Local administration of vancomycin powder in orthopaedic fracture surgery: current practice and trends (2024)

Supplemental Digital Content is Available in the Text.

Abstract

1. Introduction

Surgical site infections (SSIs) in orthopaedic trauma are a significant problem that can have devastating consequences for patients and result in substantial costs to the health care system.^[1,2] Intravenous (IV) antibiotics have been demonstrated to be beneficial regarding infection prevention in orthopaedic trauma surgery.^[3,4] However, systemic administration of antibiotics may not be the best route of administration because concentration must be limited to avoid systemic toxicity. Therefore, local antibiotic application has gained traction in recent years because of several potential advantages over systemic antibiotic administration.

Direct antibiotic application to the surgical field enables the delivery of higher antibiotic concentrations.^[5] This route may ensure that the minimum inhibitory concentration for pathogens is surpassed, increasing infection prevention efficacy.^[5] Soft tissue injury secondary to both direct trauma and iatrogenic surgical injury may also limit the amount of IV antibiotics directly available at the surgical site, another problem circumvented by local antibiotic application.

Multiple studies have described the use of vancomycin powder to reduce SSIs. A bulk of this work has been accomplished in the area of spine surgery with data suggesting questionable efficacy of local antibiotic administration.^[5–18] Recently, the utility of local administration of vancomycin powder use in patients with fracture was investigated.^[19] Specifically, a multicenter, randomized controlled trial compared local antibiotics therapy with vancomycin powder versus no powder to prevent SSIs in patients with high-risk tibia fractures (VANCO Trial).^[20] The results of this trial found that locally administered vancomycin powder reduced gram-positive SSIs by 50% (relative risk: 0.49, 95% confidence interval [CI], 0.27–0.88, P = 0.02).^[20]

The routine local administration of vancomycin powder in orthopaedic surgery remains in question given that investigations have demonstrated both benefit and no benefit to local antibiotic use. While surgeons are motivated to lower SSI rates among patients with fracture, many surgeons may be hesitant to use local antibiotic powder because of antibiotic resistance concerns, the possibility of nephrotoxicity, or the lack of clear data to suggest a benefit of this practice. No previous work has described the rate at which antibiotic powder is being used in fracture surgery across multiple institutions. This study aimed to characterize the variability of vancomycin powder use in patients with fracture across 28 level-1 trauma centers. Specifically, we sought to determine whether there is variability in vancomycin powder use across different injury patterns, hospitals, and individual surgeons. We hypothesized that more severe soft tissue injuries and periarticular surgeries would be associated with increased use of locally administered vancomycin powder. Similarly, we hypothesized that there would be substantial variability in practice patterns between hospitals and surgeons.

2. Methods

3. Results

Prospective data were collected from 4941 fracture patients across 28 trauma centers from 448 different surgeons. Of the included patients, 3040 sustained closed fractures and 1901 had open fractures. Patient characteristics are summarized in Table 1.

Vancomycin powder was placed in 31.3% of surgical wounds (1547/4941). It was used more frequently in open fracture cases (738/1901, 38.8%) compared with closed fractures (809/3,040, 26.6%) (P < 0.001).

Increasing Gustilo grade did not seem to be associated with an increase in the rate of local administration of vancomycin powder at the fracture site (P = 0.11). The use of vancomycin powder in Gustilo Type I/II, IIIa, IIIb, and IIIc was 399/1046 (38.1%), 283/685 (41.3%), 36/111 (32.4%), and 17/33 (51.5%), respectively (Table 2). Conversely, a higher Tscherne grade (2 and 3) for closed fractures was associated with an increased odds of vancomycin powder use (odds ratio 1.70, 95% CI 1.16–2.49; P = 0.01).

The local administration of vancomycin powder also differed between high-risk and low-risk tibial fracture patterns (Table 3). It was used in 46.6% (157/337) of open tibial periarticular injuries (plateau/plafond) compared with 34.3% (186/542) of open tibial shaft fractures (P < 0.001). Similarly, in closed periarticular fractures of the tibia, it was used in 30.9% (161/521) of fractures compared with 25.6% (139/542) in closed tibial shaft fractures (P = 0.057).

There were a total of 2230 fractures that involved the tibia and fibula included in the analysis and seen in Supplemental Digital Content 1 (http://links.lww.com/OTAI/A59). There was a difference in the rate of antibiotic usage for open and closed fractures. Antibiotic powder was placed in 38.2% (362/948) of open fractures and 27.4% (351/1282) of closed fractures in this location.

