- Email: [email protected]
Urinary infection in the elderly
Rev Clin Esp. 2019;219(4):189---193
Revista Clínica Española www.elsevier.es/rce
BRIEF ORIGINAL
Urinary infection in the elderly夽 E. Álvarez Artero a , A. Campo Nu˜ nez a , M. Garcia Bravo b , O. Cores Calvo c , M. Belhassen Garcia d,∗ , J. Pardo Lledias e,∗ , en nombre del Grupo colaborativo de estudio de infecciones urinarias en el anciano♦ a
Servicio de Medicina Interna, Hospital Río Carrión, Complejo Asistencial de Palencia (CAUPA), Palencia, Spain Servicio de Microbiología, Hospital Río Carrión, CAUPA, Palencia, Spain c Servicio de Microbiología, CAUSA, Salamanca, Spain d Servicio de Medicina Interna, Sección de Enfermedades Infecciosas, CAUSA, Instituto de Investigación Biomédica de Salamanca (IBSAL), Centro de Investigación en Enfermedades Tropicales de la Universidad de Salamanca (CIETUS), Universidad de Salamanca, Salamanca, Spain e Servicio de Medicina Interna, Hospital Universitario Marqués de Valdecilla (HUMV), Santander, Cantabria, Spain b
Received 13 June 2018; accepted 8 October 2018 Available online 15 March 2019
KEYWORDS Urinary tract infection; Empirical treatment; Mortality; Elderly; Infection associated with bladder catheter
Abstract Introduction: Urinary tract infections (UTIs) are one of the most frequent infections. In the elderly, they have multiple comorbidities. The objective of this work is to describe the clinical and microbiological epidemiology of elderly persons admitted for UTIs and to evaluate the suitability of empirical treatments and their implications regarding mortality. Material and methods: An observational study was conducted during 2013---2015 in 4 public hospitals, with patients older than 65 years who were admitted to the Internal Medicine service with a microbiological diagnosis of UTI. Cases of asymptomatic bacteriuria were excluded. In-hospital mortality was analyzed. Univariate analysis and multivariate analysis was carried out. Results: A total of 349 episodes were selected, with a mean age of 82 ± 11 years, 51% female. Mortality was 10.3% and was associated with age, dementia and sepsis and septic shock (p < 0.05). The most frequent organisms were Escherichia coli (E. coli) (53.6%), Klebsiella spp. (8.7%) and Enterococcus spp. (6.6%). E. coli and Klebsiella spp. with extended-spectrum beta-lactamases (13% of the total isolated) were associated with the previous use of antibiotics,
夽
Please cite this article as: Álvarez Artero E, Campo Nu˜ nez A, Garcia Bravo M, Cores Calvo O, Belhassen Garcia M, Pardo Lledias J, et al. Infección urinaria en el anciano. Rev Clin Esp. 2019;219:189---193. ∗ Corresponding author. E-mail addresses: [email protected] (M. Belhassen Garcia), [email protected] (J. Pardo Lledias). ♦ The names of the components of the Collaborative Group for the study of urinary tract infections in the elderly are related in Appendix A. 2254-8874/© 2019 Elsevier Espa˜ na, S.L.U. and Sociedad Espa˜ nola de Medicina Interna (SEMI). All rights reserved.
190
E. Álvarez Artero et al. community care treatment and a permanent urinary catheter (p < 0.05). The empirical treatment was adequate only in 73.6% of cases. As these treatments were associated with higher mortality, they were not considered adequate. Conclusions: In the elderly, UTIs show a high mortality. Empirical treatment is often inadequate and may be associated with increased mortality. © 2019 Elsevier Espa˜ na, S.L.U. and Sociedad Espa˜ nola de Medicina Interna (SEMI). All rights reserved.
PALABRAS CLAVE Infección tracto urinario; Tratamiento empírico; Mortalidad; Anciano; Infección asociada a sonda vesical
Infección urinaria en el anciano Resumen Introducción: Las infecciones del tracto urinario (ITU) constituyen una de las infecciones más frecuentes. En el anciano presentan diversas comorbilidades. El objetivo de este trabajo es conocer la epidemiologia clínica y microbiológica en el anciano ingresado por ITU y evaluar la idoneidad de los tratamientos empíricos y su implicación con la mortalidad. Material y métodos: Estudio observacional del 2013 al 2015 en 4 hospitales en pacientes mayores de 65 a˜ nos ingresados en Medicina Interna con diagnóstico clínico y confirmación microbiológica. Se excluyeron los casos de bacteriuria asintomática. Se evaluó la mortalidad intrahospitalaria. Se realizó un análisis univariante y multivariante. Resultados: Se seleccionaron 349 episodios de pacientes con edad media 82 ±11 a˜ nos, 51% mujeres. La mortalidad fue del 10,3%, asociada a la edad, demencia y presentación como sepsis grave/shock séptico (p < 0,05). Los aislamientos más frecuentes fueron Escherichia coli (E. coli) (53,6%), Klebsiella spp. (8,7%) y Enterococcus spp. (6,6%). Un 13% del total de los aislamientos correspondían a E. coli y Klebsiella spp. con betalactamasas de espectro extendido; el uso previo de antibióticos, cuidados socio-sanitarios y catéter urinario permanente fueron predictores independientes (p < 0,05). El tratamiento empírico resultó adecuado solo en el 73,6% de los casos. La falta de adecuación se asoció a una mayor mortalidad (p < 0,05). Conclusiones: La ITU del anciano que ingresa presenta una alta mortalidad. El tratamiento empírico es frecuentemente inadecuado y puede asociarse a una mayor mortalidad. © 2019 Elsevier Espa˜ na, S.L.U. y Sociedad Espa˜ nola de Medicina Interna (SEMI). Todos los derechos reservados.
