Mediastinitis after Cardiac Surgery:

Improvement of Bacteriological Diagnosis by

Use of Multiple Tissue Samples and Strain
Typing
1. Ann Tammelin1,*,
2. Anna Hambræus1 and
3. Elisabeth Ståhle2

+ Author Affiliations

1. 1
Department of Clinical Bacteriology
2. 2
Department of Thoracic and Cardiovascular Surgery, University of Uppsala, Uppsala,
Sweden
 
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ABSTRACT
The diagnosis of postsurgical mediastinitis (PSM) among patients with sternal wound
complication (SWC) after cardiac surgery is sometimes difficult, as fever, elevated C-reactive
protein levels, and chest pain can be caused by a general inflammatory reaction to the operative
trauma and/or sternal dehiscence without infection. The definitions of PSM usually used
emphasize clinical signs and symptoms easily observed by the surgeon. The aim of the study was
to investigate whether the use of standardized multiple tissue sampling, optimal culturing
methods, and strain typing, together with a microbiological criterion for infection, could identify
more infected patients than clinical assessment alone. Patients reexplored due to SWC after
cardiac artery bypass grafting (CABG) or heart valve replacement (HVR) with or without CABG
performed at the Department for Cardio-Thoracic Surgery at the Uppsala University Hospital
between 10 March 1998 and 9 September 2000 were investigated prospectively. Tissue samples
were taken from the sternum or adjacent mediastinal tissue, preferably before the administration
of antibiotics. Culturing was performed both directly (on agar plates) and using enrichment
broth. Species identification was performed by standard methods, and strain typing was
performed by pulsed-field gel electrophoresis. A total of 41 cases with at least five tissue
samples each were included in the study group. Of these patients, 32 were infected according to
the microbiological criterion (i.e., the same strain was found in ≥50% of the samples).
Staphylococcus epidermidis was the primary pathogen in 38% of the cases (12/32), S. aureus
was the primary pathogen in 31% (10/32), P. acnes was the primary pathogen in 25% (8/32), and
S. simulans and S. haemolyticus were the primary pathogens in 3% (1/32) each. All cases of S.
aureus infection and 86% (12/14) of coagulase-negative staphylococcus (CoNS) infections were
identified from primary cultures. All cases fulfilling the microbiological criterion for S. aureus
infection were clinically diagnosed as cases of infection, but among the 14 cases fulfilling the
criterion for microbiological diagnosis of CoNS infection, only 10 appeared to qualify clinically
as cases of infection. Among the patients with sternal dehiscence in whom a microbiological
diagnosis was established, 67% (12/18) had a CoNS infection, compared to 14% (2/14) of those
without sternal dehiscence. The difference was statistically significant. PSM caused by S. aureus
is readily identified by the surgeon, whereas 30% of cases with CoNS infections may be
misinterpreted as noninfected. Multiple sampling before administration of antibiotics, primary
culturing on agar plates, species identification, strain typing, and susceptibility testing should be
used to ensure a fast and microbiologically correct diagnosis which identifies the primary
pathogen and infected patients among those with minor infective symptoms. The role of P. acnes
as a possible cause of PSM needs further investigation. PSM caused by CoNS is significantly
related to sternal dehiscence.

Postoperative deep sternal wound infection occurs in 0.6 to 16% of patients who have undergone
cardiac surgical procedures performed using median sternotomy (13, 19). The variance in
reported incidence levels may depend on differences in definitions of infection.

The diagnosis of postsurgical mediastinitis (PSM) among patients with sternal wound
complication after cardiac surgery is sometimes difficult, since fever, elevated C-reactive protein
levels, and chest pain can be caused by a general inflammatory reaction to the operative trauma
and/or sternal dehiscence without infection (1).

According to the definition suggested by The Hospital Infection Control Practices Advisory
Committee, Centers for Disease Control and Prevention (CDC), Atlanta, Georgia, and the
adjustments made to that definition by R. M. El Oakley et al. for cases involving cardiothoracic
surgery, PSM is a deep infection involving retrosternal tissue and/or the sternal bone (3, 5). The
list of criteria for organ or space surgical-site infection (SSI) used by the National Nosocomial
Infection Surveillance system of the CDC (5) includes signs and symptoms that can be directly
observed by the surgeon. The National Nosocomial Infection Surveillance system also offers the
possibility of using a microbiological criterion for detection of infection without visible signs of
infection (“Organisms isolated from an aseptically obtained culture of fluid or tissue in the organ
or space”). The criterion does not specify the requirements for culturing, species identification,
strain typing, and interpretation of bacteriological findings.

The criteria used by the individual researcher for defining PSM are often modifications of the
suggestions from The Hospital Infection Control Practices Advisory Committee and usually
emphasize the signs and symptoms easily observed by the surgeon. Those often include purulent
discharge from the mediastinal area (11, 12, 16), in some cases together with fever (≥38°C) and
sternal dehiscence (4, 10, 18). L'Ecuyer et al., who did not include purulent discharge or sternal
dehiscence in their criteria for chest infection, found that those signs occurred in only 67% and
26% of the patients, respectively (8).

In many studies on PSM, there is a requirement for a positive bacteriological culture in addition
to observable signs and symptoms (4, 9, 11, 12, 18, 20). This requirement might serve to limit
diagnostic accuracy, as even in cases with undoubted and visible signs of infection,
bacteriological cultures can return negative results due to antibiotics given to the patient pre- or
intraoperatively.
Coagulase-negative staphylococci (CoNS) are recognized as important pathogens in PSM but are
also known not to produce the same fulminant clinical signs and symptoms of infection as, for
instance, S. aureus. The finding of staphylococci in a sample from mediastinal tissue or fluid is
difficult to evaluate, as CoNS, and sometimes also S. aureus, are inhabitants of human skin and
thus can easily contaminate a sample.

A majority of the CoNS causing PSM have been reported as methicillin resistant (MR) during
the last decade (9, 13). As this resistance limits the therapeutic options, it is important not to
overestimate the proportion of MR strains or the number of infected patients.

To be able to choose an adequate long-term treatment and avoid unnecessary use of broad-
spectrum antibiotics, a definition of PSM should be established which is based on both clinical
and bacteriological criteria. This is especially important concerning infections caused by CoNS,
as those infections seem to increase, thus creating great diagnostic difficulties.

This study was undertaken to investigate whether it was possible to use a microbiological
criterion for PSM to identify infected patients among those with sparse clinical signs and
symptoms while avoiding inclusion of those patients for whom the microbiological findings
represent contamination. A similar approach has been used in orthopedic surgery to differentiate
between infectious and noninfectious loosening after total hip arthroplasty (6).

