Healthcare-acquired infections (HAIs) have received significant attention in recent years. Surgical site infections (SSI) are among the most common HAIs and result in significant morbidity, mortality, and health care costs. Use of prophylactic antibiotics directed against skin organisms is a standard of care process for preventing SSI. An increasing prevalence of methicillin-resistant S. aureus (MRSA) carriage has complicated the traditional approach of using a beta-lactam for antimicrobial prophylaxis because it does not work against MRSA. In patients known to have MRSA, vancomycin is recommended. However, it is not clear whether vancomycin should be used alone or in addition to a beta-lactam drug. Thus, there are critical gaps in knowledge to fully inform policies and best practices for SSI prevention.
This proposal will provide an evidence-based and standardized approach to prevention of SSI in veterans. The main aims of this proposal include: 1) Conduct a retrospective cohort study to determine the risk of SSI in MRSA positive and MRSA negative patients undergoing surgical procedures, stratified by surgical prophylaxis regimen and other risk factors such as age, type of surgery, and ASA classification to test the hypothesis that preoperative nasal MRSA status is an effect modifier of the association between receipt of vancomycin surgical prophylaxis and SSI risk; 2) Evaluate the comparative effectiveness of vancomycin alone vs. vancomycin plus a beta-lactam as surgical prophylaxis in prevention of SSI to test the hypothesis that the combination regimen is more effective in preventing SSI than vancomycin alone; and 3) Evaluate the comparative and cost-effectiveness of pre-operative screening followed by directed vancomycin surgical prophylaxis vs. universal vancomycin for high risk surgeries to test the hypothesis that the cost efficiency of screening-directed surgical prophylaxis compared to universal vancomycin surgical prophylaxis depends on the MRSA prevalence.
We will utilize existing national VA databases to conduct a retrospective cohort study of patients undergoing surgeries that are assessed for specific performance measures by the Surgical Care Improvement Project's External Peer Review Program (EPRP). We will use regression and Markov modeling to evaluate comparative effectiveness and cost-effectiveness of MRSA-screening directed surgical prophylaxis approaches and regimens.
All databases and approvals for use were obtained. The study cohort has been created and consists of 94,133 unique surgeries with a discharge date between FY 2009-2013. The surgical procedures include cardiac, orthopedic implants (knee and hip), vascular, and other.
In the 70,101 procedures reviewed by VASQIP for SSI and receiving either a beta-lactam alone, vancomycin alone, or a combination, there were 2,466 (3.5%) SSI. Among cardiac surgery patients, combination prophylaxis was associated with a lower incidence of SSI (66/6953, 0.95%) than single-agent prophylaxis (190/12834, 1.48%); adjusted RR 0.61, 95% CI, 0.46, 0.83. After controlling for other factors, there was no association between reduced incidence of SSI and receipt of combination antimicrobial prophylaxis for the other types of surgical procedures evaluated, including total joint replacement procedures.
in cardiac surgery patients, the number needed to treat to prevent one SSI among MRSA-colonized was 53, compared to 176 in MRSA negative patients. The number needed to harm to cause one episode of Stage 3 (serious) AKI in cardiac surgery patients receiving combination therapy was 167. There was no change in risk of C. difficile infection.
In separate analyses, combination therapy also was found to increase AKI risk without a decrease in SSI in patients undergoing hysterectomy. In addition, screening and treatment of asymptomatic bacteriuria was not found to be of benefit in preventing postoperative SSI or UTI.
In this study, combination prophylaxis was associated with both benefits (reduction in SSIs following cardiac surgical procedures) and harms (increase in postoperative AKI). In cardiac surgery patients, the difference in risk-benefit profile by MRSA status suggests that MRSA-screening directed prophylaxis may optimize benefits while minimizing harms in this selected population. The study has highlighted some of the unintended consequences of broadened antimicrobial prophylaxis regimens.
The main findings were published in a high impact journal (impact factor 13) and were featured in New England Journal Watch for Informing Practice, August 2017
- Strymish JM, O' Brien W, Itani K, Gupta K, Branch-Elliman W. What Is the Primary Driver of Preoperative Vancomycin Use? It's Not Methicillin-resistant Staphylococcus aureus-or Allergy. Clinical infectious diseases : an official publication of the Infectious Diseases Society of America. 2020 Dec 17; 71(10):2732-2735.
- Gupta K, O'Brien W, Gallegos-Salazar J, Strymish J, Branch-Elliman W. How Testing Drives Treatment in Asymptomatic Patients: Level of Pyuria Directly Predicts Probability of Antimicrobial Prescribing. Clinical infectious diseases : an official publication of the Infectious Diseases Society of America. 2020 Jul 27; 71(3):614-621.
- Branch-Elliman W, O'Brien W, Strymish J, Itani K, Wyatt C, Gupta K. Association of Duration and Type of Surgical Prophylaxis With Antimicrobial-Associated Adverse Events. JAMA surgery. 2019 Jul 1; 154(7):590-598.
- Gallegos Salazar J, O'Brien W, Strymish JM, Itani K, Branch-Elliman W, Gupta K. Association of Screening and Treatment for Preoperative Asymptomatic Bacteriuria With Postoperative Outcomes Among US Veterans. JAMA surgery. 2019 Mar 1; 154(3):241-248.
- Pindyck T, Gupta K, Strymish J, Itani KM, Carter ME, Suo Y, Bessesen MT, Topkoff J, Steele AS, Barón AE, Gundlapalli AV, Branch-Elliman W. Validation of an electronic tool for flagging surgical site infections based on clinical practice patterns for triaging surveillance: Operational successes and barriers. American journal of infection control. 2018 Feb 1; 46(2):186-190.
- Branch-Elliman W, Ripollone JE, O'Brien WJ, Itani KMF, Schweizer ML, Perencevich E, Strymish J, Gupta K. Risk of surgical site infection, acute kidney injury, and Clostridium difficile infection following antibiotic prophylaxis with vancomycin plus a beta-lactam versus either drug alone: A national propensity-score-adjusted retrospective cohort study. PLoS Medicine. 2017 Jul 1; 14(7):e1002340.
- Branch-Elliman W, Ripollone J, O W, Itani K, Strymish J, Gupta K. Combination antimicrobial prophylaxis for hysterectomy: harm without the benefit? American journal of obstetrics and gynecology. 2018 May 1; 218(5):536-537.
Treatment - Comparative Effectiveness