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Prolonged prophylactic antibiotic use following megaprosthesis surgery may reduce periprosthetic infection
⁎Corresponding author: Vincent Y. Ng. vng@som.umaryland.edu
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Received: ,
Accepted: ,
This article was originally published by Reed Elsevier India Pvt. Ltd. and was migrated to Scientific Scholar after the change of Publisher.
Abstract
Abstract
Megaprostheses provide a reconstructive option for patients with bone loss after musculoskeletal tumor resection. However, the postoperative surgical site infection (SSI) risk is significant. This study aims to evaluate outcomes of extended postoperative antibiotic regimens in patients after megaprosthesis surgery and gather insight into strategies to minimize SSI.
This retrospective cohort study evaluated patients who underwent megaprosthesis surgery by a single surgeon at a single center from 2014 to 2022. Patient demographics, comorbidities, cancer treatment details, and antibiotic regimens were collected. Excluded were patients with less than 1 year of follow-up, active infection at time of surgery, non-healing wounds unrelated to SSI, and preoperative antibiotic regimens secondary to being immunocompromised. Measures of interest included the development of SSI within 1 year of surgery and development of antibiotic-related complications.
Included were 49 patients, with a mean age of 61.2 ± 2.0 years and a mean BMI of 29.4 ± 7.0. The mean drain duration was 6.5 days (standard deviation [SD], 6.9 days), and the mean intravenous antibiotic administration duration was 6.4 days (SD, 6.9 days). The median time to drain removal was five days, and the median time for intravenous antibiotic cessation was five days. The mean total antibiotic administration duration (intravenous and oral) was 25.4 days (SD, 13.4 days). Only 1 patient in the included cohort (2.04 %) developed an SSI requiring operative intervention. No other patient within the cohort experienced an antibiotic-related complication.
This study suggests that the site's current protocol for managing post-megaprosthesis antibiotic prophylaxis based on drain duration and incision healing status has resulted in a low rate of SSI and antibiotic-related complications. Further research is needed to validate these findings and gain additional insights into managing antibiotic prophylaxis after megaprosthesis surgery.
1 Introduction
Orthopaedic megaprostheses are complex, modular, endoprosthetic implants that provide an ideal reconstructive option in patients with substantial bone loss. Megaprostheses are frequently indicated and most commonly used for limb salvage in musculoskeletal tumors requiring wide excisional margins of bone. However, the risk of postoperative surgical site infection (SSI) is significant following megaprosthesis surgery,1–4 with a large systematic review from Racano et al. revealing an approximate infection rate of 10 % in lower extremity megaprostheses (95 % confidence interval, 8 %–11 %).5 Prior literature has shown variable rates of megaprosthesis infection based on anatomic location, with proximal tibia replacement infection rates as high as 25.8 %,6 7.3 % in proximal femur replacement,7 17 % in distal femur replacement,8 and up to a 25 % in total femoral replacement.9 Jeys et al. have shown that radiation exposure is an added risk factor, reporting an infection rate of 9.8 % in non-irradiated patients versus rates of 20.7 % and 35.3 % in patients receiving pre- and postoperative radiation, respectively.10 As such, antibiotic prophylaxis is critical to mitigate postoperative infection among patients requiring megaprostheses.12
Proper antibiotic stewardship is an important consideration to limit potential antibiotic-related complications, chiefly Clostridioides difficile (C. diff) related colitis. The PARITY study—a large, multicenter, blinded, randomized control trial—sought to compare the efficacy of a 5-day versus a 1-day regimen of an intravenous cephalosporin among patients with lower extremity bone tumors undergoing megaprosthesis reconstruction. The investigators found no significant difference in SSI between the treatment arms but noted a significantly greater percentage of antibiotic-related complications in the 5-day study arm.11 These results highlight an existing need for a safe, effective regimen of antibiotic prophylaxis that limits additional patient morbidity.