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Aim.
The aim of the study was to investigate whether the use of standardized multiple tissue sampling,
optimal culturing methods, and strain typing, together with a microbiological criterion for
infection, could identify a greater number of infected patients than clinical assessment alone.

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MATERIALS AND METHODS

Design.The study was a prospective cohort study of reexplorative surgical procedures after
primary elective operations for cardiac artery bypass grafting or heart valve replacement with or
without cardiac artery bypass grafting, performed at the Department for Cardio-Thoracic Surgery
at the Uppsala University Hospital from 10 March 1998 to 9 September 2000. According to the
study protocol, five tissue samples for bacteriological culturing were to be taken from the
sternum or adjacent mediastinal tissue of each patient. Sampling was made irrespective of
clinical assessment of the reason for reexploration. The clinical diagnosis was not known to the
bacteriologist who processed the samples.

Microbiological diagnosis of infection.The microbiological diagnostic criterion for infection

was, in cases in which the infecting bacterial species was CoNS or S. aureus, the finding of the
same strain in at least half of the samples, and in cases in which the infecting bacterial species
was other than CoNS or S. aureus, the finding of the same species in at least half of the samples.
Bacterial isolates whose pulsed-field gel electrophoresis (PFGE) patterns were identical were
defined as belonging to the same strain (17).

Clinical diagnosis of infection.Six reasons for reexploration were identified: bleeding,

arrhythmia or restenosis, reconstructive surgery, sternal dehiscence without signs or symptoms
of SSI, sternal dehiscence with signs or symptoms of SSI, and SSI without signs or symptoms of
sternal dehiscence.

The clinical diagnosis of infection or noninfection was made by the surgeon performing the
reexploration. The diagnosis was based on preoperative signs and symptoms, such as fever, chest
pain, purulent or serous secretion from the wound, sternal dehiscence, and bleeding, and
intraoperative findings, such as pus, necrotized tissue, bleeding vessels, and a gap between the
sternal halves. The assessment of infection or noninfection was noted in the patient's record.
After termination of the study period, the patients' records (with the clinical diagnoses) were read
and compared with the microbiological results.

Tissue sampling.Pieces of tissue were taken from the sternum or adjacent mediastinal tissue.
Each specimen was put into a sterile glass tube which contained Transport medium for anaerobes
(in-house modification of Cary and Blair pre-reduced anaerobic sterilized Transport medium)
and had been gassed out with carbon dioxide.

Samples were taken before administration of peroperative antibiotics if possible.

Bacteriological methods.All samples were processed by either of two microbiological technical

assistants and interpreted by the investigator. Culturing of specimens took place in a laminar
airflow bench. Each specimen was handled with a sterile forceps and cultured on plates
containing blood agar (Columbia blood agar base [Acumedia], supplemented with horse blood),
chocolate agar (Columbia blood agar base [Acumedia], supplemented with heated horse blood)
and anaerobic agar (Fastidious anaerobe agar [Lab M], supplemented with horse blood). The
specimen was then put into a sterile tube containing enrichment broth for anaerobic bacteria
(brain heart infusion broth [BBL], supplemented with yeast extract [Acumedia], hemin, vitamin
K1, cysteine hydrochloride, and resazurin). Subculturing from broth to agar plates (same plates
as described above) was performed whenever growth was visible and on days 4 and 14,
irrespective of visible growth.

Plates were incubated according to standard recommendations and inspected after 24 h, 48 h, and
7 days. Bacteria belonging to the genera Staphylococcus, Enterobacteriaceae, Streptococcus, and
Propionibacterium were identified according to standard methods. Staphylococci were tested for
DNase activity (DNase agar; Acumedia). DNase-negative isolates not fermenting trehalose or
mannitol, resistant to bacitracin, and sensitive to novobiocin were identified as S. epidermidis.
DNase-negative isolates not fulfilling the criteria for S. epidermidis were identified to the species
level using Staph-API (Biomérieux SA, Marcy l'Etoile, France). DNase-positive isolates were
identified as S. aureus. All staphylococcal isolates were subjected to PFGE.
Chromosomal analysis of staphylococci by PFGE.Isolates were grown overnight in 3 ml of Todd
Hewitt broth at 35°C. Absorbance was read at wavelength 420 nm (Novaspec 11; Pharmacia,
Uppsala, Sweden) and adjusted to an optical density of 1.0. The bacteria were harvested by
centrifugation for 15 min at 3,500 rpm. They were resuspended in 3 ml of Tris-HCl buffer, pH
7.6. A total of 150 μl of the suspension was mixed with 150 μl of 2% InCert agarose (FMC,
Rockland, Maine) in Tris-HCl buffer at 55°C. The mixture was poured into the slots of a plastic
mold (Bio-Rad, Richmond, Calif.) and cooled for 1 h at 4°C. The plugs were incubated at 35°C
overnight in 4 ml of lysis buffer 1 (6 mM Tris-HCl [pH 7.6], 1 M NaCl, 100 mM EDTA [pH
7.5], 0.5% Brij 58, 0.2% deoxycholate, 0.5% sodium lauryl sarcosine [Sarcosyl], 20 μg of RNase
[Boehringer Mannheim, Mannheim, Germany]/ml, 1 mg of lysozyme [Boehringer
Mannheim]/ml, 1 mg of lysostaphin [Sigma, St. Louis, Mo.]/ml). The lysis buffer 1 medium was
replaced by 4 ml of lysis buffer 2 (1% sodium lauryl sarcosine [Sarcosyl], 0.5 M EDTA [pH
9.5], 50 μg of proteinase K [Boehringer Mannheim]/ml), and the plugs were incubated overnight
at 55°C. The plugs were washed three times in 4 ml of Tris-EDTA buffer at 35°C. Digestion by
restriction enzyme was performed overnight at 25°C by placing a 2-mm-thick slice of each plug
in 225 μl of restriction buffer containing 20 IU of SmaI (Boehringer Mannheim). The plugs were
placed into the slots of a 1% agarose (Ultra Pure Agarose; GIBCO BRL, Paisley, United
Kingdom) gel in 0.5× Tris-EDTA buffer and sealed with 1% agarose. Electrophoresis was
performed in a contour-clamped homogenous electric field apparatus (Gene Path; Bio-Rad) at
6.0 V/cm for 20 h at 14°C, with initial pulse times of 5.3 s and final pulse times of 34.9 s.

