Staphylococcus aureus Bacteremia After Median Sternotomy

Clinical Utility of Blood Culture Results in the Identification of

Postoperative Mediastinitis
Vance G. Fowler, Jr, MD, MHS; Keith S. Kaye, MD, MPH; David L. Simel, MD, MHS;
Christopher H. Cabell, MD; Douglas McClachlan, MD, MPH; Peter K. Smith, MD; Scott Levin, MD;
Daniel J. Sexton, MD; L. Barth Reller, MD; G. Ralph Corey, MD; Eugene Z. Oddone, MD, MHS

Background—Mediastinitis is a complication of coronary artery bypass graft surgery (CABG) that can be difficult to
diagnose. This study evaluated the utility of blood culture results in identifying patients with mediastinitis.
Methods and Results—All unique patients undergoing CABG at our institution over a 60-month study period (n⫽5500)
and all blood cultures performed on these patients ⱕ90 days after CABG were identified. Mediastinitis was identified
by prospective active infection control surveillance. Eight hundred fifty-five (15.5%) patients had ⱖ1 blood culture
drawn within 90 days of CABG. Mediastinitis occurred in 46 of 60 (76.7%) patients with blood cultures positive for
Staphylococcus aureus, 15 of 126 (11.9%) patients with blood cultures positive for other pathogens, 37 of 669 (5.5%)
patients with blood cultures with no growth, and 44 of 4645 (0.9%) patients with no blood cultures obtained. The
isolation of S aureus from even 1 blood culture drawn after ⱕ90 days of CABG was strongly associated with
mediastinitis (likelihood ratio [LR], 25; 95% CI, 14.7 to 44.4). Bacteremia attributable to other organisms did not alter
pretest suspicion for mediastinitis (LR, 1.0; 95% CI, 0.6 to 1.7). Patients with negative blood cultures were less likely
to have mediastinitis (LR, 0.45; 95% CI, 0.35 to 0.58). The association between S aureus bacteremia and mediastinitis
remained highly significant when all unique patients undergoing CABG were analyzed in a logistic regression model
and when a case-control analysis was used to evaluate patients with ⱖ1 blood culture obtained after CABG.
Conclusions—Among patients with blood cultures drawn after CABG, S aureus bacteremia strongly suggests the presence
of mediastinitis. (Circulation. 2003;108:73-78.)
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Key Words: infection 䡲 diagnosis 䡲 bypass 䡲 surgery

P ostoperative mediastinitis occurs in 1% to 3% of all

patients undergoing median sternotomy. This devastating
complication carries an associated mortality of up to 40%,
perhaps in part because it is often difficult to make an early
diagnosis.1 Definitive diagnosis and treatment of mediastini-
tis requires reopening the mediastinum for direct inspection
and debridement. These procedures subject patients to addi-
tional risks and significant health care costs.2,3 Although
several diagnostic strategies have been evaluated, none reli-
ably identified patients with mediastinitis.
Previously, we reported an association between S aureus
bacteremia and mediastinitis. Among 23 patients with S
aureus bacteremia after a median sternotomy, the positive
predictive value for mediastinitis was 91.3%.4 However,
because the positive predictive value varies with disease
prevalence5 and because these data were generated from a
small number of patients, the results may not generalize to
other clinical settings.
In the present investigation, we evaluated the clinical
utility of blood cultures in identifying mediastinitis using a
large sample size and methods that would result in greater
generalizability. We hypothesized that the isolation of S
aureus from blood cultures drawn as a part of routine care in
a patient who had recently undergone median sternotomy
would be highly associated with mediastinitis.
Methods
Patient Selection
This investigation was approved by the Duke University Institutional
Review Board and was performed in accordance with institutional
guidelines. Patients were considered for inclusion if they underwent
median sternotomy for coronary artery bypass graft surgery (CABG)
at Duke University Medical Center from January 1, 1994, until
December 31, 1998, and had ⱖ1 blood culture drawn within 90 days
of the median sternotomy. Exclusion criteria included median
sternotomy performed for procedures other than, or in addition to,
CABG; CABG performed by surgical approaches other than median

