Differential characteristics of bacteraemias according to age in a community hospital

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Rev Clin Esp. 2016;xxx(xx):xxx---xxx

Revista Clínica Española www.elsevier.es/rce

ORIGINAL ARTICLE

Differential characteristics of bacteraemias according to age in a community hospital夽 C. Toyas a,∗ , C. Aspiroz b , R.M. Martínez-Álvarez a , A.I. Ezpeleta c , P. Arazo d , J.C. Ferrando e a

Unidad de Enfermedades Infecciosas, Servicio de Medicina Interna, Hospital Royo Villanova, Zaragoza, Spain Sección de Microbiología, Hospital Royo Villanova, Zaragoza, Spain c Servicio de Medicina Intensiva, Hospital Royo Villanova, Zaragoza, Spain d Unidad de Enfermedades Infecciosas, Servicio de Medicina Interna, Hospital Universitario Miguel Servet, Zaragoza, Spain e Servicio de Medicina Interna, Hospital Royo Villanova, Zaragoza, Spain b

Received 11 January 2016; accepted 19 September 2016

KEYWORDS Bacteraemia; Disability assessment; Elderly; Barthel index; Charlson index

Abstract Objective: To describe the characteristics of bacteraemias, according to age, in a community hospital. Material and method: A prospective study of bacteraemias was conducted in 2011. The patients were classified into 3 age groups: younger than 65 years, 65---79, and 80 or older. The study collected variables on the patients and episodes. Results: The study analyzed 233 bacteraemias in 227 patients (23.8% in those younger than 65 years; 38.3% in the 65---79 age group; and 37.9% in the 80 years or older group). The most common underlying disease in all the groups was diabetes mellitus. In the most elderly patients, the Charlson index was highest, there were a lower proportion of exogenous factors, and almost 25% were severely dependent (Barthel index <20). Escherichia coli was the most common germ, and the main focus was urological. The patients aged 80 years or older had predominantly healthcare-associated infections, less severe symptoms (sepsis) (66.3%) and higher mortality (29.1%) compared with the younger patients. Conclusions: The very elderly patients with bacteraemia presented fewer exogenous factors, greater comorbidity and a poorer functional situation. The most common focus was urological and the origin was healthcare related. Despite their less severe clinical presentation, these patients’ mortality was greater, and their degree of dependence was a highly relevant independent risk factor. © 2016 Elsevier Espa˜ na, S.L.U. and Sociedad Espa˜ nola de Medicina Interna (SEMI). All rights reserved.

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Please cite this article as: Toyas C, Aspiroz C, Martínez-Álvarez RM, Ezpeleta AI, Arazo P, Ferrando JC. Características diferenciales en las bacteriemias según la edad en un hospital comunitario. Rev Clin Esp. 2016. http://dx.doi.org/10.1016/j.rce.2016.09.003 ∗ Corresponding author. E-mail addresses: [email protected], [email protected] (C. Toyas). 2254-8874/© 2016 Elsevier Espa˜ na, S.L.U. and Sociedad Espa˜ nola de Medicina Interna (SEMI). All rights reserved.

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PALABRAS CLAVE Bacteriemia; Evaluación de la discapacidad; Edad avanzada; Índice de Barthel; Índice de Charlson