Background Urinary tract infections (UTIs) are the second leading cause of community-acquired infection resulting in hospitalization,1,2 the third leading cause of nosocomial infection and a risk factor associated with mortality in patients hospitalized for any reason.3,4 Advanced age is the risk factor most closely linked to the onset of UTIs and one of the main indicators of mortality.5,6 In elderly patients, UTIs consistently present the characteristics of a complicated infection generally associated with diabetes, immunosuppression, obstructive uropathy and urinary catheterization. In a recent study conducted in Europe, the highest antimicrobial resistance rates occurred in the elderly.7 In Spain, individuals older than 65 years already exceed 16% of the total population and, according to estimates, will reach approximately 32% percent before 2050.8 The aim of this study was to describe the main epidemiological, clinical and microbiological characteristics of elderly patients hospitalized for UTI and to assess the
suitability of empiric treatments according to the final cultures and their relationship with mortality.
Methodology We conducted an observational study during 2013---2015 in 4 hospitals of Castilla y León, Spain: Hospital Río Carrión and Hospital of San Telmo (Palencia) and Hospital Virgen de la Vega and Hospital Martínez Anido (Salamanca). The inclusion criteria for the patients were the following: (a) age >65 years and hospitalization in an internal medicine department; (2) cystic syndrome, acute pyelonephritis or criteria for systemic inflammatory response syndrome (severe sepsis or septic shock were considered when it met the criteria of the 2001 SCCM/ESICM/ACCP/ATS/SIS consensus conference9 ); and (3) microbiological criteria of UTI, confirmed through uropathogen isolation in urine cultures (>105 colony-forming units/mL) or blood cultures (in this case, always accompanied by a systematic urinalysis with
Urinary infection in the elderly Table 1
191
Results
Patient characteristics.
Main characteristic Mean age ± SD, years Sex (female), n (%)
82 ± 11 178 (51)
Location of the infection, n (%) Community Healthcare Nosocomial
169 (48.6) 93 (24.9) 87 (24.3)
Risk factors, n (%) Charlson index Diabetes mellitus Indwelling urinary catheter Immunosuppression Structural uropathy Antibiotic in the past 6 months Hospitalization in the past 3 months Previous UTI Dementia
6.6 ± 2.8 128 (36.6) 192 (56.7) 38 (10.9) 181 (51.9) 158 (45.3) 102 (29.3) 154 (44.1) 157 (44.9)
Clinical context, n (%) Cystitis Pyelonephritis Severe sepsis or shock Positive blood culturesa In-hospital mortality
59 (16.9) 290 (83.1) 57 (16.3) 87 (40.2) 36 (10.4)
Isolated strainsb , n (%) Escherichia coli Klebsiella spp. Proteus spp. Enterococcus spp. Pseudomonas aeruginosa Morganella morganii Citrobacter spp. Enterobacter spp. Providencia spp. Others
199 (57.0) 34 (9.7) 27 (7.7) 26 (7.4) 30 (8.5) 7 (2.0) 5 (1.4) 8 (2.2) 4 (1.1) 16 (4.5)
a
86% of 211 patients with blood cultures performed. 9.3% of the patients who had more than one isolated strain (polymicrobial). b
positive esterases or nitrites). The diagnostic criterion of polymicrobial UTI was established upon detecting 2 isolated strains in the urine culture. We employed the Friedman criteria for classifying the UTIs as nosocomial (healthcare-related) or communityacquired10 and used the SPSS-22 software for the statistical study. The results are expressed as mean ± standard deviation (SD) and percentage. The risk factors are expressed as odds ratios (OR) with a 95% confidence interval (95% CI). We employed the chi-squared test for the bivariate analysis and to assess factors related to the microbiological isolates and the detection of extended-spectrum beta-lactamase (ESBL)producers. The multivariate analysis was only performed on those variables that showed statistical significance (p < 0.05) in the univariate analysis. To assess and compare the validity of the biomarkers of shock, we created receiver operating characteristic (ROC) curves.