Test for methicillin susceptibility.The testing was performed by disk diffusion according to the
recommendations by the Swedish Reference Group for Antibiotics (www.srga.org). A dense
inoculum with abundant growth was prepared on an Iso-Sense agar plate (Oxoid Ltd.,
Basingstoke, Hampshire, England), supplemented with horse blood. A disk containing 1 μg of
oxacillin was placed on the agar surface. The plate was incubated at 30°C for 20 to 24 h. A zone
of ≥12 mm in diameter was interpreted as indicating susceptibility, and a zone of ≤9 mm in
diameter was interpreted as indicating resistance.

Statistical methods.Risk ratios (RR) were calculated by chi-square tests and Fisher's exact test,
using the program EPI-INFO (CDC and the World Health Organization). An RR of >1.0 with a
95% confidence interval (CI) not including 1.0 was regarded as significant, as was a P value of
<0.01.

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RESULTS
Study group.A total of 112 reexplorative surgical procedures were performed with 74 patients
during the study period.

When investigating the microbiological findings and comparing microbiological and clinical
findings, each operation was regarded a new case. Sampling according to protocol (≥five tissue
samples) was performed in 41 operations.
Samples.A total of 210 tissue samples were obtained from the 41 study group operations. Of
these samples, 166 were culture positive and 44 were culture negative.

Bacterial isolates.In the 166 positive samples, 213 bacterial isolates were found. Among these
were 103 CoNS isolates, 55 P. acnes isolates, and 46 S. aureus isolates. The numbers of isolates
of different species are presented in Table 1.

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TABLE 1.

Number of species isolates found in 166 culture-positive tissue samples

MR among staphylococcal isolates.Among the 89 S. epidermidis isolates, susceptibility to

methicillin was tested in 88. Of the tested isolates, 56.8% (n = 50) were MR and 43.2% (n = 38)
were methicillin susceptible (MS). All S. simulans (5) and S. haemolyticus (5) isolates were MR,
and the single isolate of S. lugdunensis was MS. Among the CoNS species, one was MS and the
other two were not tested. In total, 60% (60/100) of the tested CoNS isolates were MR and 40%
(40/100) were MS.

All S. aureus isolates were susceptible to methicillin.

PFGE.All 89 S. epidermidis isolates were analyzed by PFGE. A total of 24 different patterns

(i.e., strains) were recognized. Of the strains, 50% (12/24) were MR and 50% (12/24) were MS.

Of 46 S. aureus isolates, 40 were analyzed by PFGE. Eight different patterns were found.

Microbiological diagnosis of infection.Using the microbiological diagnostic criteria, 32 of the 41

cases were identified as infected. S. epidermidis was the primary pathogen in 38% (12/32), S.
aureus was the primary pathogen in 31% (10/32), P. acnes was the primary pathogen in 25%
(8/32), and S. simulans and S. haemolyticus were the primary pathogens in 3% (1/32) each.

Nine cases were categorized as noninfected. Among those, all samples were culture negative for
five patients. For the remaining four patients, the same species or strain was found in less than
half of the samples.

The findings in the individual cases are summarized in Table 2.

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TABLE 2.

Number of samples per operation and primary pathogen in the 41 cases with ≥5 tissue samples

Duration from culturing to positive culture.All 10 cases of S. aureus infection were identified
from primary cultures on day 2 or 3, as were 11 out of 12 cases of S. epidermidis infections and
the S. simulans infection. Only one case of S. epidermidis infection and the S. haemolyticus
infection were identified in subcultures from the day 4 enrichment broth. All eight cases of P.
acnes infection were identified in subcultures from the day 4 enrichment broth.

For the four cases with same species or strain in less than half of the samples, there was no
evidence of growth in the primary cultures.

Clinical diagnosis of infection.Among the 41 cases included in the study group, 6 were
reexplored due to bleeding, 1 was reexplored due to arrhythmia or restenosis, 8 were reexplored
due to sternal dehiscence without signs or symptoms of SSI, 16 were reexplored due to sternal
dehiscence with signs or symptoms of SSI, and 10 were reexplored due to SSI without signs or
symptoms of sternal dehiscence. According to our definition, 15 were clinically noninfected and
26 were infected.

Comparison of microbiological and clinical diagnosis of infection.Among the 32 cases fulfilling

the criterion for microbiological infection, 21 were clinically assessed as infected and 11 were
clinically assessed as noninfected. The corresponding figures for the 9 cases not fulfilling the
criterion for microbiological infection were 5 clinically infected and 4 noninfected. The figures
are presented in Table 3.

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TABLE 3.

Comparison of clinical and microbiological diagnoses of infection

The overall probability for agreement between the results which were positive by clinical
assessment and those fulfilling the microbiological criterion for diagnosis of infection was not
significant (RR, 1.2; CI [95%], 0.63 to 2.23; P = 0.7).

All 10 cases fulfilling the microbiological criterion for S. aureus infection were clinically
assessed as infected. Among the 14 cases fulfilling the microbiological criterion for CoNS
infection, 10 were clinically assessed as infected and 4 were clinically assessed as uninfected.

The overall probability for agreement between the results which were positive by clinical
assessment and those fulfilling microbiological criterion for infection was significant when the
pathogen was S. aureus (RR, 2.0; CI [95%], 1.3 to 3.0; P = 0.005) but was not significant for the
other pathogens.

The figures for the different pathogens are presented in Table 4.

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TABLE 4.

Cases fulfilling the microbiological criterion for infection grouped according to infective
pathogen found in tissue samples and clinical assessment of infection/non-infection

Bacterial findings and sternal dehiscence.According to clinical findings, the cases could be
divided into two groups, based on the presence or absence of sternal dehiscence. Among the 41
cases in the study group, 24 had sternal dehiscence and 17 did not. Of the cases with and without
sternal dehiscence, 75% (18/24) and 82% (14/17), respectively, fulfilled the microbiological
criterion for infection. According to the microbiological definition, infection caused by CoNS
was significantly more prevalent among cases with sternal dehiscence (RR, 2.6; CI [95%], 1.3 to
5.1; P = 0.009).

The bacteriological findings for the two groups are presented in Table 5.

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TABLE 5.

