- Email: [email protected]
Antibiotic prophylaxis for cardiac surgery in a setting with high prevalence of extended-spectrum beta-lactamase-producing Gram-negative bacteria
Accepted Manuscript Antibiotic prophylaxis for cardiac surgery in a setting with high prevalence of extended-spectrum beta-lactamase-producing Gram-negative bacteria A. Phuphuakrat, A. Choomai, S. Kiertiburanakul, K. Malathum PII:
S0195-6701(16)30016-0
DOI:
10.1016/j.jhin.2016.03.025
Reference:
YJHIN 4796
To appear in:
Journal of Hospital Infection
Received Date: 23 March 2016 Accepted Date: 29 March 2016
Please cite this article as: Phuphuakrat A, Choomai A, Kiertiburanakul S, Malathum K, Antibiotic prophylaxis for cardiac surgery in a setting with high prevalence of extended-spectrum beta-lactamaseproducing Gram-negative bacteria, Journal of Hospital Infection (2016), doi: 10.1016/j.jhin.2016.03.025. This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.
ACCEPTED MANUSCRIPT
Antibiotic prophylaxis for cardiac surgery in a setting with high prevalence
of
extended-spectrum
beta-lactamase-producing
RI PT
Gram-negative bacteria
Sir,
The prevalence of extended-spectrum beta-lactamase (ESBL)-producing Gram-
SC
negative bacteria may be highest in the Asia-Pacific region.1 In Thailand, ESBL-producing Gram-negative bacteria (ESBL-GNB) represent the main cause of healthcare-associated
M AN U
infections.2 Community-acquired cases are also reported increasingly. Data from our hospital laboratory in 2014 showed that the prevalence of ESBL-producing Escherichia coli and ESBL-producing Klebsiella pneumoniae were 46% and 35%, respectively. At our hospital, approximately 350 cardiac procedures, including coronary artery
TE D
bypass graft (CABG) and valve repairs, are performed each year. Broad-spectrum agents (i.e. carbapenems) are frequently used as prophylaxis in cardiac surgery because of concerns about the risk of infection with ESBL-GNB. However, the role of carbapenems as
EP
prophylactic antibiotics for cardiac surgery in settings with high prevalence of ESBL-GNB has never been studied. Surgical site infection (SSI) is a common complication of cardiac
AC C
surgery, reported to occur in 1–3% of these patients.3 Deep sternal infection and mediastinitis are of particular concern because of their association with high mortality.4 We compared the effectiveness of carbapenems as prophylactic antibiotics in cardiac surgery with standard agents (e.g. cefazolin and cefuroxime)5,6 in terms of the prevention of postoperative infections in a centre with high prevalence of ESBL-GNB. We performed a retrospective study of 266 patients aged >15 years who underwent urgent or scheduled cardiac surgical procedures requiring sternotomy at Ramathibodi
ACCEPTED MANUSCRIPT Hospital between January and September 2014. Patients with documented or suspected preexisting infection before the procedure, those who received antibiotics for treatment prior to surgical prophylaxis, and patients with pre-operative hospital stay of more than three days were excluded.