The study included 349 episodes corresponding to 330 patients. Table 1 shows the main characteristics of the study population. Of all the episodes, 48.6% (169/349) were community-acquired, 24.9% (87/349) were healthcarerelated, and 26.6% (93/349) were nosocomial. Fifty-five percent of the UTI episodes were associated with indwelling bladder catheters. The percentage of patients with urinary catheterization was significantly higher in the group with healthcare and nosocomial-related UTIs than in the group with community-acquired UTIs (OR, 2.6; 95% CI 1.6---4.0; p < 0.001). Some 83.1% (290/349) of the patients presented episodes of pyelonephritis, 57 of whom (16.3%) developed severe sepsis or septic shock. In terms of the inflammatory markers, procalcitonin was a better biomarker of severe sepsis/septic shock than C-reactive protein (area under the ROC curve, 0.73 vs. 0.57; p < 0.001). Total mortality was 10% (37), with a range of 4.85% (community-acquired infections) to 16.8% (healthcare-related/nosocomial infections), half of which was directly attributable to UTI. Of the analyzed epidemiological and clinical variables, age (p < 0.05), healthcarerelated or nosocomial UTIs (OR, 3.8; 95% CI 1.72---8.78, p < 0.001), dementia (OR, 4.1; 95% CI 1.75---9.9; p < 0.001) and clinical presentation such as severe sepsis/septic shock (OR, 4.89; 95% CI 2.3---10.1; p < 0.001) were associated with mortality. The most frequently isolated microorganism was Escherichia coli (E. coli) (57.0%), followed by Klebsiella species (9.7%) (Table 1). We detected polymicrobial infection in 9.3% of the cases. In general, we found no significant differences between the patient groups in terms of microbial spectrum, except in the case of UTI associated with indwelling bladder catheters, which showed a higher rate of infection by Pseudomonas aeruginosa (P. aeruginosa) (OR, 3.9; 95% CI 1.3---11.9; p = 0.009), as well as polymicrobial infections (OR, 3.3; 95% CI 1.3---7.8; p = 0.004). Of all isolated strains, 48 (13.9%) exhibited the ESBL phenotype: E. coli (38), Kleibsella spp.6 and polymicrobials.4 There were no strains of Kleibsella spp. or E. coli resistant to carbapenem. Table 2 shows the variables statistically associated with ESBL infection. In the multivariate analysis, the only predictors of ESBL were the previous use of antibiotics (OR, 5.5; 95% CI 2.4---12.6; p < 0.001), healthcarerelated/nosocomial UTI (OR, 2.8; 95% CI 1.3---6.0; p = 0.008) and infection associated with indwelling bladder catheter (OR, 2.3; 95% CI 1.04---5.1; p = 0.039). Some 87.2% of the isolated strains of ESBL E. coli showed multiresistance criteria (resistant to 3 or more classes of antibiotics). In our series, Enterococcus spp. showed sensitivity rates of 84% to ampicillin and 100% to vancomycin. Empiric antibiotic treatment was administered in 294 (84.2%) episodes. The most widely employed empiric antibiotics in our setting were third-generation cephalosporins (21%), followed by penicillins with beta-lactamase inhibitors (piperacillin/tazobactam) (19%) and amoxicillin/clavulanic acid (15%), carbapenem (12%) and fluoroquinolones (10%). Combined antibiotic therapy was chosen for 8% of the patients. The use of carbapenem was associated with patients with bladder catheters (OR, 3.04; 95% CI 1.4---6.6;
192
E. Álvarez Artero et al.
Table 2 Risk factors for infection by extended-spectrum beta-lactamase-producing Escherichia coli and Klebsiella spp. in urinary tract infections in elderly hospitalized patients univariate study. Study variables
% ESBL
Age >85 vs. ≤85 years Women vs. men Dementia vs. no dementia Diabetes vs. no diabetes Steroids vs. no steroids PU vs. no PU Healthcare vs. community Previous UTI vs. no UTI Antibiotics <6 monthsa vs. no antibiotics Previous hospitalization < 3 monthsb Indwelling urinary catheter
20.4 14.8 23.8 18.6 33.3 37.7 30.4 26.7 34.3 36.7 28.5
vs. vs. vs. vs. vs. vs. vs. vs. vs. vs. vs.
20.3 27.2 15.7 20.8 18.3 18.5 10.6 15.0 7.6 14.6 11.1
OR (95% CI)
p
1.0 (0.53---1.889) 0.4 (0.24---0.88) 1.98 (1.01---3.85) 0.8 (0.44---1.70) 2.2 (0.93---5.33) 2.64 (1.18---5.91) 3.70 (1.80---7.44) 2.06 (1.07---3.96) 6.33 (2.85---14.04) 3.39 (1.69---6.78) 3.18 (1.58---6.38)
0.096 0.018 0.042 0.68 0.066 0.015 <0.001 0.027 <0.001 <0.001 0.001
Abbreviations: UTIs, urinary tract infections; PUs, pressure ulcers. a Use of prescribed antibiotics in the 6 months prior to admission. b Hospital admission in the past 3 months.
p = 0.004), especially with a clinical presentation of septic shock (OR, 4.9; 95% CI 1.8---13.4; p < 0.001). The initial empiric antibiotic treatment was appropriate for only 72.6% of the final isolates. We found no differences related to the patients’ residence (p < 0.05). Appropriate treatment was associated with a lower mortality than was associated with inadequate treatment (6.6 vs. 17.2%; OR, 0.38; 95% CI 0.8---1; p = 0.009).
