1302

Staphylococcus aureus Prosthetic Valve Endocarditis: Optimal Management and

Risk Factors for Death
Malcolm D. V. John, Patricia L. Hibberd, From the Medical Services and Division of Infectious Diseases,
Adolf W. Karchmer, Lynn A. Sleeper, Massachusetts General Hospital, and the Division of Infectious
Diseases, Beth Israel Deaconess Medical Center, Boston;
and Stephen B. Calderwood
and New England Research Institutes, Watertown, Massachusetts

The mortality rate associated with Staphylococcus aureus prosthetic valve endocarditis (PVE)
remains high. To identify clinical events associated with an increased risk of death among patients
with S. aureus PVE and to evaluate the role of valve replacement surgery in reducing mortality,
we conducted a retrospective cohort study of patients who met strict criteria for definite S. aureus
PVE. The primary endpoint for the study was survival at 3 months from the date of diagnosis.

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S. aureus PVE was diagnosed in 33 patients. Of these, 14 (42%) died within 90 days of the diagnosis.
Cardiac complications were detected in 22 (67%), and central nervous system (CNS) complications
were detected in 11 (33%). A stepwise logistic regression multivariate model demonstrated that
cardiac complications, but not CNS complications, were associated with increased mortality and
that performing valve replacement surgery during antibiotic therapy was associated with decreased
mortality. These associations were confirmed by using a Cox proportional hazards model with time-
dependent covariates to control for survival bias. Performing valve replacement surgery during
antimicrobial therapy will reduce the mortality among patients with S. aureus PVE, even those
without evidence of cardiac complications.

Prosthetic valve endocarditis (PVE) occurs in 1.4%–3.1% of
patients within 12 months of valve replacement surgery and in
3.2%–5.7% within 60 months after surgery [1–4]. In spite of
increasingly sophisticated therapy, overall mortality rates among
patients with PVE remain high (23%–48%) [5, 6]. In a recent
report, mortality among patients with PVE was 41% and 46% at
60 days and 6 months after the onset of bacteremia, respectively
[7]. We have previously noted that PVE complicated by conges-
tive heart failure, a murmur of prosthesis dysfunction, new electro-
cardiographic conduction abnormalities, or unexplained fever per-
sisting for §10 days increased the risk of death during initial
hospitalization as well as that of subsequent poor outcome (endo-
carditis-related death, relapse, or readmission for valve surgery)
among patients who survived after receiving medical therapy
alone [5]. In addition, it has been recognized that mortality is
higher among patients with PVE caused by Staphylococcus aureus
[7–9]; treatment of uncomplicated PVE caused by nonstaphylo-
coccal, antibiotic-susceptible pathogens has been more successful
[5, 9, 10].
See editorial response by Fowler and Sexton on pages 1310–1.
Since mortality among patients with PVE is concentrated
among selected subsets of patients, such as those with S. aureus
Received 6 October 1997; revised 15 December 1997.
Reprints or correspondence: Dr. Stephen B. Calderwood, Division of Infec-
tious Diseases, Massachusetts General Hospital, Boston, Massachusetts, 02114.
Clinical Infectious Diseases 1998;26:1302–9
q 1998 by the Infectious Diseases Society of America. All rights reserved.
1058–4838/98/2606–0010$03.00
infection, an observational study of predictors of survival may
assist with treatment decisions. For example, the results of
some studies have suggested that patients with PVE may benefit
from valve replacement surgery [5, 7, 9, 11]. Clinical events,
patient characteristics, and therapeutic interventions can be
modeled to determine which of these variables are associated
with survival. We used this approach to analyze a cohort of
patients with S. aureus PVE treated at a single medical institu-
tion, to evaluate predictors of death due to this infection, and in
particular, to determine whether performing valve replacement
surgery is associated with improved outcome.
Methods
Study Group
We identified cases of S. aureus PVE that occurred between
1 January 1975 and 30 June 1995 by reviewing computerized
discharge diagnoses for patients hospitalized at the Massachu-
setts General Hospital (Boston); we also reviewed data from
the clinical microbiology laboratory and from the records of the
infectious disease consultation service. Patients with prosthetic
heart valves were eligible for inclusion in the study if S. aureus
was isolated from cultures of blood and/or a cardiac valve
during the illness and the patients fulfilled the criteria for defi-
nite endocarditis proposed by Durack et al. [12]. The present
study was reviewed and approved by the Institutional Review
Board of Massachusetts General Hospital.
Data Collection
We abstracted the following data from the medical records
onto predesigned study forms: age, sex, type(s) of prosthetic

