Antibiotics for Prevention of Infection Following Orthognathic Surgery

Background

Orthognathic surgery describes a group of procedures whose main goal is to correct congenital and acquired dentofacial deformities, thereby improving speech, mastication, aesthetics, and symptoms of sleep apnea. These outcomes may be achieved by surgical repositioning of the maxilla and mandible using a variety of methods, the most common being Lefort I osteotomies, bilateral sagittal split osteotomies, intraoral vertical ramus osteotomies, and functional genioplasty. As access for these methods involves trans-oral approaches, these procedures are considered to be clean-contaminated surgeries due to the high intra-oral bacterial load. As a result, surgical site infection (SSI) rates are reported in the literature to range from 10-15% following orthognathic surgery. SSIs are associated with patient discomfort, prolonged hospital stays, increased morbidity, and increased cost to healthcare systems.

The use of peri-operative antibiotics has been demonstrated to significantly reduce the incidence of SSI following orthognathic surgery. However, there is continued debate regarding the most effective antibiotic protocol, and no consensus regarding timing or specific antibiotic has been achieved. A 1999 study conducted demonstrated a significant difference in SSI rates between patients treated with a single pre-operative dose of antibiotics compared to placebo. A systematic review in 2011 reported that there likely is a benefit to the use of post-operative antibiotics extended for 1-7 days versus a single pre-operative dose. Antibiotic course length was further evaluated in 2016, the investigators demonstrated a significant difference in effectiveness of 3-day courses of antibiotics vs 1-day. However, the number needed to treat was 10, due to which the conclusion was made that the potential harms may not outweigh the risks. Several studies conducted have failed to justify the prolonged use of post-operative antibiotics past 24 hours. As such, it seems that the common standard is the use of pre-operative antibiotics in conjunction with short-term (24-hours or less) post-operative antibiotic courses. To date, few studies have been conducted comparing SSI rates in patients receiving a single pre-operative antibiotic dose to those in patients receiving a pre-operative dose in conjunction with a 24-hour post-operative course. A trial conducted in 2017 found an SSI rate of 9.3% in patients receiving a single pre-operative antibiotic dose compared to 2.6% in patients receiving a pre-operative dose in conjunction with a 24-hour post-operative course, however, the results were not statistically significant. The group attributed this result to an inadequate sample size. In a 2013 study, researchers demonstrated a significant difference in SSI rate between patients receiving a single dose of pre-operative intravenous (IV) Amoxicillin compared to those receiving an additional two doses post-operatively. This, however, is in contrast to several studies which failed to demonstrate a benefit of post-operative antibiotics compared to single pre-operative doses. Overall, there seems to be no robust data supporting the use of post-operative antibiotics following orthognathic surgery. With limited data supporting prolonged antibiotic use, one must question if there are any benefits to offset the risks of antibiotic over-use, which include medication adverse effects, increased healthcare costs, and most importantly, antibiotic resistance. The World Health Organization (WHO) published guidelines recommend no prolongation of antibiotic administration post-operatively following orthognathic surgery, as it was deemed that the low quality evidence supporting its use did not outweigh the potential harm of antimicrobial resistance.

In addition to course length and timing, the choice of antibiotic also plays a major role in SSI rate following orthognathic surgery. The most commonly reported antibiotics used in clinical trials appear to be penicillin, amoxicillin, cefazolin, clindamycin, and ampicillin. A systematic review was conducted in 2019, which reported improved efficacy of cefazolin compared to clindamycin and penicillin in preventing post-orthognathic surgery SSIs.

The most common bacterial isolates from odontogenic infections are Viridans group streptococci, Peptostreptococcus, Prevotella, Fusobacterium, and Bacteroides. Overall, cefazolin has high susceptibility rates against the most common oral bacteria. Cefazolin shows excellent susceptibility rates against Viridans group streptococci, Peptostresptococcus, Prevotella, and Fusobacterium.

The purpose of this study is thus to compare the efficacy of a single pre-operative dose vs a short-term (24-hour) course of cefazolin in preventing SSIs following orthognathic surgery. To our knowledge, no such study has been completed to date. In particular, due to the fact that the vast majority of SSIs following orthognathic surgery occur in the mandible, the investigators will be considering orthognathic surgical procedures including bilateral sagittal split osteotomies, with and without concurrent osteotomies.

Our department's current standardized protocol at the QEII Health Sciences Center for perioperative antibiotic administration is a single pre-operative dose of 2g of cefazolin IV, followed by further doses every 8 hours for a total of 24 hours (3 doses). Here the investigators propose a plan for a prospective, randomized controlled trial comparing this standard regimen to one utilizing a single pre-operative dose of 2g IV cefazolin.

Purpose

To determine the effectiveness of single pre-operative dose vs 24-hour peri-operative IV ampicillin and IV cefazolin in preventing surgical site infection following orthognathic surgery, in particular following bilateral sagittal split osteotomy. The primary outcome of this study is the rate of development of surgical site infection following the described antibiotic protocols. Secondary outcomes are incidence of medication adverse effects, SSI rates in relation to age, sex, smoking status, type of surgery, length of surgery, surgical complications, and medication adverse effects.