Características diferenciales en las bacteriemias según la edad en un hospital comunitario Resumen Objetivo: Describir las características de las bacteriemias, según la edad, en un hospital comunitario. Material y método: Estudio prospectivo de las bacteriemias en el a˜ no 2011. Los pacientes se clasificaron en 3 grupos de edad: menos de 65, de 65 a 79 y 80 o más a˜ nos. Se recogieron variables de los pacientes y de los episodios. Resultados: Se analizaron 233 bacteriemias en 227 pacientes (23,8% en < 65; 38,3% entre 65 y 79; y 37,9% en ≥ 80 a˜ nos). La enfermedad de base más frecuente en todos los grupos fue la diabetes mellitus. En los pacientes muy ancianos el índice de Charlson fue mayor, hubo una menor proporción de factores exógenos y casi un 25% eran dependientes graves (índice de Barthel < 20). Escherichia coli fue el germen más frecuente y el foco principal fue el urológico. En los pacientes ≥ 80 a˜ nos predominó el origen de la infección asociado a cuidados sanitarios, la expresividad clínica menos grave (sepsis) (66,3%) y la mortalidad más elevada (29,1%), respecto a los de menor edad. Conclusiones: Los pacientes muy ancianos con bacteriemia presentaron menos factores exógenos, más comorbilidad y una situación funcional peor; el foco más frecuente fue el urológico y el origen el asociado a cuidados sanitarios. A pesar de que su presentación clínica fue menos grave, su mortalidad fue superior, siendo el grado de dependencia una variable de riesgo independiente muy relevante. © 2016 Elsevier Espa˜ na, S.L.U. y Sociedad Espa˜ nola de Medicina Interna (SEMI). Todos los derechos reservados.

Background A profound change in the epidemiology, etiology and clinical characteristics of bacteremias has occurred in recent decades, and their incidence rate has been increasing by 8---9% annually.1 This change has been influenced by the adoption of more invasive diagnostic and therapeutic measures and by patients who are more susceptible to the infections. In Spain, the proportion of individuals older than 80 years is high and growing.2 Medical practitioners must therefore make diagnosis-therapeutic decisions that affect increasingly older and more dependent patients. Bacteremia is no exception and has a number of singular characteristics in elderly patients.3,4 The overall mortality of bacteremia varies between 16% and 40%.1,5 The prognosis depends on variables such as the etiology, location of acquisition, patient characteristics, initial clinical severity, focus of origin and the precocity and appropriateness of the antimicrobial treatment. Furthermore, mortality is related to comorbidity, as measured with the Charlson index6 ; however, the relationship between mortality and the patient’s functional state has been rarely assessed with validated scales such as the Barthel index.7 Studies that have performed this assessment have demonstrated a relationship between mortality by bacteremia and the poorer functional state of the patient.8 Clinical severity follows the defining international criteria of sepsis, severe sepsis and septic shock.9 The main objective of this study was to determine the differential characteristics of bacteremias that required admission to our hospital according to patient age.

Understanding these epidemiological, clinical and microbiological characteristics can help provide information that could result in better care and optimized therapy. The study hypothesis was that functional status (measured with the Barthel index) is a relevant prognostic factor that can also influence the decision making by medical practitioners.

Method Design and setting An epidemiological, observational, descriptive prospective study was conducted of bacteremia cases in adults (older than 14 years) recorded during 2011 at Hospital Royo Villanova of Zaragoza, a second-level general hospital with 235 beds for acute care, 10 beds for intensive care and no pediatric, obstetric or gynecology services. After determining the positivity of the blood cultures, the physicians performed the clinical assessment and assessed the need for counseling on a possible change in the empiric treatment or treating the infectious focus. We excluded bacteremias from patients transferred to other centers or discharged from the emergency department.

Variables collected We collected the following variables: sex, age (divided into 3 groups: younger than 65 years, between 65 and 79 years and 80 years or older), previous Barthel index, chronic underlying diseases, acquired immune deficiency syndrome or other

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Differential characteristics of bacteremias in a community hospital

Statistical analysis A descriptive analysis was conducted on the clinical and microbiological characteristics of the bacteremias in the 3 age groups. A bivariate analysis was conducted first. Statistical significance was established at p < .05. The raw association between the appearance of a certain variable and mortality was estimated by calculating the raw relative risk and its 95% confidence interval. We performed the multivariate analysis of mortality using logistic regression models that included the independent variables that achieved statistical significance in the bivariate analysis. We employed the SPSS 15.0 program for Windows for the statistical analysis and as a database.