Received February 4, 2003; revision received April 7, 2003; accepted April 9, 2003.
From the Department of Medicine (D.M.), Divisions of Infectious Diseases (V.G.F., K.S.K., D.J.S., L.B.R., G.R.C.), Cardiology (C.H.C.), and General
Internal Medicine (D.L.S., E.Z.O.); Clinical Microbiology Laboratory (L.B.R.); Department of Surgery, Divisions of Cardiovascular (P.K.S.) and Plastic
and Reconstructive Surgery (S.L.), Duke University Medical Center; and Center for Health Services Research in Primary Care (D.L.S., E.Z.O.), VA
Medical Center, Durham, NC.
Correspondence to Vance Fowler, Box 3281, Duke University Medical Center, Durham, NC 27710. E-mail fowle003@mc.duke.edu
© 2003 American Heart Association, Inc.
Circulation is available at http://www.circulationaha.org DOI: 10.1161/01.CIR.0000079105.65762.DB

73
 74 Circulation July 8, 2003

TABLE 1. Characteristics Associated With Postoperative Mediastinitis Among 5500 Consecutive Patients
Undergoing CABG
Entire Cohort, Bivariate Multivariate*
n (%)
(n⫽5500) OR 95% CI P OR 95% CI P
Age ⬎70 y 1633 (29.7) 0.99 0.69 to 1.43 1.00
Race, white 4164 (75.7) 1.02 0.69 to 1.50 0.92
Sex, male 3733 (67.9) 1.61 1.15 to 2.26 0.006 1.33 0.89 to 2.00 0.1631
Weight ⬎90 kg 1506 (27.4) 1.32 0.93 to 1.89 0.127
Diabetes mellitus 1771 (32.2) 2.03 1.45 to 2.84 ⬍0.0001 1.56 1.04 to 2.32 0.0309
Previous cerebrovascular disease 640 (11.6) 1.41 0.89 to 2.23 0.1452
Hypertension 3751 (68.2) 2.02 1.32 to 3.08 0.0007 1.57 0.96 to 2.55 0.0703
Chronic obstructive pulmonary disease 750 (13.6) 1.80 1.20 to 2.70 0.0062 1.72 1.07 to 2.78 0.0258
Previous CABG 285 (5.2) 1.10 0.53 to 2.26 0.7031
Mean cross-clamp time ⬎90 minutes 261 (4.8) 0.88 0.39 to 2.02 1.00
Blood culture†
Not done‡ 4645 (84.4) 0.163 0.10 to 0.25 ⬍0.001 0.17 0.11 to 0.26 ⬍0.0001
S aureus bacteremia 60 (1.1) 56.123 28.32 to 111.22 ⬍0.001 52.98 26.46 to 106.08 ⬍0.0001
Bacteremia other than S aureus 126 (2.3) 2.308 1.23 to 4.35 0.001 2.05 1.08 to 3.91 0.0273
No growth 669 (12.2) Referent category
*Multivariate model controlled for confounding effects of male sex and hypertension. Additional variables (previous cerebrovascular
disease, weight ⬎90 kg) did not achieve statistical significance in multivariate analyses, did not confound any model covariates, and
were removed from the final model.
†Sum of patients⫽5500.
‡Includes patients in whom no blood cultures were obtained (n⫽4624) and patients in whom blood culture was obtained only after
diagnosis of mediastinitis (n⫽21).

Patient Follow-Up
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sternotomy; or no blood cultures obtained before the date of

