Division of Perioperative Clinical Research, Duke Clinical Research Institute, Duke University Medical Center, PO Box 3094, Durham, NC 27710, USA.
JAMA. 2010 Aug 18;304(7):755-62. doi: 10.1001/jama.2010.1152.
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.
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.
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.
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).
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).
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.
clinicaltrials.gov Identifier: NCT00600483.
尽管预防性全身使用抗生素已成为常规做法，但心脏外科患者中仍有 5%或更多患者发生胸骨伤口感染，这与显著增加的发病率、死亡率和成本相关。庆大霉素-胶原海绵是一种可手术植入的局部抗生素，目前已在 54 个国家获得批准。2005 年瑞典进行的一项大型、双中心、随机试验报告称，该海绵可使心脏患者的手术部位感染减少 50%。
检验假设，即在有发生胸骨伤口感染风险的心脏外科患者中，海绵可预防感染。
设计、地点和参与者：这是一项 3 期单盲、前瞻性随机对照试验，在 2007 年 12 月 21 日至 2009 年 3 月 11 日期间，在美国 48 个地点招募了 1502 名有发生胸骨伤口感染高风险（糖尿病、体重指数>30 或两者兼有）的心脏外科患者。
在手术关闭时，将 2 片庆大霉素-胶原海绵（总庆大霉素 260mg）单盲随机插入胸骨两半之间（753 例）或不进行干预（对照组：749 例）。所有患者均接受标准化治疗，包括预防性全身抗生素和刚性胸骨固定。
主要终点是通过临床事件分类委员会盲法评估术后 90 天内发生的胸骨伤口感染。主要研究比较是在意向治疗人群中进行的。次要结局包括（1）浅表伤口感染（涉及皮下组织，但不延伸至胸骨固定线），（2）深部伤口感染（涉及胸骨线、胸骨骨和/或纵隔），以及（3）额外治疗评分、浆液性分泌物、红斑、脓性渗出物、深层组织分离、细菌分离和住院时间（ASEPSIS；最低得分为 0，无理论最大值）。
在 1502 名患者中，1006 名患有糖尿病（67%），1137 名肥胖（体重指数>30）（76%）。在主要分析中，与随机分配至庆大霉素-胶原海绵组的 753 名患者中的 63 名（8.4%）相比，随机分配至对照组的 749 名患者中的 65 名（8.7%）在胸骨伤口感染方面无显著差异（P=.83）。与对照组相比，庆大霉素-胶原海绵组分别在浅表胸骨伤口感染（49/753 [6.5%] vs 46/749 [6.1%]；P=.77）、深部胸骨伤口感染（14/753 [1.9%] vs 19/749 [2.5%]；P=.37）、ASEPSIS 评分（平均值[标准差]，1.9[6.4] vs 2.0[7.2]；P=.67）或因胸骨伤口感染再次住院（23/753 [3.1%] vs 24/749 [3.2%]；P=.87）方面均无显著差异。
在美国接受心脏手术的糖尿病、高体重指数或两者兼有的患者中，与不干预相比，使用 2 片庆大霉素-胶原海绵并不能降低 90 天胸骨伤口感染率。
clinicaltrials.gov 标识符：NCT00600483。