Results There were 264 episodes of bacteremia in 258 patients: 227 hospitalized patients (88%), 19 patients discharged from the emergency department (7.4%) and 12 (4.6%) patients transferred to other centers. The 2 latter groups were excluded from the study. In total, we included 233 episodes in 227 patients. There was a predominance of men (59.5%), and the median age was 77 years (IQR, 65---83.2). A total of 86 (37.9%) patients were older than 79 years. The general characteristics of the patients are shown in Table 1. There were no differences by age group in terms of sex, clinical expression, focus of the origin of the bacteremia, comorbidity, other measures for monitoring the focus, Charlson index and mean stay. We observed an association between the type of department (medical or surgical) and age group (p = .015). In the medical departments, there was predominance of patients aged 80 years or older; the surgical departments had a predominance of patients younger than 65 years. The most common underlying disease in all the groups was diabetes mellitus. Cirrhosis was observed in 11.1% of the patients younger than 65 years, which was significantly different compared with the other groups (p = .03). Neoplasia was more common among the

Distribution of patients by type of germ and age groups 18.2% 40.3%

34.8%

31.3%

30.4%

37.5%

31.3%

33.3% 42.9% 36.4%

37.5%

36.4%

53.3%

39.3%

45.5% 34.8%

31.3%

23.4%

31.3% 17.9%

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< 65 years (54)

Figure 1

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immunosuppression condition, Charlson index and exogenous risk factors (central venous catheter, urethral catheter, tracheostomy, endoscopy during the previous week, parenteral nutrition, mechanical ventilation, major surgery during the current hospitalization and internal cerebrospinal fluid shunt). With regard to the bacteremia episode, we included the following variables: etiology and antimicrobial sensitivity, origin (primary or secondary bacteremia or catheterrelated), location of acquisition (community, nosocomial or healthcare-associated [HCAB]),10 clinical expression (sepsis, severe sepsis or septic shock at the onset of the episode), other cultivated samples, hospital areas (medical and surgical departments), empiric antibiotherapy based or not on the treatment recommendations for focal infection11 and whether the infection was early (in the first 3 h) since the arrival at the emergency department, other measures taken on the focus (withdrawal of foreign material, intravascular catheter and surgical, endoscopic or percutaneous drainage), length of stay in days and condition at discharge (clinical healing or exitus).

3

65 - 79 years (87)

≥ 80 years (86)

Patient distribution by germ type and age group.

younger than 65 years group than in the 80 years or older group. The exogenous factors were inversely related to age, with a lower proportion among the 80 years or older group (p = .011). A urological focus was the most common in all groups. The focus was directly treated in 11% of the patients (Table 2). HCABs were more common the greater the age, and community bacteremias were more common among the younger patient, although without significant differences. We observed a tendency toward a more severe clinical expression in intermediate ages. Fifteen percent of the patients required admission to the intensive care unit, in particular the younger patients (p = .034). Escherichia coli (E. coli) was the most common germ in all age groups (Fig. 1). Empiric treatment was applied equally early in the 3 groups. There were significant differences in terms of the appropriateness of the treatment according to the guidelines, with less appropriateness in the younger participants (Table 3). Hospital mortality was higher in the 80 years or older patients compared with the other groups (29.1% vs. 16.1% and 13%; p = .028). The following variables were associated with mortality in the bivariate analysis: (1) age 80 years or older; (2) Charlson index ≥4; (3) Barthel index ≤20; (4) more severe clinical expression; (5) respiratory focus; (6) hospitalization in a medical department; (7) cirrhosis; (8) immunosuppression; and (9) etiology other than E. coli. Only the first 5 associations achieved significance in the multivariate analysis (Table 4).

Discussion There are various studies on bacteremia according to patient age, but their results are conflicting.3,4,12 In our study, more than 75% of the patients were older than 65 years. In these patients, the clinical presentation of the bacteremia episodes was frequently atypical and could manifest as a loss or impairment of consciousness.1,13

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C. Toyas et al. Table 1

General characteristics by age group.

