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The DENOVA score efficiently identifies patients with monomicrobial Enterococcus faecalis bacteremia where echocardiography is not necessary


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Objectives Enterococcal bacteremia can be complicated by infective endocarditis (IE) and when suspected, transesophageal echocardiography (TEE) should be performed. The previously published NOVA score can identify patients with enterococcal bacteremia at risk for IE and we aimed to improve the score. Methods Factors associated with IE were studied retrospectively in a population-based cohort of patients with monomicrobial Enterococcus faecalis bacteremia (MEFsB). Factors associated with IE in multivariable analysis were included in a new score system which was compared to the NOVA score and validated in a cohort of patients with MEFsB from another region. Results Among 397 episodes of MEFsB, 44 episodes with IE were compared to those without IE. Long Duration of symptoms (≥ 7 days) and Embolization were associated with IE in the multivariate analysis and hence were added to the NOVA variables (Number of positive cultures, Origin of infection unknown, Valve disease, and Auscultation of murmur) to generate a novel score; DENOVA. The area under the curve in ROC analyses was higher for DENOVA (0.95) compared to NOVA (0.91) (p = 0.001). With a cutoff at ≥ 3 positive variables the DENOVA score has a sensitivity of 100% and specificity of 83% which is superior to the NOVA score (specificity 29%). The DENOVA score was applied to the validation cohort (26 IE episodes and 256 non-IE episodes) and the resulting sensitivity was 100% and the specificity was 85% compared to 35% for NOVA. Conclusions The DENOVA score is a useful tool to identify patients with MEFsB where TEE is not needed.
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Infection (2019) 47:45–50
The DENOVA score efficiently identifies patients withmonomicrobial
Enterococcus faecalis bacteremia whereechocardiography
AndreasBerge1,2· AndreaKrantz3· HelenaÖstlund1· PontusNauclér1,2· MagnusRasmussen3,4
Received: 13 June 2018 / Accepted: 27 August 2018 / Published online: 3 September 2018
© The Author(s) 2018
Objectives Enterococcal bacteremia can be complicated by infective endocarditis (IE) and when suspected, transesophageal
echocardiography (TEE) should be performed. The previously published NOVA score can identify patients with enterococcal
bacteremia at risk for IE and we aimed to improve the score.
Methods Factors associated with IE were studied retrospectively in a population-based cohort of patients with monomicro-
bial Enterococcus faecalis bacteremia (MEFsB). Factors associated with IE in multivariable analysis were included in a new
score system which was compared to the NOVA score and validated in a cohort of patients with MEFsB from another region.
Results Among 397 episodes of MEFsB, 44 episodes with IE were compared to those without IE. Long Duration of symp-
toms (≥ 7 days) and Embolization were associated with IE in the multivariate analysis and hence were added to the NOVA
variables (Number of positive cultures, Origin of infection unknown, Valve disease, and Auscultation of murmur) to generate
a novel score; DENOVA. The area under the curve in ROC analyses was higher for DENOVA (0.95) compared to NOVA
(0.91) (p = 0.001). With a cutoff at ≥ 3 positive variables the DENOVA score has a sensitivity of 100% and specificity of
83% which is superior to the NOVA score (specificity 29%). The DENOVA score was applied to the validation cohort (26IE
episodes and 256 non-IE episodes) and the resulting sensitivity was 100% and the specificity was 85% compared to 35%
for NOVA.
Conclusions The DENOVA score is a useful tool to identify patients with MEFsB where TEE is not needed.
Keywords Endocarditis· Enterococcus faecalis· Bacteremia· Echocardiography· Management score
Enterococci are part of the normal human gut flora and can
cause severe infections including urinary tract infections,
gastrointestinal infections, catheter-related infections, and
infective endocarditis (IE). IE is defined by the modified
Duke criteria [1] in which the identification of a causative
bacterium and echocardiographic evidence of endocardial
infection are major criteria.
Enterococcal bacteremia is a relatively common condi-
tion and has a mortality rate of around 20% [2, 3]. A sub-
stantial proportion of patients with enterococcal bacteremia
are diagnosed with IE [2, 46], and recent population-based
studies suggest that up to 25% of patients with community-
acquired Enterococcus faecalis bacteremia (EFsB) have this
condition [5, 6]. A number of factors have been associated
with the presence of IE in enterococcal bacteremia including
the species E. faecalis compared to other enterococci [3, 4,
Electronic supplementary material The online version of this
article (https :// 0-018-1208-3) contains
supplementary material, which is available to authorized users.
* Magnus Rasmussen
1 Unit ofInfectious Diseases, Department ofMedicine, Solna,
Karolinska Institutet, Stockholm, Sweden
2 Department ofInfectious Diseases, Karolinska University
Hospital, Stockholm, Sweden
3 Department ofClinical Sciences Lund, Division ofInfection
Medicine, Lund University, BMC B14, Tornavägen 10,
22363Lund, Sweden
4 Division forInfectious Diseases, Skåne University Hospital,
Lund, Sweden
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46 A.Berge et al.
1 3
6, 7], prosthetic heart valves [3, 5, 7], heart murmur [2, 4],
previous endocarditis [5], other valve disease [25], emboli-
zation [4], monomicrobial bacteremia [2, 3, 5], a high num-
ber of positive cultures [3, 4], an unknown focus of infection
[2, 4, 5], community acquisition, subacute syndrome [2],
age [2, 3], and male sex [2, 5]. It is important to detect all
cases of IE since the condition has a high mortality, and
cure necessitates a long treatment course with a combination
of antibiotics and sometimes surgery. Therefore, a scoring
system to identify which patients with enterococcal bacte-
remia that have IE has to have a sensitivity close to 100%.
Transesophageal echocardiography (TEE) is the method
of choice to diagnose IE and identifies changes compatible
with IE with a higher sensitivity than transthoracic echo-
cardiography (TTE) [4]. However, TEE is a semi-invasive,
resource-demanding procedure which is not readily available
at all sites and it is not without discomfort for the patient.