Discussion The aging of the population, which is especially relevant in our community, and the high rate of UTIs in this group have led to a growing interest in knowing how UTIs behave in elderly patients and how they should be treated.11 In this study, we included elderly patients with a definitive diagnosis, with significant comorbidities and who, in many cases, carried indwelling urinary catheters. The most common clinical presentation was pyelonephritis with systemic inflammatory response syndrome, which was often associated with severe sepsis or septic shock. Our study found that E. coli was responsible for more than half of the UTIs, followed by Klebsiella spp., Enterococcus spp., P. aeruginosa and Proteus spp. We found no significant differences between microorganisms or subgroups, except in UTIs associated with urinary catheters, in which the most common infection was by P. aeruginosa or polymicrobial. The prevalence of ESBL-producing enterobacteria was lower than expected, and independent predictors were the prior use of antibiotics, healthcare-related UTIs and indwelling catheter-associated infection. These factors are similar to those described in a recent study on urinary tract infection.12 Another of our study’s objectives was to report on the overall mortality and attributable mortality. Given the patients’ advanced age and the importance of present comorbidities, we considered only the hospital mortality and not the mortality at 30 days. During the hospitalization, more than 10% of the patients died, although only half of these were directly attributable to the UTI. This mortality rate was somewhat higher than that recorded in other
series on overall UTIs in which the rate ranged from 3% to 8.8%13---15 and was identical to that provided by other series on UTIs in the elderly. 16 Among the study variables, only age, healthcare-associated/nosocomial infection, dementia and severe sepsis/septic shock were associated with mortality. In our series, we found no other previously described epidemiological, clinical or laboratory variables associated with high mortality.15,16 Our study assessed the antibiotic treatment protocol administered during the study period. We have shown that inadequate empiric treatment, based on the microbiological results, was generally associated with higher mortality. These data are similar to those of a recent meta-analysis of infection by Gram-negative bacilli17,18 and differ from those of a recent study on catheter-associated UTI.19 This high mortality rate supports the implementation of empiric treatment protocols to treat UTIs in elderly patients with mortality risk factors using broad-spectrum beta-lactams and carbapenems, as suggested in the recent guidelines of the Spanish Society of Infectious Diseases and Clinical Microbiology (SEIMC).20 Lastly, it is worth noting that therapeutic compliance with the SEIMC guidelines increases the use of empiric antibiotic treatments with broad-spectrum carbapenems or beta-lactams in our elderly patients, which would lead to an increase in the consumption of these antibiotics in our hospitals. It is also possible, however, that in the near future, with the implementation of new microbiological rapid-identification methods, such as matrix-assisted laser desorption ionization time-of-flight mass spectrometry, for direct sampling of urine cultures and blood cultures, we could identify the uropathogen causing the infection and determine its resistance profile in a timely manner.21 In conclusion, UTIs in elderly hospitalized patients are frequently associated with the use of urinary catheters and present high mortality. In our setting, the presence of ESBLproducing Enterobacteriaceae is still low and is linked to the use of antimicrobial agents, a nursing home origin and the carrying of an indwelling urinary catheter. Inadequate selection of empiric antimicrobial treatments is associated with high mortality.
Urinary infection in the elderly
Acknowledgements The authors would like to thank Virginia Velasco-Tirado and Jose Angel Martin Oterino for collaborating in this study.
Appendix A. Collaborative Study Group for Urinary Infections in the Elderly María Garcia García, Department of Internal Medicine, University Healthcare Complex of Salamanca (CAUSA), Salamanca, Spain; Inmaculada Galindo Pérez, Primary Care Center, Puente San Miguel, Santander, Cantabria, Spain; Adela Carpio-Pérez, Department of Internal Medicine, CAUSA, Salamanca, Spain.
References 1. Llor C, Hernández S. Infectious disease in primary care: 1-year prospective study. Enferm Infecc Microbiol Clin. 2010;28:222---6, doi:10.1016/j.eimc.2009.03.014. 2. Accessed 8 Jan 2018. Available in: https://www.vallhebron.com/ca [Internet]. 3. Neuman MD, Archan S, Karlawish JH, Schwartz JS, Fleisher LA. The relationship between short-term mortality and quality of care for hip fracture: a meta-analysis of clinical pathways for hip fracture. J Am Geriatr Soc. 2009;57:2046---54, doi:10.1111/j.1532-5415.2009.02492.x. 4. Gruneir A, Bell CM, Bronskill SE, Schull M, Anderson GM, Rochon PA. Frequency and pattern of emergency department visits by long-term care residents ---- a population-based study. J Am Geriatr Soc. 2010;58: 510---7, doi:10.1111/j.1532-5415.2010.02736.x. 5. Al-Hasan MN, Eckel-Passow JE, Baddour LM. Bacteremia complicating gram-negative urinary tract infections: a population-based study. J Infect. 2010;60: 278---85, doi:10.1111/1469-0691.12085. 6. Cinza Sanjurjo S, Cabarcos Ortiz de Barrón A, Nieto Pol E, Torre Carballada JA. Analises of the mortality in aged in an Internal Medicine Department. An Med Int. 2007;24: 67---71. 7. Kresken M, Körber-Irrgang B, Biedenbach DJ, Batista N, Besard V, Cantón R, et al. Comparative in vitro activity of oral antimicrobial agents against Enterobacteriaceae from patients with community-acquired urinary tract infections in 3 European countries. Clin Microbiol Infect. 2016;22, doi:10.1016/j.cmi.2015.08.019, 63.e1---63.e5. 8. Accessed 18 Jul 2015. Available in: http://www.ine.es/ [Internet]. 9. Levy MM, Fink MP, Marshall JC, Abraham E, Angus D, Cook D, et al. SCCM/ESICM/ACCP/ATS/SIS. 2001 SCCM/ESICM/ACCP/ATS/SIS International Sepsis Definitions Conference. Crit Care Med. 2003;31:1250---6.