definitive/surgical diagnosis of mediastinitis. Only the first median
sternotomy during the study period was included for each patient.
Potential study patients undergoing median sternotomy for CABG
were identified using the Duke Database for Cardiovascular Diseases
(DDCD), an ongoing prospective registry of all patients undergoing
a cardiac procedure at our institution since 1971 (n⫽⬇120 000).6
Missing data occurred in less than 0.5% of variables. Next, a
database link was performed between the DDCD and the electroni-
cally archived records of all blood cultures performed in our clinical
microbiology laboratory since 1992 (Cerner Pathnet, Kansas City,
Mo). Thus, the final data set included all patients with ⱖ1 blood
culture drawn within 90 days of CABG and the results of all blood
cultures performed on these patients.
Mediastinitis Identification
Our primary outcome, mediastinitis within 90 days of CABG, was
prospectively identified using active surveillance by infection con-
trol practitioners. Mediastinitis was defined according to Center for
Disease Control (CDC) criteria as isolation of an organism from a
culture of mediastinal tissue or fluid during surgery or needle
aspiration; evidence of mediastinitis observed at surgery or by
histopathologic examination; or fever (⬎38°C), chest pain, or sternal
instability, plus purulent drainage from the mediastinal area, isola-
tion of an organism from blood culture or drainage from the
mediastinal area, or mediastinal widening on x-ray examination.7
The date of definitive diagnosis was defined as the date the patient
met CDC criteria for mediastinitis.
Blood Culture Identification
Patients were defined as having S aureus bacteremia if any blood
culture result yielded S aureus within the 90-day period. Patients
were defined as having bacteremia attributable to other pathogens if
blood cultures yielded any organism other than S aureus during the
90-day period. Patients whose blood cultures remained negative
were defined as having blood cultures with no growth.
The outcomes of all study patients were established for a period of
90 days after CABG using the DDCD. Follow-up in this database is
obtained for each patient at regular intervals for the first year after
the procedure and annually thereafter. The self-reported follow-up is
more than 97% complete and includes details regarding rehospital-
ization and adverse events (including death). The records of all study
patients who were readmitted to a different hospital within 90 days
of their median sternotomy were reviewed using a standard protocol
followed by the DDCD.
Analysis
The association of S aureus bacteremia and mediastinitis was
considered using multilevel test table, cohort, and case-control
analyses. All statistics were obtained using SAS, version 8.1.
Bivariate comparisons were performed using Fisher’s exact or ␹2
tests; and to determine the association between blood culture results,
a logistic regression model was created that included only different
categories of blood culture results (eg, S aureus bacteremia and
bacteremia other than S aureus). Continuous variables were analyzed
with either the Student’s t test or Wilcoxon rank-sum test.
Multivariate analyses for data from Table 1 and Table 3 were
performed using logistic regression. Each model included all vari-
ables from the respective table with P⬍0.2 in the bivariate analysis.
Stepwise selection was used for retaining significant variables and
was specified before any multivariate results were known. Risk
factors were checked for confounding, and confounders were in-
cluded in multivariate models if inclusion of the covariate changed
the coefficient of any statistically significant variable in the regres-
sion model by 10% or greater. All tests were 2-tailed, and Pⱕ0.05
was considered significant in the multivariate model.
Multilevel Test Table Analysis
To consider the use of blood cultures as a diagnostic test for
mediastinitis, 3 possible test results were identified: positive (S
aureus bacteremia), nonpositive nonnegative (bacteremia other than
 Fowler et al
S aureus), and negative (blood culture yields no growth). A 6-cell
matrix approach was used as previously defined.8 The positive
likelihood ratio (LR) and 95% CI was then calculated to provide the
odds of disease (mediastinitis) given a positive test result (S aureus
bacteremia).
Cohort Study of CABG Patients
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Bivariate analyses were performed on the entire cohort (n⫽5500) to
identify clinical characteristics independently associated with medi-
astinitis. A multivariate logistic regression model was built to
identify independent predictors of mediastinitis.
Case-Control Analysis
Only patients with ⱖ1 blood cultures obtained after CABG were
included in the case-control analysis. Cases included patients with
mediastinitis and ⱖ1 blood culture drawn within 90 days of CABG
but before the diagnosis of mediastinitis. Controls included patients
who had ⱖ1 blood culture drawn within 90 days of CABG and did
not develop mediastinitis. Controls were randomly selected from the
study data set. Characteristics for 95 of the 98 possible cases and 95
controls were collected on the calendar date that blood cultures were
drawn and before surgical debridement. A logistic regression model
was generated to determine independent predictors for mediastinitis.
Results
A total of 5500 unique patients underwent median sternotomy
for CABG during the study period (Table 1). Eight hundred
seventy-six patients (15.9%) had at least 1 blood culture
performed during the 90-day follow-up period. Blood cul-
tures drawn after definitive diagnosis of mediastinitis from 21
patients were excluded. Thus, 855 patients were included in
the final analysis (Figure).
Mediastinitis
The overall rate of mediastinitis for the 5500 patients was
2.58%. Ninety-eight of the 855 study patients in whom blood
cultures were obtained developed mediastinitis. All 98 pa-
tients fulfilled CDC criteria for mediastinitis independent of
blood culture results. Mediastinitis occurred in 46 of 60
S aureus Bacteremia and Postoperative Mediastinitis 75
Identification of 855 patients with at least 1
blood culture drawn within 90 days of median
sternotomy for CABG.
(76.7%) patients with blood cultures positive for S aureus, 15
of 126 (11.9%) patients with blood cultures positive for other
pathogens, 37 of 669 (5.5%) patients with blood cultures with
no growth, and 44 of 4645 (0.9%) patients with no blood
cultures obtained. None of the 48 study patients readmitted to
different hospitals during the 90-day follow-up were diag-
nosed with mediastinitis.
S aureus was identified in sternal cultures from 65 of the 98
study patients (66%) with mediastinitis. Methicillin-resistant
S aureus was present in 32 of 65 sternal isolates (49%). Other
pathogens isolated from the mediastinum included coagulase-
negative staphylococci in 13 patients (13%), Gram-negative
bacteria in 10 patients (10%), and other pathogens (Entero-
coccus species, viridans group streptococci, Candida species,
Bacteroides species, and polymicrobial infection) in 6 pa-
tients (6%). Mediastinal cultures were negative in 4 patients
(4%). Among the 46 patients with S aureus bacteremia and
mediastinitis, another potential source of bacteremia was
identified by culture of S aureus from other sites in 6 patients
(endotracheal suction culture in 3 patients; saphenous vein
harvest site, empyema, and central venous catheter in 1
patient each).
Blood Cultures
A total of 2884 blood cultures were obtained from 855 study
patients. Eighty-four percent (2421 of 2884) of these blood
cultures yielded no growth. S aureus was the most frequently
identified pathogen, present in 177 blood cultures from 60
patients. Among the 126 patients with pathogens other than S
aureus (including 19 patients with polymicrobial bacteremia),
a total of 33 pathogens were isolated in 198 blood cultures.
These pathogens included coagulase negative staphylococci
(81 patients), Enterococcus species (19 patients), yeast (10
patients), enteric Gram-negative bacteria (35 patients), and 9
other pathogens from 18 patients.
 76 Circulation July 8, 2003

