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Local Antibiotics to Prevent Surgical Site Infections: Another Zeno's Paradox?

Local Antibiotics to Prevent Surgical Site Infections: Another Zeno's Paradox? Abstract JAMA Effect of an Implantable Gentamicin-Collagen Sponge on Sternal Wound Infections Following Cardiac Surgery: A Randomized Trial Elliott Bennett-Guerrero, MD; T. Bruce Ferguson Jr, MD; Min Lin, PhD; Jyotsna Garg, MS; Daniel B. Mark, MD, MPH; Vincent A. Scavo Jr, MD; Nicholas Kouchoukos, MD; John B. Richardson Jr, MD; Renee L. Pridgen, BS; G. R. Corey, MD; for the SWIPE-1 Trial Group Context:  Despite the routine use of prophylactic systemic antibiotics, sternal wound infection still occurs in 5% or more of cardiac surgical patients and is associated with significant excess morbidity, mortality, and cost. The gentamicin-collagen sponge, a surgically implantable topical antibiotic, is currently approved in 54 countries. A large, 2-center, randomized trial in Sweden reported in 2005 that the sponge reduced surgical site infection by 50% in cardiac patients. Objective:  To test the hypothesis that the sponge prevents infection in cardiac surgical patients at increased risk for sternal wound infection. Design, Setting, and Participants:  Phase 3 single-blind, prospective randomized controlled trial, 1502 cardiac surgical patients at high risk for sternal wound infection (diabetes, body mass index >30, or both) were enrolled at 48 US sites between December 21, 2007, and March 11, 2009. Intervention:  Single-blind randomization to insertion of 2 gentamicin-collagen sponges (total gentamicin of 260 mg) between the sternal halves at surgical closure (n = 753) vs no intervention (control group: n = 749). All patients received standardized care including prophylactic systemic antibiotics and rigid sternal fixation. Main Outcome Measures:  The primary end point was sternal wound infection occurring through 90 days postoperatively as adjudicated by a clinical events classification committee blinded to study treatment group. The primary study comparison was done in the intent-to-treat population. Secondary outcomes included (1) superficial wound infection (involving subcutaneous tissue but not extending down to sternal fixation wires), (2) deep wound infection (involving the sternal wires, sternal bone, and/or mediastinum), and (3) score for additional treatment, presence of serous discharge, erythema, purulent exudate, separation of the deep tissues, isolation of bacteria, and duration of inpatient stay (ASEPSIS; minimum score of 0 with no theoretical maximum). Results:  Of 1502 patients, 1006 had diabetes (67%) and 1137 were obese (body mass index >30) (76%). In the primary analysis, there was no significant difference in sternal wound infection in 63 of 753 patients randomized to the gentamicin-collagen sponge group (8.4%) compared with 65 of 749 patients randomized to the control group (8.7%) (P = .83). No significant differences were observed between the gentamicin-collagen sponge group and the control group, respectively, in superficial sternal wound infection (49/753 [6.5%] vs 46/749 [6.1%]; P = .77), deep sternal wound infection (14/753 [1.9%] vs 19/749 [2.5%]; P = .37), ASEPSIS score (mean [SD], 1.9 [6.4] vs 2.0 [7.2]; P = .67), or rehospitalization for sternal wound infection (23/753 [3.1%] vs 24/749 [3.2%]; P = .87). Conclusion:  Among US patients with diabetes, high body mass index, or both undergoing cardiac surgery, the use of 2 gentamicin-collagen sponges compared with no intervention did not reduce the 90-day sternal wound infection rate. Trial Registration:  clinicaltrials.gov Identifier: NCT00600483 As reported in JAMA, the SWIPE-1 trial used the implantation of 2 gentamicin-collagen sponges between the sternal halves in an effort to prevent sternal wound infections after cardiac surgery. The trial was based on an earlier large trial (2000 patients at 2 sites) that demonstrated a benefit to the sponge application. SWIPE-1 was a phase 3, single-blind, prospective, randomized controlled trial conducted at 48 sites and enrolling 1500 patients. While there was variability in the surgical preparation and operations, there were no significant differences between the treated group and the untreated control group. The investigators are to be congratulated for conducting this large randomized trial in high-risk patients in an attempt to eliminate a morbid and potentially lethal complication. Unfortunately, the results did not demonstrate a benefit for those treated with the sponge. The timely administration of intravenous antibiotics is efficacious but unable to completely eliminate surgical site infections. Adjuvant antibiosis may augment intravenous regimens, and studies such as SWIPE-1 are necessary. Nevertheless, the history of topical antibiotic use in surgery is replete with many similar equivocal studies. Recently, an identical trial in colorectal surgery yielded the same results.1 It would seem that local antibiotics should be beneficial, but they must be chosen to combat the pathogens usually encountered in the operation. For sternotomies, the offending pathogens are typically gram-positive bacteria, specifically Staphylococcus. Improved prevention may need to focus on the skin. In addition to the usual skin preparation measures that are the standard of care, other topical applications targeting skin flora have demonstrated improved outcomes.2,3 Futuristic nanotechnology may provide additional local protection when applied to the wound.4 The SWIPE-1 trial confirms that superficial and deep sternal wound infections remain a real and serious problem. However, these infections may occur despite the use of perfect preoperative, intraoperative, and postoperative technique. Insurers have put the onus on the caregivers by threatening nonpayment when these complications occur. Sadly, the surgical wound infection rates may asymptotically approach but never reach zero. Patient factors, such as nutritional status, age, diabetes mellitus, obesity, reoperations, and corticosteroid use, will prevent “infectionless” operations. This is not to excuse technique. Adhering to the proven surgical tenets of hemostasis, asepsis, stable closure, and avoidance of devascularization still play critical roles and, even if accounted for by randomization in trials, may affect the results more than does the use of local antibiotics. Nevertheless, additional studies on appropriate local antibiotic use are needed. Back to top Article Information Correspondence: Dr Horvath, Cardiothoracic Surgery, NIH Heart Center at Suburban Hospital, 8600 Old Georgetown Rd, Bethesda, MD 20814 (khorvath@nih.gov). References 1. Bennett-Guerrero EPappas TNKoltun WASWIPE 2 Trial Group, Gentamicin-collagen sponge for infection prophylaxis in colorectal surgery. N Engl J Med 2010;363 (11) 1038- 1049PubMedGoogle ScholarCrossref 2. MacIver RHStewart RFrederiksen JWFullerton DAHorvath KA Topical application of bacitracin ointment is associated with decreased risk of mediastinitis after median sternotomy. Heart Surg Forum 2006;9 (5) E750- E753PubMedGoogle ScholarCrossref 3. Bonomo RAVan Zile PSLi QShermock KMMcCormick WGKohut B Topical triple-antibiotic ointment as a novel therapeutic choice in wound management and infection prevention: a practical perspective. Expert Rev Anti Infect Ther 2007;5 (5) 773- 782PubMedGoogle ScholarCrossref 4. Martinez LRHan GChacko M Antimicrobial and healing efficacy of sustained release nitric oxide nanoparticles against Staphylococcus aureus skin infection [published correction appears in J Invest Dermatol. 2010;130(3):908]. J Invest Dermatol 2009;129 (10) 2463- 2469PubMedGoogle ScholarCrossref http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png Archives of Surgery American Medical Association

