Diagnostic Microbiology and Infectious Disease xxx (2016) xxxxxx

Contents lists available at ScienceDirect

Diagnostic Microbiology and Infectious Disease

journal homepage: www.elsevier.com/locate/diagmicrobio

Risk factors and outcomes of afebrile bacteremia patients in an

emergency department,,
Chia-Hung Yo a, Meng-tse Gabriel Lee b,
Yenh-Chen Hsein c, Chien-Chang Lee b, National Taiwan University Hospital Health Outcome and
Economics Research Group
a
b
c

Department of Emergency Medicine, Far Eastern Memorial Hospital, Taipei, Taiwan

Department of Emergency Medicine, National Taiwan University Hospital, Taipei, Taiwan
Department of Laboratory Medicine, National Taiwan University Hospital Yun-Lin Branch, Yun-Lin, Taiwan

a r t i c l e

i n f o

a b s t r a c t

Article history:
Received 24 March 2016
Received in revised form 16 August 2016
Accepted 22 August 2016
Available online xxxx
Keywords:
Afebrile
Bacteremia
Risk factors

Objective: There is limited research on afebrile bacteremia. We aimed to compare the risk factors and outcomes of
patients with afebrile and febrile infections.
Methods: This was a retrospective cohort study of bloodstream isolates from 994 adults admitted to the
emergency department of a university hospital. Afebrile infections, dened as the absence of fever history or
measured fever through the emergency department course, was compared with febrile infection. Frequencies
and proportions of sources of infection, comorbidities, along with organ failure and mortality were presented.
The major outcome measure was 30-day survival. chi-Square or Student's t test was used for univariate analysis,
and Cox proportional hazard model was used for multivariate analysis.
Results: We found that the risk factors and outcomes of febrile and afebrile bacteremia patients were very
different. The afebrile patients were older, have higher Charlson comorbidity index, and had poorer outcomes
than the febrile patients. We also found that oldest old age, nonhematologic malignancy, necrotizing fasciitis,
spontaneous bacterial peritonitis, and pneumonia were each positive independent predictors of afebrile
bacteremia, whereas Escherichia coli infection and liver abscess were independent negative predictors of afebrile
bacteremia. Finally, the 30-day all-cause mortality was higher in the afebrile group than in the febrile group
(45% versus 12%, log-rank P b 0.001).
Conclusions: This series of patients with afebrile bacteremia conrmed the previously reported associations with old
age and immunocompromised conditions. Clinicians should explore the possibility of occult severe infection, and initiate early hemodynamic support and empirical antimicrobial therapy for patients with the aforementioned risk factors.
2016 Elsevier Inc. All rights reserved.

1. Introduction
The establishment of systemic inammatory reaction syndrome
(SIRS) criteria has greatly aided clinicians to detect systemic infection
(Dellinger et al., 2013; Jones and Lowes, 1996; Levy et al., 2003).
However, fever is still the most commonly used criterion for initiating
infection workup. Fever is a complex and often nonspecic host defense
Following guideline: STROBE.
This study is supported by the Taiwan National Science Foundation Grant NSC 1022314-B-002-131-MY3; Taiwan National Ministry of Science and Technology Grants MOST
104-2314-B-002-039-MY3, and MOST 105-2811-B-002-031; Far Eastern Memorial
Hospital Grants FEMH-2015-C-016 and FEMH-2016-C-028; and Far Eastern Memorial
Hospital and National Taiwan University Hospital Cooperation Grant 105-FTN14.
No funding bodies had any role in the study design, data collection and analysis, decision
to publish, or preparation of the manuscript.
The authors have no conicts of interest to disclose.
Corresponding author. Tel.: +886-2-23565926; fax: +886-2-23223150.
E-mail address: cclee100@gmail.com (C.-C. Lee).

mechanism against infection. Frequently, patients with bacteremia may

be presented to the emergency department (ED) without any fever
(Gleckman and Hibert, 1982; Norman, 2000). Unfortunately, the clinical
characteristics and outcomes of this group of afebrile patients were
rarely described in the literature. In this study, clinical and laboratory
features of 140 consecutive afebrile bacteremic patients presented
to the ED were described and compared with the rest of 797 febrile
bacteremic patients during the 1-year study period. Our goal is to identify specic independent risk factors and source of infections associated
with afebrile bacteremia.