TABLE 2. Clinical Utility of Blood Culture Results in the
Identification of Mediastinitis in 855 Patients Undergoing
Median Sternotomy for CABG
Mediastinitis Mediastinitis
Present Absent
Blood Culture Results (n⫽98) (n⫽757)
S aureus 46 14
Other pathogen 15 111
No growth 37 632
Of the 61 patients with both positive blood cultures and
mediastinitis, data on clinical signs and symptoms were
available for 60 (98.4%). Of these 60 patients, 8 patients
(13.3%) had no obvious signs of mediastinitis (sternal pain,
drainage, or instability). Six of these 8 patients (75%) had S
aureus bacteremia; 1 patient each had bacteremia attributable
to Enterococcus species and coagulase negative staphylo-
cocci. Signs of mediastinitis (sternal pain, drainage, or
instability) were present in the remaining 52 patients with
mediastinitis and positive blood cultures. Of these, 39 pa-
tients (75%) had S aureus bacteremia, and 13 patients had
other pathogens (coagulase negative staphylococci in 6 pa-
tients, enteric Gram-negative rods in 5 patients, viridans
group streptococci and Candida species in 1 patient each).
Timing of Blood Cultures and Mediastinitis
The median time from CABG to diagnosis of mediastinitis
was 21 days (interquartile range [IQR], 13 to 36 days). The
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nitis (15 days [IQR, 10 to 26 days] versus 11 days [IQR, 6 to
19 days], P⫽0.008).
Likelihood Multilevel Test Table Analysis
Ratio The isolation of S aureus from even 1 blood culture drawn
(95% CI) within 90 days of CABG was strongly associated with the
25 (14.7 to 44.4) subsequent diagnosis of mediastinitis. Patients with S aureus
1.0 (0.64 to 1.7)
bacteremia were significantly more likely to have mediasti-
nitis than patients without S aureus bacteremia (LR, 25; 95%
0.45 (0.35 to 0.58)
CI, 14.7 to 44.4) (Table 2). Bacteremia attributable to other
pathogens did not alter the pretest suspicion for mediastinitis,
(LR, 1.0; 95% CI, 0.6 to 1.7). Patients with negative blood
cultures were less likely to have mediastinitis (LR, 0.45; 95%
CI, 0.35 to 0.58).
Cohort Study of CABG Patients
In bivariate analysis of the entire cohort of 5500 patients, S
aureus bacteremia was strongly associated with mediastinitis
(Table 1). When multivariate modeling was performed on the
entire cohort, S aureus bacteremia remained strongly associ-
ated with mediastinitis (OR, 52.98; 95% CI, 26.46 to 106.08)
(model c-index, 0.844) (Table 1). When the model was
repeated to include both 90-day all-cause mortality and
mediastinitis as end points, the association between S aureus
bacteremia and mediastinitis persisted (OR, 49.61; 95% CI,
20.50 to 120.08). Multivariate modeling of S aureus–specific
demographic parameters demonstrated no characteristics sig-
nificantly associated with mediastinitis among patients with S
aureus bacteremia because of the small sample size of this

