Perioperative Systemic Antibiotics in Open Reduction and Internal Fixation (ORIF) of Maxillofacial Fractures: A Systematic Review and Meta-Analysis

Perioperative Systemic Antibiotics in Open Reduction and Internal Fixation (ORIF) of Maxillofacial Fractures: A Systematic Review and Meta-Analysis | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Systematic Review Perioperative Systemic Antibiotics in Open Reduction and Internal Fixation (ORIF) of Maxillofacial Fractures: A Systematic Review and Meta-Analysis Chandrashekhar Chattopadhyay, Vikas Deo, Charu Chouhan, Mamta Patel, and 3 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-7544028/v1 This work is licensed under a CC BY 4.0 License Status: Posted Version 1 posted You are reading this latest preprint version Abstract Background: Maxillofacial fractures, commonly caused by road traffic accidents or interpersonal violence, represent a substantial global health challenge. Surgical management via open reduction and internal fixation (ORIF) is standard but is associated with risks of surgical site infections (SSIs) due to the polymicrobial oral environment. Perioperative systemic antibiotic prophylaxis (PAP) is routinely used, but debates persist on its necessity, duration, and role in antimicrobial resistance (AMR). Objective: This systematic review and meta-analysis assess the efficacy and safety of systemic PAP in preventing SSIs following ORIF for maxillofacial fractures, emphasizing infection reduction versus no prophylaxis and short (≤24 hours) versus extended (>24 hours) regimens. Methods: Adhering to PRISMA guidelines, searches were performed in PubMed, Embase, Cochrane CENTRAL, Scopus, and Web of Science up to August 31, 2025. Inclusion criteria covered RCTs and cohort studies in adults undergoing ORIF, comparing PAP regimens or versus no prophylaxis. Primary outcome was SSI incidence; secondary outcomes included osteomyelitis and AMR. Risk ratios (RRs) were pooled using random-effects meta-analysis, with subgroup analyses by fracture site. Results: From 1,856 records, 16 verified studies (8 RCTs, 8 cohorts; n=3,285) were included. Perioperative antibiotics reduced SSI risk compared to no prophylaxis (RR 0.48, 95% CI 0.32–0.72; p=0.0004; I²=52%). Mandibular fractures showed pronounced benefits (RR 0.41, 95% CI 0.25–0.67), while midface results were inconclusive. Extended prophylaxis (>24 hours) provided no additional advantage over short regimens (RR 1.0; I²<25%). Infection rates ranged 3–12%, with limited data on AMR. Conclusions: Systemic PAP effectively lowers SSI risk in maxillofacial ORIF, particularly for mandibular fractures. Limiting to a preoperative dose discontinued within 24 hours is sufficient, promoting stewardship by reducing AMR and costs. Further RCTs are required for site-specific protocols. Dentistry Keywords: Maxillofacial fractures ORIF surgical site infection antibiotic prophylaxis antimicrobial stewardship systematic review meta-analysis. Figures Figure 1 Figure 2 Figure 3 Introduction Maxillofacial fractures involve injuries to the mandible, midface (zygomatic, orbital, maxillary), and upper facial regions, primarily resulting from road traffic accidents, assaults, or falls (1). These fractures impose a notable public health burden, with incidence rates of 10–50 per 100,000 annually, elevated in low- and middle-income countries due to underdeveloped trauma care (1). Open reduction and internal fixation (ORIF) serve as the standard surgical intervention, enabling accurate anatomical alignment, expedited recovery, and enhanced functional and aesthetic results (2). Nonetheless, ORIF is prone to postoperative complications, notably surgical site infections (SSIs), which may evolve into superficial infections, abscesses, hardware complications, or chronic osteomyelitis (3,4). Untreated or poorly managed cases exhibit infection rates of 5–20%, escalating healthcare costs via extended hospitalizations, reoperations, and prolonged antimicrobial treatments (3,5). The anatomical proximity to the polymicrobial oral cavity, nasal sinuses, and salivary glands exacerbates risks, as flora including Streptococcus spp., Staphylococcus aureus, and anaerobes can contaminate sites (3). Perioperative systemic antibiotic prophylaxis (PAP) is employed to attain therapeutic concentrations during surgery, curtailing bacterial colonization (4). Conventional regimens favour broad-spectrum agents such as cephalosporins or amoxicillin-clavulanate, initiated preoperatively and frequently prolonged postoperatively (5). However, variability persists in guidelines regarding timing, duration, and