In both open and closed fractures, the pelvis was the most likely fracture location to receive antibiotic powder with open injuries receiving antibiotics 88.9% (8/9) of the time and closed injuries 39.7% (123/310) (Supplemental Digital Content 1, http://links.lww.com/OTAI/A59).

There was significant variation in the frequency of local administration of vancomycin powder between hospitals. For example, within the two highest enrolling centers, one site used vancomycin powder in 79.2% of cases while the second site used it in 1.2% of cases (P < 0.001) (Supplemental Digital Content 2, http://links.lww.com/OTAI/A60). There was also a difference in vancomycin powder use among hospitals that did and did not participate in the VANCO Trial (Table 4). For those sites that participated in the VANCO Trial, vancomycin powder was placed in the surgical wound in 38.0% of cases (994/2613) compared with 23.8% (553/2328) of cases performed at sites which did not participate in the VANCO Trial (P < 0.001).

Most of the surgeons use vancomycin antibiotic powder in less than one-quarter of their cases in both open and closed fractures (Table 5). Conversely, only 21.2% and 8.8% of surgeons used vancomycin powder in 75% or more of their closed and open fractures cases, respectively.

4. Discussion

The burden of extremity fractures requiring surgical intervention is significant and continues to grow.^[24] Unfortunately, these surgical procedures are associated with an infection rate much higher than that of many elective orthopaedic procedures.^[1,2,22] Preventing SSI is an important goal of surgical intervention in extremity fractures, and opportunities for improvement in this area remain. The high infection rates have encouraged the growth of adjuvant treatments, such as topical antibiotic powder, to reduce the occurrence of SSI and the sequelae that results from both catastrophic and indolent infections.

Current evidence regarding the local administration of vancomycin powder in spine surgery has been mixed, while the most recent data of its use in high-risk extremity fractures is encouraging.^{[7–10,12–19]} Data from the VANCO trial suggest a 50% decrease in gram-positive SSI when vancomycin powder was placed in the surgical wounds during the operative management of tibial plateau and plafond fractures.^[20] Our current results demonstrate significant variability in the placement of antibiotic powder in surgical wounds, suggesting variable interpretation of these results.

There may be several reasons for this observation. The VANCO trial only reported the efficacy of powder placed into surgical wounds for tibial plateau and plafond fractures, and additional research in the orthopaedic trauma literature has not convincingly demonstrated a benefit to vancomycin powder use.^[23] This study demonstrates that vancomycin powder was used more frequently in these high-risk fracture patterns as compared with others; however even in these injuries, vancomycin powder was used just over 30% of the time. Furthermore, outside of periarticular tibia fractures and open injuries, it does not seem as though surgeons have expanded vancomycin powder's application. The reluctance to place antibiotic powder in the surgical wounds of other injuries may stem from the lack of available evidence. Most of the surgeons seem to be very discerning and selective in regard to which cases they use vancomycin powder. This is likely the result of a responsibility toward antibiotic stewardship that many surgeons may feel.

Previous work has also demonstrated an increased risk of gram-negative and polymicrobial infections when vancomycin powder is used.^[25] This concern may be another reason surgeons are reticent to place antibiotic powder in their surgical wounds. In the VANCO trial, a strong protective effect of vancomycin against gram-positive infections was reported as a secondary analysis. This is not surprising because vancomycin is only active against gram-positive organisms and therefore should not be expected to reduce SSI from other pathogens. Importantly, no reciprocal increase in the infection rate among gram-negative or polymicrobial organisms was seen in this trial, but this concern may still dissuade some surgeons from its use.

The decision to apply local antibiotics at the surgical site is further complicated by recommendations from the Centers for Disease Control and Prevention (CDC) and consensus guidelines from orthopaedic infection specialists. The CDC has recommended against local antibiotic use at the surgical incision, while at the 2018 International Consensus Meeting on Musculoskeletal Infections, the conclusion was drawn that there is “moderate” evidence to support the use of local antibiotics in contaminated wounds.^[26] These recommendations were based on prior best available evidence and may have had a significant impact on the decision to use these adjuncts.

The current variability in the adoption of local antibiotic application may also be related to concerns surrounding the potential to develop antibiotic-resistant organisms or nephrotoxicity. While these are important considerations, several studies suggest these problems are unlikely to occur and should have limited impact on the decision to use intrawound local antibiotics.^[27–29] To date, no clinical data have shown an increase in vancomycin-resistant organisms when local antibiotic powder is applied during surgery.