Primary pathogen according to microbiological criterion of infection in cases with and without
sternal dehiscence

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DISCUSSION
Possibility of identification of staphylococcal strains.In this study, species identification and MS
or MR were insufficient markers for determination of whether staphylococcal isolates belonged
to the same strain or not. Eighty-six percent (89/103) of CoNS isolates were S. epidermidis, and
among those, MS and MR strains were approximately equally common. All S. aureus isolates
were susceptible to methicillin. Using PFGE, we identified 24 different S. epidermidis strains
and 8 different S. aureus strains.
Number of samples and culturing method.Most studies do not define the number of samples in
which a pathogen must be found for that pathogen to be considered the causative agent (9, 11,
12). It can be technically difficult to obtain a sample from fluid or tissue aseptically, especially
during an ongoing surgical procedure in infected tissue. When dealing with organisms that
belong to the normal skin flora, the question of contamination always arises. For one of our
previous studies (14, 15), six samples were taken at the end of the operation from the
subcutaneous wound wall of each of a number of patients undergoing elective cardiothoracic
surgery. Contamination of the wound with CoNS and/or S. aureus occurred in 71% (44/62) of
the patients. However, the same strain was found in ≥50% of the samples for only three patients.
A finding of the same species or strain in at least half of the samples, provided that five or more
tissue samples were obtained, thus seemed to rule out a significant level of contamination.

In 53% (17/32) of the cases fulfilling the microbiological criterion for infection, one or more
species or strains other than the primary pathogen were isolated from the samples. If only one
sample had been taken from those patients, that other species or strain could have been
misinterpreted as being the infective agent.

It is obvious that in most cases, there are sufficient numbers of bacteria in the infected tissue to
make it possible to detect them in primary cultures. We detected all cases of S. aureus infection
and 86% (12/14) of the microbiologically defined CoNS infections from primary cultures. This
made it possible to report culturing results (i.e., microbe and antibiogram) to the clinician faster
than with the traditional way, i.e., that of subculturing only from enrichment broth.

In two cases, subculturing from enrichment broth on day 4 was necessary to microbiologically
identify a CoNS infection. All eight cases of P. acnes infection were identified in subcultures
from the day 4 enrichment broth. It is thus obvious that to be recognized as an infective agent,
this slowly growing anaerobic organism needs culturing conditions that differ from those of the
staphylococci.

The subculturing on day 14 did not add any information and can thus be omitted in future
clinical use.

Microbiological infection and species in relation to clinical infection.In the study group of 41
patients, 26 (63%) were clinically considered to have an infection and 15 (37%) were considered
noninfected. Adding a microbiological criterion for infection could help identify infected patients
among those lacking obvious visible signs of infection. In the group of 15 clinically uninfected
patients, the use of a microbiological criterion identified 11 more infected patients, four with
CoNS and seven with P. acnes.

The probability for agreement between diagnosis of infection based on clinical signs and
symptoms and diagnosis of infection based on our microbiological criterion was significant only
for cases caused by S. aureus, as no case of microbiologically detected S. aureus infection was
defined as noninfected according to clinical determination. The conclusion is that infection
caused by S. aureus was easily identified by the surgeon, based on local and/or general signs and
symptoms of infection. Microbiologically defined infections caused by CoNS and P. acnes
apparently did not always cause clinical infective signs and symptoms to the same extent as S.
aureus.

Among the 14 cases with microbiological CoNS infection, 4 were not assessed by the surgeon as
examples of infection. The reasons for the conflicting diagnoses could have been sparse clinical
signs and symptoms of infection or symptoms and intraoperative findings of sternal dehiscence
and/or sternal gap masking the infection. All four were microbiologically diagnosed from
primary cultures on day 2, which supports the infective diagnosis. In cases of this kind, the
microbiological diagnosis might help the surgeon to avoid making the mistake of misclassifying
the patient as noninfected and the consequential mistake of not prescribing adequate long-term
treatment with antibiotics.

The role of P. acnes in SSI has been under debate. There are undoubted cases of P. acnes osteitis
reported (7). The findings by Kamme and Lindberg (6) of a substantial number of P. acnes
isolates in cases of orthopedic surgery, both from control patients (i.e., without loosening of the
hip prosthesis) and from patients with loosened prostheses and nonsignificant bacterial growth
levels, convince us that the findings for P. acnes should be evaluated carefully. In our study eight
cases were identified as infected with P. acnes. If, however, the microbiological diagnostic
criterion for P. acnes infection had included the same requirement as for CoNS and S. aureus,
i.e., the finding of the same strain in at least half of the samples, some or all of those patients
might not have been identified as infected. No method for strain typing of the P. acnes isolates
was easily available, unfortunately. The role of P. acnes as a cause of PSM needs further
investigation. The aspect of species identification versus strain typing should be included in such
studies.

Five patients were clinically assessed as infected but microbiologically assessed as uninfected.
The reason for the differences in assessment was that the results included negative samples (2
patients), multiple samples with less than half of the samples testing as positive (2 patients), and
samples which tested positive for a mixture of species or strains (1 patient). These results could
be due to antibiotic treatment of the patient, nonrepresentative samples, or prolonged
transportation of samples.

The accuracy of clinical diagnosis of infection is hard to question, and one advantage of an
improved diagnostic tool for postoperative SSI is the potential to avoid underdiagnosis of CoNS
infections, which were missed in 29% (4/14) of the examined cases when not using the
microbiological criterion. The answer to the question of which patient is to be regarded as having
a true infection depends, however, on the diagnostic criteria used for infection.

Species in relation to sternal dehiscence.Among the patients with sternal dehiscence for whom a
microbiological diagnosis was established, 67% (12/18) had a CoNS infection, compared to 14%
(2/14) among those without sternal dehiscence. The difference was statistically significant.

Among the 24 patients with sternal dehiscence, 8 were clinically diagnosed as noninfected. Six
of these fulfilled the criteria for microbiological diagnosis of infection, four for CoNS and two
for P. acnes. Our conclusion is that infection, especially infection caused by CoNS, should be
highly suspected for patients with sternal dehiscence, irrespective of clinical signs and symptoms
of infection. Based on our data, we suggest that in patients with sternal dehiscence, there should
be extensive effort made to improve the accuracy of microbiological diagnosis by multiple
sampling before the administration of antibiotics and by the use of good diagnostic methods in
the laboratory, including species and strain identification.