Thus, TEE should only be performed when there is a risk
of IE. For this purpose, a diagnostic score termed NOVA
[Number of positive blood cultures 3 (5 points), Origin of
infection unknown (4 points), Valve disease (2 points) and
Auscultation of heart murmur (1 point)] was developed by
Bouza etal. meant to guide the use of TEE in enterococcal
bacteremia [4]. The authors set the cutoff at 4 points, mean-
ing that TEE is recommended in patients with three or more
positive cultures (N) or unknown origin of infection (O). The
NOVA score was later validated in an adapted form and was
found to have a high sensitivity (97%) but limited specificity
(23%) [5]. The majority of cases with enterococcal IE is due
to E. faecalis and have a monomicrobial blood culture and
in such cases IE should be considered [2, 4, 5]. We therefore
aimed to improve the NOVA score using easy accessible
clinical parameters in a population-based cohort of patients
with monomicrobial E. faecalis bacteremia (MEFsB) from
southern Sweden and to externally validate the NOVA score
and the improved score in another cohort of patients from a
tertiary referral center in another part of Sweden.
Calibration cohort
All consecutive blood cultures positive for E. faecalis from
January 2012 through December 2016 were obtained from
the database of the Laboratory for Clinical Microbiology in
Skåne County, in southern Sweden. This is the only labo-
ratory in the region and has a catchment area of 1.3mil-
lion inhabitants and nine hospitals. The medical records of
patients with MEFsB were studied retrospectively. Data col-
lection was carried out from 90days prior to an episode until
1year after the episode. Patients under the age of 18years or
where medical records could not be retrieved were excluded.
Ethical approval was obtained from the Ethics Committee of
Lund University (2013/31).
A detailed description of data collection and definitions is
given in supplementary material 1. An episode was defined
as a clinical situation in which a patient had MEFsB and the
episode was ended after 7 days of effective treatment. IE was
defined using the modified Dukes criteria considering defi-
nite cases only as IE [1]. Scoring of patients was performed
using the information available to the clinician at the time
of the receipt of the positive blood culture results. NOVA
score parameters were defined as described by Bouza etal.
[4] with modifications of number of cultures as described by
Dahl etal. [5]. The origin of infection (O in NOVA, defini-
tion not detailed by Bouza etal. [4]) was defined as a focal
infection (fulfillment of at least two of the following criteria
(a) typical signs or symptoms of infection, (b) isolation of
E. faecalis at the site of infection, and (c) imaging results
compatible with focal infection which was likely to be the
point of entry for the bacteria. Valve disease in NOVA (V)
was defined as a history of any of the predisposing heart
conditions that constitute a high or moderate risk of devel-
oping IE, including (1) native valve disease, (2) previous
IE, or (3) the presence of a valve prosthesis [8, 9]. Auscul-
tation of murmur (A in NOVA) included those with any
murmur reported. Duration of symptoms was defined as the
number of days before the first positive blood culture was
taken with any symptom compatible with IE. Embolization
was defined by signs on clinical examination or by findings
using imaging techniques. A previous EFsB was defined as a
blood culture with growth of E. faecalis, within the previous
90 days preceding an episode. Community and health-care
site of acquisition was defined as previously described [10],
whereas nosocomial acquisition was defined as a blood cul-
ture drawn after 48 or more hours of hospitalization [11].
Comorbidities were classified according to the Charlson
index [12].
Validation cohort
The validation cohort was from Karolinska University Hos-
pital, Stockholm, Sweden, a tertiary referral center serv-
ing the Stockholm County with a population of 2.3million
inhabitants. All blood culture data for patients with growth
of enterococci were retrieved from January 2012 through
December 2016 from the Department of Clinical Microbiol-
ogy, Karolinska University Hospital. Records from patients
with MEFsB were studied retrospectively and data were col-
lected as described for the calibration cohort above. Ethical
approval was obtained from the ethics committee review
board in Stockholm (Dnr 2015/1184-31).
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The DENOVA score efficiently identifies patients withmonomicrobial Enterococcus faecalis
1 3
For the results to be valid in the clinical setting, all episodes
of MEFsB were included in the analyses. Hence, each patient
could have more than one episode. To account for repeated
events, we applied the statistical method generalized esti-
mation equations (GEE). This method takes into account
clustering and was used both in univariate and multivariate
analyses [13]. P values are based on GEE estimates with a
significance level of < 0.05. For the multivariate model, we
were limited by the number of IE outcomes in the calibration
test set (n = 44). We first performed a multivariate model that
included all variables significantly associated with IE in uni-
variate analyses. We then removed variables from the model
that were not significantly associated with the outcome.
Calibration cohort
653 patients with EFsB were identified, of whom 36 were
excluded since they were < 18years old, 6 due to lack of
access to medical files, and 249 because they had polymi-
crobial bacteremia. The 362 included patients had 397 epi-
sodes of MEFsB, of which 44 episodes in 44 patients (11%)
fulfilled the Duke criteria for IE (Supplementary material 2).
Four episodes, in which the Dukes criteria were not fulfilled,
were treated as possible IE by the physician.
Most patients (336) had only one episode of MEFsB.
However, 26 patients had at least one more episode of
MEFsB (in total, 35 additional episodes). The first episode
was a non-IE in all these patients, but six of these patients
later had an episode with IE. 153 patients died within the
study period of 360 days for reasons presumed to be unre-
lated to IE based on comorbidities, clinical presentation, and
absence of positive blood culture for EFs.
Differences in distribution of variables between episodes
of IE and non-IE that could tentatively be included in a score
are given in Table1 with odds ratios and significance lev-
els. Additional information on the treatment, investigations,
and outcome is given in Supplementary material 3. In the
univariate analysis, the number of positive blood cultures,
unknown origin of infection, valve disease, heart murmur,
a long duration of symptoms, embolization, age, commu-
nity acquisition, and previous EFsB were associated with
IE. These variables were included in a multivariate model.
Community acquisition, previous EFsB, and valve disease
were not significantly associated with IE in the multivariate
analysis and were thus removed from the model. Further-
more, we removed age from the model since this variable
resulted in very large standard errors of other estimates indi-
cating a numerical problem.
In the final multivariate model, symptom duration, embo-
lization, number of positive blood cultures, unknown ori-
gin of infection, and heart murmur were associated with IE
(Table2). These variables were included in a novel score,
and despite not being significantly correlated with IE in mul-
tivariate analysis, we chose to include also the valve disease
criterion of NOVA in our new score to conform with earlier
studies [4, 5]. The novel score was termed DENOVA and
each variable was given one point to make it easy to use
The DENOVA score was tested for its ability to separate
episodes with IE from episodes without IE and the resulting
receiver operator characteristics (ROC) curve had an area
under the curve (AUC) of 0.95 (95% CI, 0.94–0.97) com-
pared to the adapted NOVA score which had a significantly
lower AUC of 0.91 (95% CI, 0.89–0.95) (p = 0.001 for dif-
ference) (Fig.1). With a cutoff at ≥ 3 points DENOVA had
a sensitivity of 100% and a specificity of 83% to identify
episodes of IE in MEFsB, while at the suggested cutoff of 4
points [4], the NOVA score had a sensitivity of 100% and a
specificity of 29%.