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CID 1998;26 (June) S. aureus PVE
valves infected, the date that the prosthesis was inserted, the
date of onset of PVE, location(s) of infected valve(s), duration
of symptoms before presentation, development of complica-
tions (cardiac, CNS, or systemic) associated with the infection,
the details of antimicrobial and surgical therapy, and the methi-
cillin susceptibility of the causative S. aureus isolate. Surgery
was performed on the basis of the clinical judgment of physi-
cians caring for the patients. The duration of antibiotic therapy
before and after surgery was noted. Outcome at discharge was
obtained from hospital records. Follow-up data for the period
after the initial hospitalization for PVE (minimum duration of
follow-up from initial hospitalization, 1 year), were obtained
from patients’ medical records or by contact with the primary
care physicians. Operative reports or autopsy results during the
follow-up period were also reviewed.
Definitions
Date of onset of PVE was defined as the earlier of either
(1) date of onset of a clinical syndrome believed to be caused
by PVE or (2) the date on which a blood culture first yielded
S. aureus. Early PVE was defined as that occurring õ12 months
after valve implantation, whereas late PVE was defined as that
beginning §12 months after valve implantation, as previously
defined [2].
The definition of complicated PVE used for this study was
derived from a previously described definition [5]. PVE was
considered complicated if any of the following cardiac compli-
cations were noted: (1) a new or worsening murmur of valve
dysfunction; (2) new or worsening congestive heart failure
(CHF) prompting therapy; (3) new or changing electrocardio-
graphic conduction abnormalities; or (4) an intracardiac abscess
detected on an echocardiogram, at surgery, or at autopsy.
CNS complications included intracranial hemorrhage, in-
farction, abscess, mycotic aneurysm, or cerebritis, as docu-
mented by CT, MRI, or angiography. Systemic complications
included large-vessel emboli or hematogenously seeded focal
S. aureus infection evident on physical examination, radiogra-
phy, or autopsy.
Surgical therapy for PVE was defined as replacement of the
infected valve(s) during the initial hospitalization for PVE. The
mortality associated with PVE was determined for the period
from the initial hospitalization through 3 months after diagno-
sis. The 3-month period was chosen because it encompasses
most of the mortality related to PVE [7].
Statistical Analysis
The primary endpoint for the study was survival at 3 months
after the diagnosis of S. aureus PVE. All but two covariates
were fixed and represented baseline characteristics. The covari-
ates analyzed included age (ú60 years or £60 years), sex,
year that the prosthetic valve was infected (1975 – 1984 vs.
1985 – 1995), type of prosthetic valve (bioprosthetic vs. me-
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1303
chanical), valve infected (aortic valve, mitral valve, or both),
early vs. late PVE, the occurrence of complications (cardiac,