Additional explanations for the findings of this study may relate to the hesitancy of surgeons to adapt practice based on available data. There is a clear deficit in translating research results into clinical practice, the reasons for which are multifactorial but important to consider in the context of the present article.^[30] Lack of familiarity with research in this arena and an adverse reaction to adopting new practice may be at play.

Perhaps the most interesting finding from this study is the high discordance between vancomycin use at the two highest enrolling centers. This result underscores the current state of vancomycin use which is undoubtedly influenced by the mixed literature, personal opinion, and recommendations from governing bodies. This practice variability presents a clear opportunity to standardize care.

Although the data for the current analysis were collected prospectively, the trend of vancomycin powder use was investigated in a retrospective manner, and thus, the conclusion of this study should be interpreted with this limitation. Because the primary aim of the parent trials does not evaluate the efficacy or usage rates of vancomycin, this study is subject to issues of missing data or misclassification. In addition, the data presented herein provide usage rates over a relatively short period of 18 months. Finally, we do not report on the use of other antibiotic powder types or where the powder was specifically applied because these data were not available.

The results of the current analysis are strengthened by the large number of fractures, surgeons, and trauma centers included. While having data over a longer period of time may provide further insight, these data do provide the best available evidence describing current practice and ongoing hesitation for the widespread use of local administration of vancomycin powder for fracture management surgery.

Vancomycin powder has many properties that make it an excellent local delivery device. It is safe, cost-effective, does not take up substantial space, is widely available, easy to use, and has not been associated with significant wound drainage.^[11–18] Vancomycin is effective against common infectious agents in orthopaedic trauma including Staphylococcus aureus and other gram-positive bacteria.^[31–33] There is also minimal concern regarding local cytotoxicity leading to healing issues or other systemic toxicity side effects.^[18,34] Additional investigations regarding other types of antibiotic powder and the application of these adjuvants in all types of skeletal trauma may further clarify the role these treatments play in improving care and help in efforts to create consensus regarding their use.

5. Conclusion

Prophylactic intrawound vancomycin powder use remains controversial with varied support throughout the literature. This study demonstrates wide variability in its use across institutions, fracture types, and surgeons. This study highlights the lack of definitive data in this arena and represents an opportunity for practice standardization as more decisive research is published.

Appendix 1. The PREP-IT Investigators

Executive Committee: Gerard P. Slobogean (Principal Investigator, University of Maryland School of Medicine, Baltimore, MD); Sheila Sprague (Principal Investigator, McMaster University, Hamilton, ON); Jeffrey Wells (Patient Representative, Trauma Survivors Network, Falls Church, VA); Mohit Bhandari (Principal Investigator, McMaster University, Hamilton, ON)

Steering Committee: Gerard P. Slobogean (Co-Chair, University of Maryland School of Medicine, Baltimore, MD); Mohit Bhandari (Co-Chair, McMaster University, Hamilton, ON); Sheila Sprague (Principal Investigator, McMaster University, Hamilton, ON); Jean-Claude D'Alleyrand (Walter Reed National Military Medical Center, Bethesda, MD); Anthony D. Harris (University of Maryland School of Medicine, Baltimore, MD); Daniel C. Mullins (University of Maryland, Baltimore, MD); Lehana Thabane (McMaster University, Hamilton, ON); Jeffrey Wells (Trauma Survivors Network, Falls Church, VA); Amber Wood (Association of periOperative Registered Nurses, Denver, CO)

Adjudication Committee: Gregory J. Della Rocca (Chair, University of Missouri, Columbia, MO); Anthony D. Harris (University of Maryland School of Medicine, Baltimore, MD); Joan Hebden (University of Maryland School of Medicine, Baltimore, MD); Kyle J. Jeray (Greenville Health System, Greenville, SC); Lucas Marchand (University of Maryland, Baltimore, MD); Lyndsay M. O'Hara (University of Maryland School of Medicine, Baltimore, MD); Robert Zura (LSU Health, New Orleans, LA)

Data and Safety Monitoring Committee: Michael J. Gardner (Chair, Stanford University School of Medicine, Palo Alto, CA); Jenna Blasman (Patient Representative, Kitchener, ON); Jonah Davies (University of Washington, Seattle, WA); Stephen Liang (Washington University, St. Louis, MO); Monica Taljaard (Ottawa Hospital Research Institute, Ottawa, ON)