The current study aims to evaluate the efficacy of extended prophylactic antibiotics postoperatively to identify trends in antibiotic usage and outcomes, including rates of SSI and antibiotic-related complications, from a single-center, single-surgeon subset of patients having undergone megaprosthesis surgery. Furthermore, this study aims to gather insights regarding ideal elements within an antibiotic prophylaxis strategy that could help minimize complications and improve patient outcomes following these complex reconstructive operations.
2 Methods
2.1 Study design
This retrospective cohort study reviewed the postoperative prophylactic antibiotic usage trends and outcomes for all patients treated at a single center by a single surgeon from 2014 to 2022. Inclusion criteria were patients who underwent upper or lower extremity megaprosthesis surgery and had a minimum of 1 year of follow-up data available in the medical record, or who died between 6 and 12 months after surgery. Exclusion criteria were patients who died within 6 months of surgery, patients who had an active infection at the time of megaprosthesis surgery (i.e., the implant was used as part of a functional antibiotic spacer), patients who had pre-existing long-term antibiotic prophylaxis regimens due to a chronic immunocompromised state, and patients who had early and ongoing failure of wound coverage due to skin necrosis (avascularity) and/or plastic surgery complications. Of note, the reasons for mortality of patients who died within 6 months of surgery were confirmed to be related to cancer progression or medical complications of surgery (i.e., bone-cement implantation syndrome) rather than any SSI sequellae. External medical records, including regional shared electronic health records and obituaries in the public record, were accessed (up to June 2023) to obtain adequate follow-up information. The site's Institutional Review Board reviewed the study and deemed it exempt.
2.2 Data collection
Eligible megaprostheses consisted of proximal tibial replacement (PTR), distal femoral replacement (DFR), proximal femoral replacement (PFR), total femur replacement (TFR), and proximal humeral replacement (PHR). Patient medical records were reviewed to abstract patient demographics, comorbidities, cancer treatment details, and employed antibiotic regimens. Patient outcome data, including antibiotic-related complications and mortality, were similarly recorded.
2.3 Clinical details
In all megaprosthesis surgeries performed by the study surgeon, a single dose of intravenous antibiotics was administered within 1 h before the initial skin incision. Skin preparation in the operating room consisted of 70 % isopropyl alcohol rub followed by ChloraPrep™ (2 % chlorhexidine gluconate and 70 % isopropyl alcohol). An additional application of DuraPrep™ (0.7 % iodine povacrylex and 74 % isopropyl alcohol) followed by the antimicrobial surgical drape adhesive Ioban™ (3M Company, Saint Paul, MN) was used at the site of the incision. Intraoperatively, all personnel involved with surgical care wore “space suits,” which are highly protective closed-air helmet systems donned in addition to the surgical gown. Gloves were changed every 30–45 min and after handling bone cement. PALACOS® or Refobacin® (Zimmer-Biomet, Warsaw, IN) bone cement with gentamicin or Simplex™ (Stryker Corporation, Kalamazoo, MI) bone cement with tobramycin was used for stem fixation. Drain tubes were secured at the skin with 2-0 nylon sutures and the site where the tubing emerges from the skin sealed with gauze and the tubing sandwiched between two Tegaderm™ (3M, St Paul, MN) dressings as a “mesentery”. Patients were continued on prophylactic intravenous antibiotics postoperatively beyond 24 h and were converted to oral antibiotics when all drains were removed or when the patient was discharged. The drains were removed prior to discharge from the hospital.
The perioperative intravenous antibiotic of choice was cefazolin. Intravenous vancomycin was added if the patient was colonized or had a history of methicillin-resistant Staphylococcus aureus. Vancomycin was used instead of cefazolin if there was a contraindication to cefazolin. Doxycycline 100 mg BID was the oral regimen of choice. Oral antibiotics were continued at least until the surgical incision was deemed fully healed by the study surgeon.
2.4 Population filtering
Of the 73 patients with megaprostheses reviewed, 24 were excluded. Four patients had inadequate follow-up data available for study inclusion, following searches in the institutional and external records. Thirteen patients experienced mortality within 6 months of the megaprosthesis surgery, all deemed to be related to causes other than infectious sequelae from surgery. Four patients with an active infection received a megaprosthesis as part of a functional antibiotic spacer and, thus, were excluded. Two patients were excluded due to non-healing wounds at 1 year, unrelated to infection. These non-healing wounds were described as frank skin necrosis or failure of soft tissue coverage due to poor perfusion rather than a true primary prosthetic or deep space infection. One patient was excluded due to preoperative long-term antibiotic use secondary to an immunocompromised state.