Validation cohort
The NOVA and the DENOVA score were validated in a
separate cohort of 485 patients with EFsB, 233 patients
were excluded due to polymicrobial bacteremia (n = 168),
age under 18years (n = 42), or unavailable records (n = 23).
Finally, 268 episodes in 252 patients were included in the
analyses, 26 classified as IE and 242 as non-IE.
The majority (238 patients) had only one episode of
MEFsB. Sixteen episodes, 4 with IE and 12 non-IE, were
followed by a new episode within 360 days. The episodes
that followed an IE were always another episode of IE. Six
non-IE episodes were followed by a new non-IE and six
were followed by an episode of IE. Two patients had three
episodes. 62 patients died within 360 days because of rea-
sons presumed to be unrelated to IE.
The characteristics of patients in the validation cohort
were similar to that of the calibration cohort, though some
differences were noted (Supplementary material 4).
When the DENOVA score was applied to the valida-
tion cohort, the resulting ROC curve had an AUC of 0.95
(95% CI, 0.93–0.98) which was significantly higher than
that of the adapted NOVA (AUC 0.92 (95% CI 0.88–0.95),
p = 0.007). At the predefined cutoff of three points, DEN-
OVA had a sensitivity of 100% and a specificity of 85%
compared to the NOVA score (with cutoff 4 [4]) with a sen-
sitivity of 100% and a specificity of 35%.
Combining the calibration and validation cohorts and
analyzing the subgroup of patients where echocardiography
had been performed, DENOVA had a sensitivity of 100%
and a specificity of 62%. The numbers needed to screen to
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48 A.Berge et al.
1 3
find one case of IE was 2.4 for DENOVA (≥ 3) and 7 for
NOVA (> 4).
Bacteremia with enterococci is a condition which can be
complicated by IE, and tools to aid clinicians, to decide
whether echocardiography should be performed, are poten-
tially very useful. We propose the use of the DENOVA scor-
ing system to guide the use of TEE in MEFsB. Importantly,
Table 1 Characteristics of
episodes of MEFsB with and
without IE at the time of scoring
a Consisting of any of previous IE, native valve disease, or valve prosthesis and is Valve disease (V) in
b Most common other infections were wound infections and intravascular infections
IE (n = 44) Non-IE (n = 353) Odds ratio (95% CI) p value
General demographics
Age (years, median) 70 76 0.98 (0.95–1.00) 0.039
<55 7 (16) 18 (5) 1 (ref)
55–64 6 (14) 48 (14) 0.34 (0.10–1.2) 0.10
65–74 11 (25) 98 (28) 0.31 (0.10–0.97) 0.044
75–84 14 (32) 111 (31) 0.34 (0.11-1.0) 0.054
≥85 6 (14) 78 (22) 0.22 (0.06–0.76) 0.017
Sex (% women) 8 (18) 92 (26) 0.61 (0.27–1.4) 0.22
Underlying conditions
Charlson score (median) 2 3 0.89 (0.79–1.0) 0.052
0–1 16 (36) 99 (28) 1 (ref)
2–3 17 (39) 115 (33) 0.93 (0.45–1.9) 0.84
≥4 11 (25) 139 (39) 0.50 (0.22–1.1) 0.087
Predisposing heart conditiona26 (59) 65 (18) 6.2 (3.3–12) < 0.001
Previous IE (%) 7 (16) 5 (1) 13 (5.0–34) < 0.001
Native valve disease (%) 10 (23) 39 (11) 2.3 (1.0–5.0) 0.046
Valve prosthesis (%) 16 (36) 34 (10) 5.2 (2.5–11) < 0.001
Intracardiac device (%) 5 (11) 40 (11) 0.99 (0.37–2.7) 0.21
Previous EFsB (%) 9 (20) 27 (8) 3.0 (1.3–7.0) 0.01
Site of acquisition (%)
Community 22 (50) 90 (26) 2.9 (1.5–5.5) 0.001
Health care 21 (48) 181 (51) 0.87 (0.47–1.6) 0.66
Nosocomial 1 (2) 81 (23) 0.08 (0.01–0.57) 0.01
Fever (%) 36 (82) 288 (82) 1.0 (0.46–2.3) 0.94
Murmur (%) 36 (82) 49 (14) 28 (12–66) < 0.001
Embolization (%) 8 (18) 1 (0) 76 (9.4–610) < 0.001
Duration of symptoms ≥ 7 days 30 (68) 43 (12) 15 (7.6–31) < 0.001
≥2 positive cultures (%) 43 (98) 221 (62) 27 (3.4–210) 0.002
Origin of infection (%)
Urinary tract 1 (2) 159 (45) 0.03 (0.003–0.21) < 0.001
Gastrointestinal and biliary 0 52 (15) N/A
Otherb2 (5) 38 (11) 0.38 (0.09–1.6) 0.19
Unknown 41 (93) 104 (29) 34 (10–110) < 0.001
Table 2 Variables of the DENOVA score, each giving 1 point, and
their association with IE in multivariate analyses
Odds ratio (95% CI) p value
Duration of symptoms ≥ 7 days 9.7 (3.6–26) < 0.001
Embolization 50 (6.2–400) < 0.001
Number of positive cultures 2 6.8 (1.5–32) 0.01
Origin of infection unknown 7.3 (2.0–26) 0.003
Valve disease 1.7 (0.57–4.9) 0.35
Auscultation of murmur 13 (4.7–36) < 0.001
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The DENOVA score efficiently identifies patients withmonomicrobial Enterococcus faecalis
1 3
DENOVA had a high sensitivity and specificity both in
the original cohort and in the separate validation cohort.
DENOVA had a higher specificity than the previously pro-
posed NOVA score and the number needed to screen to find
one case of IE was 2.4 for DENOVA, as compared to 7 for
NOVA. Using DENOVA to guide the use of TEE could
reduce the number of procedures for patients at low risk
of IE and the costs for the health-care system. Moreover,
DENOVA is easy to use since each variable gives one point
as compared to the more differentiated NOVA score [4].