193 10. Friedman ND, Kaye KS, Stout JE, McGarry SA, Trivette SL, Briggs JP, et al. Health care-associated bloodstream infections in adults: a reason to change the accepted definition of community-acquired infections. Ann Intern Med. 2002;137:791---7. 11. Htwe TH, Mushtaq A, Robinson SB, Rosher RB, Khardori N. Infection in the elderly. Infect Dis Clin North Am. 2007;21:711---43, doi:10.1016/j.idc.2007.07.006-ix. 12. García-Tello A, Gimbernat H, Redondo C, Meilán E, Arana DM, Cacho J, et al. Prediction of infection caused by extended-spectrum beta-lactamase-producing Enterobacteriaceae: development of a clinical decision-making nomogram. Scand J Urol. 2017;3:1---6. 13. Van der Starre WE, Zunder SM, Vollaard AM, van Nieuwkoop C, Stalenhoef JE, Delfos NM, et al. Prognostic value of pro-adrenomedullin, procalcitonin and C-reactive protein in predicting outcome of febrile urinary tract infection. Clin Microbiol Infect. 2014;20:1048---54, doi:10.1111/1469-0691.12645. 14. García Viejo MA, Noguerado Asensio A. Grupo de Trabajo de las Infecciones Urinarias del Grupo de Trabajo de Enfermedades Infecciosas de la Sociedad Espa˜ nola de Medicina Interna. RCE. 2010;210:537---44, doi:10.1016/j.rce.2009.12.015 [Urinary tract infections in internal medicine]. 15. Horcajada JP, Shaw E, Padilla B, Pintado V, Calbo E, Benito N, et al. Healthcare-associated, community-acquired and hospitalacquired bacteraemic urinary tract infections in hospitalized patients: a prospective multicentre cohort study in the era of antimicrobial resistance. Clin Microbiol Infect. 2013;19:962---8, doi:10.1111/1469-0691.12089. 16. Chin BS, Kim MS, Han SH, Shin SY, Choi HK, Chae YT, et al. Risk factors of all-cause in-hospital mortality among Korean elderly bacteremic urinary tract infection (UTI) patients. Arch Gerontol Geriatr. 2011;52, doi:10.1016/j.archger.2010.05.011, e50---5. 17. Raman G, Avendano E, Berger S, Menon V. Appropriate initial antibiotic therapy in hospitalized patients with gram-negative infections: systematic review and meta-analysis. BMC Infect Dis. 2015;15:395, doi:10.1186/s12879-015-1123-5. 18. Esparcia A, Artero A, Eiros JM, Balaguer M, Madrazo M, Alberola J, et al. Influence of inadequate antimicrobial therapy on prognosis in elderly patients with severe urinary tract infections. Eur J Intern Med. 2014;25:523---7, doi:10.1016/j.ejim.2014.04.009. 19. Babich T, Zusman O, Elbaz M, Ben-Zvi H, Paul M, Leibovici L, et al. Empirical antibiotic treatment does not improve outcomes in catheter-associated urinary tract infection: prospective cohort study. Clin Infect Dis. 2017;65:1799---805, doi:10.1093/cid/cix680. PubMed PMID: 29020203. 20. de Cueto M, Aliaga L, Alós JI, Canut A, Los-Arcos I, Martínez JA, et al. Executive summary of the diagnosis and treatment of urinary tract infection: Guidelines of the Spanish Society of Clinical Microbiology and Infectious Diseases (SEIMC). Enferm Infecc Microbiol Clin. 2017;35:314---20, doi:10.1016/j.eimc.2016.11.005. 21. Ovia˜ no M, Gómara M, Barba MJ, Revillo MJ, Barbeyto LP, Bou G. Towards the early detection of -lactamase-producing Enterobacteriaceae by MALDI-TOF MS analysis. J Antimicrob Chemother. 2017;72:2259---62, doi:10.1093/jac/dkx127.
Revista Clínica Española www.elsevier.es/rce
BRIEF ORIGINAL
Urinary infection in the elderly夽 E. Álvarez Artero a , A. Campo Nu˜ nez a , M. Garcia Bravo b , O. Cores Calvo c , M. Belhassen Garcia d,∗ , J. Pardo Lledias e,∗ , en nombre del Grupo colaborativo de estudio de infecciones urinarias en el anciano♦ a
Servicio de Medicina Interna, Hospital Río Carrión, Complejo Asistencial de Palencia (CAUPA), Palencia, Spain Servicio de Microbiología, Hospital Río Carrión, CAUPA, Palencia, Spain c Servicio de Microbiología, CAUSA, Salamanca, Spain d Servicio de Medicina Interna, Sección de Enfermedades Infecciosas, CAUSA, Instituto de Investigación Biomédica de Salamanca (IBSAL), Centro de Investigación en Enfermedades Tropicales de la Universidad de Salamanca (CIETUS), Universidad de Salamanca, Salamanca, Spain e Servicio de Medicina Interna, Hospital Universitario Marqués de Valdecilla (HUMV), Santander, Cantabria, Spain b
Received 13 June 2018; accepted 8 October 2018 Available online 15 March 2019
KEYWORDS Urinary tract infection; Empirical treatment; Mortality; Elderly; Infection associated with bladder catheter
Abstract Introduction: Urinary tract infections (UTIs) are one of the most frequent infections. In the elderly, they have multiple comorbidities. The objective of this work is to describe the clinical and microbiological epidemiology of elderly persons admitted for UTIs and to evaluate the suitability of empirical treatments and their implications regarding mortality. Material and methods: An observational study was conducted during 2013---2015 in 4 public hospitals, with patients older than 65 years who were admitted to the Internal Medicine service with a microbiological diagnosis of UTI. Cases of asymptomatic bacteriuria were excluded. In-hospital mortality was analyzed. Univariate analysis and multivariate analysis was carried out. Results: A total of 349 episodes were selected, with a mean age of 82 ± 11 years, 51% female. Mortality was 10.3% and was associated with age, dementia and sepsis and septic shock (p < 0.05). The most frequent organisms were Escherichia coli (E. coli) (53.6%), Klebsiella spp. (8.7%) and Enterococcus spp. (6.6%). E. coli and Klebsiella spp. with extended-spectrum beta-lactamases (13% of the total isolated) were associated with the previous use of antibiotics,
夽
Please cite this article as: Álvarez Artero E, Campo Nu˜ nez A, Garcia Bravo M, Cores Calvo O, Belhassen Garcia M, Pardo Lledias J, et al. Infección urinaria en el anciano. Rev Clin Esp. 2019;219:189---193. ∗ Corresponding author. E-mail addresses: [email protected] (M. Belhassen Garcia), [email protected] (J. Pardo Lledias). ♦ The names of the components of the Collaborative Group for the study of urinary tract infections in the elderly are related in Appendix A. 2254-8874/© 2019 Elsevier Espa˜ na, S.L.U. and Sociedad Espa˜ nola de Medicina Interna (SEMI). All rights reserved.
