Open Journal of Anesthesiology, 2013, 3, 383-387
Published Online November 2013 (
Open Access OJAnes
Intraoperative vs 24-Hour Administration of Cefamandole
to Prevent Deep Sternal Wound Infection and Endocarditis
after Adult Cardiac Surgery
Jean-Michel Maillet1*, Stéphane Thierry1, Grégoire Oghina2, Paul Le Besnerais3, Patrick Mesnildrey3,
Nicolas Bonnet3, François Simoneau4, Denis Brodaty1
1Department of Cardiovascular and Thoracic Intensive Care, Centre Cardiologique du Nord, Saint-Denis, France; 2Department of
Microbiology, Centre Cardiologique du Nord, Saint-Denis, France; 3Department of Cardiac Surgery, Centre Cardiologique du Nord,
Saint-Denis, France; 4Department of Anesthesiology, Centre Cardiologique du Nord, Saint-Denis, France.
Email: *
Received September 6th, 2013; revised September 26th, 2013; accepted October 6th, 2013
Copyright © 2013 Jean-Michel Maillet et al. This is an open access article distributed under the Creative Commons Attribution Li-
cense, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
Background and Objectives: Duration of antibiotic prophylaxis for cardiac surgery is still debated and controversial.
International guidelines are vague: French guidelines recommend an intraoperative administration, while the Society of
Thoracic Surgeons’ guidelines suggest that optimal postoperative prophylactic antibiotics be given for 48 hours or less.
Very few studies have compared the same antibiotic with 2 different administration durations. The study was designed
to compare the efficacy of 24-hour administration of cefamandole vs intraoperative cefamandole to prevent deep sternal
wound infection and endocarditis after cardiac surgery. Methods: This retrospective and observational study compared
the rates of severe surgical site infections (deep sternal wound infection, endocarditis) after cardiac surgery between
period 1, 01/01/2008-31/08/2008, with 24-hour administration of cefamandole, and period 2, 01/09/2008-30/04/2009
with intraoperative cefamandole. Results: Among 933 patients, 14 patients (1.5%) developed surgical site infection
during the 16-month study: 1.3% during the first period and 1.7% during the second (ns). The populations (470 patients
in period 1 and 463 in period 2) were homogeneous and comparable for pre-, intra- and postoperative characteristics.
Surgical site infection characteristics (pathogens involved, time to diagnosis) and consequences (longer hospital stay,
outcomes) were comparable in the 2 groups. Conclusions: Intraoperative cefamandole was as safe as its 24-hour ad-
ministration to prevent deep sternal wound infection and endocarditis after adult cardiac surgery.
Keywords: Surgical Site Infection; Deep Sternal Wound Infection; Endocarditis; Antibiotic Prophylaxis; Cardiac
Surgery; Cefamandole
1. Introduction
“Does the duration of perioperative antibiotic prophy-
laxis matter in cardiac surgery?” was the provocative title
of a systematic review and meta-analysis recently pub-
lished by Mertz and associates [1]. Shorter duration of
antibiotic prophylaxis definitively has many advantages:
lower costs, decrease selection pathogen pressure [2],
less drug toxicity and simplification of the very complex
procedure of correct routine daily administration of anti-
biotic prophylaxis [3]. Duration of antibiotic prophylaxis
remains controversial. The Society of Thoracic Sur-
geons’ recommendations are vague, seem to support a
duration of 24 hours, perhaps less, but no longer than
48 hours [4]. Mertz and associates’ conclusions were
elusive because of the lack of well-designed studies and
emphasized the heterogeneity of antibiotic regimens and
the risk of bias in the published studies [1]. In our insti-
tute, the local Nosocomial Infection Control Committee
modified and shortened the antibiotic prophylaxis dura-
tion with single dose despite some local surgeons’ reluc-
tance. This study was undertaken to evaluate whether
intraoperative cefamandole was as effective as its 24-
hour administration to prevent the most severe SSI after
adult cardiac surgery, deep sternal wound infection (DSWI)
and endocarditis.
*Corresponding author.