2. Methods
2.1. Population and setting
A retrospective observational study was conducted in the ED at
National Taiwan University Hospital (NTUH) from June 1, 2010, to

http://dx.doi.org/10.1016/j.diagmicrobio.2016.08.020
0732-8893/ 2016 Elsevier Inc. All rights reserved.

Please cite this article as: Yo C-H, et al, Risk factors and outcomes of afebrile bacteremia patients in an emergency department, Diagn Microbiol
Infect Dis (2016), http://dx.doi.org/10.1016/j.diagmicrobio.2016.08.020
Downloaded from ClinicalKey.com at UNIVERSIDAD AUTONAMA DE NUEVA LEON September 19, 2016.
For personal use only. No other uses without permission. Copyright 2016. Elsevier Inc. All rights reserved.

C-H. Yo et al. / Diagnostic Microbiology and Infectious Disease xxx (2016) xxxxxx

June 1, 2011. NTUH is a primary and tertiary care hospital with 2400
beds and annual ED census more than 100,000 visits. This study is approved
by the institutional review board of National Taiwan University Hospital.
During the study period, ED patients who were presented with a
clinical manifestation of SIRS or clinical indication of severe infection
such as pneumonia, cellulitis, abscess formation, cholecystitis, or pyelonephritis in the absence of SIRS were enrolled. Patients under 15 years
of age and a negative blood culture were excluded in this study. True
bacteremia was dened as positive blood cultures for at least 2 sets at
separate sites, or alternatively 1 set for gram-positive pathogen/gramnegative pathogen in a patient with an intravascular device and clinical
compatibility.
The following data were collected retrospectively for all eligible
patients from admission to discharge: demographic characteristics,
preexisting comorbid medical conditions, exposure to indwelling
catheters, initial vital signs, and laboratory tests, admission and nal discharge diagnoses, and microorganisms isolated from the blood cultures.
Vital sign data were taken from both the physician and nursing records.
Information included initial values and maximum temperature over a
patient's ED course, oxygen saturation, blood pressure, respiratory rate,
and heart rate. Patient outcomes were dened as 30-day all-cause mortality acquired either by hospital records or telephone interviews.

percentage. For univariate analysis, the comparison between categorical

variables was done using the chi-square test or Fisher exact test.
MannWhitney test was used for continuous variables because they
were not normally distributed. Characteristics identied by the univariate analyses as potential risk factors were considered for inclusion in a
multivariate logistic regression analysis. A multiple logistic regression
analysis was conducted to determine the independent nature of the
risk factors while adjusting for other characteristics. To select the best
combination of explanatory variables, only those variables with a
P b 0.020 were included in the model. In addition, these variables only
remained in the model if they were signicantly related to the response
variable (P b 0.10).
Kaplan-Meier survival analysis was used to test survival differences
between febrile and afebrile bacteremic patients. The means were compared by log-rank test. Cox proportional hazards regression model was
used to estimate the independent effects of absence of fever on 30-day
survival. Assumptions of the Cox regression were tested and met.
Included controlled factors include age, sex, comorbidity by Charlson
index, and clinical severity. Statistical analyses were performed using
SPSS software for Window (Release 13.0; SPSS, Chicago, IL).

2.2. Denitions

During the 12-month study period, 994 consecutive episodes of

bacteremia were enrolled in the study. Fifty-seven episodes were
excluded from the analysis because of repeated infection and nally
937 episodes were enrolled. Afebrile bacteremia was detected in
140 of 937 (14.9%) episodes.