median interval from obtaining blood cultures to definitive
diagnosis of mediastinitis was 3 days for both the overall
cohort (IQR, 1 to 9 days) and patients with S aureus
bacteremia (IQR, 1 to 8 days). Blood cultures from patients
with mediastinitis were drawn significantly later after CABG
than blood cultures from patients without mediastinitis (16
days [IQR, 9 to 26 days] versus 5 days [IQR, 3 to 13 days],
P⬍0.001). Similarly, positive blood cultures among patients
with mediastinitis occurred significantly later after CABG
than positive blood cultures from patients without mediasti-
subpopulation and because most patients with S aureus
bacteremia had mediastinitis.
Case-Control Analysis of Patients With >1 Blood
Cultures After CABG
Clinical signs and symptoms of infection among the 95 cases
with mediastinitis and ⱖ1 blood culture were compared with
95 randomly selected control patients with ⱖ1 blood culture
and no mediastinitis (Table 3). Among these 190 patients, S
aureus bacteremia was strongly associated with mediastinitis

TABLE 3. Case-Control Analysis of 95 Patients With Mediastinitis and at Least 1 Blood Culture Performed
(Cases) and 95 Randomly Selected Patients With at Least 1 Blood Culture Performed but Without
Mediastinitis (Controls)
Bivariate Multivariate