2.5 Study measures
The primary measure of interest was the development of an SSI around the megaprosthesis within 1 year of surgery. Surgical site infection was defined as any complication requiring irrigation and debridement or exchange or removal of components. The secondary measures of interest included the development of antibiotic-related complications, such as C. diff or any adverse clinical reaction to the prescribed antibiotic regimen that required cessation of the offending antibiotic.
3 Results
The final analysis included 49 patients, with a mean age of 61.2 ± 21.0 years and a mean BMI of 29.4 ± 7.0. Additional demographic characteristics of the included group are detailed in Table 1. Details on surgical procedure type and location are detailed in Table 2. Sixteen patients underwent surgery as an isolated treatment, while 30 patients underwent preoperative or postoperative chemotherapy or radiation therapy (Table 3).
| Sex | N | % of Total |
| Male | 23 | 46.9 % |
| Female | 26 | 53.1 % |
| Ethnicity | ||
| Native American | 1 | 2.0 % |
| Asian | 1 | 2.0 % |
| Black | 15 | 30.6 % |
| Hispanic | 3 | 6.1 % |
| White | 28 | 57.1 % |
| Other | 1 | 2.0 % |
| Diabetes Status | ||
| Yes | 9 | 18.8 % |
| No | 39 | 81.3 % |
| Smoking Status | ||
| Yes | 5 | 10.9 % |
| No | 41 | 89.1 % |
| Immunocompromised Status | ||
| Yes | 11 | 23.4 % |
| No | 36 | 76.6 % |
| Procedure Type1 | N | % of Total |
| PTR | 3 | 6.1 % |
| DFR | 19 | 38.8 % |
| PFR | 17 | 34.7 % |
| TFR | 1 | 2.0 % |
| PHR | 5 | 10.2 % |
| Combined DFR/PTR | 4 | 8.2 % |
| Treatment Strategy | N | % of Total |
| Surgery only | 16 | 34.8 % |
| Multimodal | 30 | 63.8 % |
| Multimodal Treatment Strategies a | ||
| Preoperative chemotherapy | 14 | |
| Preoperative radiation therapy | 8 | |
| Postoperative chemotherapy | 28 | |
| Postoperative radiation therapy | 15 | |
| Both pre- and postoperative chemotherapy | 14 | |
| Both pre- and postoperative radiation therapy | 4 | |
Surgical drains were kept in place for a mean of 6.5 days (standard deviation [SD], 6.9 days), and intravenous antibiotics were continued for a mean of 6.4 days (SD, 6.9 days). The median time to drain removal was 5 days, and the median time to intravenous antibiotic cessation was 5 days. The mean number of days of postoperative intravenous and oral antibiotics was 25.4 days (SD, 13.4 days), as described in Table 4.
| Local Antibiotics (including Vancomycin in Cement) | N | % of Total |
| Yes | 16 | 34.8 % |
| No | 30 | 63.8 % |
| Days of Drain Placement | Standard Deviation | |
| Mean | 6.5 | 6.9 |
| Median | 5 | |
| Days of Antibiotic Prophylaxis (I ntravenous Only) | Standard Deviation | |
| Mean | 6.4 | 6.9 |
| Median | 5 | |
| Days of Antibiotic Prophylaxis (Combined I ntravenous & Oral) | Standard Deviation | |
| Mean | 25.3 | 13.4 |
| Median | 25.5 |
Within the study cohort, only 1 patient of the included 49 (2.0 %) developed an SSI. This patient was a 19-year-old female with a BMI of 34.3 who underwent a DFR for osteosarcoma. She had received 17 days of prophylactic antibiotics postoperatively. She ultimately underwent removal of hardware, irrigation and debridement, and antibiotic spacer placement 5 months postoperatively. Her infection resolved successfully with intravenous antibiotics and a standard 2-stage exchange. No patient within the cohort experienced an antibiotic-related complication.