The afebrile state was dened as tympanic temperature less than

38 C through a patient's ED course and absence of a history of fever
by the patient himself or the primary caregiver. Elderly and oldest old
were dened as age equal or greater than 65 years and 85 years, respectively. Patients presented to the ED within 48 hours of hospital discharge were deemed as nosocomial infections and the remainder was
viewed as community-onset bacteremia. Comorbidities were measured
by Charlson index, a well-validated, 19-item index for the prediction of
short-term and long-term mortality (Charlson et al., 1987).
To investigate the severity of bacteremia associated with the patients, we used common laboratory data and 4 clinical signs to indicate
organ failures. 1) Altered level of consciousnessGlasgow Coma Scale
score of less than 12 or a decrease in the score of at least 3 if primary central nervous system injury is present; 2) acute respiratory distresspulse
oxygen saturation less than 90%; 3) acute renal failureserum creatinine
level greater than 265 mol/L or, in the case of preexisting renal dysfunction, a doubling of previous serum creatinine values; 4) acute upper gastrointestinal bleedingbleeding derived from a source proximal to the
ligament of Treitz, as conrmed by endoscopy.
We used modied versions of previously dened consensus criteria
for dening the different sepsis syndromes (Dellinger et al., 2013; Levy
et al., 2003). SIRS was dened as the presence of 2 or more of the following: a) tachycardia (heart rate 90); b) tachypnea (respiratory rate 20) or
hypoxia (oxygen saturation b95% or need for oxygen supplementation);
c) hyperthermia 38 C or hypothermia 35.5 C; d) leukocytosis (white
blood cell count 15,000 cells/mm3 or bands 10%). Severe sepsis was dened as 2 or more criteria for SIRS plus organ failure. Septic shock was
dened as severe sepsis plus hypotension (systolic blood pressure
b90 mmHg). The presence and source of a focal infection were classied
as primary bacteremia, urinary tract infection, biliary tract infection,
pneumonia, liver abscess, spontaneous bacterial peritonitis, skin and
musculoskeletal infection, intraabdomen infection, infective endocarditis, necrotizing fasciitis, central nervous system infection, and catheter
related infection. The surveillance strategy, denitions did not change
over the study period.
2.3. Statistical analysis
The characteristics of the afebrile and febrile patients were
described and compared. Continuous variables were presented as mean
and SD, whereas categorical variables were presented as frequency and

3. Results

3.1. Demographic characteristics and underlying comorbidities

We stratied 937 patients into febrile and afebrile groups, as shown
in Table 1. The male to female ratio was approximately the same in
both groups. The afebrile patients were older than febrile patients
(P = 0.007). The oldest old (age 85) patients, rather than the elderly
(age 65), were associated with the development of afebrile bacteremia
(P = 0.003). Patients with underlying nonhematologic malignancy
have a signicantly higher propensity to develop afebrile bacteremia
(P = 0.002). Patients with liver cirrhosis also tend to have afebrile bacteremia, but the statistical signicance was not attained (P = 0.055).
Other underlying comorbid conditions were not found to be signicantly associated with afebrile bacteremia. In general, patients with higher
Charlson comorbidity index tend to have more afebrile episodes and
vice versa.
3.2. Selected microbiological features and sources of infection
Microbiological data for patients with primary bloodstream infections were given in Table 2. Of the 937 infections, the majority of infections involved gram-negative aerobic organisms (663, 70.8%), followed
by gram-positive aerobes (230, 27.7%), and anaerobes (51, 5.4%).
Eighty-four (9.0%) episodes were polymicrobial infections in which
more than 1 organism was identied. The distributions of bacteria isolated from blood cultures were similar in febrile and afebrile patients
except for E. coli. E. coli was associated with more febrile bacteremia
(P = 0.002). Besides, in our study E. coli was the most common bacterium among gram-negative bacteria, and was seen more often in patients
with diabetes or urinary tract infection (P b 0.001).
The sources of bacteremia were different between afebrile
and febrile patients (Table 3). Certain types of infections were
more commonly seen in afebrile patients including pneumonia (P =
0.02), spontaneous bacterial peritonitis (P = 0.006), and necrotizing
fasciitis (P = 0.012). On the other hand, liver abscess (P = 0.018)
and urinary tract infection (P = 0.003) were more commonly seen in
febrile patients.

Please cite this article as: Yo C-H, et al, Risk factors and outcomes of afebrile bacteremia patients in an emergency department, Diagn Microbiol
Infect Dis (2016), http://dx.doi.org/10.1016/j.diagmicrobio.2016.08.020
Downloaded from ClinicalKey.com at UNIVERSIDAD AUTONAMA DE NUEVA LEON September 19, 2016.
For personal use only. No other uses without permission. Copyright 2016. Elsevier Inc. All rights reserved.

C-H. Yo et al. / Diagnostic Microbiology and Infectious Disease xxx (2016) xxxxxx
Table 1
A comparison of demographic characteristics and underlying comorbidities between
patients with afebrile and febrile bacteremia.