190
E. Álvarez Artero et al. community care treatment and a permanent urinary catheter (p < 0.05). The empirical treatment was adequate only in 73.6% of cases. As these treatments were associated with higher mortality, they were not considered adequate. Conclusions: In the elderly, UTIs show a high mortality. Empirical treatment is often inadequate and may be associated with increased mortality. © 2019 Elsevier Espa˜ na, S.L.U. and Sociedad Espa˜ nola de Medicina Interna (SEMI). All rights reserved.
PALABRAS CLAVE Infección tracto urinario; Tratamiento empírico; Mortalidad; Anciano; Infección asociada a sonda vesical
Infección urinaria en el anciano Resumen Introducción: Las infecciones del tracto urinario (ITU) constituyen una de las infecciones más frecuentes. En el anciano presentan diversas comorbilidades. El objetivo de este trabajo es conocer la epidemiologia clínica y microbiológica en el anciano ingresado por ITU y evaluar la idoneidad de los tratamientos empíricos y su implicación con la mortalidad. Material y métodos: Estudio observacional del 2013 al 2015 en 4 hospitales en pacientes mayores de 65 a˜ nos ingresados en Medicina Interna con diagnóstico clínico y confirmación microbiológica. Se excluyeron los casos de bacteriuria asintomática. Se evaluó la mortalidad intrahospitalaria. Se realizó un análisis univariante y multivariante. Resultados: Se seleccionaron 349 episodios de pacientes con edad media 82 ±11 a˜ nos, 51% mujeres. La mortalidad fue del 10,3%, asociada a la edad, demencia y presentación como sepsis grave/shock séptico (p < 0,05). Los aislamientos más frecuentes fueron Escherichia coli (E. coli) (53,6%), Klebsiella spp. (8,7%) y Enterococcus spp. (6,6%). Un 13% del total de los aislamientos correspondían a E. coli y Klebsiella spp. con betalactamasas de espectro extendido; el uso previo de antibióticos, cuidados socio-sanitarios y catéter urinario permanente fueron predictores independientes (p < 0,05). El tratamiento empírico resultó adecuado solo en el 73,6% de los casos. La falta de adecuación se asoció a una mayor mortalidad (p < 0,05). Conclusiones: La ITU del anciano que ingresa presenta una alta mortalidad. El tratamiento empírico es frecuentemente inadecuado y puede asociarse a una mayor mortalidad. © 2019 Elsevier Espa˜ na, S.L.U. y Sociedad Espa˜ nola de Medicina Interna (SEMI). Todos los derechos reservados.
Background Urinary tract infections (UTIs) are the second leading cause of community-acquired infection resulting in hospitalization,1,2 the third leading cause of nosocomial infection and a risk factor associated with mortality in patients hospitalized for any reason.3,4 Advanced age is the risk factor most closely linked to the onset of UTIs and one of the main indicators of mortality.5,6 In elderly patients, UTIs consistently present the characteristics of a complicated infection generally associated with diabetes, immunosuppression, obstructive uropathy and urinary catheterization. In a recent study conducted in Europe, the highest antimicrobial resistance rates occurred in the elderly.7 In Spain, individuals older than 65 years already exceed 16% of the total population and, according to estimates, will reach approximately 32% percent before 2050.8 The aim of this study was to describe the main epidemiological, clinical and microbiological characteristics of elderly patients hospitalized for UTI and to assess the
suitability of empiric treatments according to the final cultures and their relationship with mortality.
Methodology We conducted an observational study during 2013---2015 in 4 hospitals of Castilla y León, Spain: Hospital Río Carrión and Hospital of San Telmo (Palencia) and Hospital Virgen de la Vega and Hospital Martínez Anido (Salamanca). The inclusion criteria for the patients were the following: (a) age >65 years and hospitalization in an internal medicine department; (2) cystic syndrome, acute pyelonephritis or criteria for systemic inflammatory response syndrome (severe sepsis or septic shock were considered when it met the criteria of the 2001 SCCM/ESICM/ACCP/ATS/SIS consensus conference9 ); and (3) microbiological criteria of UTI, confirmed through uropathogen isolation in urine cultures (>105 colony-forming units/mL) or blood cultures (in this case, always accompanied by a systematic urinalysis with
Urinary infection in the elderly Table 1
191
Results
Patient characteristics.
