Intraoperative vs 24-Hour Administration of Cefamandole to Prevent Deep Sternal Wound Infection and Endocarditis after Adult Cardiac Surgery

doi:10.4236/ojanes.2013.39081

Paper Menu >>

Journal Menu >>

Open Journal of Anesthesiology, 2013, 3, 383-387

Published Online November 2013 (http://www.scirp.org/journal/ojanes)

http://dx.doi.org/10.4236/ojanes.2013.39081

Open Access OJAnes

383

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: *[email protected]

Received September 6th, 2013; revised September 26th, 2013; accepted October 6th, 2013

cense, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

ABSTRACT

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

384

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

stay.

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

385

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

endocarditis.

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

386

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-

tocol.

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

SSI.

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-

sible.

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.

REFERENCES

[1] D. Mertz, J. Johnstone and M. Loeb, “Does Duration of

Perioperative Antibiotic Prophylaxis Matter in Cardiac

Surgery? A Systematic Review and Meta-Analysis,” An-

nals of Surgery, Vol. 254, No. 1, 2011, pp. 48-54.

http://dx.doi.org/10.1097/SLA.0b013e318214b7e4

[2] S. Habarth, M. H. Samore, D. Lichtenberg and Y. Car-

meli, “Prolonged Antibiotic Prophylaxis after Cardiovas-

cular Surgery and Its Effects on Surgical Site Infections

and Antimicrobial Resistance,” Circulation, Vol. 101, No.

25, 2000, pp. 2916-2921.

http://dx.doi.org/10.1161/01.CIR.101.25.2916

[3] D. W. Bratzler, P. M. Houck, C. Richards, L. Steele, E. P.

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

387

Dellinger, D. E. Fry, et al., “Use of Antimicrobial Pro-

phylaxis for Major Surgery. Baseline Results from the

National Surgical Prevention Project,” Archives of Sur-

gery, Vol. 140, No. 2, 2005, pp.174-182.

http://dx.doi.org/10.1001/archsurg.140.2.174

[4] F. H. Edwards, R. M. Engelman, P. Houck, D. M. Sha-

hian and C. R. Bridges, “The Society of Thoracic Sur-

geons Practice Guideline Series: Antibiotic Prophylaxis

in Cardiac Surgery, Part I: Duration,” The Annals of Tho-

racic Surgery, Vol. 81, No. 1, 2006, pp. 397-404.

http://dx.doi.org/10.1016/j.athoracsur.2005.06.034

[5] F. Roques, S. A. Nashef, P. Micheal, E. Gauducheau, C.

de Vincentis, E. Baudet, et al., “Risks Factors and Out-

come in European Cardiac Surgery: Analysis of the Eu-

roSCORE Multinational Database of 19030 Patients,”

European Journal of Cardio-Thoracic Surgery, Vol. 15,

No. 6, 1999, pp .816-822.

http://dx.doi.org/10.1016/S1010-7940(99)00106-2

[6] J. S. Garner, W. R. Jarvis, T. G. Emori, T. C. Horan and J.

M. Hughes, “CDC Definitions for Nosocomial Infec-

tions,” In: R. N. Olmsted, Ed., APIC Infection Control

and Applied Epidemiology: Principles and Practice, Mos-

by, St Louis, 1996, pp. A1-A20.

[7] Antibioprophylaxie en Chirurgie et Médecine Interven-

tionnelle. Société Française D’Anesthésie et de Réanima-

tion, 2010.

http://www.sfar.org/article/669/antibioprophylaxie-en-chi

rurgie-et-medecine-interventionnelle-patients-adultes-cc-

2010

[8] J. E. Conte, S. N. Cohen, B. B. Roe and R. M. Elashoff,

“Antibiotic Prophylaxis and Cardiac Surgery. A Prospec-

tive Double-Blind Comparison of Single-Dose versus

Multiple-Dose Regimens,” Annals of Internal Medicine,

Vol. 76, No. 6, 1972, pp. 943-949.

http://dx.doi.org/10.7326/0003-4819-76-6-943

[9] E. Tamayo E. J. Gualis, S. Florez, J. Castrodeza, J. M.

Eiros Bouza and J. Alvarez, “Comparative Study of Sin-

gle-Dose and 24-Hour Multiple-Dose Antibiotic Prophy-

laxis for Cardiac Surgery,” The Journal of Thoracic and

Cardiovascular Surgery, Vol. 136, No. 6, 2008, pp. 1522-

1527. http://dx.doi.org/10.1016/j.jtcvs.2008.05.013

[10] A. Konvalinka, L. Errett and I. W. Fong, “Impact of Trea-

ting Staphylococcus aureus Nasal Carriers on Wound In-

fection in Cardiac Surgery,” Journal of Hospital Infec-

tion, Vol. 64, No. 2, 2006, pp. 162-168.

http://dx.doi.org/10.1016/j.jhin.2006.06.010

[11] E. Bennett-Guerrero, T. B. Fergusson, M. Lin, et al., for

the SWIPE-1 Trial Group, “Effect of an Implantable

Gentamicin-Collagen Sponge on Sternal Wound Infection

Following Cardiac Surgery. A Randomized Trial,” The

Journal of the American Medical Association, Vol. 304,

No. 7, 2010, pp. 755-762.

http://dx.doi.org/10.1001/jama.2010.1152

[12] S. Stadler and T. Fleck, “Triclosan-Coated Sutures for the

Reduction of Sternal Wound Infections? A Retrospective

Observational Analysis,” Interactive Cardiovascular and

Thoracic Surgery, Vol. 13, No. 3, 2011, pp. 296-299.

http://dx.doi.org/10.1510/icvts.2011.269001