Research Methodology Core: PJ Devereaux (McMaster University, Hamilton, ON); Gordon H. Guyatt (McMaster University, Hamilton, ON); Lehana Thabane (McMaster University, Hamilton, ON); Diane Heels-Ansdell (McMaster University, Hamilton, ON)

Patient Centred Outcomes Core: Debra Marvel (Patient Representative, Baltimore, MD); Jana Palmer (Patient Representative, Baltimore, MD); Jeffrey Wells (Patient, Trauma Survivors Network, Falls Church, VA); Jeff Friedrich (Editor, Slate Magazine, Washington DC); Daniel C. Mullins (University of Maryland, Baltimore, MD); Nathan N. O'Hara (University of Maryland School of Medicine, Baltimore, MD); Ms. Frances Grissom (Trauma Survivor Network, Baltimore, MD)

Orthopaedic Surgery Core: Gregory J. Della Rocca (University of Missouri, Columbia, MO); I. Leah Gitajn (Dartmouth University, Hanover, NH); Kyle J. Jeray (Greenville Health System, Greenville, SC); Saam Morshed (San Francisco General Hospital, San Francisco, CA); Robert V. O'Toole (University of Maryland School of Medicine, Baltimore, MD); Bradley A. Petrisor (Hamilton Health Sciences, Hamilton, ON)

Operating Room Core: Megan Camara (R Adams Cowley Shock Trauma Center, Baltimore, MD); Franca Mossuto (Hamilton Health Sciences, Hamilton, ON)

Infectious Disease Core: Anthony D. Harris (University of Maryland School of Medicine, Baltimore, MD); Manjari G. Joshi (University of Maryland School of Medicine, Baltimore, MD)

Military Core: Jean-Claude D'Alleyrand (Walter Reed National Military Medical Center, Bethesda, MD); Justin Fowler (United States Army, USA); Jessica Rivera (San Antonio Military Medical Center, San Antonio, TX); Max Talbot (Canadian Armed Forces, Montreal, QC)

McMaster University Methods Center (Hamilton, ON): Sheila Sprague (Principal Investigator); Mohit Bhandari (Principal Investigator); Shannon Dodds (Research Coordinator); Alisha Garibaldi (Research Coordinator); Silvia Li (Research Coordinator); Uyen Nguyen (Research Coordinator); David Pogorzelski (Research Coordinator); Alejandra Rojas (Research Coordinator); Taryn Scott (Research Coordinator); Gina Del Fabbro (Research Assistant); Olivia Paige Szasz (Research Assistant); Diane Heels-Ansdell (Statistician); Paula McKay (Manager)

University of Maryland School of Medicine Administrative Center (Baltimore, MD): Gerard P. Slobogean (Principal Investigator); Nathan N. O'Hara (Manager); Andrea Howe (Project Manager); Joshua Rudnicki (Project Manager)*; Haley Demyanovich (Project Manager); Kelly Little (Financial Manager); Adam Boissonneault (Co-Investigator)

University of Maryland School of Pharmacy, The PATIENTS Program (Baltimore, MD): C. Daniel Mullins (Executive Director); Michelle Medeiros (Director of Research); Genevieve Polk (Assistant Director, Dissemination and Research); Eric Kettering (Senior Instructional Technology and Dissemination Specialist); Diamond Hale (Project Manager)*, Nirmen Mahal (Program Specialist)

Footnotes

Contributor Information

Sheila Sprague, Email: sprags@mcmaster.ca.

Nathan N. O'Hara, Email: hara@som.umaryland.edu.

Chuan Silvia Li, Email: silviali@mcmaster.ca.

Robert V. O'Toole, Email: rotoole@som.umaryland.edu.

Manjari Joshi, Email: MJoshi@som.umaryland.edu.

Darius Viskontas, Email: dariusviskontas@yahoo.ca.

Nicholas Romeo, Email: nromeo@metrohealth.org.

Robert A. Hymes, Email: Robert.Hymes@inova.org.

William T. Obremskey, Email: william.obremskey@vumc.org.

Thomas F. Higgins, Email: Thomas.Higgins@hsc.utah.edu.

Gorden D. Potter, Email: gdpotter@gmail.com.

Patrick F. Bergin, Email: PBergin@umc.edu.

Mark Gage, Email: mark.gage@duke.edu.

Joshua L. Gary, Email: joshua.l.gary@uth.tmc.edu.

Mohit Bhandari, Email: bhandam@mcmaster.ca.

Gerard P. Slobogean, Email: gslobogean@som.umaryland.edu.

References