Is the Addition of Anaerobic Coverage to Perioperative Antibiotic Prophylaxis During Soft Tissue Sarcoma Resection Associated With a Reduction in the Proportion of Wound Complications?

BACKGROUND: 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? METHODS: 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. RESULTS: 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). CONCLUSION: 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 OF EVIDENCE: Level III, therapeutic study.

Effects of delayed postoperative void and preoperative urologic symptoms on delay in time of discharge for elective lumbar decompression surgery.

BACKGROUND CONTEXT: Almost half of all patients undergoing lumbar spine surgery have preoperative lower urinary tract symptoms (LUTS). These symptoms could affect postoperative voiding and subsequently length of stay. PURPOSE: To investigate the association between preoperative LUTS and time to first void and between time to first void and time to discharge among patients undergoing elective lumbar decompression surgery. STUDY DESIGN/SETTING: Retrospective analysis of prospectively collected data among patients at a single academic medical center. PATIENT SAMPLE: All patients ≥18 years of age undergoing elective lumbar decompression surgery between July 2017 and March 2020. OUTCOME MEASURES: The physiologic measure of a delayed time to first void was defined as an initial postoperative void of > 4 hours after anesthesia stop time. The outcome of prolonged time to discharge was defined as a stay of >24 hours after anesthesia stop time. METHODS: At their preoperative visit, patients completed the validated International Prostate Symptom Score (IPSS) (range, 0-35 points), which is applicable for LUTS assessment in both sexes. Clinically relevant LUTS are defined as an IPSS score of ≥8. Patients were followed from their preoperative visit to surgery admission discharge. Association of LUTS with time to first void and time to first void with admission discharge were estimated using risk ratios (RR) and 95% confidence intervals (CI) from a multivariable Poisson regression with a robust variance estimate adjusted for potential confounding variables including age, sex, IPSS, and intraoperative Foley catheter use. RESULTS: The analytic cohort included 170 patients with an average age of 57 years and 103 (61%) were men. Preoperative LUTS prevalence was 45%, and 111 (65%) of patients voided within 4 hours after surgery. For patients with preoperative LUTS, the unadjusted RR for a first void of >4 hours was 1.04 (95% CI: 0.82-1.32) (p=.77). Adjustment for age, sex, intraoperative Foley catheter use, revision surgery, previous spine surgery, single versus multiple levels, and lumbar location did not materially alter the risk: the multivariable RR was 1.04 (95% CI: 0.82-1.31) (p=.74). The unadjusted RR for a discharge of > 24 hours for patients with a time to first void of > 4 hours was 2.17 (95% CI: 1.51-3.10) (p<.001). After adjusting for age, sex, intraoperative Foley catheter use, IPSS, revision surgery, previous spine surgery, single versus multiple levels, and lumbar location, the multivariable RR was 1.72 (95% CI: 1.22-2.41) (p=.002). CONCLUSIONS: Regardless of preoperative LUTS status, an initial first void of >4 hours after surgery is associated with a longer time to discharge among patients undergoing elective lumbar decompression surgery. Future studies are needed to determine if encouraging early postoperative voiding results in timely discharge and shorter length of stay.

A Review of the Microbial Production of Bioactive Natural Products and Biologics.

A variety of organisms, such as bacteria, fungi, and plants, produce secondary metabolites, also known as natural products. Natural products have been a prolific source and an inspiration for numerous medical agents with widely divergent chemical structures and biological activities, including antimicrobial, immunosuppressive, anticancer, and anti-inflammatory activities, many of which have been developed as treatments and have potential therapeutic applications for human diseases. Aside from natural products, the recent development of recombinant DNA technology has sparked the development of a wide array of biopharmaceutical products, such as recombinant proteins, offering significant advances in treating a broad spectrum of medical illnesses and conditions. Herein, we will introduce the structures and diverse biological activities of natural products and recombinant proteins that have been exploited as valuable molecules in medicine, agriculture and insect control. In addition, we will explore past and ongoing efforts along with achievements in the development of robust and promising microorganisms as cell factories to produce biologically active molecules. Furthermore, we will review multi-disciplinary and comprehensive engineering approaches directed at improving yields of microbial production of natural products and proteins and generating novel molecules. Throughout this article, we will suggest ways in which microbial-derived biologically active molecular entities and their analogs could continue to inspire the development of new therapeutic agents in academia and industry.