RI PT
In total, 132 (49.6%) patients received standard agents and 134 (50.4%) patients received carbapenems as prophylaxis. The median age was 65 [interquartile range (IQR) 56– 72] years and 181 (68.1%) were men. Most underlying diseases did not differ significantly
SC
between patients who received standard prophylaxis and patients who received carbapenem prophylaxis, except that patients with hyperlipidaemia were more likely to receive
M AN U
carbapenems [87 (64.9% vs 57 (43.2%), P<0.001]. Cardiac procedures included 157 CABGs (59.0%), 83 valve repairs (31.2%), 19 CABGs plus valve repairs (7.1%), and seven other cardiac procedures (2.6%). Most patients [248 (93.2%)] had elective surgery. The median operative time was 4.3 (IQR 3.2–4.8) h and 3.1 (IQR 2.5–3.8) h in the standard antibiotic
TE D
group and the carbapenem group, respectively (P<0.001). The risk factors for infection with ESBL-GNB (recent hospital stay or antibiotic exposure, presence of intravascular devices), and the median duration of mechanical ventilation [1 (IQR 1–2) day in both groups, P=0.322]
EP
did not differ between the two groups. The duration of antibiotic prophylaxis also did not
AC C
differ significantly between the two groups [48 (IQR 48–73) h in standard antibiotic group vs 60 (IQR 24–72) h in carbapenem group, P=0.521]. Twenty-four postoperative infections (9.0%) occurred, including five SSIs. Other
infections were pneumonia (13 cases), urinary tract infection (three cases) and bacteraemia (three cases). The overall incidence of postoperative infection was comparable between the two groups (Table I). Although the numbers were very small, subgroup analysis showed no difference in the incidence of SSIs between the groups, but pneumonia was less common in the carbapenem group. The median duration of mechanical ventilation did not differ between
ACCEPTED MANUSCRIPT the two groups [1 (IQR 1–2) day in both groups, P=0.322]. On multivariate logistic regression, body mass index (BMI) [odds ratio (OR) 1.17, 95% confidence interval (CI) 1.01–1.34; P=0.034] and intra-operative hypotension (OR 7.87, 95% CI 1.10–56.53; P=0.040) were found to be independently associated with postoperative infection. The cost of
RI PT
antibiotics was higher and the total length of stay was longer in the carbapenem group.
This study revealed that respiratory tract infection was the most common nosocomial infection following cardiac surgery. GNB predominated in respiratory and urinary infections,
SC
which may explain the lower incidence of pneumonia in the carbapenem group. A systematic review and meta-analysis showed that second- and third-generation cephalosporins were
M AN U
superior to regimens with inferior anti-GNB cover.7 This study suggests that carbapenems are associated with a lower rate of postoperative pneumonia in settings with high prevalence of ESBL-GNB; SSI numbers were too small to detect a significant difference. The use of carbapenems as prophylaxis for cardiac surgery in settings with high
TE D
prevalence of ESBL-GNB may not decrease SSIs, but appears to increase length of hospital stay and the cost of antibiotics. Overuse of broad-spectrum antibiotics is known to be associated with increasing drug resistance.8 Given the emergence of carbapenem-resistant
EP
bacteria, use of carbapenems for surgical prophylaxis should be discouraged when safer and
AC C
equally effective alternatives are available.
Conflict of interest statement None declared.
Funding sources None.
ACCEPTED MANUSCRIPT References 1. Lob SH, Badal RE, Bouchillon SK, Hawser SP, Hackel MA, Hoban DJ. Epidemiology and susceptibility of Gram-negative appendicitis pathogens: SMART 2008–2010. Surg Infect (Larchmt) 2013;14:203–208.
RI PT
2. Hongsuwan M, Srisamang P, Kanoksil M et al. Increasing incidence of hospital-acquired and healthcare-associated bacteremia in northeast Thailand: a multicenter surveillance study. PLoS One 2014;9:e109324.
SC
3. Lemaignen A, Birgand G, Ghodhbane W, et al. Sternal wound infection after cardiac surgery: incidence and risk factors according to clinical presentation. Clin Microbiol Infect
M AN U
2015;21:674e11–e18.
4. Milano CA, Kesler K, Archibald N, Sexton DJ, Jones RH. Mediastinitis after coronary artery bypass graft surgery. Risk factors and long-term survival. Circulation 1995;92:2245–2251. 5. Bratzler DW, Dellinger EP, Olsen KM, et al. Clinical practice guidelines for antimicrobial
TE D
prophylaxis in surgery. Am J Health Syst Pharm 2013;70:195–283. 6. Gorski A, Hamouda K, Ozkur M, et al. Cardiac surgery antibiotic prophylaxis and calculated empiric antibiotic therapy. Asian Cardiovasc Thorac Ann 2015;23:282–288.