Total
Age (y)
Elderly patients
Oldest old (age 85 years)
Gender (Male)
Nosocomial infection
Prior use of steroids
Indwelling catheter
Underlying comorbidity
Diabetes mellitus
End-stage renal disease
Liver cirrhosis
Hemiparetic stroke
HIV infection
Hematologic malignancy
Nonhematologic malignancy
Charlson Score
01
25
69

Afebrile bacteremia
(n = 140)

Febrile bacteremia
(n = 797)

140/937 (14.94%)
66.67 17.46
80 (57.1%)
19 (13.6%)
70 (50.0%)
11 (7.9%)
5 (3.6%)
15 (10.7%)

797/937 (85.05%)
62.35 17.37
416 (52.2%)
54 (6.8%)
418 (52.4%)
36 (4.5%)
30 (3.8%)
88 (11.0%)

0.007
0.279
0.006
0.593
0.095
0.912
0.909

35 (25.0%)
7 (5.0%)
23 (16.4%)
24 (17.1%)
1 (0.7%)
3 (2.1%)
45 (32.1%)

249 (31.2%)
43 (5.4%)
86 (10.8%)
140 (17.6%)
7 (0.9%)
38 (4.8%)
162 (20.3%)

0.138
0.848
0.055
0.901
0.846
0.161
0.002

41 (29.3%)
69 (49.3%)
30 (21.4%)

324 (40.7%)
377 (47.3%)
96 (12.0%)

0.011
0.665
0.003

Table 3
A comparison of microbiological ndings between patients with afebrile and febrile
bacteremia.
Independent factors associated with afebrile bacteremia
Positive predictors
Necrotizing fasciitits
Spontaneous bacterial peritonitis
Age 85
Pneumonia
Nonhematologic malignancy
Negative predictors
E. coli infection
Liver abscess

Adjusted odds ratio,

95% condence interval
9.49, 2.0643.75
2.71, 1.305.64
2.22, 1.33.97
1.88, 1.063.33
1.67, 1.112.53
0.54, 0.350.83
0.14, 0.201.06

were diagnosed with severe sepsis or septic shock, while a lower

percentage with SIRS.
3.4. Outcome and survival

Results on the multivariate analysis of risk factors for afebrile bloodstream infection in the study cohort were shown in Table 3. Necrotizing
fasciitis, spontaneous bacterial peritonitis, age greater than 85,
pneumonia, and nonhematologic malignancy were independent risk
factors associated with the development of afebrile bacteremia,
whereas E. coli infection and liver abscess were independently associated
with febrile bacteremia.

The overall mortality rate of bacteremia in this study was 17.0%. The
30-day all-cause mortality was higher in the afebrile group than in the
febrile group (45% versus 12%, log-rank P b 0.001). Kaplan-Meier survival curves for 30-day survival comparing afebrile and febrile patients
were shown in Fig. 1. The mean length of hospitalization was longer
for surviving afebrile patients than for surviving febrile patients (29.25
versus 21.46 days, P = 0.049). Controlling for age, sex, underlying comorbidities (Charlson index), and clinical severity (sepsis classication)
in the Cox-regression model, afebrile episodes was independently associated with an increased probability of 30-day mortality (adjusted hazard ratio, 95% condence interval, 2.76, 1.9833.836).

3.3. Clinical and laboratory manifestations

4. Discussion

Afebrile patients tend to be more critically ill than febrile ones

(Table 4). A higher percentage of afebrile patients were noted to
develop organ failures. These organ failures include altered level of
consciousness (P b 0.001), acute respiratory distress (P b 0.001), acute
renal failure (P b 0.001), and acute upper gastrointestinal bleeding
(P b 0.001). The laboratory manifestations were generally comparable
in both groups, except for a higher proportion of bandemia in afebrile
patients. On sepsis classication, a higher percentage of afebrile patients

In this study of 994 bacteremia patients, we found that the epidemiology and outcome of febrile and afebrile patients are very different.
The afebrile patients were older, have higher Charlson comorbidity
index, and have a poorer outcome than the febrile patients. We also
found that oldest old age, nonhematologic malignancy, necrotizing
fasciitis, spontaneous bacterial peritonitis, and pneumonia were each
positive independent predictors of afebrile bacteremia, whereas E. coli
infection and liver abscess were independent negative predictors of
afebrile bacteremia.
Previous studies described that afebrile bacteremia is a unique manifestation of geriatric or immunocompromised patients (Drewry et al.,
2013; Girard et al., 2005; Gleckman and Hibert, 1982; Hernandez-Bou
et al., 2014; Kameda et al., 2015; Norman, 2000; Richardson, 1993).