Intraoperative vs 24-Hour Administration of Cefamandole to Prevent Deep Sternal Wound Infection
and Endocarditis after Adult Cardiac Surgery
2. Methods
During a 16-month period, we retrospectively studied all
consecutive adults (>18 years of age) who underwent
cardiac surgery with cardiopulmonary bypass (CPB): pe-
riod 1: 01/01/2008 to 31/08/2008 and period 2: 01/09/
2008 to 30/04/2009. No included in this study were pa-
tients with ß-lactam allergy, acute endocarditis and/or
vascular surgery with CPB. Our institution is private with
more than 200 beds dedicated exclusively to medical and
surgical cardiovascular and thoracic pathologies and where
700 - 850 interventions are performed annually.
The following parameters were extracted from the lo-
cal database which is registred at the French National
Commission Informatics and Liberty: sex, age, body
mass index, cardiovascular risk factors (diabetes, current
smoker, hypercholesterolemia, hypertension), presence
of chronic obstructive pulmonary disease (COPD), chro-
nic renal insufficiency (creatinemia 200 µmol/L), pe-
ripheral vascular disease, type of cardiac surgery [coro-
nary artery bypass graft (CABG) ± valve replacement
(VR), VR and other], use of 1 or 2 internal thoracic arter-
ies, Euroscore I [5], duration of ICU length of stay, pro-
longed mechanical ventilation (48 hours), use of nonin-
vasive ventilation, red-cell transfusion, vasopressor use,
rate of acute renal insufficiency (defined as a 2-fold in-
crease of the preoperative creatinemia), dialysis required.
In our institution, anesthesiologists and intensivists are
responsible for antibiotic-prophylaxis prescription, intra-
operatively and post-operatively, respectively. Each pre-
scriber received the written local protocol recommenda-
tion before the switch to the shorter regimen in August
2008. This local protocol, validated by our local Noso-
comial Infection-Control Committee, recommends the
use of cefamandole as the first-line antibiotic in the ab-
sence of ß-lactam allergy. In the operating room, infusion
of 1.5 g of cefamandole within the 1 hour preceding the
incision is recommended. It is also specified that another
infusion 750 mg of cefamandole is mandatory when the
surgery lasts 120 minutes, with repeated infusions every
120 minutes, as needed. Lastly, for period 1, 750 mg of
cefamandole were infused every 6 hours during the first
24 postoperative hours during the intensive care unit
The Centers for Disease Control definitions were used
to for DSWI and endocarditis [6]. Occurrence of those
infections was recorded and validated independently by
our local Nosocomial Infection-Control Committee. For
each infection, we studied the date of its diagnosis, the
interval between surgery and infection, the pathogen(s)
involved, their susceptibilities to antibiotics and the de-
velopment of concomitant bacteriemia. All patients with
healing problems, suspected wound infection or sus-
pected postoperative endocarditis were systematically re-
addressed to their surgeon postoperatively.
There were no changes in measures to prevent infec-
tion between the study periods. Skin preparation was
performed as follow: the night before surgery, patients
took two showers with an antiseptic solution. The day of
surgery, 2 hours before surgery, patients took a third
shower with an antiseptic solution and hair was removed.
No specific outbreaks occurred during the study period.
The concerned database had been approved by the
French national commission for computerized files and
liberty. According to French law, its subsequent use for
epidemiologic work does not require additional regula-
tory or ethic commission approval.
Statistical Analysis
Continuous variables are presented as median with range
and categorical variables as n (%). Comparisons were
made using the chi-square or Fisher’s exact test (when
needed) to analyze differences in categorical variables.
The Student’s t-test or the Mann-Witney test was used,
as appropriate, for continuous variables. A p value < 0.05
was considered statistically significant. Statistical analy-
ses were performed using Statview version 5.1 software
(SAS Institute Inc., Cary, NC).
3. Results
During the study, 987 adults [499 (50.5%) during period
1 and 488 (49.5%) during period 2] had heart surgery
with CPB in our institution. Fifty-four patients were not
included, 29 from period 1 and 25 from period 2, because
of ß-lactam allergy, acute endocarditis and/or vascular
surgery with CPB. Thus, 933 patients were included in
the study: 470 during period 1 and 463 during period 2.
Detailed preoperative, intraoperative and postoperative
patient characteristics, categorized according to the anti-
biotic regimen used during those periods, are given in
Table 1. The 2 groups were homogeneous and compara-
ble for their demographic profiles and clinical character-
istics. The 3 surgeons’ activities were comparable during
the 2 periods (data not shown).