Local Antibiotics to Prevent Surgical Site Infections: Another Zeno's Paradox?

Archives of Surgery , Volume 146 (3) – Mar 1, 2011

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Publisher
American Medical Association
Copyright
Copyright © 2011 American Medical Association. All Rights Reserved.
ISSN
0004-0010
eISSN
1538-3644
DOI
10.1001/archsurg.2011.21
Publisher site
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Abstract

Abstract JAMA Effect of an Implantable Gentamicin-Collagen Sponge on Sternal Wound Infections Following Cardiac Surgery: A Randomized Trial Elliott Bennett-Guerrero, MD; T. Bruce Ferguson Jr, MD; Min Lin, PhD; Jyotsna Garg, MS; Daniel B. Mark, MD, MPH; Vincent A. Scavo Jr, MD; Nicholas Kouchoukos, MD; John B. Richardson Jr, MD; Renee L. Pridgen, BS; G. R. Corey, MD; for the SWIPE-1 Trial Group Context:  Despite the routine use of prophylactic systemic antibiotics, sternal wound infection still occurs in 5% or more of cardiac surgical patients and is associated with significant excess morbidity, mortality, and cost. The gentamicin-collagen sponge, a surgically implantable topical antibiotic, is currently approved in 54 countries. A large, 2-center, randomized trial in Sweden reported in 2005 that the sponge reduced surgical site infection by 50% in cardiac patients. Objective:  To test the hypothesis that the sponge prevents infection in cardiac surgical patients at increased risk for sternal wound infection. Design, Setting, and Participants:  Phase 3 single-blind, prospective randomized controlled trial, 1502 cardiac surgical patients at high risk for sternal wound infection (diabetes, body mass index >30, or both) were enrolled at 48 US sites between December 21, 2007, and March 11, 2009. Intervention:  Single-blind randomization to insertion of 2 gentamicin-collagen sponges (total gentamicin of 260 mg) between the sternal halves at surgical closure (n = 753) vs no intervention (control group: n = 749). All patients received standardized care including prophylactic systemic antibiotics and rigid sternal fixation. Main Outcome Measures:  The primary end point was sternal wound infection occurring through 90 days postoperatively as adjudicated by a clinical events classification committee blinded to study treatment group. The primary study comparison was done in the intent-to-treat population. Secondary outcomes included (1) superficial wound infection (involving subcutaneous tissue but not extending down to sternal fixation wires), (2) deep wound infection (involving the sternal wires, sternal bone, and/or mediastinum), and (3) score for additional treatment, presence of serous discharge, erythema, purulent exudate, separation of the deep tissues, isolation of bacteria, and duration of inpatient stay (ASEPSIS; minimum score of 0 with no theoretical maximum). Results:  Of 1502 patients, 1006 had diabetes (67%) and 1137 were obese (body mass index >30) (76%). In the primary analysis, there was no significant difference in sternal wound infection in 63 of 753 patients randomized to the gentamicin-collagen sponge group (8.4%) compared with 65 of 749 patients randomized to the control group (8.7%) (P = .83). No significant differences were observed between the gentamicin-collagen sponge group and the control group, respectively, in superficial sternal wound infection (49/753 [6.5%] vs 46/749 [6.1%]; P = .77), deep sternal wound infection (14/753 [1.9%] vs 19/749 [2.5%]; P = .37), ASEPSIS score (mean [SD], 1.9 [6.4] vs 2.0 [7.2]; P = .67), or rehospitalization for sternal wound infection (23/753 [3.1%] vs 24/749 [3.2%]; P = .87). Conclusion:  Among US patients with diabetes, high body mass index, or both undergoing cardiac surgery, the use of 2 gentamicin-collagen sponges compared with no intervention did not reduce the 90-day sternal wound infection rate. Trial Registration:  clinicaltrials.gov Identifier: NCT00600483 As reported in JAMA, the SWIPE-1 trial used the implantation of 2 gentamicin-collagen sponges between the sternal