MR among CoNS isolates.A total of 60% of the CoNS isolates and 57% of the S. epidermidis
strains were MR. Among the 14 cases microbiologically infected with CoNS, 64% (9/14) were
infected with MR strains. This is a lower proportion than that reported by other authors, who
have found MR CoNS in 73% (16) and 92% (9) of studied cases. It is also a slightly lower
proportion than that reported for a retrospective study covering the years 1984 to 1995 in the
same setting, for which we found that 69% of CoNS isolates were MR (13). To correctly
diagnose a postoperative mediastinitis caused by staphylococci, the susceptibility to methicillin
in the infective strain is essential, as the MS strains are possible to treat with
isoxazolylpenicillins and cephalosporins. An overestimation of MR might lead to unnecessary
use of vancomycin. This should be avoided, in consideration of both the risk for selection of
genes coding for vancomycin resistance (2) and the interest of the patient, who would otherwise
have to undergo a long-term course of intravenously administered antibiotic treatments.

Summary and conclusions.Clinical diagnosis of PSM has a good accuracy for cases that, as
determined by findings in tissue samples, are caused by S. aureus. When adding a
microbiological criterion for infection, requiring multiple tissue samples and finding of the same
species or strain in ≥50% of samples, another 30% of cases with CoNS infections, in addition to
those clinically assessed as infected, were identified. Our bacteriological method made it
possible to obtain a fast diagnosis, as the tissue pieces were cultured directly on to the agar plate
before they were put in enrichment broth. This method identified all S. aureus infections and a
majority of CoNS infections. To ensure a microbiologically correct diagnosis, both with respect
to the identification of infective cases among patients lacking clinical symptoms of infection and
with respect to correct identification of the primary pathogen, multiple samples before
administration of antibiotics, species identification, strain typing, and susceptibility testing
should be used. P. acnes needs further investigation as a possible cause of PSM. PSM caused by
CoNS is significantly related to sternal dehiscence, which is not the case for PSM caused by S.
aureus. Among our patients was one with PSM caused by S. simulans, which to our knowledge
is a finding that has not been reported before.

Mediastinitis after cardiac valve operations.

Impact upon survival.
Cheung EH, Craver JM, Jones EL, Murphy DA, Hatcher CR Jr, Guyton RA.

Abstract

Mediastinitis after cardiac valve replacement is a dreaded complication with consequent

mortality estimated as high as 70%. We have reviewed 2,491 patients with cardiac valve
operations to assess the impact of mediastinitis upon mortality in our institution in the past 10
years. Mediastinitis developed after valve replacement in 36 patients (1.4%). All patients
required operative intervention for mediastinal infection with positive bacterial cultures. Twelve
of these patients had other perioperative problems associated with a high mortality independent
of mediastinitis: bacterial endocarditis not cured by valve replacement (three), recent
preoperative myocardial infarction (four), triple valve disease with biventricular failure (one),
and severe perioperative cerebral damage (four). Ten of these high-risk patients died (83.3%).
The impact of mediastinitis upon survival is best evaluated in the remaining 24 patients without
high-risk perioperative problems. Eight of these patients were managed before 1980 with
débridement and irrigation as the primary treatment, with two hospital deaths (25%). Pectoral or
rectus muscle flaps were frequently used after 1980 (flaps in 11 of 16 patients), leading to a
significantly shorter time between diagnosis of infection and hospital discharge free of infection
(62 versus 385 days, p less than 0.05). Only one of these 16 patients died. Valve re-replacement
for endocarditis was performed in three of these 24 patients although 13 of 24 had positive blood
cultures. Mediastinitis after valve operations in the absence of other high-risk perioperative
problems can be successfully managed. Early débridement and muscle flap closure has led to a
94% survival rate in 16 patients during the past 4 years.

Risk factors for mortality in patients with

mediastinitis after cardiac surgery
Évaluation des facteurs de mortalité associés aux médiastinites après chirurgie cardiaque

 Didier Lepelletiera, d, , ,
 Luc Poupelinb,
 Stéphane Corveca, d,
 Céline Bourigaulta,
 Philippe Bizouarnb,
 Yvonnic Blanloeilb,
 Alain Reynauda, d,
 Daniel Duveauc,
 Philippe Despinsc

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doi:10.1016/j.acvd.2008.11.003

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Summary
Background

Patients with mediastinitis after cardiac surgery have higher morbidity and mortality.

Aims

Describe the characteristics of patients with mediastinitis, determine the mortality within one
month, and assess the risk factors associated with mortality.

Methods

Retrospective cohort study including all adult patients with mediastinitis during the 2002–2006
period at the Nantes University Hospital. Multivariate analysis by logistic regression and
Kaplan-Meier curve of survey were done.

Results

Nearly 5574 patients were operated during the study period, with a mediastinitis incidence rate
of 0.7%, 28 patients (72%) had coronary artery bypass graft. The mortality rate increased from
de 12.8% during hospital stay to 20.5% within one year. Only two deaths were associated with
mediastinitis. The occurrence of a co-infection was the only independent risk factor associated
with mortality (OR 13, P < 0.04). The instantaneous risk of death was increased by 7 in patient
with co-infection, particularly mechanical ventilator-associated pneumonia (CR 1,97).

Conclusion

Mortality varied according to the duration of surveillance, and mediastinitis was not the major
cause of death. Mechanical ventilator-associated pneumonia after mediastinitis increases the
mortality and needs specific prevention.

Résumé
Contexte

Les patients pris en charge pour médiastinite ont une morbidité et une mortalité plus élevées que
ceux n’ayant pas de complication infectieuse.

Objectifs

Analyser les caractéristiques des patients ayant présenté une médiastinite, mesurer la mortalité à
30 jours et définir les facteurs de mortalité associés.
Méthodes

Nous avons réalisé une enquête de cohorte rétrospective dans le service de chirurgie
cardiothoracique du CHU de Nantes incluant les patients adultes réopérés pour médiastinite entre
avril 2002 et août 2006. L’analyse statistique comprenait une régression logistique et une analyse
de survie, selon Kaplan-Meier afin de mesurer la probabilité de survie à un mois et à un an.

Résultats

Sur les 5574 patients opérés, 39 patients ont développé une médiastinite (0,7 %) ; 28 patients
(72 %) avaient bénéficié d’un pontage coronarien. Le taux de mortalité était de 12,8 % pendant
l’hospitalisation (dont 2,6 % à j30) et de 20,5 % à un an. Seul deux décès étaient imputables à la
médiastinite. Parmi les facteurs étudiés, seule la présence d’une coinfection était associée au
risque de décès (OR 13, P < 0,04). Le risque instantané de décès était multiplié par un facteur 7
chez les patients présentant une infection associée, notamment une pneumopathie (CR 1,97).

Conclusion

Le taux de mortalité variait en fonction de la durée de suivi des patients, la médiastinite n’étant
pas la cause principale de décès. Les pneumopathies survenant au décours d’une médiastinite
aggraveraient le taux de mortalité.