Main characteristic Mean age ± SD, years Sex (female), n (%)
82 ± 11 178 (51)
Location of the infection, n (%) Community Healthcare Nosocomial
169 (48.6) 93 (24.9) 87 (24.3)
Risk factors, n (%) Charlson index Diabetes mellitus Indwelling urinary catheter Immunosuppression Structural uropathy Antibiotic in the past 6 months Hospitalization in the past 3 months Previous UTI Dementia
6.6 ± 2.8 128 (36.6) 192 (56.7) 38 (10.9) 181 (51.9) 158 (45.3) 102 (29.3) 154 (44.1) 157 (44.9)
Clinical context, n (%) Cystitis Pyelonephritis Severe sepsis or shock Positive blood culturesa In-hospital mortality
59 (16.9) 290 (83.1) 57 (16.3) 87 (40.2) 36 (10.4)
Isolated strainsb , n (%) Escherichia coli Klebsiella spp. Proteus spp. Enterococcus spp. Pseudomonas aeruginosa Morganella morganii Citrobacter spp. Enterobacter spp. Providencia spp. Others
199 (57.0) 34 (9.7) 27 (7.7) 26 (7.4) 30 (8.5) 7 (2.0) 5 (1.4) 8 (2.2) 4 (1.1) 16 (4.5)
a
86% of 211 patients with blood cultures performed. 9.3% of the patients who had more than one isolated strain (polymicrobial). b
positive esterases or nitrites). The diagnostic criterion of polymicrobial UTI was established upon detecting 2 isolated strains in the urine culture. We employed the Friedman criteria for classifying the UTIs as nosocomial (healthcare-related) or communityacquired10 and used the SPSS-22 software for the statistical study. The results are expressed as mean ± standard deviation (SD) and percentage. The risk factors are expressed as odds ratios (OR) with a 95% confidence interval (95% CI). We employed the chi-squared test for the bivariate analysis and to assess factors related to the microbiological isolates and the detection of extended-spectrum beta-lactamase (ESBL)producers. The multivariate analysis was only performed on those variables that showed statistical significance (p < 0.05) in the univariate analysis. To assess and compare the validity of the biomarkers of shock, we created receiver operating characteristic (ROC) curves.
The study included 349 episodes corresponding to 330 patients. Table 1 shows the main characteristics of the study population. Of all the episodes, 48.6% (169/349) were community-acquired, 24.9% (87/349) were healthcarerelated, and 26.6% (93/349) were nosocomial. Fifty-five percent of the UTI episodes were associated with indwelling bladder catheters. The percentage of patients with urinary catheterization was significantly higher in the group with healthcare and nosocomial-related UTIs than in the group with community-acquired UTIs (OR, 2.6; 95% CI 1.6---4.0; p < 0.001). Some 83.1% (290/349) of the patients presented episodes of pyelonephritis, 57 of whom (16.3%) developed severe sepsis or septic shock. In terms of the inflammatory markers, procalcitonin was a better biomarker of severe sepsis/septic shock than C-reactive protein (area under the ROC curve, 0.73 vs. 0.57; p < 0.001). Total mortality was 10% (37), with a range of 4.85% (community-acquired infections) to 16.8% (healthcare-related/nosocomial infections), half of which was directly attributable to UTI. Of the analyzed epidemiological and clinical variables, age (p < 0.05), healthcarerelated or nosocomial UTIs (OR, 3.8; 95% CI 1.72---8.78, p < 0.001), dementia (OR, 4.1; 95% CI 1.75---9.9; p < 0.001) and clinical presentation such as severe sepsis/septic shock (OR, 4.89; 95% CI 2.3---10.1; p < 0.001) were associated with mortality. The most frequently isolated microorganism was Escherichia coli (E. coli) (57.0%), followed by Klebsiella species (9.7%) (Table 1). We detected polymicrobial infection in 9.3% of the cases. In general, we found no significant differences between the patient groups in terms of microbial spectrum, except in the case of UTI associated with indwelling bladder catheters, which showed a higher rate of infection by Pseudomonas aeruginosa (P. aeruginosa) (OR, 3.9; 95% CI 1.3---11.9; p = 0.009), as well as polymicrobial infections (OR, 3.3; 95% CI 1.3---7.8; p = 0.004). Of all isolated strains, 48 (13.9%) exhibited the ESBL phenotype: E. coli (38), Kleibsella spp.6 and polymicrobials.4 There were no strains of Kleibsella spp. or E. coli resistant to carbapenem. Table 2 shows the variables statistically associated with ESBL infection. In the multivariate analysis, the only predictors of ESBL were the previous use of antibiotics (OR, 5.5; 95% CI 2.4---12.6; p < 0.001), healthcarerelated/nosocomial UTI (OR, 2.8; 95% CI 1.3---6.0; p = 0.008) and infection associated with indwelling bladder catheter (OR, 2.3; 95% CI 1.04---5.1; p = 0.039). Some 87.2% of the isolated strains of ESBL E. coli showed multiresistance criteria (resistant to 3 or more classes of antibiotics). In our series, Enterococcus spp. showed sensitivity rates of 84% to ampicillin and 100% to vancomycin. Empiric antibiotic treatment was administered in 294 (84.2%) episodes. The most widely employed empiric antibiotics in our setting were third-generation cephalosporins (21%), followed by penicillins with beta-lactamase inhibitors (piperacillin/tazobactam) (19%) and amoxicillin/clavulanic acid (15%), carbapenem (12%) and fluoroquinolones (10%). Combined antibiotic therapy was chosen for 8% of the patients. The use of carbapenem was associated with patients with bladder catheters (OR, 3.04; 95% CI 1.4---6.6;
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E. Álvarez Artero et al.
