.43–9.27, P = 0.007) were significantly related to longer duration of hospital stays ( 5 days). The proportions of isolates with antimicrobial-resistant E. coli are summarised in Table 3. The overall resistance rates were 7.9% (11/139) for cefotaxime, 2.9% (4/139) for ceftazidime, 27.3% (38/ 139) for ciprofloxacin, 23.7% (33/139) for gentamicin, 8.7% (12/ 138) for piperacillin/tazobactam and 33.1% (46/139) for trimethoprime/sulfamethoxazole. Fourteen isolates, including six isolates from patients aged 65 years, were extended spectrum beta lactamase (ESBL) producing isolates. All isolates were susceptible to imipenem. The resistance rates to ciprofloxacin among E. coli isolated from patients aged 65 years had a trend towards higher resistance than those isolated from patients aged < 65 years, but
Table 3 Antibiotic resistance of Escherichia coli isolates causing community-onset acute pyelonephritis in patients aged < 65 years versus 65 yearsa.
Ampicillin Gentamicin Ceftazidime Cefotaxime Aztreonam Ciprofloxacin Piperacillin/tazobactam Trimethoprime/ sulfamethoxazole Imipenem
Age < 65 years n = 80
Age 65 years n = 59
P-value
57 17 3 6 3 19 8 24
41 16 1 5 5 19 4 22
0.822 0.422 0.637 1.000 0.284 0.269 0.558 0.367
(71.3) (21.3) (3.8) (7.5) (3.8) (23.8) (10.0) (30.0)
0 (0.0)
(69.5) (27.1) (1.7) (8.5) (8.5) (32.2) (6.8) (37.3)
0 (0.0)
–
Intermediate resistance was also considered as resistance. Minimal inhibitory concentration (MIC, ug/mL) interpretative standards were followed the performance standards for antimicrobial susceptibility testing: seventeenth information supplement M100-S16. For each antibiotics, the criteria for susceptible, intermediates, resistance were ampicillin 8, 16, 32, gentamicin 4, 8, 16, ceftazidime 8, 16, 32, cefotaxime 8, 16–32, 64, aztreonam 8, 16, 32, ciprofloxacin 1, 2, 4, piperacillin-tazobactam 16/4, 32/4–64/4, 128/4, trimethoprime/sulfamethoxazole 2/38, –, 4/76, imipenem 4, 8, 16. a Data are the number (%) of patients, unless otherwise indicated.
this difference was not statistically significant (32.2% vs 23.8%, P = 0.269). The antibiotic resistance rate to other kinds of antibiotics did not significantly differ between the two groups.
3. Discussion In the present study, the clinical presentation of APN in elderly patients was observed to markedly differ from that of younger patients. Atypical presentations, such as altered mental status and gastrointestinal symptoms, were more common in the elderly patients than in younger patients, which is consistent with other infectious diseases in the elderly [2–4,12]. Furthermore, at the time of admission, the severity of the disease, which is reflected by concomitant bacteraemia and acute kidney injury, was higher among elderly patients than among younger patients. Gleckman et al. [16] suggested that APN in the elderly leads to a higher incidence of bacteraemia than that in younger patients. However, only elderly patients with APN were assessed in this study, and the results were compared to those in younger patients from a separate previous report [17]. The study’s findings indicated that elderly patients required longer duration of hospital stays compared with younger patients, although the mortality rate did not differ between the two groups. Differences relating to age groups in UTIs have been previously described, but these findings may be exaggerated, for instance, in the context of clinical manifestations and outcomes in the elderly [18]. The present study was confined to patients with community-onset APN caused by E. coli to investigate the impact of ageing on infection by reducing confounding factors, such as co-morbidities and etiologic agents. The mortality rate from APN in elderly patients was similar to that found in younger patients. In this study, the overall mortality rate for APN was 3.1%, which corresponds to the results found in previous studies [15,19]. It was difficult to demonstrate any differences in the mortality rate between elderly and younger patients because of the low mortality rate associated with APN. These findings are consistent with those of previous studies, which showed the elderly are not associated with higher mortality rates for UTI compared to the younger patients, while most other common infections are associated with at least a two-fold or higher death rate in the elderly population [5,20]. However, APN in elderly patients is related to poorer outcomes compared to that in younger individuals. In this study, elderly patients had longer duration of