Keywords

 Mediastinitis;
 Mortality;
 Staphylococcus aureus;
 Risk factors;
 Survival

Mots clés

 Médiastinite;
 Mortalité;
 Staphylococcus aureus;
 Facteur de risque;
 Survie

Introduction

Mediastinitis is a serious infectious complication of cardiac surgery affecting 0.25 to 2.9% of

patients in the poststernotomy period [1], [2] and [3]. It prolongs hospitalisation, adds to the
financial burden of medical care [4] and [5] and is associated with a higher risk of mortality
[2] and [6].
The risk factors associated with mediastinitis of the patients undergoing surgery in our Institute
were analysed and allowed us to better orient our prevention programs [1]. However, the
relationship between mediastinitis and death is still poorly evaluated. Excess mortality persists
long-term even if both diagnosis and treatment are satisfactory and if the in-hospital outcome is
positive [6] and [7]. The risk of mortality has already been evaluated, either by comparing closed
drainage with Redon-type vacuum drains versus irrigation-drainage [8] or by identifying peri-
operative risk factors in patients hospitalised in the Intensive Care Unit (ICU) [9]. A clearer
definition of these risk factors could improve management of patients developing post-surgical
mediastinitis and prevent the related excess mortality. The primary endpoints of this study were
to analyse the characteristics of patients presenting with mediastinitis, measure mortality at
30 days and define the associated risk factors.

Materials and methods

Study population

This cohort study was conducted in the Chest and Heart Surgery Department of the Institut du
Thorax at the Laënnec Hospital (Nantes Teaching Hospital Centre or CHU), where 1300 adult
cardiac surgery procedures are performed every year. All cases of re-operation for mediastinitis
in adult patients between April 2002 and July 2006 were analysed and included in the study. The
outcome of patients was recorded in August 2007 to obtain a minimum follow-up of one year.
The exhaustive list of cases was obtained from the Bacteriology-Hygiene Department which has
coordinated continuous monitoring of surgical wound infections since 2002. Each case of
suspected mediastinitis was reported on an infection control form by the operating theatre
Manager, then discussed in the weekly multi-disciplinary staff meeting. A diagnosis of
mediastinitis was based on the need for sternal re-operation and insertion of an irrigation-
drainage system and/or combined with positive mediastinal sample bacteriology cultures or
macroscopic appearance of mediastinitis. Patients with strictly cutaneous and sub-cutaneous
infection were not included, their infection being defined as superficial.

Data collection

The criteria explored in our study included:

the demographic data of the patients and their history;

peri-operative management of the initial cardiac procedure;

•
 time to re-operation for mediastinitis, post-operative management and in-hospital
survival.

Survival of patients after their discharge from the Nantes CHU was determined by phoning GPs
at the beginning of August 2007 and enquiring about the patient's status (alive/deceased),
irrespective of the interval between mediastinitis and death.

Causes of death, both in-hospital and after discharge, were listed.

Patient management

All patients received standard surgical management and medical care. Re-operation consisted in
mediastinal exploration via a sternotomy under a general anaesthetic. The original sternotomy
was re-opened, any fibrin deposits were removed and the skin and underlying tissue debrided.
Several swabs were obtained for bacteriological analysis. Non vascularised areas of the sternum
were resected with a surgical saw. Finally, the pericardial cavity was cleaned and the mediastinal
region abundantly irrigated with 0.5% iodinated povidone. Drains for drainage and irrigation
were inserted and, wherever possible, sternal synthesis achieved. Irrigation-drainage was
immediately started with saline solution and 0.5% iodinated povidone (100 ml/hour) and was
continued for several days with close monitoring of input/output to avoid tamponnade.
Irrigation-drainage was only withdrawn once the patient no longer presented with systemic or
local signs of sepsis and several consecutive drainage samples were found to be bacteriologically
sterile. If it was impossible to close the thorax, a muscle advancement flap was created or, if this
also was impossible, then open wound treatment was necessary. Medical care consisted in
starting early broad spectrum antibiotics as soon as the diagnosis was reached and post-operative
care in the ICU if organ failure arose. The gold standard first line antibiotic treatment in our
Institute comprises two antibiotics with known efficacy against Staphylococcus aureus and
coagulase-negative staphylococci. Antibiotics were initially administered intravenously as a
combination of an aminoside (gentamicin) and a glycopeptide (vancomycin). The drugs
administered were adjusted as required once the causal bacteria had been identified and
antibiotic susceptibility testing completed. Patients received six weeks of antibiotics with
possible follow-on treatment with an oral antibiotic if no signs of systemic sepsis were observed
and after discussion of the case at the weekly multi-disciplinary staff meeting. If necessary,
patients with haemodynamic, respiratory, renal, liver or hematological failure were treated in the
ICU. Patients who did not have organ failure subsequently were treated in the hospital's heart
surgery department. After their discharge from hospital, most patients were admitted to a
readaptation centre for three weeks before returning home.

Statistical analysis

Data were processed and analysed with Excel and Systat software. Continuous variables were
expressed as the mean and standard deviation or median. Qualitative data were expressed as the
absolute value and/or percentage. Univariate analysis was performed on the quantitative
variables using the Student t-test or Mann-Whitney test and on the qualitative variables using the
Chi2 test of Fisher's exact test. Variables with P < 0.1 in the univariate analysis were included in
a logistic regression model to determine the independent factors associated with death. Model
calibration was tested using the Hosmer-Lemeshow test. Time to onset of death was measured
via Kaplan-Meier type survival analysis.

Results

Patient characteristics

During the period covered by this study, 5574 patients underwent cardiac surgery, 39 of which
developed mediastinitis, i.e. an overall incidence of 0.7%. History of the first operation and peri-
operative characteristics for all patients are shown in Table 1 and Table 2. None of the factors
studied was associated with a risk of mortality. Twenty-eight (28) patients or 72% of the cases of
mediastinitis, underwent coronary bypass surgery (CBS) both with and without valve
replacement, i.e. an incidence of 1.1% during the study period. Twenty-three patients (59%) had
undergone CBS with grafts of one or two mammary arteries. Eleven patients (28%) required
early re-operation (within 72 hours). The mean interval between the first intervention and re-
operation for mediastinitis was 21.4 ± 15 days (median = 18 days; 5th percentile = 4.95; 95th
percentile = 49.80). Irrigation lasted a mean of 9.2 ± 5 days (median = 9 days; 5th
percentile = 7.50; 95th percentile = 13.45) and drainage, a mean of 13 ± 5 days
(median = 12 days; 5th percentile = 10.20; 95th percentile = 15.84) for all patients. The peri-
operative characteristics during surgery for mediastinitis are shown in Table 3.