Another strength of our study is that the DENOVA score was
generated in a population-based cohort avoiding the poten-
tial bias of single center studies and further it was validated
in a separate cohort, from a referral hospital with partly dif-
ferent epidemiology, with similar performance. Finally, our
design avoids the bias introduced when patients subjected to
TEE with a finding of IE are compared to patients subjected
to TEE without a finding of IE (a type of over-matching)
such as in the study behind the NOVA score [4]. When
we applied the DENOVA score only to patients that had
undergone echocardiography, the sensitivity was still 100%,
whereas the specificity dropped to 62%. This was expected
since the decision by the treating physician to perform TEE
was likely based on a perceived increased risk for IE.
However, there are several limitations to this study. First,
the DENOVA score cannot be applied to E. faecium bac-
teremia and not to polymicrobial EFsB. In both these con-
ditions, IE is uncommon [2, 4, 6] and separate very large
studies would be needed to adapt the score to these condi-
tions. Secondly, the retrospective design of our study makes
it sensitive to misclassification, potentially non-differential.
For example, a clinician who suspects IE might be more
prone to take additional blood cultures, make a more thor-
ough heart auscultation, or look for emboli, which will
potentially increase the DENOVA score. Further external
validation and most importantly prospective studies are
needed to address this concern.
Thirdly, a limited number of patients underwent TEE in
our study. This is a common problem in this type of studies
[4, 5, 14, 15] and a consequence of the retrospective design.
Even in prospective studies, however, a high frequency of
TEE in bacteremia is not always obtained [16] and, impor-
tantly, a negative TEE does not rule out the presence of IE
or that a visible vegetation can develop after TEE. To assess
the risk of misclassification, we followed the patients for
360 days. Patients with a non-IE MEFsB were rarely treated
more than 14 days and it is thus unlikely that a misclassi-
fied IE would have been without a relapse. However, a large
number of patients died within 360 days after a non-IE epi-
sode (142 and 62 in the calibration and validation cohorts,
respectively). We cannot rule out that some of these patients
died from a missed IE, yet the analysis of patient records did
not indicate that this was the cause of death. The proportion
of patients diagnosed with IE was very similar in our cohort
and a recent Danish cohort also indicating that we did not
miss a substantial number of IE cases [6].
In patients with multiple MEFsB episodes, the first classi-
fied as non-IE, in both the calibration and validation cohort
together, a new episode of IE was detected in 12 patients
during 360 days of follow-up. In eight of these, no TEE was
Fig. 1 Receiver operator charac-
teristics (ROC) curve for the
ability of the NOVA (blue) and
DENOVA (red) score to sepa-
rate episodes with IE from non-
IE episodes. The inset shows the
number of episodes of IE (black
bars) and non-IE (gray bars) in
relation to the score obtained
using DENOVA (data from the
calibration cohort)
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50 A.Berge et al.
1 3
done during the first episode. The initial episodes might thus
have been misclassified in these cases. However, DENOVA
score in these eight episodes was ≥ 3 in five cases, which
would have been subjected to TEE if DENOVA would have
been used.
In summary, the use of DENOVA in clinical decision-
making will help physicians to focus echocardiographic
investigations on persons at high risk for IE.
Acknowledgements This work was supported by the Swedish Govern-
ment Fund for Clinical Research (ALF), the Stockholm County Coun-
cil, the foundations of Marianne and Marcus Wallenberg, Crafoord,
Österlund. Lundgren, and the Royal Physiographic Society in Lund.
We acknowledge the advice by Dr Per Åkesson and the invaluable help
of Mrs. Lena Hyllebusk at the Department for Clinical Microbiology,
Lund. Part of this work has been presented at the ISCVID meeting in
Dublin 2017.
Author contributions MR concieved the study and wrote the manu-
script together with AB. All authors contributed to the design of the
study. AK, AB and HÖ collected data and PN performed statistical
analyses. All authors contributed to the writing and gave their final
Compliance with ethical standards
Conflict of interest On behalf of all authors, the corresponding author
states that there is no conflict of interest.
Open Access This article is distributed under the terms of the Crea-
tive Commons Attribution 4.0 International License (http://creat iveco
mmons .org/licen ses/by/4.0/), which permits unrestricted use, distribu-
tion, and reproduction in any medium, provided you give appropriate
credit to the original author(s) and the source, provide a link to the
Creative Commons license, and indicate if changes were made.
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... 3 Numerous patients with enterococcal bacteremia have concurrent infective endocarditis; populationbased studies have shown that up to 25% of patients with community-acquired E. faecalis bacteremia have infective endocarditis. 4 Furthermore, because infective endocarditis has a high mortality rate, it is imperative to perform a bedside screening test with close to 100% sensitivity to rule out infective endocarditis. ...
... The bedside screening test with the highest sensitivity (100%) to rule out infective endocarditis is the DENOVA scoring system. 4 The DENOVA system assesses the duration of symptoms lasting !7 days, embolization, the number of positive blood cultures (3/3 or the majority if >3), unknown origin of bacteremia, prior heart valve disease, and auscultation of a heart murmur, with each scored item assigned 1 point. 4 The DENOVA scoring system is used to determine whether to perform transesophageal echocardiography (TEE) if there is high clinical suspicion for infective endocarditis in a patient with enterococcal bacteremia. ...
... 4 The DENOVA system assesses the duration of symptoms lasting !7 days, embolization, the number of positive blood cultures (3/3 or the majority if >3), unknown origin of bacteremia, prior heart valve disease, and auscultation of a heart murmur, with each scored item assigned 1 point. 4 The DENOVA scoring system is used to determine whether to perform transesophageal echocardiography (TEE) if there is high clinical suspicion for infective endocarditis in a patient with enterococcal bacteremia. Specifically, if the patient attains a score of !3 on the DENOVA checklist, TEE is warranted to further investigate for infective endocarditis. ...
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A 69-year-old woman was airlifted to the emergency department after awakening with angina, diaphoresis, and shortness of breath. She was found to have ST-elevation myocardial infarction with 100% occlusion of her left anterior descending artery, and aspiration thrombectomy was performed. Blood cultures confirmed Enterococcus faecalis bacteremia. Our team used a clinical tool to determine whether transesophageal echocardiography was warranted to investigate for infective endocarditis. The patient’s transesophageal echocardiogram showed a large mobile vegetation on her mitral valve. Given the presence of infective endocarditis in the absence of known coronary artery disease, we determined that the patient had likely developed acute coronary syndrome from a septic embolus originating from her mitral valve vegetation. Further investigation for the source of the bacteremia revealed a perforation 20 cm from the anal verge at the rectosigmoid junction. After perforation repair, the patient became hypoxic and tachycardic with diffuse abdominal pain, guarding, rebound tenderness, and loss of pulse. Exploratory laparotomy revealed air in the mesentery consistent with extraperitoneal perforation of the rectum, and an end-colostomy was performed. Unfortunately, the patient subsequently died.