4 Discussion
Appropriate antibiotic prophylaxis is critical to mitigate postoperative infection among patients requiring megaprostheses.12 Within the current study cohort, only 1 patient of the included 49 developed an SSI, for an overall infection rate of 2.0 %. This is substantially lower than the rates reported in the literature.1,5–9,11 Furthermore, no patient in the cohort experienced a documented antibiotic-related complication, and no patients were diagnosed with C. diff in the study follow-up period. In comparison, the PARITY study reported C. diff-related colitis in 3.8 % of patients undergoing a 5-day prophylactic antibiotic regimen, and 1.3 % for a 1-day antibiotic regimen.11 These comparative findings are encouraging, as the relative success of our cohort may provide insight into mitigating SSI after complex megaprosthesis reconstructions.
We also found similar mean and median times to drain removal and intravenous antibiotic cessation. Notably, the mean drain duration was 6.5 days with the mean intravenous antibiotics length at 6.4 days, while the median drain and intravenous antibiotic duration was 5 days. A study by Byers et al. reported a comparable mean drain duration of 4 days,12 while another study by Liu et al. reported a median drain duration of 7 days.13 A third study also had a mean drain duration of 4 days but found that the risk of postoperative wound complications increased with increased lengths of drain duration. This study suggested early drain removal postoperatively.14 In our experience, drains are important to reduce the risk of incisional drainage and failure of incisional healing, but drains also can be a theoretical route for microbial infection. Our study's concordance between intravenous antibiotic use and drain duration may contribute to the overall low infection rate. Successful closure and ultimate healing of the overlying soft tissue envelope are critical components of avoiding periprosthetic infection. The use of antibiotics throughout this vulnerable phase of healing may reduce the risk of infection. It should be noted however that infection obviously will eventually set in despite antibiotics if there is soft tissue necrosis or failure of soft tissue flaps/grafts and macroscopic exposure or communication of the implant to the external environment.
These results, albeit retrospective, support the use of postoperative prophylactic antibiotics in concordance with drain duration and incision healing. The proposed protocol is described as follows: intravenous antibiotics (continuation of preoperative antibiotic) until the drain is removed. Drains are removed at the surgeon's discretion, generally within 5 days postoperatively, and always before discharge from the hospital. Patients are switched to an oral antibiotic (e.g., doxycycline 100 mg BID) once the drains are removed and continued until the incisions are completely healed, generally at about 2–3 weeks postoperatively.
There are limitations to our study. This is a retrospective chart review. It is subject to the inherent limitations of this study design. This study reflects the experience of a single center and single surgeon, which limits the study's generalizability. Furthermore, as the event rate was low and the overwhelming majority of patients were treated with prolonged antibiotics, comparative analysis for SSI risk factors could not be adequately evaluated. Nevertheless, the infection rate and the results of this study compare favorably to the published historical literature.
5 Conclusions
In a single surgeon series of megaprostheses, administration of intravenous antibiotics and placement of a surgical drain for approximately 5 days postoperatively followed by an additional 1–2 week course of oral antibiotics demonstrated a very low rate of SSI and no instances of antibiotic-related complications. A comparative group that did not receive prolonged antibiotics was not available so causation could not be established. Future studies with larger patient cohorts and multiple surgeons and institutions are needed to validate the efficacy of this prophylactic strategy and gain additional insights.
Funding
This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors.
Patient guardian consent
This study was deemed as exempt by the University of Maryland, Baltimore Institutional Review Board: HP-00101029, and thus did not require written or verbal consent.
CRediT authorship contribution statement
Ali Aneizi: Conceptualization, Data curation, Formal analysis, Methodology, Writing – original draft, Writing – review & editing. Murali Kovvur: Data curation, Methodology, Project administration, Writing – original draft. Matthew Chrencik: Data curation, Investigation, Methodology, Validation. Vincent Y. Ng: Conceptualization, Formal analysis, Investigation, Methodology, Supervision, Validation, Writing – review & editing.
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