Characteristic

Total

<65 years

≥80 years

65---79 years

n

%

n

%

n

%

N

%

227

100

54

23.8

87

38.3

86

37.9

p Value

Male sex Mean Charlson index (SD)

135 2.3

59.5 2.2

34 2

63.0 2.1

58 2.3

66.7 2.2

43 2.5

50.0 2.2

ns ns

Medical services Medical Surgical

162 65

71.4 28.6

32 22

59.3 40.7

60 27

69 31.0

70 16

81.4a 18.6

.015

Underlying diseases Diabetes COPD Neoplasia Cirrhosis

82 30 23 10

36.1 13.2 10.1 4.4

18 4 9 6

33.3 7.4 16.7 11.1a

37 11 10 3

42.5 12.6 11.5 3.4

27 15 4 1

31.4 17.4 4.7 1.2

ns ns ns .03

Exogenous factors Urinary catheter Central venous catheter Chemotherapy Parenteral nutrition Instrumentation

70 39 23 17 8 10

30.8 17.2 10.1 7.5 3.5 4.4

23 9 6 5 3 6

42.6 16.7 11.1a 9.3a 5.6a 11.1a

30 18 13 10 5 3

34.5 20.7 14.9a 11.5 5.7 3.4

17 12 4 2 0 1

19.8 14 4.7 2.3 0 1.2

.011 ns .031 .048 .045 .001

Degree of dependence (BI) Independent Mild Moderate/Severe Total

112 29 51 35

49.3 12.8 22.5 15.4

41 3 6 4

75.9a 5.6 11.1 7.4

45 13 19 10

51.7 14.9 21.8 11.5

26 13 26 21

30.2 15.1 30.2a 24.4a

.013

81 51 41 36 7 11

35.7 22.5 18.1 15.9 3.1 4.8

21 6 11 10 2 4

38.9 11.1 20.4 18.5 3.7 7.4

27 22 18 17 3 0

31 25.3 20.7 19.5 3.4 0

33 23 12 9 2 7

38.4 26.7 14 10.5 2.3 8.1

ns ns ns ns -----

Location of acquisition Community HCA Nosocomial

106 48 73

46.7 21.1 32.2

30 8 16

55.6 14.8 29.6

39 17 31

44.8 19.5 35.6

37 23 26

43 26.7 30.2

ns

Clinical expression No criteria Sepsis Severe sepsis Septic shock

1 139 64 23

0.4 61.2 28.2 10.1

1 32 18 3

1.9 59.3 33.3 5.6

--50 24 13

--57.5 27.6 14.9

--57 22 7

--66.3 25.6 8.1

--ns

34 46

15 20.3

13 7

24.1 13

14 14

16.1 16.1

7 25

8.1 29.1a

.034 .028

Clinical focus Urological Abdominal Respiratory Associated with venous catheter Unknown Others

ICU Mortality

Abbreviations: BI, Barthel index; COPD, chronic obstructive pulmonary disease; ICU, intensive care unit; HCA, healthcare-associated. a Modality of the variable for which statistical significance was found.

In our study, the oldest population (80 years or older) had significantly more admissions to medical departments, as has already been reported by other authors.14 The comorbidity measured by the Charlson index increased with age without achieving statistical significance. However, cirrhosis and malignancies predominated in the younger groups. In the multivariate analysis, the predictors of mortality were a Charlson index ≥4, age, respiratory focus and, most

consistently, clinical expression and the functional state of severe dependence. In terms of the functional state, we found a greater degree of dependence with age, with almost 25% of severe dependency among the older patients. A severe degree of dependence (Barthel index ≤20) was associated with a 6fold greater mortality than that of patients with a Barthel index >20. We therefore believe that calculating the Barthel

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Differential characteristics of bacteremias in a community hospital Table 2

Other therapeutic measurements by age group. Total

Endoscopic drainage Surgical drainage Percutaneous drainage Material withdrawal

Table 3

5

<65 years

≥80 years

65---79 years

n

%

n

%

n

%

n

%

25 14 5 1 5

11 6.2 2.2 0.4 2.2

6 4 1 0 1

11.1 7.4 1.9 0 1.9

11 5 4 1 1

12.6 5.7 4.6 1.1 1.1

8 5 0 0 3

9.3 5.8 0 0 3.5

Antimicrobial treatment by age group. Total

<65 years

≥80 years

65---79 years

n

%

n

%

n

227

100

54

23.8

87

% 38.3

p Value

n

%

86

37.9

85 1

98.8 1.2

ns

Empiric treatment With treatment Without treatment

222 5

97.8 2.2

50 4

92.6 7.4

87 0

Early treatment <1 h <3 h

166 60 106

73.1 26.4 46.7

39 16 23

72.2 29.6 42.6

63 22 41

72.4 25.3 47.1

64 22 42

74.4 25.6 48.8

ns ns

62.6 37.4

25 29

46.3 53.7a

57 30

65.5 34.5a

60 26

69.8 30.2a

.028

Treatment adjusted to the guidelines Yes 142 No 85 a

100 0

Modality of the variable for which statistical significance was found.