selection. Prior systematic reviews indicate unequivocal benefits for mandibular fractures owing to intraoral exposure and vascular compromise, yet efficacy in midface fractures is debated (2,4,5). The escalating global AMR crisis, fueled by antibiotic overuse, necessitates revaluation of extended regimens, which may promote resistance without superior outcomes (6,7). Recent studies post-2020 offer insights into short-course prophylaxis and site-specific effects, highlighting the need for updated evidence (8,9). This systematic review and meta-analysis synthesize current evidence on PAP efficacy in maxillofacial ORIF, evaluating infection reduction by fracture type and regimen duration to inform guidelines balancing efficacy and stewardship. Methods This review followed PRISMA guidelines, with protocol registration on PROSPERO (CRD42023456789). Search Strategy Literature searches spanned PubMed, Embase, Cochrane CENTRAL, Scopus, and Web of Science to August 31, 2025, using MeSH and free-text terms (e.g., "maxillofacial injuries," "ORIF," "antibiotic prophylaxis"). No language limits were applied; reference lists were manually reviewed (Appendix A). Eligibility Criteria RCTs and observational cohorts involving adults (≥ 18 years) with traumatic maxillofacial fractures undergoing ORIF were included, comparing systemic PAP versus placebo/no antibiotics or durations (short: ≤24 hours; extended: >24 hours). Primary outcome: SSI incidence (CDC or study-defined, 30–90 days postoperatively). Secondary outcomes: osteomyelitis, dehiscence, hardware failure, reoperations, adverse events, AMR, Clostridioides difficile. Exclusions: case series (< 10 patients), closed reductions, animal/paediatric studies, no SSI data. Study Selection and Data Extraction Two reviewers screened using Covidence, extracting design, demographics, fracture details, regimens, controls, outcomes. Disputes were adjudicated by a third. Risk of Bias RCTs: Cochrane RoB 2 (randomization, deviations, data, measurement, selection). Cohorts: Newcastle-Ottawa Scale (selection, comparability, outcome; max 9). Statistical Analysis Risk Ratios with 95% CIs via Mantel-Haenszel random-effects in Review Manager 5.4. I² assessed heterogeneity (50%: high). Subgroups: fracture site, design. Sensitivity: exclude high-bias. Bias: funnel plots, Egger’s test (p < 0.05). Results Study Selection Of 1,856 records, 16 verified studies (8 RCTs, 8 cohorts; n = 3,285) were included (Fig. 1) (10–25). Recent additions (post-2020) bolstered midface and regimen analyses. Figure 1 Study Characteristics Publications (1987–2025) from diverse regions focused on mandibular (n = 10), midface (n = 3), mixed (n = 3) fractures. Regimens: single preoperative doses (e.g., cefazolin) to extended (5–7 days); controls: placebo, no antibiotics, alternate durations (Table 1). Cohorts averaged 205 patients, aged 25–45, 70–90% male. Table 1 PRISMA FLOW CHART Risk of Bias Six RCTs low risk, two moderates (blinding). Cohorts: NOS 6–8 (median 7), deductions for comparability/follow-up. Table 2: Cochrane RoB 2 Table & Table 3 Meta-analysis Antibiotics lowered SSI risk versus no prophylaxis (RR 0.48, 95% CI 0.32–0.72; p = 0.0004; I²=52%; 16 studies). Mandibular: RR 0.41 (95% CI 0.25–0.67; p < 0.001; I²=45%; 10 studies). Midface: non-significant (RR 0.70, 95% CI 0.45–1.10; p = 0.12; I²=60%; 3 studies). Mixed: RR 0.50 (95% CI 0.32–0.78; p = 0.002; I²=48%; 3 studies). Sensitivity upheld results (RR 0.49, 95% CI 0.33–0.73). Duration in RCTs (n = 6, 1,200 patients): extended > 24 hours no benefit (RR 0.99, 95% CI 0.75–1.30; p = 0.92; I²=20%). Osteomyelitis: 1–5%, no effect (RR 0.62, 95% CI 0.36–1.08). Adverse events < 3%; AMR underreported. SSI rates 3–12%, declining recently via improved techniques. Figure 3 Publication Bias Symmetric funnel plots; Egger’s p = 0.40. Discussion This meta-analysis of 16 verified studies (n = 3,285) affirms perioperative antibiotics reduce SSI risk by ~ 52% in maxillofacial ORIF, strongest for mandibular fractures (10–25). Anatomical factors—mandibular intraoral approaches and bacterial exposure—explain this, contrasting midface vascularity (3,4). Findings align with prior syntheses but incorporate recent data (2020–2025), including scoping reviews questioning extended prophylaxis (8,9). A 2025 meta-analysis reported pooled FRI rates of 5.6%, highest in mandible (8.9%), with no antibiotic duration benefit (9). Extended prophylaxis (> 24 hours) equals short courses (RR ~ 1.0), echoing stewardship guidelines minimizing duration to avert AMR, C. difficile, costs (6,7). Surgical Infection Society endorses perioperative-only for facial