Table 2
A comparison of the source of bacteremia between patients with afebrile and febrile
bacteremia.
Source of bacteremia

Afebrile
bacteremia
(n = 147)

Febrile
bacteremia
(n = 847)

Gram-negative pathogen
Gram-positive pathogen
Anaerobe
Polymicrobial infection
E. coli

Primary bacteremia
Urinary tract infection
Biliary tract infection
Pneumonia
Liver abscess
Spontaneous bacterial peritonitis
Skin and musculoskeletal infection

Intraabdomen infection
Infective endocarditis
Necrotizing fasciitis
Central nervous system infection
Catheter related infection

94 (67.1%)
35 (23.8%)
7 (5.0%)
15 (10.7%)
32 (22.9%)
31 (22.1%)
22 (15.7%)
19 (13.6%)
20 (14.3%)
1 (0.7%)
12 (8.6%)
9 (6.4%)
6 (4.1%)
6 (4.3%)
4 (2.9%)
2 (1.4%)
5 (3.6%)

569 (71.4%)
195 (23.0%)
44 (5.5%)
69 (8.7%)
292 (36.6%)
136 (17.1%)
221 (27.7%)
127 (15.9%)
54 (6.8%)
42 (5.3%)
28 (3.5%)
78 (9.8%)
28 (3.4%)
36 (4.5%)
3 (0.4%)
8 (1.0%)
34 (4.3%)

0.308
0.301
0.802
0.432
0.002
0.148
0.003
0.477
0.002
0.018
0.006
0.207
0.652
0.903
0.012
0.652
0.704

Sources of unknown origin.

Including hollow organ perforation, appendcitis, pancreatitis, neutropenic enterocolitis,
and diverticulitis.

Table 4
A comparison of the severity of clinical and laboratory manifestations between patients
with afebrile and febrile bacteremia.
Clinical and laboratory manifestations

Afebrile
bacteremia
(n = 147)

Febrile
bacteremia
(n = 847)

Altered level of consciousness

Acute respiratory distress
Acute renal failure
Acute upper gastrointestinal bleeding
Anemia (hemoglobin b10 mg/dL)
Bandemia (band N10%)
Leukopenia (white blood cell b4000/mm3)
Thrombocytopeina (platelets b5000/mm3)
Tachycardia (pulse rate N90)
Simple bacteremia
SIRS
Severe sepsis
Septic shock

44 (31.4%)
37 (26.4%)
30 (21.4%)
32 (22.9%)
41 (29.3%)
36 (25.7%)
19 (13.6%)
16 (11.4%)
96 (66.7%)
7 (5.0%)
37 (20.0%)
48 (36.4%)
54 (38.6%)

100 (12.5%)
56 (7.0%)
73 (9.2%)
66 (8.3%)
193 (24.2%)
97 (12.2%)
87 (10.9%)
96 (12.0%)
679 (80.6%)
39 (4.9%)
452 (56.7%)
169 (21.2%)
137 (17.2%)

b0.001
b0.001
b0.001
b0.001
0.301
b0.001
0.360
0.797
b0.001
0.957
b0.001
b0.001
b0.001

Please cite this article as: Yo C-H, et al, Risk factors and outcomes of afebrile bacteremia patients in an emergency department, Diagn Microbiol
Infect Dis (2016), http://dx.doi.org/10.1016/j.diagmicrobio.2016.08.020
Downloaded from ClinicalKey.com at UNIVERSIDAD AUTONAMA DE NUEVA LEON September 19, 2016.
For personal use only. No other uses without permission. Copyright 2016. Elsevier Inc. All rights reserved.

C-H. Yo et al. / Diagnostic Microbiology and Infectious Disease xxx (2016) xxxxxx

2000; Richardson, 1993), and illustrates the newly found positive or

negative association with certain diseases or bacteria. Delayed or inappropriate antimicrobial therapy might occur for these patients. When
caring for patients with aforementioned risk factors manifested with
unexplained deterioration (such as, altered level of consciousness,
respiratory distress, upper gastrointestinal bleeding, acute renal failure,
or shock), clinicians should explore the possibility of occult severe
infection and initiate early hemodynamic support and empirical
antimicrobial therapy as indicated.
Author contributions
Chia-Hung Yo: data collection, data management, statistics, wrote
rst draft and reviewed nal draft.
Meng-Tse Gabriel Lee: statistics, reviewed rst draft and reviewed
nal draft.
Yenh-Chen Hsein: data review and analysis, and reviewed nal draft.
Chien-Chang Lee: study design, data collection, data management,
statistics, wrote rst draft, reviewed nal draft and research funding.
Fig. 1. Kaplan-Meier survival analysis between afebrile 1) and febrile 0) bacteremic
patients. Log-rank test, P b 0.001.