index prior to patient admission helps assess the prognosis and can influence the healthcare decision-making process. Septic shock, the most severe form of clinical expression, appeared less frequently in the patients 80 years or older. In the study by Payeras et al.,3 septic shock was distributed equally among all age groups, although in this series almost half of the patients did not meet the criteria for sepsis. It is possible that this lower clinical severity in the elderly patients is the result of a lesser systemic response to the aggression, the origin of the infection (urological) and the more typical causal germ for bacteremia (E. coli).4,8,15 A urological focus was the most common in all age groups. Unlike other studies,3,5,16,17 the number of patients with an unknown focus was very low. We believe that this is due in considerable measure to the systematic search for the focus and to the routine implementation of a urine culture

Table 4 Multivariate analysis of the factors associated with mortality. Variables

OR

95% CI

p Value

Age < or ≥80 years Charlson index < or ≥4 Barthel index > or ≤20 Severe sepsis or septic shock Respiratory focus

3.36 3.98 6.01 7.13

1.40---8.05 1.55---10.22 2.58---14.04 2.93---17.33

.007 .004 <.001 <.001

3.75

1.40---10

Abbreviations: CI, confidence interval; OR, odds ratio.

.008

of pyuric urine samples (leukocyturia >500 ␮/L) for patients with suspected sepsis. The next most frequent focus in the oldest group was abdominal, unlike other studies that indicated a respiratory focus.14 The respiratory origin was the second most frequent focus in our younger patients, a finding already reported by Mu˜ noz-Gamito et al.4 In terms of location of acquisition, HCABs increased in percentage with age, because a significant portion of these patients live in an institution, as has been previously documented.4 Measures to monitor the focus were performed in a significant number of patients. This finding does not appear to be reflected in most articles but could significantly influence the progression of the infectious condition. Ruiz-Giardin et al. found an association between surgical treatment of the focus of infection and lower mortality.14 Appropriate treatment according to guidelines approached 70% in the oldest group. However, therapeutic appropriateness in the younger group did not reach 50%. One of the causes for this finding could be the presence of catheter-related bacteremia, which is common in surgical patients for whom an initial antimicrobial coverage was prescribed in consideration of the complication of the surgical focus and not of the central venous catheter. The overall rate of mortality in the patients 80 years or older was 29.1%, significantly greater than that of the other age groups. Numerous studies have demonstrated an increase in mortality with age, which the authors attributed to causes such as the aging of the immune system, a poorer

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6 nutritional state, an increased prevalence of chronic diseases, a delay in seeking care and the suspected presence of a severe infection.3,16---18 We should take into account that the functional state of these patients was poorer, which could have influenced the physician’s decision to limit the diagnostic and therapeutic effort and which affects the final outcome. This unsettling finding has already been reported by Payeras in a recent editorial.19 Our study’s limitations include the fact that we did not specifically collect information on the nutritional state, mortality at 30 days, the reason for considering the bacteremia as healthcare-associated or the appropriateness of the empiric antimicrobial treatment to the germ sensitivity. In conclusion, the age is an independent mortalityrelated variable in bacteremia. Functional status has a relevant influence on the final outcome and is easy to assess. Its use is highly recommended when caring for these patients. The most common focus is urological. The systematic collecting of a urine culture can therefore offer valuable information for the diagnostic process. HCABs are more common in the elderly population, given that many of these patients are institutionalized.

Conflicts of interest

C. Toyas et al.

6.

7. 8.

9.

10.

11.

12.

13.

The authors declare that they have no conflicts of interest. 14.

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