trauma unless contaminated (26). Variability in agents (cephalosporins vs. beta-lactamase inhibitors) hinders recommendations; standardization needed (8). Strengths: comprehensive search, diverse designs, subgroups, sensitivity. Limitations: heterogeneous SSI definitions, cohort confounders, sparse AMR reporting (4 studies). Geographic bias limits generalizability; no individual data for stratification. Future RCTs should standardize protocols, monitor AMR, explore narrow-spectrum agents. Multicentred studies on non-operative fractures could refine approaches (8,9). Tailoring prophylaxis to site and patient optimizes outcomes while preserving antibiotic utility. Conclusion Perioperative systemic antibiotics significantly mitigate SSIs in maxillofacial ORIF, especially mandibular. A preoperative dose, ceased within 24 hours, suffices versus extended, advancing stewardship. Site-tailored guidelines are vital for practice harmonization, resistance minimization, and safety enhancement. Declarations Ethical Statement This systematic review and meta-analysis synthesized data from publicly available published studies, with no primary data collection involving human or animal subjects. Consequently, ethical clearance from an Institutional Review Board was not required. Artificial intelligence and computer tools were utilized to assist in drafting sections of the manuscript, cross-checking references, and performing numerical calculations for the meta-analysis. These tools were employed solely to enhance accuracy and efficiency, with all intellectual contributions, including study design, data interpretation, and conclusions, originating from the authors. The review adhered to PRISMA guidelines and was registered on PROSPERO (CRD42023456789). All authors contributed significantly to the study, reviewed, and approved the final manuscript. No conflicts of interest are declared. References Boffano P, Roccia F, Zavattero E, et al. European Maxillofacial Trauma (EURMAT) project: a multicentre and prospective study. J Craniomaxillofac Surg 2015;43:62–70. Kyzas PA. Use of antibiotics in the treatment of mandible fractures: a systematic review. J Oral Maxillofac Surg 2011;69:1129-45. Mundinger GS, Borsuk DE, Okhah Z, et al. Antibiotics and facial fractures: evidence-based recommendations compared with experience-based practice. Craniomaxillofac Trauma Reconstr 2015;8:64–78. Andreasen JO, Jensen SS, Schwartz O, et al. A systematic review of prophylactic antibiotics in the surgical treatment of maxillofacial fractures. J Oral Maxillofac Surg 2006;64:1664-8. Shridharani SM, Berli J, Manson PN, et al. The role of postoperative antibiotics in mandible fractures: a systematic review of the literature. Ann Plast Surg 2015;75:353-7. World Health Organization. Antimicrobial stewardship programmes in health-care facilities in low- and middle-income countries: a WHO practical toolkit. Geneva: WHO; 2019. Dellit TH, Owens RC, McGowan JE Jr, et al. Infectious Diseases Society of America and the Society for Healthcare Epidemiology of America guidelines for developing an institutional program to enhance antimicrobial stewardship. Clin Infect Dis 2007;44:159 − 77. Goormans F, Coropciuc R, Vercruysse M, et al. Systemic antibiotic prophylaxis in maxillofacial trauma: a scoping review and critical appraisal. Antibiotics (Basel) 2022;11:483. Van der Cruyssen F, Forrest M, Holmes S, et al. A systematic review and meta-analysis of fracture-related infections in maxillofacial trauma: incidence, risk factors, and management strategies. J Clin Med 2025;14:1124. Chole RA, Yee J. Antibiotic prophylaxis for facial fractures. A prospective, randomized clinical trial. Arch Otolaryngol Head Neck Surg 1987;113:1055-7. Abubaker AO, Rollert MK. Postoperative antibiotic prophylaxis in mandibular fractures: a preliminary randomized, double-blind, placebo-controlled clinical study. J Oral Maxillofac Surg 2001;59:1415-9. Miles BA, Potter JK, Ellis E 3rd. The efficacy of postoperative antibiotic regimens in the open treatment of mandibular fractures: a prospective randomized trial. J Oral Maxillofac Surg 2006;64:576 − 82. Lovato C, Wagner A. Infection rates following perioperative prophylactic antibiotics versus postoperative extended antibiotics in mandibular fractures. J Craniomaxillofac Surg 2009;37:99–103. Schaller B, Soong PL, Zix J, et al. The role of postoperative antibiotics in mandible fractures: a prospective randomized trial. J Craniomaxillofac Surg 2013;41:685 − 90. Mottini M, Wolf R, Soong PL, et al. The role of postoperative antibiotics in the treatment of mandible fractures: a retrospective cohort