EP
7. Lador A, Nasir H, Mansur N, et al. Antibiotic prophylaxis in cardiac surgery: systematic
AC C
review and meta-analysis. J Antimicrob Chemother 2012;67:541–550. 8. Lynch JP, 3rd, Clark NM, Zhanel GG. Evolution of antimicrobial resistance among Enterobacteriaceae (focus on extended spectrum beta-lactamases and carbapenemases). Expert Opin Pharmacother 2013;14:199–210.
A. Phuphuakrat*, A. Choomai, S. Kiertiburanakul, K. Malathum Department of Medicine, Faculty of Medicine Ramathibodi Hospital, Mahidol University, Bangkok, Thailand
ACCEPTED MANUSCRIPT *
Corresponding author. Address: Division of Infectious Diseases, Department of Medicine,
Faculty of Medicine Ramathibodi Hospital, Mahidol University, Bangkok, 10400, Thailand. Tel.: +66 2 2011581; fax: +66 2 2012232
AC C
EP
TE D
M AN U
SC
RI PT
E-mail address: [email protected] (A. Phuphuakrat).
ACCEPTED MANUSCRIPT Table I Outcomes of patients receiving standard antibiotics vs carbapenems as prophylaxis for cardiac surgery
Overall infection
16 (12.1)
Surgical site infection
3 (2.3)
Pneumonia
11 (8.3)
Cost of antibiotics (Baht)b
0.090
2 (1.5)
0.683a
2 (1.5)
0.011
8868
<0.001
(7735–11,083)
10.0 (9.0–13.5)
11.5 (10.0–15.0)
<0.001
ICU-days
3.0 (2.0–5.0)
4.0 (3.0–6.0)
0.027
Ward-days
6.0 (5.0–8.0)
7.0 (5.0–10.0)
0.013
Fisher’s exact test.
TE D
ICU, intensive care unit.
EP
1 US$=35.3 Thai Baht on 29th March 2016.
AC C
b
8 (6.0)
(436–2237) Total length of stay
a
N=134
M AN U
726
P-value
RI PT
N=132
Carbapenems
SC
Standard
S0195-6701(16)30016-0
DOI:
10.1016/j.jhin.2016.03.025
Reference:
YJHIN 4796
To appear in:
Journal of Hospital Infection
Received Date: 23 March 2016 Accepted Date: 29 March 2016
Please cite this article as: Phuphuakrat A, Choomai A, Kiertiburanakul S, Malathum K, Antibiotic prophylaxis for cardiac surgery in a setting with high prevalence of extended-spectrum beta-lactamaseproducing Gram-negative bacteria, Journal of Hospital Infection (2016), doi: 10.1016/j.jhin.2016.03.025. This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.
ACCEPTED MANUSCRIPT
Antibiotic prophylaxis for cardiac surgery in a setting with high prevalence
of
extended-spectrum
beta-lactamase-producing
RI PT
Gram-negative bacteria
Sir,
The prevalence of extended-spectrum beta-lactamase (ESBL)-producing Gram-
SC
negative bacteria may be highest in the Asia-Pacific region.1 In Thailand, ESBL-producing Gram-negative bacteria (ESBL-GNB) represent the main cause of healthcare-associated
M AN U
infections.2 Community-acquired cases are also reported increasingly. Data from our hospital laboratory in 2014 showed that the prevalence of ESBL-producing Escherichia coli and ESBL-producing Klebsiella pneumoniae were 46% and 35%, respectively. At our hospital, approximately 350 cardiac procedures, including coronary artery
TE D
bypass graft (CABG) and valve repairs, are performed each year. Broad-spectrum agents (i.e. carbapenems) are frequently used as prophylaxis in cardiac surgery because of concerns about the risk of infection with ESBL-GNB. However, the role of carbapenems as
EP
prophylactic antibiotics for cardiac surgery in settings with high prevalence of ESBL-GNB has never been studied. Surgical site infection (SSI) is a common complication of cardiac
AC C
surgery, reported to occur in 1–3% of these patients.3 Deep sternal infection and mediastinitis are of particular concern because of their association with high mortality.4 We compared the effectiveness of carbapenems as prophylactic antibiotics in cardiac surgery with standard agents (e.g. cefazolin and cefuroxime)5,6 in terms of the prevention of postoperative infections in a centre with high prevalence of ESBL-GNB. We performed a retrospective study of 266 patients aged >15 years who underwent urgent or scheduled cardiac surgical procedures requiring sternotomy at Ramathibodi
ACCEPTED MANUSCRIPT Hospital between January and September 2014. Patients with documented or suspected preexisting infection before the procedure, those who received antibiotics for treatment prior to surgical prophylaxis, and patients with pre-operative hospital stay of more than three days were excluded.