Table 1.

Demographic data, history and death risk in patients with mediastinitis between April
2002 and July 2006 (n = 39).

Données démographiques, antécédents et risque de décès des patients ayant développé

une médiastinite entre avril 2002 et juillet 2006 (n = 39).

Patients
Variables P

Surviving (n = 31) Deceased (n = 8)

Obesity 15 (48.4%) 4 (50%) 1.00

Diabetes 10 (32.2) 3 (37.5) 1.00

Smoking 16 (51.6) 4 (50) 1.00

Chronic obstructive bronchopulmonary disease 5 (16.1) 2 (25) 0.61

Arteriopathy 8 (25.8) 4 (50) 0.22

Corticosteroid therapy 3 (7.7) 1 (12.5) 1.00

 Patients
Variables P

Surviving (n = 31) Deceased (n = 8)

Left ventricular ejection fraction < 40% 12 (9.7) 5 (62.5) 0.26

ASA score 3 19 (61) 6 (75) 0.68

ASA score 4 12 (39) 2 (25) 0.68

Mean age (years) ± standard deviation 62.5 ± 12.6 62 ± 14.5 0.92

Mean body mass index ± standard deviation 29.0 ± 3.8 28.9 ± 3.7 0.88

ASA: American Society of Anesthiologists.

Table options

Table 2.

Peri-operative data for the initial surgical operation and risk of death in 39 patients with
mediastinitis between April 2002 and July 2006.

Données périopératoires de l’intervention chirurgicale initiale et risque de décès des

39 patients ayant développé une médiastinite entre avril 2002 et juillet 2006.

Patients
Variables P

Surviving (n = 31) Deceased (n = 8)

Type of surgery

 Coronary bypass 19 (61%) 4 (50%) 0.69

 Valve 3 (9.7) 1 (12.5) 1.00

 Valve + coronary bypass 4 (13) 1 (12.5) 1.00

 Heart transplant 3 (9.7) 1 (12.5) 1.00

 Patients
Variables P

Surviving (n = 31) Deceased (n = 8)

 Other 2 (6.7) 1 (12.5) 0.51

Emergency surgery 9 (29) 5 (62.5) 1.11

Duration of surgery > 240 mina 14 (45) 5 (63) 0.45

Number of mammary grafts if coronary bypass

 One internal mammary artery 16 (52) 3 (38) 0.69

 Two internal mammary arteries 2 (6.5) 2 (25) 0.18

Duration of hospitalisation in Intensive Care > 48 hrs 16 (51) 6 (75) 0.42

Duration of mechanical ventilation > 24 hrs 5 (16) 2 (25) 0.61

Amines required in ICU 16 (52) 6 (75) 0.42

Early surgical re-operation (< 72 hrs) 9 (29) 2 (25) 1.00

Mean duration of ECC (min) 94 ± 70 133 ± 72 0.17

75th percentile of the usual duration of a surgical intervention at the Nantes CHU [1].

Table options

Table 3.

Diagnostic and peri-operative data after re-operation for mediastinitis and risk of death in
39 patients with mediastinitis between April 2002 and July 2006.

Données diagnostiques et périopératoires après reprise chirurgicale pour médiastinite et

risque de décès des 39 patients ayant développé une médiastinite entre avril 2002 et
juillet 2006.
 Patients
Variables P

Surviving (n = 31) Deceased (n = 8)

Discharge from sternotomy 26 (83.9) 7 (87.5) 1.00

Positive bacteremia 17 (54.8) 7 (87.5) 0.12

Transfer from ICU possible before re-operation 28 (90.3) 5 (62.5) 0.08

Microbiological strain

 Methicillin-sensitive Staphylococcus aureus 15 (48.4) 5 (62.5) 0.69

 Methicillin-resistant Staphylococcus aureus 1 (3.2) 0 1.00

 Coagulase-negative Staphylococcus aureus 8 (25.8) 2 (25) 1.00

 Gram-negative bacillae 2 (6.5) 1 (12.5) 0.51

 Polymicrobial culture 2 (6.5) 0 1.00

Mean interval before re-operation (days) 20.8 ± 13.5 23.7 ± 20.8 0.63

Mean duration of irrigation (days) 9.5 ± 6 8 ± 4 0.51

Mean duration of drainage (days) 12.5 ± 4.8 15.4 ± 5.6 1.15

Table options

Microbiological documentation

Three cases of mediastinitis were not documented. Of the documented cases, 34 involved a
single bacteria and two were polymicrobial involving Staphylococcus aureus and an
enterobacteria. Of the 38 bacteria isolated, staphylococci were predominant: methicillin-sensitive
Staphylococcus aureus (21), coagulase-negative Staphylococcus aureus (10) and methicillin-
resistant Staphylococcus aureus (1). Of the other bacteria, five enterobacteria (Enterobacter
aerogenes, Enterobacter cloacae, Escherichia coli, Serratia marcescens × 2) and a
Pseudomonas aeruginosa were isolated.

Twenty-four patients (62%) had positive hemocultures obtained during treatment of

mediastinitis, with methicillin-resistant Staphylococcus aureus in 71% of cases; this complies
with the results obtained for samples obtained per-operatively.

Co-infections
Thirteen patients presented with a co-infection, either simultaneously (4) or as a result of the
mediastinitis (9), with a mean time to onset of 7 ± 7 with a median time of three days. In order of
frequency, these infections were as follows: pneumonia acquired under mechanical ventilation
(10), urine infection (1), infectious thrombophlebitis (1) and endocarditis (1). The primary
causative bacteria were Staphylococcus aureus (6) and P. aeruginosa (3). In four cases,
methicillin-sensitive Staphylococcus aureus was responsible for the co-infection and
mediastinitis. The three P. aeruginosa respiratory infections arose in heart transplant patients.

Mortality rates

By August 1st 2007, a total of eight patients had died during the period studied, i.e. an incidence
of 20.5%. Five patients died in-hospital (12.8%), with one death arising within 30 days, i.e. a
mortality rate at one month of 2.6%. The three-month and one-year mortality rates were 15.4 and
7% respectively. One patient died 598 days after mediastinitis was diagnosed. The main cause of
death was heart failure. Two patients died as a direct result of their methicillin-sensitive
Staphylococcus aureus mediastinitis ( Table 4). A Kaplan-Meier survival curve was plotted (Fig.
1). The mean survival time was 505 days. Survival was 97 ± 2% after 30 days, 90 ± 5% after
60 days, 82 ± 6% after 218 days, and 79 ± 7% after 598 days. There were no deaths between the
218th day and the 598th day. The one-year survival rate was 82%. Three patients died within a
maximum of 298 days after leaving the hospital.