OR 95% CI P OR 95% CI P
Hypotension present 0.94 0.49 to 1.83 1.00
Fever present (ⱖ38.0°C) 0.96 0.53 to 1.72 1.00
Sternal pain present 11.57 5.67 to 23.60 ⬍0.0001 5.40 1.81 to 16.08 0.0025
Sternal drainage present 21.05 9.98 to 44.42 ⬍0.0001 68.48 14.37 to 326.42 ⬍0.0001
Sternal instability present* 253.36 14.98 to 4285.27 ⬍0.0001
Leukocytosis present 0.68 0.35 to 1.31 0.3198
Blood cultures
S aureus bacteremia 35.13 10.23 to 120.62 ⬍0.0001 152.13 21.40 to ⬎999.99 ⬍0.0001
Bacteremia other than S aureus 3.51 1.44 to 8.58 ⬍0.0001 10.60 1.65 to 68.19 0.0129
No growth Referent category
*No control subjects had sternal instability. Adjusted using logit estimators with a correction of 0.5 in every cell that contained a
zero.
 Fowler et al
by both bivariate (OR, 35.13; 95% CI, 10.23 to 120.62) and
multivariate (OR, 152.12; 95% CI, 21.40 to ⬎999.99) anal-
yses. Sternal instability was also strongly associated with
mediastinitis by bivariate analysis. Because no control pa-
tients had sternal instability, we could not evaluate this
variable in the multivariate model. However, when the final
multivariate model was performed among patients without
sternal instability, S aureus bacteremia remained strongly
associated with mediastinitis.
Discussion
Although mediastinitis is frequently fatal, rapid diagnosis is
often difficult.9 The ability to more easily identify this
complication would help clinicians to rapidly provide effec-
tive treatment. To our knowledge, this investigation is the
first to evaluate the clinical utility of blood culture results in
the identification of mediastinitis.
The current investigation’s findings depended on several
factors: (1) a database containing clinical and follow-up
information on a large cohort of consecutive, prospectively
identified patients undergoing the same surgical procedure
for the same therapeutic indication; (2) a second database
incorporating the timing and results of all blood cultures
taken from the study group; and (3) a third database contain-
ing prospectively identified patients with mediastinitis using
well-accepted diagnostic criteria. Combining information
from these databases led to the conclusion that S aureus
bacteremia identified during routine clinical care was
strongly associated with mediastinitis. This finding persisted
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when multilevel test table analysis, logistic regression, or
case-control analysis was performed and is consistent with
prior investigations.1,10 –13 However, unlike these prior stud-
ies, our investigation provides a clinically relevant means of
quantifying the clinical significance of blood culture results
to identify the presence of a devastating complication that is
often difficult to diagnose.
Clinicians managing patients who have recently undergone
median sternotomy need to know if a febrile patient with
positive blood cultures is likely or unlikely to have medias-
tinitis. The findings of our study help such clinicians answer
this question with three key observations: (1) if S aureus is
present in blood cultures, the likelihood of mediastinitis
greatly increases; (2) if another organism is present in blood
cultures, the finding does not alter the pretest suspicion and
additional evaluation will be needed when the suspicion is
high; and (3) if blood cultures are negative, the patient is less
likely to have mediastinitis.
Before the results of the current investigation, there were
no diagnostic tests to reliably identify mediastinitis. Because
of this limitation, a variety of diagnostic approaches to the
diagnosis of mediastinitis have been evaluated, including
aspiration of the mediastinal space,14,15 ␣1 acid glycoprotein
and C-reactive protein measurements,16 procalcitonin level,17
and culture of perioperative instruments.18 Even advanced,
expensive methods of radiographic imaging such as com-
puted tomography,19,20 fluorine-18 fluorodeoxyglucose
positron emission tomography,21,22 gallium-67 scintigraphy,23
99Tcm-labeled leukocyte scintigraphy,24,25 or single photon
emission computed tomography with 99mTc-hexamethylpropylene
S aureus Bacteremia and Postoperative Mediastinitis 77
amine oxime–labeled leukocytes26 are either of limited ben-
efit in identifying patients with postoperative mediastinitis or
are widely unavailable. For example, the sensitivity and
positive predictive value of computed tomography in the
diagnosis of mediastinitis were as low as 25% and 71%,
respectively.19 By contrast, the presence of S aureus bactere-
mia has high clinical utility (LR ⬇25). Thus, a simple,
inexpensive, and widely available diagnostic test such as
blood culture is of great potential benefit to clinicians in
identifying the presence of mediastinitis.
Likelihood ratios help clinicians to interpret the diagnostic
value of a test before the disease status is known. In the
present investigation, the LR for mediastinitis among patients
with S aureus bacteremia is ⬇25. A LR of this magnitude is
clinically meaningful.27 This association between S aureus
bacteremia and mediastinitis remained strong when the entire
cohort was evaluated with logistic regression modeling and
when a case-control analysis was conducted among patients
with blood cultures performed after CABG. Finally, because
LR estimates are independent of disease prevalence, the
significance of these findings should extend to other patient
populations.
The investigation has several limitations. First, blood
cultures were drawn based on clinical practice rather than as
part of a study protocol. However, we believe that this fact
enhances the utility of these results when applied to blood
cultures drawn as a part of routine clinical care and expands
the generalizability of the findings. Second, patients with
mediastinitis dying before accurate diagnosis may also be a
source of bias. However, when the analysis was adjusted for
study patients who died during the 90-day follow-up period,
the association of S aureus bacteremia and mediastinitis
persisted. Similarly, when the analyses were repeated to
include blood cultures obtained after the definitive diagnosis
of mediastinitis, the association between mediastinitis and S
aureus bacteremia also persisted. Finally, the findings in this
study require validation within a separate cohort.
In summary, these results should help clinicians interpret
blood culture results from patients who have recently under-
gone median sternotomy. The finding of S aureus bacteremia
should make such clinicians highly suspicious for mediasti-
nitis even if the clinical findings of a surgical site infection
are minimal or indeterminate. The prompt identification of
mediastinitis in such patients may in turn lead to early
surgical drainage and a better outcome of this serious and
sometimes fatal complication.
Acknowledgments
Supported by K23 Awards AI-01647 (to Dr Fowler) and HL70861 to
(to Dr Cabell) from the National Institutes of Health. The authors
gratefully acknowledge the assistance of Lawrence H. Muhlbaier,
PhD (Department of Biostatistics, Duke University Medical Center,
Durham, NC).
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