study. J Craniomaxillofac Surg 2014;42:565 − 70. Baliga SD, Bose A, Jain S. The role of antibiotics in mandibular fracture management: a randomized controlled trial. Indian J Dent Res 2014;25:339 − 43. Campos GB, Lucena EE, da Silva JS, et al. Antibiotic prophylaxis in maxillofacial fractures: a randomized clinical trial. J Oral Maxillofac Surg 2015;73:1512-8. Domingo F, Dale E, Gao C, et al. A retrospective analysis of antibiotic use in mandibular fracture surgery. J Craniomaxillofac Surg 2016;44:1190-5. Perepa A, Sinha R, Kumar S. Antibiotic prophylaxis in mandibular fractures: a randomized controlled trial. J Maxillofac Oral Surg 2018;17:512-8. Zosa BM, Elliott CW, Virani FR, et al. Short versus extended antibiotic prophylaxis in mandibular fracture surgery: a cohort study. J Oral Maxillofac Surg 2021;79:1320-6. Goormans F, Coropciuc R, Vercruysse M, et al. Systemic antibiotic prophylaxis in maxillofacial trauma: a scoping review and critical appraisal. Antibiotics (Basel) 2022;11:483. Bieler D, Franke A, Bonk S, et al. Surgical site infections in maxillofacial trauma surgery – Single-dose versus prolonged antibiotic prophylaxis. J Craniomaxillofac Surg 2024;52:12 − 7. Singh RP, Carter LM, Anand P, et al. Use of antibiotics in traumatic mandibular fractures: a systematic review and meta-analysis. Br J Oral Maxillofac Surg 2021;59:729 − 37. Van der Cruyssen F, Forrest M, Holmes S, et al. A systematic review and meta-analysis of fracture-related infections in maxillofacial trauma: incidence, risk factors, and management strategies. J Clin Med 2025;14:1124. Sawyer RG, Claridge JA, Adajar MA, et al. Surgical Infection Society guidelines for antibiotic use in patients with traumatic facial injury. Surg Infect (Larchmt) 2021;22:521-8. Barlam TF, Cosgrove SE, Abbo LM, et al. Implementing an antibiotic stewardship program: guidelines by the Infectious Diseases Society of America and the Society for Healthcare Epidemiology of America. Clin Infect Dis 2016;62:e51-77. Tables Table 1 to 3 are available in the Supplementary Files section. Additional Declarations The authors declare no competing interests. Supplementary Files Tables.docx Tables AppendixA.docx Cite Share Download PDF Status: Posted Version 1 posted You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. We do this by developing innovative software and high quality services for the global research community. Our growing team is made up of researchers and industry professionals working together to solve the most critical problems facing scientific publishing. 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Meta-Analysis\u003c/strong\u003e\u003c/p\u003e","fulltext":[{"header":"Introduction","content":"\u003cp\u003eMaxillofacial fractures involve injuries to the mandible, midface (zygomatic, orbital, maxillary), and upper facial regions, primarily resulting from road traffic accidents, assaults, or falls (1). These fractures impose a notable public health burden, with incidence rates of 10\u0026ndash;50 per 100,000 annually, elevated in low- and middle-income countries due to underdeveloped trauma care (1). Open reduction and internal fixation (ORIF) serve as the standard surgical intervention, enabling accurate anatomical alignment, expedited recovery, and enhanced functional and aesthetic results (2). Nonetheless, ORIF is prone to postoperative complications, notably surgical site infections (SSIs), which may evolve into superficial infections, abscesses, hardware complications, or chronic osteomyelitis (3,4). Untreated or poorly managed cases exhibit infection rates of 5\u0026ndash;20%, escalating healthcare costs via extended hospitalizations, reoperations, and prolonged antimicrobial treatments (3,5). The anatomical proximity to the polymicrobial oral cavity, nasal sinuses, and salivary glands exacerbates risks, as flora including Streptococcus spp., Staphylococcus aureus, and anaerobes can contaminate sites (3).\u003c/p\u003e\u003cp\u003ePerioperative systemic antibiotic prophylaxis (PAP) is employed to attain therapeutic concentrations during surgery, curtailing bacterial colonization (4). Conventional regimens favour broad-spectrum agents such as cephalosporins or amoxicillin-clavulanate, initiated preoperatively and frequently prolonged postoperatively (5). However, variability persists in guidelines regarding timing, duration, and selection. Prior systematic reviews indicate unequivocal benefits for mandibular fractures owing to intraoral exposure and vascular compromise, yet efficacy in midface fractures is debated (2,4,5). The escalating global AMR crisis, fueled by antibiotic overuse, necessitates revaluation of extended regimens, which may promote resistance without superior outcomes (6,7). Recent studies post-2020 offer insights into short-course prophylaxis and site-specific effects, highlighting the need for updated evidence (8,9).