CNS, or systemic), and the performance of valve replacement
surgery during antibiotic therapy. Valve surgery and CNS com-
plications were modeled both as fixed covariates and as time-
dependent covariates.
A Kaplan-Meier product limit analysis was performed to
estimate the probability of surviving after the diagnosis of PVE.
Factors potentially associated with mortality were analyzed two
ways. First, all variables (including valve surgery and CNS
complications) were treated as though they were fixed at base-
line, since previous studies of prognostic factors for patients
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with PVE have not included time-dependent variables. Univari-
ate correlates of mortality (P õ 0.2) were entered into a step-
wise logistic regression model for multivariate comparisons.
Calibration of the model was evaluated by using the Hosmer-
Lemeshow goodness-of-fit test [13]. Next, we analyzed pa-
tients’ actual survival time by means of the Cox proportional
hazards model (adjusted for ties by the exact method) with use
of time-dependent covariates for CNS complications and valve
surgery to eliminate potential survivor biases. The Cox model
was also used for multivariate analysis [14]. SAS software
(SAS Institute, Cary, NC) was used.
Results
Thirty-three patients with PVE caused by S. aureus were
identified. Of these patients, 13 who were admitted between 1
January 1975 and 31 December 1982 had been included in a
previous series of patients with PVE [5]. The clinical character-
istics of the 33 patients are summarized in table 1. Twenty
(61%) of the patients were male. Twenty-two cases of PVE
occurred in patients with mechanical valves, and 11 occurred
in patients with bioprostheses. Eighteen of the infections were
on aortic valves, 14 were on mitral valves, and one was on
both the aortic and mitral valve prostheses. Twenty-two pa-
tients (67%) had cardiac complications of the infection, includ-
ing intracardiac abscesses (nine [27%]). Eleven patients (33%)
had CNS complications. Fifteen patients in the more recent
period of the study underwent transesophageal echocardiogra-
phy, and 13 (87%) of the echocardiograms revealed vegetations
or other findings suggestive of endocarditis; five (33%) of these
studies revealed intracardiac abscesses. The infected valves
were replaced in 14 patients (42%) during antibiotic therapy
for endocarditis. Fourteen patients (42%) died during the 3-
month period after the diagnosis of PVE.
Table 2 correlates the pathological evidence of endocarditis
with the definite clinical criteria for the diagnosis of endocardi-
tis that were proposed by Durack et al. [12]. Four patients did
not meet the clinical criteria for definite endocarditis; however,
each of these patients had PVE that was confirmed by patholog-
ical criteria. Each of these patients met one major and two
minor clinical criteria for endocarditis. Data on valve pathology
were available for 14 of the 29 patients who met the clinical
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1304 John et al. CID 1998;26 (June)