RI PT
In total, 132 (49.6%) patients received standard agents and 134 (50.4%) patients received carbapenems as prophylaxis. The median age was 65 [interquartile range (IQR) 56– 72] years and 181 (68.1%) were men. Most underlying diseases did not differ significantly
SC
between patients who received standard prophylaxis and patients who received carbapenem prophylaxis, except that patients with hyperlipidaemia were more likely to receive
M AN U
carbapenems [87 (64.9% vs 57 (43.2%), P<0.001]. Cardiac procedures included 157 CABGs (59.0%), 83 valve repairs (31.2%), 19 CABGs plus valve repairs (7.1%), and seven other cardiac procedures (2.6%). Most patients [248 (93.2%)] had elective surgery. The median operative time was 4.3 (IQR 3.2–4.8) h and 3.1 (IQR 2.5–3.8) h in the standard antibiotic
TE D
group and the carbapenem group, respectively (P<0.001). The risk factors for infection with ESBL-GNB (recent hospital stay or antibiotic exposure, presence of intravascular devices), and the median duration of mechanical ventilation [1 (IQR 1–2) day in both groups, P=0.322]
EP
did not differ between the two groups. The duration of antibiotic prophylaxis also did not
AC C
differ significantly between the two groups [48 (IQR 48–73) h in standard antibiotic group vs 60 (IQR 24–72) h in carbapenem group, P=0.521]. Twenty-four postoperative infections (9.0%) occurred, including five SSIs. Other
infections were pneumonia (13 cases), urinary tract infection (three cases) and bacteraemia (three cases). The overall incidence of postoperative infection was comparable between the two groups (Table I). Although the numbers were very small, subgroup analysis showed no difference in the incidence of SSIs between the groups, but pneumonia was less common in the carbapenem group. The median duration of mechanical ventilation did not differ between
ACCEPTED MANUSCRIPT the two groups [1 (IQR 1–2) day in both groups, P=0.322]. On multivariate logistic regression, body mass index (BMI) [odds ratio (OR) 1.17, 95% confidence interval (CI) 1.01–1.34; P=0.034] and intra-operative hypotension (OR 7.87, 95% CI 1.10–56.53; P=0.040) were found to be independently associated with postoperative infection. The cost of
RI PT
antibiotics was higher and the total length of stay was longer in the carbapenem group.
This study revealed that respiratory tract infection was the most common nosocomial infection following cardiac surgery. GNB predominated in respiratory and urinary infections,
SC
which may explain the lower incidence of pneumonia in the carbapenem group. A systematic review and meta-analysis showed that second- and third-generation cephalosporins were
M AN U
superior to regimens with inferior anti-GNB cover.7 This study suggests that carbapenems are associated with a lower rate of postoperative pneumonia in settings with high prevalence of ESBL-GNB; SSI numbers were too small to detect a significant difference. The use of carbapenems as prophylaxis for cardiac surgery in settings with high
TE D
prevalence of ESBL-GNB may not decrease SSIs, but appears to increase length of hospital stay and the cost of antibiotics. Overuse of broad-spectrum antibiotics is known to be associated with increasing drug resistance.8 Given the emergence of carbapenem-resistant
EP
bacteria, use of carbapenems for surgical prophylaxis should be discouraged when safer and
AC C
equally effective alternatives are available.