During the study, 14 (1.5%) SSI were diagnosed: 1.3%
(n = 6) during period 1 vs 1.7% (n = 8) during for period
2. SSI characteristics were comparable concerning the
median time to infection onset 28 days (range, 5 - 129
days) vs. 23 days (range, 4 - 112 days). Eleven (5 in pe-
riod 1 and 6 in period 2) bacteriemia were diagnosed
with SSI. Of 17 pathogens isolated, 12 (70.5%) were
Gram-positive cocci and 5 (20.9%) Gram-negative bacilli.
They were similarly distributed in the 2 periods.
Median postoperative hospital stay was comparable
during periods: 1 and 2, respectively: 9 (range 0 - 372) vs
9 (range 0 - 113) days. SSI occurrence significantly pro-
Open Access OJAnes
Intraoperative vs 24-Hour Administration of Cefamandole to Prevent Deep Sternal Wound Infection
and Endocarditis after Adult Cardiac Surgery
Open Access OJAnes
Table 1. Preoperative, intraoperative and postoperative characteristics.
Period 1 n = 470 Period 2 n = 463 p-Value
Preoperative characteristic
Sex, male (%) 331 (70.4) 352 (76.0) 0.94
Age (years), median (range) 69 (19 - 96) 68 (18 - 89) 0.39
Body Mass Index (kg/m2), median (range) 27 (17 - 53) 27 (14 - 44) 0.44
Hypertension, (%) 265 (56.4) 267 (57.7) 0.74
Diabetes, (%) 130 (27.7) 137 (29.6) 0.51
Hypercholesterolemia, (%) 235 (50) 227 (49.0) 0.74
Current smoker, (%) 78 (16.6) 63 (13.6) 0.23
Euroscore, point, median (range) 5 (0 - 18) 5 (0 - 16) 0.69
Intraoperative characteristic
Type of surgery, (%) 0.37
CABG ± VR 264 (56.2) 278 (60.0)
VR 162 (34.5) 142 (30.7)
Others 44 (9.4) 43 (9.3)
Total CPB time (min), median (range) 73 (29 - 287) 75 (14 - 251) 0.4
Aortic cross clamp time (min), median (range) 55 (0 - 205) 55 (8 - 203) 0.59
Bilateral ITA (n = 264 period 1; n = 278 period 2) 220 (83.3) 236 (84.9) 0.68
Postoperative course
ICU LOS (days), median (range) 2 (1 - 50) 2 (0 - 56) 0.89
MV 2 days, median (range) 31 (6.6) 39 (8.9) 0.32
Vasopressor use (%) 181 (38.5) 171 (36.9) 0.63
Noninvasive ventilation (%) 41 (8.7) 40 (8.6) 0.96
Acute renal insufficiency (%) 34 (7.2) 41 (8.9) 0.4
Hemodialysis (%) 16 (3.4) 17 (3.7) 0.86
Red-cell transfusion (%) 163 (34.7) 155 (33.5) 0.73
Postoperative hospital LOS (days), median (range) 9 (0 - 372) 9 (0 - 113) 0.82
Hospital mortality (%) 28 (6) 34 (7.3) 0.43
Data are presented as mediane, range and %. CABG: coronary artery-bypass graft; CPB: cardiopulmonary bypass; ICU: intensive care unit; ITA: internal
thoracic artery; LOS: length of stay; MV: mechanical ventilation; VR: valve replacement.
longed the median postoperative hospital stay from 9
(range 0 - 372) days without to 30 (range 5 - 77) days
with SSI (p < 0.0002), and comparably during the 2 pe-
riods. Mortality rates were comparable for periods 1 and
2, respectively, 6% and 7.3%. Mortality rate for severe
SSI was 35.7% for the study period.
4. Discussion
The results of this retrospective study showed that intra-
operative cefamandole prophylaxis was as effective as
24-hour administration to prevent the most severe surgi-
cal site infections after adult cardiac surgery, DSWI and
Antibiotic prophylaxis is one of the most important
preventive measures against SSI after major surgery,
particularly, cardiac surgery [4]. Because of the high
morbidity and mortality associated with DSWI and en-
docarditis, an adequate antibiotic regimen and its ad-
Intraoperative vs 24-Hour Administration of Cefamandole to Prevent Deep Sternal Wound Infection
and Endocarditis after Adult Cardiac Surgery
ministration are essential. The duration of antibiotic pro-
phylaxis is still being debated and remains controversial.