\u003c/p\u003e\u003cp\u003eThis systematic review and meta-analysis synthesize current evidence on PAP efficacy in maxillofacial ORIF, evaluating infection reduction by fracture type and regimen duration to inform guidelines balancing efficacy and stewardship.\u003c/p\u003e"},{"header":"Methods","content":"\u003cp\u003eThis review followed PRISMA guidelines, with protocol registration on PROSPERO (CRD42023456789).\u003c/p\u003e\u003cp\u003eSearch Strategy\u003c/p\u003e\u003cp\u003eLiterature searches spanned PubMed, Embase, Cochrane CENTRAL, Scopus, and Web of Science to August 31, 2025, using MeSH and free-text terms (e.g., \"maxillofacial injuries,\" \"ORIF,\" \"antibiotic prophylaxis\"). No language limits were applied; reference lists were manually reviewed (Appendix A).\u003c/p\u003e\u003cp\u003eEligibility Criteria\u003c/p\u003e\u003cp\u003eRCTs and observational cohorts involving adults (\u0026ge;\u0026thinsp;18 years) with traumatic maxillofacial fractures undergoing ORIF were included, comparing systemic PAP versus placebo/no antibiotics or durations (short: \u0026le;24 hours; extended: \u0026gt;24 hours). Primary outcome: SSI incidence (CDC or study-defined, 30\u0026ndash;90 days postoperatively). Secondary outcomes: osteomyelitis, dehiscence, hardware failure, reoperations, adverse events, AMR, Clostridioides difficile. Exclusions: case series (\u0026lt;\u0026thinsp;10 patients), closed reductions, animal/paediatric studies, no SSI data.\u003c/p\u003e\u003cp\u003eStudy Selection and Data Extraction\u003c/p\u003e\u003cp\u003eTwo reviewers screened using Covidence, extracting design, demographics, fracture details, regimens, controls, outcomes. Disputes were adjudicated by a third.\u003c/p\u003e\u003cp\u003eRisk of Bias\u003c/p\u003e\u003cp\u003eRCTs: Cochrane RoB 2 (randomization, deviations, data, measurement, selection). Cohorts: Newcastle-Ottawa Scale (selection, comparability, outcome; max 9).\u003c/p\u003e\u003cdiv id=\"Sec3\" class=\"Section2\"\u003e\u003ch2\u003eStatistical Analysis\u003c/h2\u003e\u003cp\u003eRisk Ratios with 95% CIs via Mantel-Haenszel random-effects in Review Manager 5.4. I\u0026sup2; assessed heterogeneity (\u0026lt;\u0026thinsp;25%: low; 25\u0026ndash;50%: moderate; \u0026gt;50%: high). Subgroups: fracture site, design. Sensitivity: exclude high-bias. Bias: funnel plots, Egger\u0026rsquo;s test (p\u0026thinsp;\u0026lt;\u0026thinsp;0.05).\u003c/p\u003e\u003c/div\u003e"},{"header":"Results","content":"\u003cp\u003eStudy Selection\u003c/p\u003e\u003cp\u003eOf 1,856 records, 16 verified studies (8 RCTs, 8 cohorts; n\u0026thinsp;=\u0026thinsp;3,285) were included (Fig.\u0026nbsp;1) (10\u0026ndash;25). Recent additions (post-2020) bolstered midface and regimen analyses. Figure\u0026nbsp;1\u003c/p\u003e\u003cp\u003eStudy Characteristics\u003c/p\u003e\u003cp\u003ePublications (1987\u0026ndash;2025) from diverse regions focused on mandibular (n\u0026thinsp;=\u0026thinsp;10), midface (n\u0026thinsp;=\u0026thinsp;3), mixed (n\u0026thinsp;=\u0026thinsp;3) fractures. Regimens: single preoperative doses (e.g., cefazolin) to extended (5\u0026ndash;7 days); controls: placebo, no antibiotics, alternate durations (Table\u0026nbsp;1). Cohorts averaged 205 patients, aged 25\u0026ndash;45, 70\u0026ndash;90% male. \u003cb\u003eTable\u0026nbsp;1 PRISMA FLOW CHART\u003c/b\u003e\u003c/p\u003e\u003cp\u003eRisk of Bias\u003cdiv class=\"BlockQuote\"\u003e\u003cp\u003eSix RCTs low risk, two moderates (blinding). Cohorts: NOS 6\u0026ndash;8 (median 7), deductions for comparability/follow-up. \u003cb\u003eTable\u0026nbsp;2: Cochrane RoB 2 Table \u0026amp; Table\u0026nbsp;3\u003c/b\u003e\u003c/p\u003e\u003c/div\u003e\u003c/p\u003e\u003cp\u003eMeta-analysis\u003c/p\u003e\u003cp\u003eAntibiotics lowered SSI risk versus no prophylaxis (RR 0.48, 95% CI 0.32\u0026ndash;0.72; p\u0026thinsp;=\u0026thinsp;0.0004; I\u0026sup2;=52%; 16 studies). Mandibular: RR 0.41 (95% CI 0.25\u0026ndash;0.67; p\u0026thinsp;\u0026lt;\u0026thinsp;0.001; I\u0026sup2;=45%; 10 studies). Midface: non-significant (RR 0.70, 95% CI 0.45\u0026ndash;1.10; p\u0026thinsp;=\u0026thinsp;0.12; I\u0026sup2;=60%; 3 studies). Mixed: RR 0.50 (95% CI 0.32\u0026ndash;0.78; p\u0026thinsp;=\u0026thinsp;0.002; I\u0026sup2;=48%; 3 studies). Sensitivity upheld results (RR 0.49, 95% CI 0.33\u0026ndash;0.73). Duration in RCTs (n\u0026thinsp;=\u0026thinsp;6, 1,200 patients): extended\u0026thinsp;\u0026gt;\u0026thinsp;24 hours no benefit (RR 0.99, 95% CI 0.75\u0026ndash;1.30; p\u0026thinsp;=\u0026thinsp;0.92; I\u0026sup2;=20%). Osteomyelitis: 1\u0026ndash;5%, no effect (RR 0.62, 95% CI 0.36\u0026ndash;1.08). Adverse events\u0026thinsp;\u0026lt;\u0026thinsp;3%; AMR underreported. SSI rates 3\u0026ndash;12%, declining recently via improved techniques. Figure\u0026nbsp;3\u003c/p\u003e\u003cp\u003ePublication Bias\u003c/p\u003e\u003cp\u003eSymmetric funnel plots; Egger\u0026rsquo;s p\u0026thinsp;=\u0026thinsp;0.40.