Table 1. Clinical characteristics of patients with Staphylococcus aureus prosthetic valve endocarditis (PVE).

Valve
replacement Outcome
Duration of Complication during
Time from symptoms antibiotic Discharge or At 3 mo
Patient Age (y)/ Type of Involved prosthesis before Extracardiac therapy death after initiation
no. sex prosthesis valve insertion admission (d) Cardiac (d of therapy) (d of therapy) (d of therapy) of therapy

1 63/F M AV 3y 2 CHF, intracardiac CNS hemorrhage, No Died (24) ...

abscess mycotic aneurysm (19)
2 76/F M/M AV/MV* 11 mo 1 CHF, intracardiac None No Died (16) ...
abscess
3 45/F M AV 4y 6 CHF, intracardiac None Yes (10) Discharged AVR 2 mo after
abscess discharge
(showed no

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PVE)
4 65/F B MV 8 mo 7 MR, CHF, CHB CNS hemorrhage (2) No Died (11) ...
5 46/F M MV 12 y 2 None Embolic CVA (7) No Discharged Alive
6 66/F M AV 4 y 3 RBBB, 17 AVB None No Died (7) ...
7 56/M M AV 6 y 5 None CVA 1 2, with No Died (11) ...
hemorrhage (4, 11)
8 46/F M/M AV/MV 9 y 6 Intracardiac abscess None Yes (14) Died (31) ...
9 62/M M AV 3 y 2 CHF Cerebritis (0) No Discharged Died (within 1 mo)
10 39/F B MV 6 mo 5 None None Yes (53) Discharged Alive
11 69/M B AV 14 mo 1 AR, CHF None Yes (22) Discharged Alive
12 34/M B AV 3 y 4 None CNS hemorrhage (0), No Died (43) ...
splenic infarct†
13 66/M M MV 6y 30 None CNS emboli (0) No Discharged Alive
14 75/M B AV 14 mo 1 AR, CHF None Yes (37) Discharged Alive
15 64/M M MV 6y 7 MR, LAH, Bilateral endogenous No Discharged Relapsed 1 w
progressive 17 endophthalmitis (0) after antibiotic
AVB therapy, requiring
repeated MVR
16 64/M M MV 6y 8 Progressive 17 CNS emboli (0) Yes (27) Discharged Alive
AVB
17 70/F B MV 10 y 1 CHF None No Died (10) ...
18 76/M M MV 11 mo 1 None None Yes (22) Discharged Alive
19 63/M M AV 4 y 1 CHF, 17 AVB None No Discharged Alive
20 58/M M MV 8 y 3 CHF, LAH, RBBB Systemic emboli (1) No Died (4) ...
21 74/M B MV 11 y 1 CHF, MR None Yes (11) Discharged Died suddenly 8 d
after discharge
22 60/F M MV 17 y 1 None Left brachial embolus (3) Yes (31) Discharged Alive
23 65/F M AV 4 mo 1 None Septic shoulder (0) No Discharged Alive
24 34/M M AV 5y NA† AR, intracardiac CNS hemorrhage (2), No Discharged Died within 2 mo
abscess systemic emboli (0)
25 72/M B AV 12 y 1 None None Yes (41) Discharged Alive
26 67/M M AV 3y 1 AR; 17, 27 AVB; None Yes (15) Discharged Alive
intracardiac
abscess
27 51/M M MV 10 y 1 CHF None Yes (14) Discharged Alive
28 57/F M MV 5y 1 None CVA with hemorrhage No Discharged Alive
(1, 7), CNS abscess
(1), osteomyelitis
29 75/M B AV 2y 1 CHF, intracardiac None No Died (30) ...
abscess, CHB,
RBBB
30 63/F B AV 11 mo 1 17 AVB, None Yes (8) Discharged Alive
intracardiac
abscess
31 61/M M MV 5y NA† None None No Discharged Alive
32 62/M B AV 7 mo 1 17 AVB CNS hemorrhage (3) No Died (18) ...
33 60/M M AV 10 y 1 AR, intracardiac None Yes (6) Discharged Alive
abscess

NOTE. AR Å aortic regurgitation; AV Å atrioventricular; AVB Å atrioventricular block; AVR Å aortic valve replacement; B Å bioprosthesis; CHB Å complete heart block; CHF Å
congestive heart failure; CVA Å cerebrovascular accident; LAH Å left anterior hemiblock; M Å mechanical valve; MR Å mitral regurgitation; MV Å mitral valve; MVR Å mitral valve
replacement; RBBB Å right bundle branch block.
* Infection limited to aortic valve on pathological examination.
†
Day of onset uncertain.

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CID 1998;26 (June) S. aureus PVE 1305

Table 2. Pathological findings in patients meeting definite clinical criteria for endocarditis.

No. with confirmation No. with nondiagnostic

Total no. by pathological findings pathological findings at No. with pathological
Clinical criteria of patients at surgery or autopsy surgery or autopsy findings unavailable

Two major criteria met 8 4 1 3

One major criterion, three minor criteria met 20 9 0 11
Five minor criteria met 1 0 0 1
Clinical criteria not met* 4 4 0 0
Total 33 17 1 15

* Each of the four patients met one major and two minor criteria.