Study Design

The aim of this study to conduct a prospective, randomized controlled trial evaluating patients undergoing orthognathic surgery including bilateral sagittal split osteotomies with or without concomitant maxillary and/or chin surgery, with or without wisdom teeth extraction.

The investigators plan to enrol roughly 400 participants in this study. Current literature on antibiotic prophylaxis for orthognathic surgery utilized sample sizes ranging between 30 - 171 participants, with individual group sizes ranging from 14 - 86 participants. Sample size calculation was done based on a study in 2010, comparing single pre-operative dose vs 24-hour peri-operative IV ampicillin. Using a significance level of 5% and a power of 80%, the required sample size was found to be 396 participants when comparing two groups, or 198 participants per group. As such, the investigators will aim to enrol 400 participants. The QEII department of Oral and Maxillofacial Surgery completes roughly 300 orthognathic surgeries per year. The investigators thus anticipate recruitment will continue for 2-3 years. Once data for 30 participants in each group has been gathered, the investigators will analyze this data as a pilot study to re-calculate the sample size needed.

Methodology

All patients meeting the inclusion criteria will be offered participation, and informed consent will be obtained at the pre-operative appointment following surgical consent. The patients will then be assigned a study number and randomly allocated to one of two groups as follows:

A) Single pre-operative dose of 2g IV Cefazolin B) Single pre-operative dose of 2g IV Cefazolin followed by a 24-hour course of 2g IV Cefazolin every 8 hours

Informed consent will be obtained at each participant's pre-operative assessment in the days leading up to the procedure. The discussion will be carried out by the resident conducting the pre-operative assessment, who will have previously completed a training session clarifying the protocol and all aspects of the consent form. Following the informed consent discussion, each new participant will be assigned a study number and asked to select an envelope from a jar which has been sufficiently mixed. Group A or B will be assigned to each study number. Group designations will correspond to a specific protocol, as listed above. The participant's group designation will be documented on the pre-operative assessment sheet. At the time of surgery, the resident completing the post-operative orders will order the corresponding protocol. All orthognathic surgical procedures will then be completed using the standard protocol.

All patients will receive the same post-operative instructions and will be discharged with 0.12% chlorhexidine mouth rinse to be used for 2 weeks following discharge. Patients will return for follow-up at 2 weeks, 4 weeks, and 6 weeks following discharge. Surgical site infection diagnosis will be made according to the CDC criteria and will be reported as either superficial, deep, or organ/space infections. Date of occurrence, location of infection, and treatment provided will be recorded on a standard form provided to each surgeon. Surgeons will be trained prior to commencement of the study regarding CDC criteria and reporting.

For each patient, the osteotomies completed will be documented, along with age, gender, smoking status, length of procedure, and complications. Complications including medication adverse reaction (allergy, toxicity, side effects), surgical complications, and any other significant complications related to the medications or deemed to be relevant to infection risk will be documented. Patients experiencing significant adverse reactions will be instructed to immediately discontinue the causative agent. Data from such cases will be utilized to analyze the rates of adverse effects within each antibiotic regimen. All members of the research team will have access to documentation regarding adverse reactions and will be notified of such events. Significant rates of adverse effects, or serious reactions will prompt a meeting to investigate and discuss further action. Semi-annual reports on adverse events will be prepared and discussed with the research team. The principal investigator will continuously monitor emerging data regarding the efficacy and safety of the agents used in the study. Should any significant issues arise, including unexpected events, serious adverse events, emergent data negatively affecting the safety of the study, privacy breaches, or significant changes to the protocol, this will be reported to the REB. In addition, any data present regarding similar events will be reviewed, and changes to avoid similar situations will be proposed. Should an ongoing concern arise, other participants will be notified, and consent forms will be modified.

At the end of the 6-week data collection period, participant data will be de-identified, and will be designated only by study number. Data from each appointment will initially be in paper format on standard forms. At the end of the 6-week data collection period, data will be converted into electronic format on an excel spreadsheet in de-identified form. The electronic data will be stored via an NSHA computer on the CDHA OMS drive. Paper data will be stored in a filing cabinet in a locked office.

Following data analysis, once data is ready for destruction, 15 years following the completion of the study, the Director of Health Information Services will be contacted, and data will be destroyed as per Nova Scotia Health procedures in a manner that does not allow information to be recognizable, retrievable, readable, or reconstructed. Physical data will be shredded, and electronic data will be deleted with further emptying of "recycle" to facilitate

• Rate of Medication Adverse Effects [Срок оценки: 6 weeks]
• Impact of sex on surgical site infection rate [Срок оценки: 6 weeks]
• Impact of smoking status on surgical site infection rate [Срок оценки: 6 weeks]
• Impact of surgery type on surgical site infection rate [Срок оценки: 6 weeks]
• Impact of surgical complications on surgical site infection rate [Срок оценки: 6 weeks]
• Impact of medication adverse effects on surgical site infection rate [Срок оценки: 6 weeks]
• Impact of surgery length on surgical site infection rate [Срок оценки: 6 weeks]