Department of Orthopaedic Surgery, University of Texas Rio Grande Valley School of Medicine, Harlingen, TX, USA.
School of Medicine, Oregon Health and Science University, Portland, OR, USA.
Clin Orthop Relat Res. 2022 Dec 1;480(12):2409-2417. doi: 10.1097/CORR.0000000000002308. Epub 2022 Jul 5.
Wound complications are common after resection of soft tissue sarcomas, with published infection rates ranging from 10% to 35%. Multiple studies have reported on the atypical flora comprising these infections, which are often polymicrobial and contain anaerobic bacteria, and recent studies have noted the high prevalence of anaerobic bacterial infections after soft tissue sarcoma resection [ 26, 35 ]. Based on this, our institution changed clinical practice to include an antibiotic with anaerobic coverage in addition to the standard first-generation cephalosporin for prophylaxis during soft tissue sarcoma resections. The current study was undertaken to evaluate whether this change was associated with a change in major wound complications, and if the change should therefore be adopted for future patients.
QUESTIONS/PURPOSES: (1) After controlling for potentially confounding variables, was the broadening of the prophylactic antibiotic spectrum to cover anaerobic bacteria associated with a lower odds of major wound complications after soft tissue sarcoma resection? (2) Was the broadening of the prophylactic antibiotic spectrum to cover anaerobic bacteria associated with a lower odds of surgical site infections with polymicrobial or anaerobic infections after soft tissue sarcoma resection? (3) What are the factors associated with major wound complications after soft tissue sarcoma resection?
We retrospectively identified 623 patients who underwent soft tissue sarcoma resection at a single center between January 2008 and January 2021 using procedural terminology codes. Of these, four (0.6%) pediatric patients were excluded, as were five (0.8%) patients with atypical lipomatous tumors and two (0.3%) patients with primary bone tumors; 5% (33 of 623) who were lost to follow-up, leaving 579 for final analysis. The prophylactic antibiotic regimen given at the resection and whether a wound complication occurred were recorded. Patients received the augmented regimen based on whether they underwent resection after the change in practice in July 2018. A total of 497 patients received a standard antibiotic regimen (usually a first-generation cephalosporin), and 82 patients received an augmented regimen with anaerobic coverage (most often metronidazole). Of the 579 patients, 53% (307) were male (53% [264 of 497] in the standard regimen and 52% [43 of 82] in the augmented regimen), and the mean age was 59 ± 17 years (59 ± 17 and 60 ±17 years in the standard and augmented groups, respectively). Wound complications were defined as any of the following within 120 days of the initial resection: formal wound debridement in the operating room, other interventions such as percutaneous drain placement, readmission for intravenous antibiotics, or deep wound packing for more than 120 days from the resection. Patients were considered to have a surgical site infection if positive cultures resulted from deep tissue cultures taken intraoperatively at the time of debridement. The proportion of patients with major wound complications was 26% (150 of 579); it was 27% (136 of 497) and 17% (14 of 82) in the standard and augmented antibiotic cohorts, respectively (p = 0.049). With the numbers we had, we could not document that the addition of antibiotics with anaerobic coverage was associated with lower odds of anaerobic (4% versus 6%; p = 0.51) or polymicrobial infections (9% versus 14%; p = 0.25). Patient, tumor, and treatment (surgical, radiotherapy, and chemotherapy) variables were collected to evaluate factors associated with overall infection and anaerobic or polymicrobial infection. Patient follow-up was 120 days to capture early wound complications. A multivariable analysis was performed for all variables found to be significant in the univariate analysis. A p value < 0.05 was used as the threshold for statistical significance for all analyses. No patients were found to have an adverse reaction to the augmented regimen, including allergic reactions or Clostridioides (formerly Clostridium) difficile infection.
After controlling for other potentially confounding factors such as neoadjuvant radiation, tumor size and anatomic location, as well as patient BMI, anaerobic coverage was associated with smaller odds of wound complications (OR 0.36 [95% confidence interval (CI) 0.18 to 0.68]; p = 0.003). Other factors associated with major wound complications were preoperative radiation (versus no preoperative radiation) (OR 2.66 [95% CI 1.72 to 4.15]; p < 0.001), increasing tumor size (OR 1.04 [95% CI 1.00 to 1.07]; p = 0.03), patient BMI (OR 1.07 [95% CI 1.04 to 1.11]; p < 0.001), and tumor in the distal upper extremity (versus proximal upper extremity, pelvis/groin/hip, and lower extremity) (OR 0.18 [95% CI 0.04 to 0.62]; p = 0.01).
The addition of anaerobic coverage to the standard prophylactic regimen during soft tissue sarcoma resection demonstrated an association with smaller odds of major wound complications and no documented adverse reactions. Treating physicians should consider these findings but note that they are preliminary, and that further work is needed to replicate them in a more controlled study design such as a prospective trial.