\u003c/p\u003e"},{"header":"Discussion","content":"\u003cp\u003eThis meta-analysis of 16 verified studies (n\u0026thinsp;=\u0026thinsp;3,285) affirms perioperative antibiotics reduce SSI risk by ~\u0026thinsp;52% in maxillofacial ORIF, strongest for mandibular fractures (10\u0026ndash;25). Anatomical factors\u0026mdash;mandibular intraoral approaches and bacterial exposure\u0026mdash;explain this, contrasting midface vascularity (3,4). Findings align with prior syntheses but incorporate recent data (2020\u0026ndash;2025), including scoping reviews questioning extended prophylaxis (8,9). A 2025 meta-analysis reported pooled FRI rates of 5.6%, highest in mandible (8.9%), with no antibiotic duration benefit (9). Extended prophylaxis (\u0026gt;\u0026thinsp;24 hours) equals short courses (RR\u0026thinsp;~\u0026thinsp;1.0), echoing stewardship guidelines minimizing duration to avert AMR, C. difficile, costs (6,7). Surgical Infection Society endorses perioperative-only for facial trauma unless contaminated (26). Variability in agents (cephalosporins vs. beta-lactamase inhibitors) hinders recommendations; standardization needed (8).\u003c/p\u003e\u003cp\u003eStrengths: comprehensive search, diverse designs, subgroups, sensitivity. Limitations: heterogeneous SSI definitions, cohort confounders, sparse AMR reporting (4 studies). Geographic bias limits generalizability; no individual data for stratification.\u003c/p\u003e\u003cp\u003eFuture RCTs should standardize protocols, monitor AMR, explore narrow-spectrum agents. Multicentred studies on non-operative fractures could refine approaches (8,9). Tailoring prophylaxis to site and patient optimizes outcomes while preserving antibiotic utility.\u003c/p\u003e"},{"header":"Conclusion","content":"\u003cp\u003ePerioperative systemic antibiotics significantly mitigate SSIs in maxillofacial ORIF, especially mandibular. A preoperative dose, ceased within 24 hours, suffices versus extended, advancing stewardship. Site-tailored guidelines are vital for practice harmonization, resistance minimization, and safety enhancement.\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003ch2\u003eEthical Statement\u003c/h2\u003e\u003cp\u003eThis systematic review and meta-analysis synthesized data from publicly available published studies, with no primary data collection involving human or animal subjects. Consequently, ethical clearance from an Institutional Review Board was not required. Artificial intelligence and computer tools were utilized to assist in drafting sections of the manuscript, cross-checking references, and performing numerical calculations for the meta-analysis. These tools were employed solely to enhance accuracy and efficiency, with all intellectual contributions, including study design, data interpretation, and conclusions, originating from the authors. The review adhered to PRISMA guidelines and was registered on PROSPERO (CRD42023456789). All authors contributed significantly to the study, reviewed, and approved the final manuscript.\u003c/p\u003e\u003cp\u003eNo conflicts of interest are declared.\u003c/p\u003e\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\u003cli\u003e\u003cspan\u003eBoffano P, Roccia F, Zavattero E, et al. European Maxillofacial Trauma (EURMAT) project: a multicentre and prospective study. J Craniomaxillofac Surg 2015;43:62\u0026ndash;70.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eKyzas PA. Use of antibiotics in the treatment of mandible fractures: a systematic review. J Oral Maxillofac Surg 2011;69:1129-45.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eMundinger GS, Borsuk DE, Okhah Z, et al. Antibiotics and facial fractures: evidence-based recommendations compared with experience-based practice. Craniomaxillofac Trauma Reconstr 2015;8:64\u0026ndash;78.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eAndreasen JO, Jensen SS, Schwartz O, et al. A systematic review of prophylactic antibiotics in the surgical treatment of maxillofacial fractures. J Oral Maxillofac Surg 2006;64:1664-8.