Table 4.

Cause of death for the eight patients with mediastinitis between April 2002 and July
2006.

Étiologies des décès des huit patients ayant développé une médiastinite entre avril 2002
et juillet 2006.

n (%)

In-hospital deaths (n = 5)

 Multiple organ failure caused by infection (mediastinitis) 2 (25)

 Cerebral anoxia due to heart failure 2 (25)

 Gastrointestinal necrosis caused by terminal heart failure 1 (12.5)

Deaths after discharge (n = 3)

 Terminal heart failure 1 (12.5)

 Serious pancreatitis 1 (12.5)

 Sudden death of unknown origin in the home 1 (12.5)

 Table options

Figure 1. 

Kaplan-Meier survival curve, expressing the probability of survival in percent (x-axis)

versus time (y-axis).

Courbe de survie par estimation de Kaplan-Meier, exprimant la probabilité de survie en

pourcentage (ordonnée) en fonction du temps en jours (abscisse).

Figure options

Risk factors for mortality

In the univariate analysis, three factors identified in the post-operative period were significantly
associated with death: co-infection (OR = 10.3, 95% confidence interval [IC95%] = 1.4 – 97.2,
P = 0.01), prescription of an amine required (OR = 6.3, IC95% = 1.0 – 18.7, P < 0.045) and time
spent in intensive care before onset of mediastinitis (29 days versus 18 days, P = 0.009). In the
logistic regression mulitvariate analysis, only the presence of a co-infection was an independent
factor related to death (OR = 13, 95% IC95% = 1.1 – 156, P = 0.043). Calibration of the model
was satisfactory (P = 0.19). The instantaneous risk of death was seven times higher in patients
with a co-infection versus those without infection (regression coefficient = 1.973, or
e1.973 = 7.19).

Discussion

Patients treated for mediastinitis are at higher risk of morbidity and mortality than patients who
do not experience infectious complications [2] and [6]. In our cohort of 39 patients presenting
with mediastinitis at the Nantes CHU between 2002 and 2006, the in-hospital mortality rate was
12.5% and survival at one year was estimated to be 82%. Mortality and survival are two facets of
a single event observed at different times. Mortality estimates are often given for different times
during treatment (mortality in the reanimation ward, at three months, at one year, etc.) for patient
populations which are not always comparable. The mortality rates reported in the literature can
therefore range from 11 to 20% including either patients undergoing re-operation for sterile
sternal dehiscence or patients who have already presented with failure of one or more organs
whilst in the ICU [6], [7] and [10].

Although mediastinitis is an infection, in most cases death does not occur as a result of
uncontrolled infection. In our cohort, only two patients died in-hospital as a direct result of
infection through multiple organ failure and septic embolism. The three other in-hospital deaths
were the result of heart failure, which caused either massive gastrointestinal necrosis or
untreatable cerebral lesions. There was no single cause of death outside the hospital (terminal
heart failure, pancreatitis). In sum, half of the deaths arising both within and outside the hospital
were caused by terminal heart failure. In addition, pre-operative changes in the left ventricular
ejection fraction were not a risk factor for death. Mediastinitis seemed to render already
vulnerable patients even more fragile from a cardiac point of view although this was impossible
to quantify at the time they were being treated.

Little is reported about causes of death in the literature. In the study conducted by Trouillet et al.
in the reanimation ward, 60% of deaths were the result of primary or secondary infection [9].
This percentage is no doubt an overestimation since only deaths arising in the ICU are taken into
account, unlike our study which observed death rates over a longer period of time. Estimates of
mean and long-term survival rates are difficult to compare. The one-year survival rate in the
study involving a series of 193 cases of mediastinitis was estimated to be 78% [11], which is
similar to the rate found in our study. In another study conducted on 183 cases of mediastinitis,
the estimated one-year survival rate was lower at 67% [12]. This excess mortality was observed
after two and five years in three studies comparing cardiac surgery patients presenting with and
without mediastinitis [2], [6] and [7]. Survival rates after treatment for mediastinitis are still
difficult to compare between studies given disparities in the inclusion and exclusion criteria
employed. The size of our cohort, and thus the lack of power of the analysis, may have masked
the role played by of some of the factors studied.

Our results show that the onset of a second infectious disease or co-infection with mediastinitis,
is an independent risk factor for mortality. The associated condition was pneumonia in 77% of
cases which resulted in a prolongation of mechanical ventilation and thus an increase in the time
spent in intensive care. This raises the question of whether the infection was transmitted by
bacterial translocation or bacteremia from the mediastinitis or conversely, whether the
mediastinitis could be secondary to the pneumonia. The second hypothesis appears unlikely,
since the co-infection was diagnosed during re-operation for mediastinitis (median three days).
In our study, the bacteria identified were staphylococci in 77% of cases. Staphylococcus aureus
was identified in 54% of cases of mediastinitis with only one methicillin-resistant strain
observed. The bacteria causing pneumonia were different from those responsible for
mediastinitis except in four cases in which methicillin-sensitive Staphylococcus aureus was
isolated at the two sites of infection. Given the proportion of methicillin-sensitive
Staphylococcus aureus mediastinitis cases in our cohort, the incidence of nasal carriage reported
in the literature and the pathogenicity of this bacteria, systematic screening for Staphylococcus
aureus and local nasal treatment with mupirocin could be integrated into surgical wound
infection prevention strategies after heart surgery [13], [14], [15] and [16].

However, in view of the relatively small size of our population, these results are to be interpreted
with caution, despite the fact that the study covers a period of six years. The logistic regression
modelling measurement of the estimated co-infection rate (OR) calculated in our population is
not precise owing to the 95% confidence interval values. Analysis of the causal relationship
between onset of co-infection in patients who developed mediastinitis and death must be
validated in a more powerful, multicentre study involving more cases of mediastinitis, to confirm
our hypothesis.

In conclusion, the mortality rate varied as a function of survival time and mediastinitis was not
the main cause of death. The risk factors for onset of mediastinitis do not appear to be the same
as those for mortality. However, co-infections arising subsequent to mediastinitis could increase
the risk of death in patients presenting with other organ failures or altered cardiac function,
without being the direct cause of death.