Level III, therapeutic study.
软组织肉瘤切除术后的并发症很常见，发表的感染率在 10%到 35%之间。多项研究报告了这些感染的非典型菌群，它们通常是多种微生物并存的，并且含有厌氧菌，最近的研究还注意到软组织肉瘤切除术后厌氧菌感染的高患病率[26,35]。基于此，我们医院改变了临床实践，在软组织肉瘤切除术中，除了标准的第一代头孢菌素外，还使用具有抗厌氧菌覆盖的抗生素进行预防。目前的研究旨在评估这种改变是否与主要伤口并发症的改变有关，如果需要，是否应该在未来的患者中采用这种改变。
问题/目的：(1)在控制了潜在的混杂因素后，软组织肉瘤切除术中抗生素谱的扩大以覆盖厌氧菌是否与降低软组织肉瘤切除术后主要伤口并发症的几率有关？(2)在软组织肉瘤切除术中扩大抗生素谱以覆盖厌氧菌是否与降低多微生物或厌氧菌感染的手术部位感染的几率有关？(3)软组织肉瘤切除术后主要伤口并发症的相关因素有哪些？
我们使用手术程序术语代码，回顾性地确定了 2008 年 1 月至 2021 年 1 月在一个中心接受软组织肉瘤切除术的 623 名患者。其中，有 4 名（0.6%）儿科患者被排除在外，有 5 名（0.8%）患有非典型脂肪肿瘤患者和 2 名（0.3%）患有原发性骨肿瘤患者被排除在外；有 5%（33 名/623 名）患者随访丢失，最终有 579 名患者进行了最终分析。记录了在切除时使用的预防性抗生素方案以及是否发生了伤口并发症。根据 2018 年 7 月实践改变后是否进行了切除，患者接受了增强方案或标准方案。497 名患者接受了标准抗生素方案（通常为第一代头孢菌素），82 名患者接受了具有抗厌氧菌覆盖的增强方案（最常用的是甲硝唑）。在 579 名患者中，53%（307 名）为男性（标准方案中为 53%[264 名/497 名]，增强方案中为 52%[43 名/82 名]），平均年龄为 59 ± 17 岁（标准组和增强组分别为 59 ± 17 岁和 60 ±17 岁）。伤口并发症定义为初次切除后 120 天内出现以下任何一种情况：在手术室进行正式清创，进行经皮引流放置等其他干预措施，因静脉内使用抗生素而再次入院，或深部伤口填塞超过 120 天。如果在清创时从深部组织培养物中获得阳性培养物，则认为患者发生了手术部位感染。主要伤口并发症的患者比例为 26%（579 名患者中有 150 名）；在标准抗生素组和增强抗生素组中，分别为 27%（497 名患者中有 136 名）和 17%（82 名患者中有 14 名）（p = 0.049）。根据我们的数据，我们无法证明添加具有抗厌氧菌覆盖的抗生素与降低厌氧菌（4%比 6%；p = 0.51）或多微生物感染（9%比 14%；p = 0.25）的几率有关。收集了患者、肿瘤和治疗（手术、放疗和化疗）变量，以评估与总感染和厌氧菌或多微生物感染相关的因素。患者的随访时间为 120 天，以捕捉早期伤口并发症。对所有在单变量分析中发现有统计学意义的变量进行了多变量分析。所有分析的 p 值<0.05 被认为具有统计学意义。没有发现患者对增强方案有不良反应，包括过敏反应或艰难梭菌（以前称为梭状芽孢杆菌）感染。
在控制了其他潜在的混杂因素，如术前放疗、肿瘤大小和解剖位置以及患者 BMI 后，抗厌氧菌覆盖与较小的伤口并发症几率相关（OR 0.36[95%置信区间（CI）0.18 至 0.68]；p = 0.003）。其他与主要伤口并发症相关的因素包括术前放疗（而非无术前放疗）（OR 2.66[95%CI 1.72 至 4.15]；p<0.001）、肿瘤大小增加（OR 1.04[95%CI 1.00 至 1.07]；p = 0.03）、患者 BMI（OR 1.07[95%CI 1.04 至 1.11]；p<0.001）和肿瘤位于远端上肢（而非近端上肢、骨盆/腹股沟/臀部和下肢）（OR 0.18[95%CI 0.04 至 0.62]；p = 0.01）。
在软组织肉瘤切除术中，将抗厌氧菌覆盖添加到标准预防方案中与降低主要伤口并发症的几率相关，且没有记录到不良反应。治疗医生应考虑这些发现，但请注意，这些发现是初步的，需要进一步的工作，以更受控的研究设计（如前瞻性试验）复制这些发现。
III 级，治疗性研究。