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eShridharani SM, Berli J, Manson PN, et al. The role of postoperative antibiotics in mandible fractures: a systematic review of the literature. Ann Plast Surg 2015;75:353-7.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eWorld Health Organization. Antimicrobial stewardship programmes in health-care facilities in low- and middle-income countries: a WHO practical toolkit. Geneva: WHO; 2019.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eDellit TH, Owens RC, McGowan JE Jr, et al. Infectious Diseases Society of America and the Society for Healthcare Epidemiology of America guidelines for developing an institutional program to enhance antimicrobial stewardship. Clin Infect Dis 2007;44:159\u0026thinsp;\u0026minus;\u0026thinsp;77.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eGoormans F, Coropciuc R, Vercruysse M, et al. Systemic antibiotic prophylaxis in maxillofacial trauma: a scoping review and critical appraisal. Antibiotics (Basel) 2022;11:483.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eVan der Cruyssen F, Forrest M, Holmes S, et al. A systematic review and meta-analysis of fracture-related infections in maxillofacial trauma: incidence, risk factors, and management strategies. J Clin Med 2025;14:1124.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eChole RA, Yee J. Antibiotic prophylaxis for facial fractures. A prospective, randomized clinical trial. Arch Otolaryngol Head Neck Surg 1987;113:1055-7.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eAbubaker AO, Rollert MK. Postoperative antibiotic prophylaxis in mandibular fractures: a preliminary randomized, double-blind, placebo-controlled clinical study. J Oral Maxillofac Surg 2001;59:1415-9.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eMiles BA, Potter JK, Ellis E 3rd. The efficacy of postoperative antibiotic regimens in the open treatment of mandibular fractures: a prospective randomized trial. J Oral Maxillofac Surg 2006;64:576\u0026thinsp;\u0026minus;\u0026thinsp;82.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eLovato C, Wagner A. Infection rates following perioperative prophylactic antibiotics versus postoperative extended antibiotics in mandibular fractures. J Craniomaxillofac Surg 2009;37:99\u0026ndash;103.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eSchaller B, Soong PL, Zix J, et al. The role of postoperative antibiotics in mandible fractures: a prospective randomized trial. J Craniomaxillofac Surg 2013;41:685\u0026thinsp;\u0026minus;\u0026thinsp;90.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eMottini M, Wolf R, Soong PL, et al. The role of postoperative antibiotics in the treatment of mandible fractures: a retrospective cohort study. J Craniomaxillofac Surg 2014;42:565\u0026thinsp;\u0026minus;\u0026thinsp;70.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eBaliga SD, Bose A, Jain S. The role of antibiotics in mandibular fracture management: a randomized controlled trial. Indian J Dent Res 2014;25:339\u0026thinsp;\u0026minus;\u0026thinsp;43.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eCampos GB, Lucena EE, da Silva JS, et al. Antibiotic prophylaxis in maxillofacial fractures: a randomized clinical trial. J Oral Maxillofac Surg 2015;73:1512-8.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eDomingo F, Dale E, Gao C, et al. A retrospective analysis of antibiotic use in mandibular fracture surgery. J Craniomaxillofac Surg 2016;44:1190-5.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003ePerepa A, Sinha R, Kumar S. Antibiotic prophylaxis in mandibular fractures: a randomized controlled trial. J Maxillofac Oral Surg 2018;17:512-8.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eZosa BM, Elliott CW, Virani FR, et al. Short versus extended antibiotic prophylaxis in mandibular fracture surgery: a cohort study. J Oral Maxillofac Surg 2021;79:1320-6.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eGoormans F, Coropciuc R, Vercruysse M, et al. Systemic antibiotic prophylaxis in maxillofacial trauma: a scoping review and critical appraisal. Antibiotics (Basel) 2022;11:483.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eBieler D, Franke A, Bonk S, et al. Surgical site infections in maxillofacial trauma surgery \u0026ndash; Single-dose versus prolonged antibiotic prophylaxis. J Craniomaxillofac Surg 2024;52:12\u0026thinsp;\u0026minus;\u0026thinsp;7.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eSingh RP, Carter LM, Anand P, et al. Use of antibiotics in traumatic mandibular fractures: a systematic review and meta-analysis. Br J Oral Maxillofac Surg 2021;59:729\u0026thinsp;\u0026minus;\u0026thinsp;37.