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criteria for definite endocarditis, and these data confirmed the
diagnosis of endocarditis in 13 (93%) of these 14 patients; the
remaining patient had received antibiotic therapy for several
weeks before cardiac surgery was performed.
The median duration of parenteral antimicrobial therapy
among hospital survivors was 42 days for those who did not
undergo valve replacement surgery and 48 days for those
who did (table 3). The majority of patients (24 [73%] of 33)
received an aminoglycoside in addition to a cell-wall-active
antibiotic (nafcillin, oxacillin, or vancomycin). The percent-
age of patients receiving an aminoglycoside increased from
50% in the period 1975 – 1984 to 90% in 1985 – 1995
(P Å .02). Eleven (33%) of 33 patients also received rifam-
pin; the percentage receiving rifampin did not change sig-
nificantly between the two decades of the study. The median
duration of preoperative parenteral antimicrobial therapy
among patients undergoing valve replacement surgery was
19 days (range, 6 – 53 days). Only two patients (6%) were
infected with methicillin-resistant S. aureus, obviating any
comparisons between infections due to methicillin-suscepti-
ble and methicillin-resistant isolates.
We analyzed the risk factors for death due to PVE by using
death in the 3 months following the initial diagnosis as the
endpoint. Multivariate analysis with use of logistic regression
(table 4) demonstrated that the presence of cardiac complica-
Table 3. Durations of parenteral antibiotic therapy among 22 pa-
tients with prosthetic valve endocarditis who were discharged from
the hospital.
Median no. of d
Duration of therapy (range)
Total duration of parenteral antiobitic therapy
Patients undergoing valve replacement (n Å 13) 48 (28 – 83)
Patients without surgery (n Å 9)* 42 (24 – 56)
Patients treated with an aminoglycoside (n Å 14) 9 (2 – 54)
Duration of parenteral antibiotic therapy before
surgery (n Å 13) 19 (6 – 53)
* One patient was considered incurable and was sent home with oral antibiot-
ics after receiving parenteral therapy for 24 days; he died 26 days later.
tions of infection and valve replacement surgery were indepen-
dent predictors of outcome, with an odds ratio of 13.7 for
complicated infection compared with uncomplicated infection
(P Å .02) and an odds ratio of 0.05 for patients who underwent
valve replacement surgery vs. those who did not (P Å .004).
Follow-up information on patients was available for a mini-
mum of 12 months after initial presentation. During the period
3 – 12 months after presentation, there were no further deaths
due to endocarditis. One patient (patient 22) died of aortic
dissection, and a second patient (patient 31) died of an unknown
illness believed to be a malignancy. One patient (patient 15)
relapsed and was subsequently cured following a mitral valve
replacement; another patient (patient 3) required aortic valve
replacement for hemodynamic reasons 2 months after hospital-
ization for endocarditis.
Eleven (33%) of 33 patients had CNS complications. Patients
with CNS complications underwent valve replacement surgery
much less frequently (1 [9%] of 11) than did patients without
CNS complications (13 [59%] of 22) (P Å .009, two-tailed
Fisher’s exact test). Because CNS complications and valve
replacement surgery were time-dependent variables in relation
to mortality, we considered the possibility that our results might
have been influenced by this time dependency and did an addi-
tional multivariate analysis by using the Cox proportional haz-
ards model, introducing CNS complications and valve replace-
ment surgery as time-dependent covariates (table 4). This
analysis confirmed that cardiac complications and valve re-
placement surgery remained the two independent predictors of
outcome during the 3 months after presentation with PVE due
to S. aureus. CNS complications were not independent pre-
dictors of mortality. Although death occurred throughout the
90-day period after initial presentation, CNS complications
largely occurred within the first week or two after presentation
(figure 1).
We also considered that the medically treated patients might
have included a subset of patients believed to be too ill for
surgery and that inclusion of these patients in the medically
treated group might have increased the mortality in this group
over that in the surgically treated group. In a partial attempt
to control for this potentially confounding factor, we repeated
the multivariate logistic regression, excluding patients in the

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1306 John et al. CID 1998;26 (June)

Table 4. Risk factors for death in the 3 months after the diagnosis of Staphylococcus aureus prosthetic valve endocarditis, as determined by
multivariate analysis.