We further claried that the oldest old group and nonhematologic

malignancy are the comorbid conditions that most prone to develop
afebrile bacteremia. Besides, we identied that certain disease categories were positively or negatively associated with afebrile bacteremia,
which may offer clinicians a clue for early recognition of the occult
severe infection.
The prognosis of the afebrile bacteremia is grave, with a 30-day all
cause mortality reaching 45% in our series. The cause of this high
mortality could be partly attributed to the lowered level of warning by
the clinicians. This can probably be reected by the signicantly higher
proportion of inappropriate or absent of antimicrobial therapy (Angus
and van der Poll, 2013; Armen et al., 2014; Kramer et al., 2015; Mouncey
et al., 2015; Paul et al., 2010; van Zanten, 2014; Yokota et al., 2014)
within 24 hour of admission, and even within 1 hour when sepsis was
found (Barie et al., 2005; Castellanos-Ortega et al., 2010; Ferrer et al.,
2009, 2014; Kumar et al., 2006).
In our study, afebrile patients had 23-fold higher incidence of
accompanying organ failures than febrile patients. It is possible that
the organ failures were associated with the compromised immune
system, as fever itself is a marker for a sound immune response.
Thus, we looked at the prognostic potential of fever after controlling
for underlying comorbidity, age, and clinical severity. Interestingly,
lack of fever response still stood out as a strong poor prognosticator
for 30-day survival.
One limitation of this study was that there's no objective measurement of body temperature for every included patient before ED visit.
The sole reliance on the subjective history of the patients or primary
care takers may inevitably lead to some recall bias. Besides, it is probable
that some patients, of whom we were unaware, presented to other institutions with afebrile bacteremia but not recognized by the physicians.
Also, the relative higher prevalence of liver cirrhosis and liver abscess,
and relative lower prevalence of HIV infections in our series may affect
the results of analysis on clinical predictors of afebrile bacteremia. Other
studies on different cohort with different background epidemiology
of comorbidities may lead to different predictors. Another limitation
of this study is the lack of information on specic pathogens, such
as hypermucoviscous Klebsiella pneumoniae, methicillin-susceptible
Staphylococcus aureus, and methicillin-resistant S. aureus. It will be
interesting to nd out whether some of these pathogens may result in
a higher frequency of afebrile bacteremia.
This series of patients with afebrile bacteremia conrmed the
previously reported associations with old age and immunocompromise
conditions (Drewry et al., 2013; Girard et al., 2005; Gleckman and
Hibert, 1982; Hernandez-Bou et al., 2014; Kameda et al., 2015; Norman,