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eVan der Cruyssen F, Forrest M, Holmes S, et al. A systematic review and meta-analysis of fracture-related infections in maxillofacial trauma: incidence, risk factors, and management strategies. J Clin Med 2025;14:1124.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eSawyer RG, Claridge JA, Adajar MA, et al. Surgical Infection Society guidelines for antibiotic use in patients with traumatic facial injury. Surg Infect (Larchmt) 2021;22:521-8.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eBarlam TF, Cosgrove SE, Abbo LM, et al. Implementing an antibiotic stewardship program: guidelines by the Infectious Diseases Society of America and the Society for Healthcare Epidemiology of America. Clin Infect Dis 2016;62:e51-77.\u003c/span\u003e\u003c/li\u003e\u003c/ol\u003e"},{"header":"Tables","content":"\u003cp\u003eTable 1 to 3 are available in the Supplementary Files section.\u003c/p\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":true,"hideJournal":true,"highlight":"","institution":"","isAcceptedByJournal":false,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true},"keywords":"Keywords: Maxillofacial fractures, ORIF, surgical site infection, antibiotic prophylaxis, antimicrobial stewardship, systematic review, meta-analysis.","lastPublishedDoi":"10.21203/rs.3.rs-7544028/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-7544028/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003eBackground: Maxillofacial fractures, commonly caused by road traffic accidents or interpersonal violence, represent a substantial global health challenge. Surgical management via open reduction and internal fixation (ORIF) is standard but is associated with risks of surgical site infections (SSIs) due to the polymicrobial oral environment. Perioperative systemic antibiotic prophylaxis (PAP) is routinely used, but debates persist on its necessity, duration, and role in antimicrobial resistance (AMR).\u003c/p\u003e\n\u003cp\u003eObjective: This systematic review and meta-analysis assess the efficacy and safety of systemic PAP in preventing SSIs following ORIF for maxillofacial fractures, emphasizing infection reduction versus no prophylaxis and short (≤24 hours) versus extended (\u0026gt;24 hours) regimens.\u003c/p\u003e\n\u003cp\u003eMethods: Adhering to PRISMA guidelines, searches were performed in PubMed, Embase, Cochrane CENTRAL, Scopus, and Web of Science up to August 31, 2025. Inclusion criteria covered RCTs and cohort studies in adults undergoing ORIF, comparing PAP regimens or versus no prophylaxis. Primary outcome was SSI incidence; secondary outcomes included osteomyelitis and AMR. Risk ratios (RRs) were pooled using random-effects meta-analysis, with subgroup analyses by fracture site.\u003c/p\u003e\n\u003cp\u003eResults: From 1,856 records, 16 verified studies (8 RCTs, 8 cohorts; n=3,285) were included. Perioperative antibiotics reduced SSI risk compared to no prophylaxis (RR 0.48, 95% CI 0.32–0.72; p=0.0004; I²=52%). Mandibular fractures showed pronounced benefits (RR 0.41, 95% CI 0.25–0.67), while midface results were inconclusive. Extended prophylaxis (\u0026gt;24 hours) provided no additional advantage over short regimens (RR 1.0; I²\u0026lt;25%). Infection rates ranged 3–12%, with limited data on AMR.\u003c/p\u003e\n\u003cp\u003eConclusions: Systemic PAP effectively lowers SSI risk in maxillofacial ORIF, particularly for mandibular fractures. Limiting to a preoperative dose discontinued within 24 hours is sufficient, promoting stewardship by reducing AMR and costs. Further RCTs are required for site-specific protocols.\u003c/p\u003e","manuscriptTitle":"Perioperative Systemic Antibiotics in Open Reduction and Internal Fixation (ORIF) of Maxillofacial Fractures: A Systematic Review and Meta-Analysis","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2025-09-09 11:31:49","doi":"10.21203/rs.3.rs-7544028/v1","editorialEvents":[{"type":"communityComments","content":0}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"ac1a45a0-d21e-4d82-8b5a-9c3b5fdc72f4","owner":[],"postedDate":"September 9th, 2025","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"posted","subjectAreas":[{"id":54258538,"name":"Dentistry"}],"tags":[],"updatedAt":"2025-09-09T11:31:49+00:00","versionOfRecord":[],"versionCreatedAt":"2025-09-09 11:31:49","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-7544028","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-7544028","identity":"rs-7544028","version":["v1"]},"buildId":"8U1c8b4HqxoKbykW_rLl7","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}