Logistic regression* Cox proportional hazards model

No. of patients who
died/no. with indicated Univariate OR Multivariate OR Univariate RR Multivariate RR
Risk factor characteristic (%) (95% CI) P value (95% CI) P value (95% CI) P value (95% CI) P value

Demographic data
Age
£60 y 9/21 (43) 1.1 (0.3 – 4.4) .95 ... 1.1 (0.4 – 3.3) .88 ...
ú60 y 5/12 (42)
Sex
Male 8/20 (40) 0.8 (0.2 – 3.2) .73 ... 0.7 (0.3 – 2.1) .56 ...
Female 6/13 (46)
Prosthetic valve

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Year infected
1975 – 1984 8/14 (57) 2.9 (0.7 – 12.1) .14 . . .† 2.2 (0.8 – 6.5) .14 . . .†
1985 – 1995 6/19 (32)
Valve type
Mechanical 8/22 (36)
Bioprosthesis 6/11 (55) 2.1 (0.5 – 9.1) .32 ... 1.6 (0.6 – 4.6) .40 ...
Location of infected
valve‡
Aortic 9/18 (50)
Mitral 4/14 (29) 0.4 (0.1 – 1.8) .23 ... 0.5 (0.2 – 1.8) .30 ...
Time of infection after
insertion of
prosthesis
£12 mo 11/26 (42) 1.0 (0.2 – 5.5) .98 ... 1.1 (0.3 – 4.0) .86 ...
ú12 mo 3/7 (43)
Complication
Cardiac complications
Yes 12/22 (55) 5.4 (0.9 – 31.0) .059 13.7 (1.4 – 131)† .02 3.8 (0.9 – 17.3) .078 6.1 (1.3 – 28.2)† .023
No 2/11 (18)
CNS complications
Yes 7/11 (64) 3.8 (0.8 – 17.2) .089 . . .† 2.6 (0.9 – 7.3) .081 . . .†§
No 7/22 (32)
Systemic complications
Yes 3/7 (43) 1.0 (0.2 – 5.5) .98 ... 1.0 (0.3 – 3.4) .94 ...
No 11/26 (42)
Valve replacement during
antibiotic therapy
Yes 2/14 (14) 0.1 (0.02 – 0.6) .0096 0.05 (0.005 – 0.42)† .004 0.3 (0.07 – 1.6) .16 0.18 (0.04 – 0.89)†§ .043
No 12/19 (63)

* Goodness-of-fit test: c Å 0.079, df Å 2, P Å .96; area under the receiver operating characteristics curve Å 0.85. There were no statistically significant interaction terms.
†
Variable included in the multivariate model.
‡
One patient had both aortic and mitral valves infected and was excluded from this analysis only.
§
Time-dependent covariates.

medically treated group who died within 7 days of diagnosis
(and might have been too ill to salvage with surgery) or who
died within 2 weeks of the onset of a CNS complication (and
might not have been surgical candidates during that interval).
These exclusions made no difference with respect to the conclu-
sions of the analysis; odds ratios and P values for cardiac
complications and valve replacement surgery were almost iden-
tical to those shown in table 4.
Discussion
In the present study we analyzed data on 33 patients with
S. aureus PVE. We used a strict case definition of endocarditis,
as proposed by Durack et al. [12]. Of patients who met the
clinical criteria proposed for definite endocarditis, the diagnosis
was confirmed pathologically in 13 of 14 for whom information
from surgery or autopsy was available. This finding suggests
that among patients fulfilling the clinical criteria for definite
S. aureus PVE, there will be relatively few false-positive diag-
noses. Of the 17 patients with S. aureus PVE confirmed patho-
logically, only 13 (76%) patients met the clinical criteria for
definite infection. Four (24%) of 17 with pathological findings
that confirmed PVE had clinical criteria indicative of possible
endocarditis. Accordingly, prosthetic valve recipients with
S. aureus bacteremia whose clinical features are consistent
with possible endocarditis, as defined by the proposed criteria,
should be treated for S. aureus PVE.