halves in an effort to prevent sternal wound infections after cardiac surgery. The trial was based on an earlier large trial (2000 patients at 2 sites) that demonstrated a benefit to the sponge application. SWIPE-1 was a phase 3, single-blind, prospective, randomized controlled trial conducted at 48 sites and enrolling 1500 patients. While there was variability in the surgical preparation and operations, there were no significant differences between the treated group and the untreated control group. The investigators are to be congratulated for conducting this large randomized trial in high-risk patients in an attempt to eliminate a morbid and potentially lethal complication. Unfortunately, the results did not demonstrate a benefit for those treated with the sponge. The timely administration of intravenous antibiotics is efficacious but unable to completely eliminate surgical site infections. Adjuvant antibiosis may augment intravenous regimens, and studies such as SWIPE-1 are necessary. Nevertheless, the history of topical antibiotic use in surgery is replete with many similar equivocal studies. Recently, an identical trial in colorectal surgery yielded the same results.1 It would seem that local antibiotics should be beneficial, but they must be chosen to combat the pathogens usually encountered in the operation. For sternotomies, the offending pathogens are typically gram-positive bacteria, specifically Staphylococcus. Improved prevention may need to focus on the skin. In addition to the usual skin preparation measures that are the standard of care, other topical applications targeting skin flora have demonstrated improved outcomes.2,3 Futuristic nanotechnology may provide additional local protection when applied to the wound.4 The SWIPE-1 trial confirms that superficial and deep sternal wound infections remain a real and serious problem. However, these infections may occur despite the use of perfect preoperative, intraoperative, and postoperative technique. Insurers have put the onus on the caregivers by threatening nonpayment when these complications occur. Sadly, the surgical wound infection rates may asymptotically approach but never reach zero. Patient factors, such as nutritional status, age, diabetes mellitus, obesity, reoperations, and corticosteroid use, will prevent “infectionless” operations. This is not to excuse technique. Adhering to the proven surgical tenets of hemostasis, asepsis, stable closure, and avoidance of devascularization still play critical roles and, even if accounted for by randomization in trials, may affect the results more than does the use of local antibiotics. Nevertheless, additional studies on appropriate local antibiotic use are needed. Back to top Article Information Correspondence: Dr Horvath, Cardiothoracic Surgery, NIH Heart Center at Suburban Hospital, 8600 Old Georgetown Rd, Bethesda, MD 20814 (khorvath@nih.gov). References 1. Bennett-Guerrero EPappas TNKoltun WASWIPE 2 Trial Group, Gentamicin-collagen sponge for infection prophylaxis in colorectal surgery. N Engl J Med 2010;363 (11) 1038- 1049PubMedGoogle ScholarCrossref 2. MacIver RHStewart RFrederiksen JWFullerton DAHorvath KA Topical application of bacitracin ointment is associated with decreased risk of mediastinitis after median sternotomy. Heart Surg Forum 2006;9 (5) E750- E753PubMedGoogle ScholarCrossref 3. Bonomo RAVan Zile PSLi QShermock KMMcCormick WGKohut B Topical triple-antibiotic ointment as a novel therapeutic choice in wound management and infection prevention: a practical perspective. Expert Rev Anti Infect Ther 2007;5 (5) 773- 782PubMedGoogle ScholarCrossref 4. Martinez LRHan GChacko M Antimicrobial and healing efficacy of sustained release nitric oxide nanoparticles against Staphylococcus aureus skin infection [published correction appears in J Invest Dermatol. 2010;130(3):908]. J Invest Dermatol 2009;129 (10) 2463- 2469PubMedGoogle ScholarCrossref

Journal

Archives of SurgeryAmerican Medical Association

Published: Mar 1, 2011

References