... E. faecalis, however, is a common cause of bacteremia and an important pathogen in endocarditis (IE) [5]. Risk factors for IE in E. faecalis bacteremia (EfsB) include monomicrobial bacteremia [6][7][8], but also high age, male sex, a long duration of symptom, signs of embolization, high number of positive blood cultures, an unknown origin of infection, heart valve disease, including prosthetic valve, presence of heart murmurs, a short time to blood culture positivity, and persistent bacteremia [6][7][8][9][10][11][12][13]. However, CIED is not an independent risk factor for IE in EfsB [8,11]. ...
... Risk factors for IE in E. faecalis bacteremia (EfsB) include monomicrobial bacteremia [6][7][8], but also high age, male sex, a long duration of symptom, signs of embolization, high number of positive blood cultures, an unknown origin of infection, heart valve disease, including prosthetic valve, presence of heart murmurs, a short time to blood culture positivity, and persistent bacteremia [6][7][8][9][10][11][12][13]. However, CIED is not an independent risk factor for IE in EfsB [8,11]. ...
... Data were collected by LA and were validated by AB and MR. Some of the episodes of the present cohort have been previously described in Berge et al. or Oldberg et al. [11,13]. ...
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Purpose In all patients with cardiac implantable electronic devices (CIED) and Enterococcus faecalis bacteremia (EfsB), endocarditis (IE) and CIED infection should be suspected. Guidelines recommend extraction of the CIED when CIED infection or IE is diagnosed. Whether extraction of the CIED should be done in other situations with EfsB is not known. We aimed to describe the management and outcome of patients with CIED and monomicrobial EfsB, in relation to extraction and recurrent EfsB. Methods A population-based cohort of patients with monomicrobial EfsB from January 2014 to November 2020 was identified through microbiology registers in the Region Skåne, Sweden. Data on CIED and other clinical features were collected from medical records. Results Among 1087 episodes of EfsB, 72 patients with CIED and monomicrobial EfsB were identified. Five of these patients were diagnosed with IE (7%), three of whom had echocardiographic changes on the CIED. Four CIED were extracted (6%). Recurrences were found in seven of 68 patients (10%) not subjected to extraction and in none of the extracted. In the group of patients without extraction, community acquisition and predisposition for IE were significantly associated with recurrent infection in univariate analyses. No infections involving the CIED were diagnosed during the recurrences. Conclusions In patient with monomicrobial EfsB, it seems safe to omit extraction if no structural changes are found on the CIED.
... Of related complications, the prevalence of infective endocarditis is rare (3.4%, 9 cases) amongst the cohort although echocardiogram is not routinely used in our institution to screen for secondary IE in enterococcal BSIs particularly when other obvious sources have been identified. This is certainly a contentious area where a scoring system such as NOVA and DENOVA has been advocated to aid risks stratification to guide selective echocardiography during management [24,25]. On the other hand, examined against our observations, many studies demonstrated reduction of mortality with appropriate empirical antimicrobial therapy [26,27]. ...
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Background and objective Enterococcus species is one of the leading causes of community and healthcare-associated infections resulting in significant morbidity and mortality. In this study, we aim to evaluate the epidemiology, microbiological and clinical characteristics of Enterococcus Blood Stream Infections (BSIs) over 10 years period in a national secondary care setting. Methods A retrospective cohort study was conducted on verified cases of enterococcal BSIs in adults from January 2009–December 2018 from specialized care hospitals at Hamad Medical Corporation, Qatar. Epidemiological, microbiological and clinical data were reported and analyzed. Results A total of 263 enterococcus BSIs cases were identified, predominant were males (65%) with a median age of 63 (IQR 48–74). E. faecalis and E. faecium were predominate at 93.5% (73.38% and 20.15% respectively). Diabetes was the commonest premorbid condition (54.3%) followed by chronic kidney disease (36.5%). Central lines and genitourinary were the most common sources (18.25%, 14.83% respectively) while no identified source was reported in 45.25% of cases. Ampicillin susceptibility was 82.51% while vancomycin resistance was reported in 10.6% of isolates. Successful bacteremia clearance was achieved in 81.37% of cases at a mean of 4 days (Range 2–5 days) while metastatic complications occurred in 5.3% of cases. Univariate mortality risk analysis was associated with ICU admission, low level of consciousness, high bacteremia scores, and presence of catheters. The 30 days mortality was high at 66.54% with CKD and cancer patients at the highest mortality risks (OR 16.334 (CI 4.2–62.4) and 16 (CI 3–84) respectively. Conclusion Significant mortality was associated with enterococcus BSI despite low rates for ampicillin and vancomycin resistance necessitating early identification of susceptible patients to instigate suitable preventive measures.
... Comorbidity was evaluated according to the updated Charlson comorbidity index by Quan et al. [11], and sepsis was defined according to Sepsis-3 [12]. Origin of infection was defined as described by Berge et al. [13]. Recurrence was defined as a new episode of SAB within 90 days after completed antibiotic therapy with clinical recovery upon completion. ...
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Patients with heart valve prosthesis (HVP) and Staphylococcus aureus bacteraemia (SAB) risk endocarditis. In this retrospective, populations-based, cohort study of 134 patients with SAB and HVP, 97 (72%) were diagnosed with possible endocarditis. Despite that most patients with possible endocarditis received short antibiotic treatment, only three patients suffered recurrent SAB.