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CID 1998;26 (June) S. aureus PVE
Figure 1. A, Kaplan-Meier product limit estimate of the probability of surviving for 60 days after the diagnosis of Staphylococcus aureus
prosthetic valve endocarditis (PVE). B, Number of patients who had CNS complications on each of the first 60 days after the diagnosis of
S. aureus PVE.
Although the overall mortality associated with PVE is rela-
tively high (range, 23% – 48%), the mortality attributable to
S. aureus PVE in each study has been consistently higher
(range, 28% – 82%) [5, 7 – 9, 11, 15 – 17]. Indeed, some investi-
gators have found that S. aureus infection is an independent
risk factor for death in both univariate and multivariate models
of PVE [8, 9]. The mortality rate of 42% in our study is
consistent with the mortality rates in these previous studies and
underscores the severity of this form of PVE and the need
to identify interventions that improve outcome. In previous
multivariate analyses, predictors of mortality among all patients
with PVE have included early onset of infection, use of medical
therapy alone, severity-of-illness score, complicated PVE, and
identity of the organism causing infection [5, 7 – 9].
In the present study we performed a multivariate analysis to
determine risk factors for death due to S. aureus PVE and
found that the presence of cardiac complications and the perfor-
mance of valve replacement surgery during treatment of infec-
tion were the only independent predictors of outcome. In a
previous study [5], 116 patients with PVE were analyzed, and
the results showed that complicated infection was the best
predictor of death (producing an approximately sixfold in-
creased mortality in a multivariate model); complicated infec-
tion was defined as PVE with (1) new or increasing murmur
due to prosthetic valve dysfunction, (2) new or worsening CHF
related to prosthetic valve dysfunction, (3) fever for §10 days
during appropriate antibiotic therapy, or (4) new or progressive
cardiac conduction abnormalities. Other studies have also con-
firmed that these cardiac complications adversely affect the
outcome of PVE [10, 18]. In the present study, we modified
the definition of complicated PVE to focus on cardiac compli-
cations (replacing persistent fever with the presence of myocar-
dial abscess) and confirmed a 13.7-fold increased risk of death
among patients with S. aureus PVE and cardiac complications.
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1307
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The results of several previous studies have suggested that
cardiac complications are an appropriate indication for surgical
treatment of PVE [5, 8 – 11]. Although some investigators have
not found a difference in mortality among patients with PVE
treated medically and those treated with medical-surgical ther-
apy [8, 16], most studies have shown a significant reduction
in mortality with medical-surgical therapy [5, 7, 9, 11], particu-
larly among patients with S. aureus PVE [7, 9]. We therefore
investigated the role of medical-surgical therapy in the manage-
ment of S. aureus PVE. In a multivariate model, the use of
medical-surgical therapy was a highly significant and indepen-
dent predictor of reduced mortality, with an odds ratio of 0.05.
This reduction in mortality was found for patients both with
and without cardiac complications (table 5), suggesting that all
patients with S. aureus PVE may benefit from medical-surgical
therapy.
The presence of CNS complications in patients with PVE
has often resulted in a delay or has prevented cardiac surgery
for fear of worsening the CNS deficit related to anticoagulation
at the time of valve replacement. Approximately 30% of cases
of PVE are associated with CNS complications [19 – 22], and
the risk of CNS complications may be even higher for patients
with S. aureus PVE [22 – 24]. Although some studies have
Table 5. Mortality among patients with and without cardiac compli-
cations of prosthetic valve endocarditis, according to type of treat-
ment.
Variable Medical therapy Surgical therapy
No. of patients who died/
no. with complications (%) 10/12 (83) 2/10 (20)
No. of patients who died/
no. without complications (%) 2/7 (29) 0/4
cida UC: CID
1308 John et al.
suggested no significant difference in mortality between pa-
tients with and without CNS complications [19], other studies
have shown a significantly increased mortality among patients
with endocarditis and CNS complications [21]. The timing of
valve replacement surgery for patients with CNS complications
is a topic of debate. Recent studies have suggested that worsen-