Recently the Society of Thoracic Surgeons’ guidelines
underscored the heterogeneity of studies (eg recommen-
dations from different scientific societies concerning this
specific question) and recommended that postoperative
optimal prophylactic antibiotics (class IIa, level B) be
given 48 hours [4]. In 2010, French guidelines validated
a very firm position recommending the shorter admini-
stration for cardiac surgery with only intraoperative ad-
ministration of prophylactic cefamandole or cefazolin [7].
A recent systematic review and meta-analysis showed that
perioperative antibiotic prophylaxis lasting 24 hours
might be more effective than shorter regimen but the
findings were limited by the heterogeneity of antibiotic
regimens and the risk of bias in the published studies [1].
Some studies compared single-dose vs longer antibiotic
prophylaxis [1], but very few used the same antibiotic in
both arms [8,9] and only the former compared single-
dose vs 24-hour doses of the same antibiotic. Tamayo
and associates, in their monocentric unblinded prospec-
tive study, compared 2 cefazolin doses over 42 months:
the single-dose was associated with significantly higher
SSI rate (8.3%) than with multiple-doses (3.6%) (p =
0.004). That significant difference was due to the sig-
nificantly higher single dose SSWI rate (5%) than with
multiple doses (1.7%) (p = 0.007). Notably, DSWI and
endocarditis rates were comparable for both groups (re-
spectively 1.9% and 1.2% for single dose vs. 1.2% and
0.2% with 24-h regimen) comparable to those of current
study [9].
Achieving rigorous daily antibiotic prophylaxis regi-
men is very difficult [3]. The antibiotic-prophylaxis pro-
tocol has many steps that must be respected. At each step,
non-adherence is possible; the type of antibiotic, the
timing of its prophylactic administration, the dose, the
need for repeated infusions because of prolonged surgery
and postoperative duration [3]. Single-dose has the major
advantage of simplifying the antibiotic-prophylaxis pro-
Cefamandole is a second-generation cephalosporin re-
commended as antibiotic prophylaxis in first line in car-
diac surgery in France [7], because it is safe, inexpensive,
bactericidal against Gram-positive cocci (MSSA and
MSCNS) and most Gram-negative bacilli and has a good
diffusion. Repeated administrations for surgery lasting
>2 hours are required because of its short half-life. It was
effective against >85% of the pathogens involved in the
Antibiotic prophylaxis is the one of the most effective
preventive measures against SSI. However, the SSI rate
after cardiac surgery range from 0.25% to 4% for DSWI
[4]; those values remain high, particularly for this type of
surgery classified as “clean surgery”. Many factors ex-
plain that fact (eg, older age patient, more co-morbidities
and/or generalization of bilateral use of internal thoracic
arteries). In this context, new strategies have been de-
veloped to try to lower the SSI rate: preoperative mupi-
rocin, collagen-gentamicin implants and triclosan-coated
sutures. Hopes raised by these approaches have not yet
been fulfilled [10-12]. It seems that the research con-
cerning antibiotic prophylaxis has been left by the way-
side, despite the numerous unanswered questions. Only,
an international multicenter study will be able to answer
the following question: What is the best duration of anti-
biotic prophylaxis? However, institutional and/or phar-
maceutical financial support is lacking, even though mil-
lions of euros or dollars spent on useless antibiotic ad-
ministration could be saved if single-dose antibiotic pro-
phylaxis were to be demonstrated as safe as 24-hour or
48-hour administration.
The major limitation of our study is its retrospective
design. However, the 2 populations, with >400 patients
in each arm, were comparable concerning important pre-,
intra- and postoperative factors associated with SSI
thereby rendering possible interpretation of our results.
We tried to be as closed as possible to the “real world”
including patients who underwent emergency surgery
and limiting the exclusion criteria. In addition, the short
duration of the study (16 months) limited the bias related
to variations of daily patients care. Second, the sample is
small. Lastly, because of the retrospective nature of the
study, no power calculation is allowed methodologically
and was not performed, and a type 2 error could be pos-
5. Conclusion
Our results suggest that single-intraoperative dose ce-
famandole is as effective as its 24-hour administration to
prevent the most severe SSI after adult cardiac surgery.
Well-designed prospective studies are urgently needed to
resolve this controversial and important issue.
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Open Access OJAnes
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and Endocarditis after Adult Cardiac Surgery
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