Background: Enterococcal bloodstream infections (EBSIs) are rare infections in children associated with 5%-10% of mortality in previous studies. The recent evolution of antimicrobial resistance and therapies require updated data. Methods: We conducted an observational retrospective study between January 2008 and December 2019 describing the characteristics of children with EBSI in a French pediatric hospital. All positive Enterococcus spp. blood cultures associated with sepsis symptoms were analyzed. We also compared characteristics of healthcare-associated infections (HAIs) and community-acquired infections (CAIs) and described antimicrobial resistance evolution during this period. Results: In total 74 EBSI were included. Enterococcus faecalis was the most common pathogen (n = 60/74, 81%) followed by Enterococcus faecium (n = 18, 24%), including 4 enterococcal coinfections. EBSIs were mainly associated with central-line associated infection (38%), surgical site infection (14%) or urinary tract infection (11%). An underlying disease was present in 95.9%. However, 4 patients died in the month following the EBSI resulting in a 5.4%, 30-day mortality. All were HAI. HAI (84% of EBSI) was associated with longer bacteremia [31% persistent bacteremia (more than 3 days) versus 0% for CAI; P = 0.029] and more antimicrobial resistance. Amoxicillin resistance is increasing since 2013 in E. faecium (63% in 2013-2019), although high-level gentamicin resistance is stable (19%). Only 1 EBSI due to vancomycin-resistant Enterococcus was described in our cohort, who died. Conclusions: EBSIs are rare infections in children mostly described in children with underlying disease. Healthcare-associated bacteremia is associated with higher rates of resistance and poorer prognosis, requiring the involvement of pediatric infectious disease specialists to improve management.
Background: Streptococcus bovis/equinus complex (SBSEC) comprise several species and subspecies and is a common cause of infective endocarditis (IE). S. gallolyticus subsp. gallolyticus (Sg gallolyticus) accounts for a majority of SBSEC IE, but the risk of IE for other subspecies is largely unknown. We aimed to investigate the clinical presentation of bacteraemia, and proportion of patients with IE in bacteraemia with the most common subspecies. Methods: A retrospective cohort study of SBSEC-bacteraemia identified in clinical laboratory databases, in Skåne Region, Sweden, 2003-2018. Bacteraemia with Sg gallolyticus, S. gallolyticus subsp. pasteurianus (Sg pasteurianus), S. lutetiensis and S. infantarius subsp. infantarius (Si infantarius) were included. Subspecies was identified by whole genome sequencing. Medical charts were reviewed according to a predetermined protocol, IE was defined by the criteria from European Society of Cardiology. Results: In total, 210 episodes of SBSEC-bacteraemia were included. Definite IE was identified in 28/210 (13%) episodes. Of these, 7/28 (25%) were prosthetic valve-IE, 1/28 (4%) related to a cardiovascular implantable electronic device and 10/28 (36%) required heart valve surgery. The proportions of IE among different subspecies were: Sg gallolyticus 17/52 (33%), Si infantarius 5/31 (16%), Sg pasteurianus 4/83 (5%) and S. lutetiensis 2/44 (5%) (p < 0.001). Sg pasteurianus and S. lutetiensis were more often associated with intra-abdominal- and polymicrobial infection. Conclusion: The proportion of IE in SBSEC-bacteraemia varies substantially depending on subspecies. Echocardiography should always be considered in bacteraemia with Sg gallolyticus and Si infantarius, and can sometimes be omitted in bacteraemia with Sg pasteurianus and S. lutetiensis.
Background: A feared cause of bacteraemia with Gram-positives is infective endocarditis. Risk stratification scores can aid clinicians in determining the risk of endocarditis. Six proposed scores for the use in bacteraemia; Staphylococcus aureus (PREDICT, VIRSTA, POSITIVE), non-β-haemolytic streptococci (HANDOC) and Enterococcus faecalis (NOVA, DENOVA) were validated for predictive ability and the utilization of echocardiography was investigated. Methods: Hospitalized adult patients with Gram-positive bacteraemia during 2017-2019 were evaluated retrospectively through medical records and the Swedish Death Registry. Baseline and score-specific data, definite endocarditis and echocardiographies performed were recorded. Sensitivity, specificity, negative and positive predictive values and echocardiography utilization were determined. Results: 480 patients with bacteraemia were included and definite endocarditis was diagnosed in 20 (7.5%), 10 (6.6%), and 2 (3.2%) patients with S. aureus, non-β-haemolytic streptococci and E. faecalis, respectively. The sensitivities of the scores were 80-100% and specificities 8-77%. Negative predictive values of the six scores were 98-100%. VIRSTA, HANDOC, NOVA and DENOVA identified all, the PREDICT5 score missed 1/20 and the POSITIVE score missed 4/20 cases of endocarditis. Transoesophageal echocardiography was performed in 141 patients (29%). Thus, the risk stratification scores suggested an increase of 3-63 (7-77%) investigations with echocardiography. Conclusions: All scores had negative-predictive values over 98%, therefore it can be concluded that PREDICT5, VIRSTA, POSITIVE, HANDOC and DENOVA are reasonable screening tools for endocarditis early on in Gram-positive bacteraemia. The use of risk stratification scores will lead to more echocardiographies.
The Modified Duke Criteria requires that Enterococcus faecalis bacteremia must be both community-acquired and without known focus in order to be considered a microbiological "Major" diagnostic criterion in the diagnosis of infective endocarditis. We believe that the microbiological diagnostic criteria should be updated to regard E. faecalis as a "typical" endocarditis bacterium as is currently the case for e.g. viridans group streptococci and Staphylococcus aureus. Using data from a prospective study of 344 patients with E. faecalis bacteremia evaluated with echocardiography, we demonstrate that designating E. faecalis as a "typical" endocarditis pathogen, regardless the place of acquisition or the portal of entry, improved the sensitivity to correctly identify definite endocarditis from 70% (Modified Duke Criteria) to 96% (Enterococcal adjusted Duke Criteria).
Resumen Los enterococos son bacterias grampositivas anaerobias facultativas que se disponen en cadenas o parejas. Las especies más relevantes son Enterococcus faecalis y Enterococcus faecium. Son colonizadores normales del aparato digestivo. Pueden sobrevivir en superficies y entornos hospitalarios durante tiempo prolongado. Los contactos frecuentes con hospitales, comorbilidades, antibióticos previos y presencia de dispositivos se asocian con un mayor riesgo de infección. Pueden dar lugar a múltiples síndromes clínicos, siendo más frecuentes en infecciones asociadas a cuidados sanitarios que en comunitarias. Destacan infecciones del tracto urinario, infecciones intraabdominales, bacteriemias asociadas a catéter venoso, endocarditis, meningitis e infecciones de herida quirúrgica. En toda bacteriemia enterocócica se debe valorar la presencia de endocarditis, siendo útiles para ello los scores NOVA y DENOVA. Enterococcus faecalis suele ser sensible a ampicilina y este es su tratamiento de elección. En casos de endocarditis o bacteriemia complicada, se recomienda la combinación con ceftriaxona o gentamicina. Enterococcus faecium suele ser resistente a ampicilina y su tratamiento de elección es vancomicina. El tratamiento de los enterococos resistentes a vancomicina no está bien definido y supone un reto, siendo las principales opciones daptomicina en dosis altas o linezolid. En el manejo de las infecciones enterocócicas, es fundamental el control adecuado del foco.