Acknowledgement
We thank Medical Wisdom Consulting Group for technical
assistance in statistical analysis, and the staff of the Core Labs, Department
of Medical Research at the National Taiwan University Hospital for
technical support.
References
Angus DC, van der Poll T. Severe sepsis and septic shock. N Engl J Med 2013;369:84051.
Armen SB, Freer CV, Showalter JW, Crook T, Whitener CJ, West C, et al. Improving outcomes
in patients with sepsis. Am J Med Qual 2014.
Barie PS, Hydo LJ, Shou J, Larone DH, Eachempati SR. Inuence of antibiotic therapy on
mortality of critical surgical illness caused or complicated by infection. Surg Infect
(Larchmt) 2005;6:4154.
Castellanos-Ortega A, Suberviola B, Garcia-Astudillo LA, Holanda MS, Ortiz F, Llorca J, et al.
Impact of the surviving sepsis campaign protocols on hospital length of stay and
mortality in septic shock patients: results of a three-year follow-up quasiexperimental study. Crit Care Med 2010;38:103643.
Charlson ME, Pompei P, Ales KL, MacKenzie CR. A new method of classifying prognostic
comorbidity in longitudinal studies: development and validation. J Chronic Dis
1987;40:37383.
Dellinger RP, Levy MM, Rhodes A, Annane D, Gerlach H, Opal SM, et al. Surviving sepsis
campaign: international guidelines for management of severe sepsis and septic
shock: 2012. Crit Care Med 2013;41:580637.
Drewry AM, Fuller BM, Bailey TC, Hotchkiss RS. Body temperature patterns as a predictor
of hospital-acquired sepsis in afebrile adult intensive care unit patients: a casecontrol study. Crit Care 2013;17:R200.
Ferrer R, Artigas A, Suarez D, Palencia E, Levy MM, Arenzana A, et al. Effectiveness of treatments for severe sepsis: a prospective, multicenter, observational study. Am J Respir
Crit Care Med 2009;180:8616.
Ferrer R, Martin-Loeches I, Phillips G, Osborn TM, Townsend S, Dellinger RP, et al. Empiric
antibiotic treatment reduces mortality in severe sepsis and septic shock from the rst
hour: results from a guideline-based performance improvement program. Crit Care
Med 2014;42:174955.
Girard TD, Opal SM, Ely EW. Insights into severe sepsis in older patients: from epidemiology to evidence-based management. Clin Infect Dis 2005;40:71927.
Gleckman R, Hibert D. Afebrile bacteremia. A phenomenon in geriatric patients. JAMA
1982;248:147881.
Hernandez-Bou S, Trenchs V, Alarcon M, Luaces C. Afebrile very young infants with urinary tract infection and the risk for bacteremia. Pediatr Infect Dis J 2014;33:2447.
Jones GR, Lowes JA. The systemic inammatory response syndrome as a predictor of
bacteraemia and outcome from sepsis. QJM 1996;89:51522.
Kameda K, Kimura SI, Akahoshi Y, Nakano H, Harada N, Ugai T, et al. High incidence of
afebrile bloodstream infection detected by surveillance blood culture in patients on
corticosteroid therapy following allogeneic hematopoietic stem cell transplantation.
Biol Blood Marrow Transplant 2015.
Kramer RD, Cooke CR, Liu V, Miller 3rd RR, Iwashyna TJ. Variation in the contents of sepsis
bundles and quality measures: a systematic review. Ann Am Thorac Soc 2015.
Kumar A, Roberts D, Wood KE, Light B, Parrillo JE, Sharma S, et al. Duration of hypotension
before initiation of effective antimicrobial therapy is the critical determinant of
survival in human septic shock. Crit Care Med 2006;34:158996.
Levy MM, Fink MP, Marshall JC, Abraham E, Angus D, Cook D, et al. 2001 SCCM/ESICM/
ACCP/ATS/SIS international sepsis denitions conference. Crit Care Med 2003;31:
12506.
Mouncey PR, Osborn TM, Power GS, Harrison DA, Sadique MZ, Grieve RD, et al. Trial of
early, goal-directed resuscitation for septic shock. N Engl J Med 2015;372:130111.

Please cite this article as: Yo C-H, et al, Risk factors and outcomes of afebrile bacteremia patients in an emergency department, Diagn Microbiol
Infect Dis (2016), http://dx.doi.org/10.1016/j.diagmicrobio.2016.08.020
Downloaded from ClinicalKey.com at UNIVERSIDAD AUTONAMA DE NUEVA LEON September 19, 2016.
For personal use only. No other uses without permission. Copyright 2016. Elsevier Inc. All rights reserved.

C-H. Yo et al. / Diagnostic Microbiology and Infectious Disease xxx (2016) xxxxxx
Norman DC. Fever in the elderly. Clin Infect Dis 2000;31:14851.
Paul M, Shani V, Muchtar E, Kariv G, Robenshtok E, Leibovici L. Systematic review and
meta-analysis of the efcacy of appropriate empiric antibiotic therapy for sepsis.
Antimicrob Agents Chemother 2010;54:485163.
Richardson JP. Bacteremia in the elderly. J Gen Intern Med 1993;8:8992.

van Zanten AR. The golden hour of antibiotic administration in severe sepsis: avoid a false
start striving for gold*. Crit Care Med 2014;42:19312.
Yokota PK, Marra AR, Martino MD, Victor ES, Durao MS, Edmond MB, et al. Impact of
appropriate antimicrobial therapy for patients with severe sepsis and septic shocka
quality improvement study. PLoS One 2014;9:e104475.

Please cite this article as: Yo C-H, et al, Risk factors and outcomes of afebrile bacteremia patients in an emergency department, Diagn Microbiol
Infect Dis (2016), http://dx.doi.org/10.1016/j.diagmicrobio.2016.08.020
Downloaded from ClinicalKey.com at UNIVERSIDAD AUTONAMA DE NUEVA LEON September 19, 2016.
For personal use only. No other uses without permission. Copyright 2016. Elsevier Inc. All rights reserved.