S.-J. Kang et al. / European Geriatric Medicine 5 (2014) 78–81
hospital stays than younger patients. In addition, diabetes mellitus and age of 65 years were independent risk factors for prolonged hospitalisation ( 5 days). There was a tendency for fever to persist longer in elderly patients, even though no statistical significance was observed. Furthermore, the proportion of clinically successful treatments and microbiologic eradication had a tendency to decrease in those aged 65 years. These results are consistent with previous studies showing that most infectious diseases in the elderly have poorer outcomes than those in younger patients [4,21]. Several factors most likely contribute to poor outcomes in the elderly. One of the most important factors is that the number of co-morbidities increases according to age [21]. In this study, for patients aged 65 years, diabetes mellitus and a history of admission within the previous 6 months were more common than in those aged < 65 years. Further study on the contributing factors related to poor outcomes should be undertaken. Antibiotic susceptibility did not differ across the different age groups of patients with APN. In a previous study, quinolone resistance and ESBL production were 26.7% and 8.9%, respectively, among E. coli isolates from patients with community-onset APN at a referral centre in Korea. The levels detected in our study are consistent with these findings [15]. We hypothesised that antibiotic susceptibility of E. coli in elderly patients may be different from that in younger patients. Although patients aged 65 years had a trend towards higher resistance to ciprofloxacin, there was no statistical difference in E. coli isolate antibiotic resistance in terms of the patients’ age. These findings suggest that antibiotic resistance is affected more by the underlying conditions, such as risk factors for health care-associated infection, than by aging itself [15]. Our study has some limitations. First, we conducted this study primarily in large referral centres. Thus, many of our patients had serious underlying illnesses and severe clinical manifestations. Our findings may not be representative of other general elderly populations, particularly those in community hospitals. Second, this observational study was performed from August 2006 to September 2007 and the results may therefore no longer reflect the current status. Changing trends in both medical practice and antimicrobial resistance of uropathogens emphasise the need to update studies on ageing populations. Third, because of the observational nature of this study, some variables were not accurately collected. In some patients, data on previous UTIs episodes or previous antibiotic use were unavailable, which may have influenced the results of this study. Despite these limitations, we believe that the findings of this investigation provide distinct clinical characteristics and outcomes of community-onset APN in elderly patients that will allow appropriate treatment of these populations. In conclusion, elderly patients with community-onset APN caused by E. coli have a higher frequency of atypical manifestations, such as gastrointestinal symptoms, altered mental status and poorer outcomes, including longer duration of hospital stays. Ageing directly affects atypical clinical manifestations and poor outcomes caused by infectious diseases. Careful diagnosis and prompt appropriate treatment are crucial in managing elderly patients with APN. Disclosure of interest The authors declare that they have no conflicts of interest concerning this article. Acknowledgements This study was supported in part by grants from the Chonnam National University Hospital Research Institute of Clinical Med-