Background Abiotrophia, Granulicatella, and Gemella are gastrointestinal microbiota, gram-positive cocci that behave like viridans group streptococci. Despite the low incidence of bacteremia from these organisms, they can lead to infective endocarditis (IE) and other clinical syndromes. Due to scant data, we aim to describe detailed clinical features, management, and outcomes of patients with bacteremia from these organisms. Methods We reviewed all adult patients who developed Abiotrophia, Granulicatella, or Gemella bacteremia from 2011 to 2020, at Mayo Clinic. Results We identified 238 patients with positive blood culture for these organisms. Of those, 161 (67.6%) patients were deemed to have bacteremia of clinical significance; 62 (38.5%) were neutropenic, - none of whom were diagnosed with IE. The primary source of bacteremia for the neutropenic group was the gastrointestinal tract. Among 161 patients, echocardiography was obtained in 88 (54.7%) patients, especially those with unknown sources of bacteremia. A total of 19 cases had IE: 5 (26.3%) Abiotrophia, 11 (57.9%) Granulicatella, and 3 (15.8%) Gemella. Based on known IE scoring systems, the negative predictive value at established cutoffs for these scores, performed with our cohort were 95.9%, 100% and 97.9% for NOVA, HANDOC and DENOVA scores, respectively. We also found that the penicillin-non-susceptible rate was high in Abiotrophia (66.7%) and Granulicatella (53.7%). Conclusions We described unique characteristics of Abiotrophia, Granulicatella, and Gemella bacteremia at our institution. Clinical significance, clinical syndrome, their proclivity of endocarditis, and susceptibility pattern should be thoroughly reviewed when encountering these organisms.
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Background: Infective endocarditis (IE) is a serious complication of Staphylococcus aureus bacteremia (SAB). There is limited clinical evidence to guide use of echocardiography in the management of SAB cases. Methods: Baseline and 12-week follow-up data of all adults hospitalized at our institution with SAB from 2006 to 2011 were reviewed. Clinical predictors of IE were identified using multivariable logistic regression analysis. Results: Of the 757 patients screened, 678 individuals with SAB (24% community acquired, 56% healthcare associated, and 20% nosocomial) met study criteria. Eighty-five patients (13%) were diagnosed with definite IE within the 12 weeks of initial presentation based on modified Duke criteria. The proportion of patients with IE was 22% (36/166) in community-acquired SAB, 11% (40/378) in community-onset healthcare-associated SAB, and 7% (9/136) in nosocomial SAB. Community-acquired SAB, presence of cardiac device, and prolonged bacteremia (≥ 72 hours) were identified as independent predictors of IE in multivariable analysis. Two scoring systems, day 1 (SAB diagnosis day) and day 5 (when day 3 culture results are known), were derived based on the presence of these risk factors, weighted in magnitude by the corresponding regression coefficients. A score of ≥ 4 for day 1 model had a specificity of 96% and sensitivity of 21%, whereas a score of <2 for day 5 model had a sensitivity of 98.8% and negative predictive value of 98.5%. Conclusions: We propose 2 novel scoring systems to guide use of echocardiography in SAB cases. Larger prospective studies are needed to validate the classification performance of these scoring systems.
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Background: Frequency of enterococcal bloodstream infection (E-BSI) is increasing, and the number of episodes complicated by infective endocarditis (IE) varies. Performing transesophageal echocardiography (TEE) in all patients with E-BSI is costly and time-consuming. Our objectives were to identify patients with E-BSI who are at very low risk of enterococcal IE (and therefore do not require TEE) and to compare the outcome of E-BSI in patients with/without IE. Methods: Between September 2003 and October 2012, we performed a prospective cohort study (all patients with E-BSI) and a case-control study (patients with/without enterococcal IE) in our center. Results: We detected 1515 patients with E-BSI and 65 with enterococcal IE (4.29% of all episodes of E-BSI, 16.7% of patients with E-BSI who underwent transthoracic echocardiography, and 35.5% of all patients with E-BSI who underwent TEE). We developed a bedside predictive score for enterococcal IE-Number of positive blood cultures, Origin of the bacteremia, previous Valve disease, Auscultation of heart murmur (NOVA) score-based on the following variables: Number of positive blood cultures (3/3 blood cultures or the majority if more than 3), 5 points; unknown Origin of bacteremia, 4 points; prior heart Valve disease, 2 points; Auscultation of a heart murmur, 1 point (receiver operating characteristic = 0.83). The best cutoff corresponded to a score ≥4 (sensitivity, 100%; specificity, 29%). A score <4 points suggested a very low risk for enterococcal IE and that TEE could be obviated. Conclusions: Enterococcal IE may be more frequent than generally thought. Depending on local prevalence of endocarditis, application of the NOVA score may safely obviate echocardiography in 14%-27% of patients with E-BSI.
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Importance Several management strategies may improve outcomes in patients with Staphylococcus aureus bacteremia.Objectives To review evidence of management strategies for S aureus bacteremia to determine whether transesophageal echocardiography is necessary in all adult cases and what is the optimal antibiotic therapy for methicillin-resistant S aureus (MRSA) bacteremia.Evidence Review A PubMed search from inception through May 2014 was performed to identify studies addressing the role of transesophageal echocardiography in S aureus bacteremia. A second search of PubMed, EMBASE, and the Cochrane Library from January 1990 through May 2014 was performed to find studies addressing antibiotic treatment for MRSA bacteremia. Studies reporting outcomes from antibiotic therapy for MRSA bacteremia were included. All searches, which were limited to English and focused on adults, were augmented by review of bibliographic references from included studies. The quality of evidence was assessed using the Grades of Recommendation, Assessment, Development and Evaluation system with consensus of independent evaluations by at least 2 of the authors.Findings In 9 studies with a total of 4050 patients, use of transesophageal echocardiography was associated with higher rates of a diagnosis of endocarditis (14%-28%) compared with transthoracic echocardiography (2%-15%). In 4 studies, clinical or transthoracic echocardiography findings did not predict subsequent transesophageal echocardiography findings of endocarditis. Five studies identified clinical or transthoracic echocardiography characteristics associated with low risk of endocarditis (negative predictive values from 93% to 100%). Characteristics associated with a low risk of endocarditis include absence of a permanent intracardiac device, sterile follow-up blood cultures within 4 days after the initial set, no hemodialysis dependence, nosocomial acquisition of S aureus bacteremia, absence of secondary foci of infection, and no clinical signs of infective endocarditis. Of 81 studies of antibiotic therapy for MRSA bacteremia, only 1 high-quality trial was identified. In that study of 246 patients with S aureus bacteremia, daptomycin was not inferior to vancomycin or an antistaphylococcal penicillin, each in combination with low-dose, short-course gentamicin (clinical success rate, 44.2% [53/120] vs 41.7% [48/115]; absolute difference, 2.4% [95% CI, −10.2% to 15.1%]).Conclusions and Relevance All adult patients with S aureus bacteremia should undergo echocardiography. Characteristics of low-risk patients with S aureus bacteremia for whom transesophageal echocardiography can be safely avoided have been identified. Vancomycin and daptomycin are the first-line antibiotic choices for MRSA bacteremia. Well-designed studies to address the management of S aureus bacteremia are needed.