Conflict of interest statement None declared.
Funding sources None.
ACCEPTED MANUSCRIPT References 1. Lob SH, Badal RE, Bouchillon SK, Hawser SP, Hackel MA, Hoban DJ. Epidemiology and susceptibility of Gram-negative appendicitis pathogens: SMART 2008–2010. Surg Infect (Larchmt) 2013;14:203–208.
RI PT
2. Hongsuwan M, Srisamang P, Kanoksil M et al. Increasing incidence of hospital-acquired and healthcare-associated bacteremia in northeast Thailand: a multicenter surveillance study. PLoS One 2014;9:e109324.
SC
3. Lemaignen A, Birgand G, Ghodhbane W, et al. Sternal wound infection after cardiac surgery: incidence and risk factors according to clinical presentation. Clin Microbiol Infect
M AN U
2015;21:674e11–e18.
4. Milano CA, Kesler K, Archibald N, Sexton DJ, Jones RH. Mediastinitis after coronary artery bypass graft surgery. Risk factors and long-term survival. Circulation 1995;92:2245–2251. 5. Bratzler DW, Dellinger EP, Olsen KM, et al. Clinical practice guidelines for antimicrobial
TE D
prophylaxis in surgery. Am J Health Syst Pharm 2013;70:195–283. 6. Gorski A, Hamouda K, Ozkur M, et al. Cardiac surgery antibiotic prophylaxis and calculated empiric antibiotic therapy. Asian Cardiovasc Thorac Ann 2015;23:282–288.
EP
7. Lador A, Nasir H, Mansur N, et al. Antibiotic prophylaxis in cardiac surgery: systematic
AC C
review and meta-analysis. J Antimicrob Chemother 2012;67:541–550. 8. Lynch JP, 3rd, Clark NM, Zhanel GG. Evolution of antimicrobial resistance among Enterobacteriaceae (focus on extended spectrum beta-lactamases and carbapenemases). Expert Opin Pharmacother 2013;14:199–210.
A. Phuphuakrat*, A. Choomai, S. Kiertiburanakul, K. Malathum Department of Medicine, Faculty of Medicine Ramathibodi Hospital, Mahidol University, Bangkok, Thailand
ACCEPTED MANUSCRIPT *
Corresponding author. Address: Division of Infectious Diseases, Department of Medicine,
Faculty of Medicine Ramathibodi Hospital, Mahidol University, Bangkok, 10400, Thailand. Tel.: +66 2 2011581; fax: +66 2 2012232
AC C
EP
TE D
M AN U
SC
RI PT
E-mail address: [email protected] (A. Phuphuakrat).
ACCEPTED MANUSCRIPT Table I Outcomes of patients receiving standard antibiotics vs carbapenems as prophylaxis for cardiac surgery
Overall infection
16 (12.1)
Surgical site infection
3 (2.3)
Pneumonia
11 (8.3)
Cost of antibiotics (Baht)b
0.090
2 (1.5)
0.683a
2 (1.5)
0.011
8868
<0.001
(7735–11,083)
10.0 (9.0–13.5)
11.5 (10.0–15.0)
<0.001
ICU-days
3.0 (2.0–5.0)
4.0 (3.0–6.0)
0.027
Ward-days
6.0 (5.0–8.0)
7.0 (5.0–10.0)
0.013
Fisher’s exact test.
TE D
ICU, intensive care unit.
EP
1 US$=35.3 Thai Baht on 29th March 2016.
AC C
b
8 (6.0)
(436–2237) Total length of stay
a
N=134
M AN U
726
P-value
RI PT
N=132
Carbapenems
SC
Standard