Table 2 Risk factors for infection by extended-spectrum beta-lactamase-producing Escherichia coli and Klebsiella spp. in urinary tract infections in elderly hospitalized patients univariate study. Study variables
% ESBL
Age >85 vs. ≤85 years Women vs. men Dementia vs. no dementia Diabetes vs. no diabetes Steroids vs. no steroids PU vs. no PU Healthcare vs. community Previous UTI vs. no UTI Antibiotics <6 monthsa vs. no antibiotics Previous hospitalization < 3 monthsb Indwelling urinary catheter
20.4 14.8 23.8 18.6 33.3 37.7 30.4 26.7 34.3 36.7 28.5
vs. vs. vs. vs. vs. vs. vs. vs. vs. vs. vs.
20.3 27.2 15.7 20.8 18.3 18.5 10.6 15.0 7.6 14.6 11.1
OR (95% CI)
p
1.0 (0.53---1.889) 0.4 (0.24---0.88) 1.98 (1.01---3.85) 0.8 (0.44---1.70) 2.2 (0.93---5.33) 2.64 (1.18---5.91) 3.70 (1.80---7.44) 2.06 (1.07---3.96) 6.33 (2.85---14.04) 3.39 (1.69---6.78) 3.18 (1.58---6.38)
0.096 0.018 0.042 0.68 0.066 0.015 <0.001 0.027 <0.001 <0.001 0.001
Abbreviations: UTIs, urinary tract infections; PUs, pressure ulcers. a Use of prescribed antibiotics in the 6 months prior to admission. b Hospital admission in the past 3 months.
p = 0.004), especially with a clinical presentation of septic shock (OR, 4.9; 95% CI 1.8---13.4; p < 0.001). The initial empiric antibiotic treatment was appropriate for only 72.6% of the final isolates. We found no differences related to the patients’ residence (p < 0.05). Appropriate treatment was associated with a lower mortality than was associated with inadequate treatment (6.6 vs. 17.2%; OR, 0.38; 95% CI 0.8---1; p = 0.009).
Discussion The aging of the population, which is especially relevant in our community, and the high rate of UTIs in this group have led to a growing interest in knowing how UTIs behave in elderly patients and how they should be treated.11 In this study, we included elderly patients with a definitive diagnosis, with significant comorbidities and who, in many cases, carried indwelling urinary catheters. The most common clinical presentation was pyelonephritis with systemic inflammatory response syndrome, which was often associated with severe sepsis or septic shock. Our study found that E. coli was responsible for more than half of the UTIs, followed by Klebsiella spp., Enterococcus spp., P. aeruginosa and Proteus spp. We found no significant differences between microorganisms or subgroups, except in UTIs associated with urinary catheters, in which the most common infection was by P. aeruginosa or polymicrobial. The prevalence of ESBL-producing enterobacteria was lower than expected, and independent predictors were the prior use of antibiotics, healthcare-related UTIs and indwelling catheter-associated infection. These factors are similar to those described in a recent study on urinary tract infection.12 Another of our study’s objectives was to report on the overall mortality and attributable mortality. Given the patients’ advanced age and the importance of present comorbidities, we considered only the hospital mortality and not the mortality at 30 days. During the hospitalization, more than 10% of the patients died, although only half of these were directly attributable to the UTI. This mortality rate was somewhat higher than that recorded in other
series on overall UTIs in which the rate ranged from 3% to 8.8%13---15 and was identical to that provided by other series on UTIs in the elderly. 16 Among the study variables, only age, healthcare-associated/nosocomial infection, dementia and severe sepsis/septic shock were associated with mortality. In our series, we found no other previously described epidemiological, clinical or laboratory variables associated with high mortality.15,16 Our study assessed the antibiotic treatment protocol administered during the study period. We have shown that inadequate empiric treatment, based on the microbiological results, was generally associated with higher mortality. These data are similar to those of a recent meta-analysis of infection by Gram-negative bacilli17,18 and differ from those of a recent study on catheter-associated UTI.19 This high mortality rate supports the implementation of empiric treatment protocols to treat UTIs in elderly patients with mortality risk factors using broad-spectrum beta-lactams and carbapenems, as suggested in the recent guidelines of the Spanish Society of Infectious Diseases and Clinical Microbiology (SEIMC).20 Lastly, it is worth noting that therapeutic compliance with the SEIMC guidelines increases the use of empiric antibiotic treatments with broad-spectrum carbapenems or beta-lactams in our elderly patients, which would lead to an increase in the consumption of these antibiotics in our hospitals. It is also possible, however, that in the near future, with the implementation of new microbiological rapid-identification methods, such as matrix-assisted laser desorption ionization time-of-flight mass spectrometry, for direct sampling of urine cultures and blood cultures, we could identify the uropathogen causing the infection and determine its resistance profile in a timely manner.21 In conclusion, UTIs in elderly hospitalized patients are frequently associated with the use of urinary catheters and present high mortality. In our setting, the presence of ESBLproducing Enterobacteriaceae is still low and is linked to the use of antimicrobial agents, a nursing home origin and the carrying of an indwelling urinary catheter. Inadequate selection of empiric antimicrobial treatments is associated with high mortality.
Urinary infection in the elderly
Acknowledgements The authors would like to thank Virginia Velasco-Tirado and Jose Angel Martin Oterino for collaborating in this study.
Appendix A. Collaborative Study Group for Urinary Infections in the Elderly María Garcia García, Department of Internal Medicine, University Healthcare Complex of Salamanca (CAUSA), Salamanca, Spain; Inmaculada Galindo Pérez, Primary Care Center, Puente San Miguel, Santander, Cantabria, Spain; Adela Carpio-Pérez, Department of Internal Medicine, CAUSA, Salamanca, Spain.
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