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icine (CRI08062-1) and the Korea Centers for Disease Control and Prevention (2007-E00037-00). The funder had no role in the study design, data collection and analysis, decision to publish, or preparation of the manuscript. The authors would like to thank all participating investigators including Jae-Hoon Song, Kyong Ran Peck, and Doo Ryeon Chung (Samsung Medical Center, Sungkyunkwan University School of Medicine, Suwon, South Korea); Joon-Sup Yeom (Kangbuk Samsung Hospital, Sungkyunkwan University School of Medicine, Seoul, South Korea); Yu Mi Wi (Samsung Changwon Hospital, Sungkyunkwan University School of Medicine, Changwon, South Korea); Hyun Kyun Ki and Hae Suk Cheong (Konkuk University Hospital, Seoul, South Korea); Jun Seong Son (Kyunghee University Hospital at Gangdong, Seoul, South Korea); Yeon-Sook Kim (Chungnam National University Hospital, Daejeon, South Korea); Sook-In Jung, Seung-ji Kang, and Kyung Hwa Park (Chonnam National University Hospital, Gwangju, South Korea); Shin-Woo Kim and Hyun-Ha Chang (Kyungpook National University Hospital, Daegu, South Korea); Ki Tae Kwon (Daegu Fatima Hospital, Daegu, South Korea); and Sang Taek Heo (Jeju National University Hospital, Jeju, South Korea). References [1] Korean Statistical Information Service Online (KOSIS): http://kosis.kr/statisticsList/statisticsList_01List.jsp?vwcd=MT_ZTITLE&parentId=A.[Accessed June 3, 2013]. [2] Norman DC, Toledo SD. Infections in elderly persons. An altered clinical presentation. Clin Geriatr Med 1992;8:713–9. [3] Chassagne P, Peridol MB, Doucet J, Trivalle C, Me´nard JF, Manchon ND, et al. Is presentation of bacteremia in the elderly the same as in younger patients? Am J Med 1996;100:65–70. [4] Cooper GS, Shlaes DM, Salata RA. Intraabdominal infection: differences in presentation and outcome between younger patients and the elderly. Clin Infect Dis 1994;19:146–8. [5] Tal S, Guller V, Levi S, Bardenstein R, Berger D, Gurevich I, et al. Profile and prognosis of febrile elderly patients with bacteremic urinary tract infection. J Infect 2005;50:296–305. [6] Lark RL, Saint S, Chenoweth C, Zemencuk JK, Lipsky BA, Plorde JJ. Four-year prospective evaluation of community-acquired bacteremia: epidemiology, microbiology, and patient outcome. Diagn Microbiol Infect Dis 2001;41:15–22. [7] Al-Hasan MN, Eckel-Passow JE, Baddour LM. Bacteremia complicating Gramnegative urinary tract infections: a population-based study. J Infect 2010;60:278–85. [8] Jerkeman M, Braconier JH. Bacteremic and non-bacteremic febrile urinary tract infection – review of 168 hospital-treated patients. Infection 1992;20:143–5. [9] Lee SS, Kim Y, Chung DR. Impact of discordant empirical therapy on outcome of community-acquired bacteremic acute pyelonephritis. J Infect 2011;62:159–64. [10] Barkham TM, Martin FC, Eykyn SJ. Delay in the diagnosis of bacteraemic urinary tract infection in elderly patients. Age Ageing 1996;25:130–2. [11] Lee CC, Chang CM, Hong MY, Hsu HC, Ko WC. Different impact of the appropriateness of empirical antibiotics for bacteremia among younger adults and the elderly in the ED. Am J Emerg Med 2013;31:282–90. [12] Jarrett PG, Rockwood K, Carver D, Stolee P, Cosway S. Illness presentation in elderly patients. Arch Intern Med 1995;155:1060–4. [13] Korea Centers for Disease Control Prevention. Result report on KCDC research – antimicrobial resistance and molecular epidemiology of clinical isolates from patients with urinary tract infection or bacteremia in Korea; 2007;e00027. [14] Performance standards for antimicrobial susceptibility testing. Sixteenth Informational Supplement. Clin. Lab. Stand. Insitutue; 2006, M100-S16. [15] Ha YE, Kang CI, Joo EJ, Park SY, Kang SJ, Wi YM, et al. Clinical implications of healthcare-associated infection in patients with community-onset acute pyelonephritis. Scand J Infect Dis 2011;43:587–95. [16] Gleckman R, Blagg N, Hibert D, Hall A, Crowley M, Pritchard A, et al. Acute pyelonephritis in the elderly. South Med J 1982;75:551–4. [17] McMurdock J, Speirs CF, Geddes AM, et al. Treatment of recurrent urinary tract infection. In: O’Grady FO, Brumfitt W, editors. Urinary Tract Infection. London: Oxford Press; 1968. p. 227–34. [18] Kang SC, Tsao HM, Liu CT, Perng CL, Hwang SJ. The characteristics of acute pyelonephritis in geriatric patients: experiences in rural northeastern Taiwan. Tohoku J Exp Med 2008;214:61–7. [19] Aguilar-Duran S, Horcajada JP, Sorlı´ L, Montero M, Salvado´ M, Grau S, et al. Community-onset healthcare-related urinary tract infections: comparison with community and hospital-acquired urinary tract infections. J Infect 2012;64:478–83. [20] Ackermann RJ, Monroe PW. Bacteremic urinary tract infection in older people. J Am Geriatr Soc 1996;44:927–33. [21] Gavazzi G, Krause KH. Ageing and infection. Lancet Infect Dis 2002;2:659–66.