ing of the CNS deficit may be diminished by delaying surgery
for 10 – 14 days after cerebral infarction and for perhaps as
long as 4 weeks after cerebral hemorrhage [19, 20, 25].
Although our univariate analysis suggested a higher mortal-
ity among patients with S. aureus PVE and CNS complications
than among those without CNS complications (64% vs. 32%),
the presence of a CNS complication was not an independent
predictor of mortality in the multivariate model. In our study
only one (9%) of 11 patients with CNS complications received
medical-surgical therapy, compared with 59% of patients with-
out CNS complications; this finding suggests that the presence
of CNS complications reduced the use of medical-surgical ther-
apy. Most of the CNS complications occurred during the first
week of hospitalization. Since the presence of CNS complica-
tions affected the subsequent decision regarding the perfor-
mance of cardiac surgery, we performed an additional multivar-
iate analysis by using the Cox model with CNS complications
and valve replacement surgery as time-dependent covariates.
This multivariate analysis confirmed that cardiac complications
and valve replacement surgery were the only independent pre-
dictors of outcome, which implies a benefit of medical-surgical
therapy regardless of the presence or absence of CNS complica-
tions. Since death due to S. aureus PVE occurs throughout
the 2-month period after initial presentation and most CNS
complications occur within the first week of hospitalization,
patients with CNS complications might still benefit from valve
replacement surgery later in the course of their illnesses. Data
suggest that this surgery can be performed without worsening
of a CNS deficit if a patient’s condition is allowed to stabilize
after the event or the event is treated (ruptured mycotic aneu-
rysm) before cardiac surgery is performed [19, 20, 25].
Our study has certain limitations. To have a large enough
sample of patients for statistical analysis, we included patients
whose PVE was diagnosed over a 20-year period. Substantial
changes in the management of endocarditis occurred over this
extended period. These include changes in antibiotic therapy
(more frequent use of combination regimens), the availability of
transesophageal echocardiography, and improvements in surgical
technique and intensive care. To partially evaluate the effects of
changes over time, we included the decade of diagnosis in our
statistical analysis. Although there was a trend in the univariate
analysis toward improved outcome in the more recent decade
of study, this factor did not significantly affect outcome in the
multivariate analyses. Although our sample size may have limited
the power for detecting an effect of changing therapy, the results
suggest that the impact of this effect, if any, is less than that of
valve replacement surgery. It is also possible that an unrecognized
referral bias may have influenced our results.
/ 9c4e$$ju69 05-12-98 14:16:51
CID 1998;26 (June)
Ideally, the safety and efficacy of valve replacement surgery
in patients with S. aureus PVE would be determined in a ran-
domized, prospective study. Although assignment to medical
or surgical therapy could not be blinded, many unrecognized
biases, such as the reasons for selecting medical or surgical
therapy for individual patients, should be eliminated. Although
S. aureus PVE is associated with significant morbidity and
mortality, this infection may be too uncommon for a random-
ized study to be logistically feasible. In addition, uncontrolled
studies of surgical therapy indicate that surgery may be benefi-
cial, so it is unlikely that patients or their physicians would
participate in such a clinical trial. In the absence of such infor-
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mation, a carefully performed retrospective study such as ours,
with use of multivariate analysis and controlling for survival
biases, may provide the best available data for clinical decision
making.
We conclude from this study that S. aureus PVE is an aggres-
sive, often fatal, form of infection, in which patients with evi-
dence of cardiac complications are at greatest risk. Our results
suggest that valve replacement surgery during medical therapy
for S. aureus PVE will improve the outcome of this infection,
even for patients without evidence of cardiac complications. In
the presence of CNS complications, valve replacement surgery
should be timed sufficiently long after a CNS event so that the
risk of exacerbating CNS deficits during surgery is reduced.
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