Background: The NOVA score is a recently developed diagnostic tool to identify patients with increased risk of infective endocarditis (IE) among patients with Enterococcus faecalis (EF) bacteremia. We aim to validate an adapted version of the NOVA score and to identify risk factors for IE in patients with EF bacteremia. Methods: From January 1, 2010 to December 31, 2013, we included 647 consecutive patients with EF bacteremia. Predictors of IE were identified with multivariable Cox regression. The NOVA score was used in a slightly adapted form; 2/2 positive blood cultures resulted in 5 points, unknown origin of infection 4 points, prior valve disease 2 points and heart murmur 1 point. Results: IE was diagnosed in 78 patients (12%). Monomicrobial EF bacteremia (HR 3.60; CI95% 1.6-8.0), prosthetic heart valve (HR 6.2; CI95% 3.8-10.1), male sex (HR 2.0; CI95% 1.1-3.8), and community acquisition (HR 1.8; CI95% 1.1-2.9) were independently associated with IE. The adapted NOVA score was applied in the 240 patients examined by echocardiography. A low score (<4) was found in 40 patients (17%), implying a low likelihood of IE. Of the 78 patients with IE, 76 had a high score (≥4), resulting in a sensitivity of 97%, specificity of 23%, a negative predictive value of 95% and a positive predictive value of 38%. Conclusion: Monomicrobial EF bacteremia, community acquisition, prosthetic heart valve and male sex are associated with increased risk of IE. In our retrospective cohort, the adapted NOVA score performed well suggesting it could be useful in guiding clinical decisions.
Objectives: To develop and validate a prediction score, to quantify, within 48 hours of Staphylococcus aureus bacteremia (SAB) diagnosis, the risk of IE, and therefore determine priority for urgent echocardiography. Methods: Consecutive adult patients with SAB in 8 French university hospitals between 2009 and 2011 were prospectively enrolled and followed-up 3 months. A predictive model was developed and internally validated using bootstrap procedures. Results: Among the 2,008 patients enrolled, 221 (11.0%) had definite IE of whom 39 (17.6%) underwent valve surgery, 25% of them within 6 days of SAB diagnosis. Ten predictors independently associated with IE were used to build up the prediction score: intracardiac device or previous IE, native valve disease, intravenous drug use, community or non-nosocomial-acquisition, cerebral or extracerebral emboli, vertebral osteomyelitis, severe sepsis, meningitis, C-reactive protein above 190 mg/L, and H48-persistent bacteremia. Patients with a score ≤ 2 (n=792, 39.4%) were at low IE-risk (1.1%; negative predictive value: 98.8% (95% CI, 98.4-99.4)) compared to those ≥3 who were at higher risk (17.4%). Conclusions: Physicians must be strongly encouraged to urgently perform echocardiography in SAB patients with a score ≥3 to establish IE diagnosis, to orient antimicrobial therapy and to help determine the need for valvular surgery.
The objective of this study was to develop a prospectively applicable method for classifying comorbid conditions which might alter the risk of mortality for use in longitudinal studies. A weighted index that takes into account the number and the seriousness of comorbid disease was developed in a cohort of 559 medical patients. The 1-yr mortality rates for the different scores were: "0", 12% (181); "1-2", 26% (225); "3-4", 52% (71); and "greater than or equal to 5", 85% (82). The index was tested for its ability to predict risk of death from comorbid disease in the second cohort of 685 patients during a 10-yr follow-up. The percent of patients who died of comorbid disease for the different scores were: "0", 8% (588); "1", 25% (54); "2", 48% (25); "greater than or equal to 3", 59% (18). With each increased level of the comorbidity index, there were stepwise increases in the cumulative mortality attributable to comorbid disease (log rank chi 2 = 165; p less than 0.0001). In this longer follow-up, age was also a predictor of mortality (p less than 0.001). The new index performed similarly to a previous system devised by Kaplan and Feinstein. The method of classifying comorbidity provides a simple, readily applicable and valid method of estimating risk of death from comorbid disease for use in longitudinal studies. Further work in larger populations is still required to refine the approach because the number of patients with any given condition in this study was relatively small.
From the reviews of the First Edition."An interesting, useful, and well-written book on logistic regression models . . . Hosmer and Lemeshow have used very little mathematics, have presented difficult concepts heuristically and through illustrative examples, and have included references."—Choice"Well written, clearly organized, and comprehensive . . . the authors carefully walk the reader through the estimation of interpretation of coefficients from a wide variety of logistic regression models . . . their careful explication of the quantitative re-expression of coefficients from these various models is excellent."—Contemporary Sociology"An extremely well-written book that will certainly prove an invaluable acquisition to the practicing statistician who finds other literature on analysis of discrete data hard to follow or heavily theoretical."—The StatisticianIn this revised and updated edition of their popular book, David Hosmer and Stanley Lemeshow continue to provide an amazingly accessible introduction to the logistic regression model while incorporating advances of the last decade, including a variety of software packages for the analysis of data sets. Hosmer and Lemeshow extend the discussion from biostatistics and epidemiology to cutting-edge applications in data mining and machine learning, guiding readers step-by-step through the use of modeling techniques for dichotomous data in diverse fields. Ample new topics and expanded discussions of existing material are accompanied by a wealth of real-world examples-with extensive data sets available over the Internet.