Rabbit Hole: Open Fracture Antibiotics

Guidelines

• Hoff, William S. MD, FACS; Bonadies, John A. MD, FACS; Cachecho, Riad MD, FACS, FCCP; Dorlac, Warren C. MD, FACS East Practice Management Guidelines Work Group: Update to Practice Management Guidelines for Prophylactic Antibiotic Use in Open Fractures, The Journal of Trauma: Injury, Infection, and Critical Care: March 2011 – Volume 70 – Issue 3 – p 751-754 doi: 10.1097/TA.0b013e31820930e5

• Upstate University Hospital, Trauma Center-  CLINICAL PRACTICE GUIDELINE: Open Fracture Guideline Accessed: 19 October 2021

• University of Nebraska Medical Center. Antibiotic Prophylaxis in Open Fractures. Accessed: 19 October 2021. 

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Primary Literature

Antibiotic Agents

• Gustilo RB, Anderson JT. Prevention of infection in the treatment of one thousand and twenty-five open fractures of long bones: retrospective and prospective analyses. J Bone Joint Surg Am. 1976 Jun;58(4):453-8. PMID: 773941.

• Gustilo RB. Use of antimicrobials in the management of open fractures. Arch Surg. 1979 Jul;114(7):805-8. doi: 10.1001/archsurg.1979.01370310047010. PMID: 454175.
• Patzakis MJ, Harvey JP Jr, Ivler D. The role of antibiotics in the management of open fractures. J Bone Joint Surg [Am] 1974;56:532–541.

• Patzakis MJ, Bains RS, Lee J, et al. Prospective, randomized, double-blind study comparing single-agent antibiotic therapy, ciprofloxacin, to combination antibiotic therapy in open fracture wounds. J Orthop Trauma. 2000;14:529-533

• Rodriguez L, Jung HS, Goulet JA, Cicalo A, Machado-Aranda DA, Napolitano LM. Evidence-based protocol for prophylactic antibiotics in open fractures: improved antibiotic stewardship with no increase in infection rates. J Trauma Acute Care Surg. 2014 Sep;77(3):400-7; discussion 407-8; quiz 524. doi: 10.1097/TA.0000000000000398. PMID: 25159242.
• Vasenius J, Tulikoura I, Vainionpää S, Rokkanen P. Clindamycin versus cloxacillin in the treatment of 240 open fractures. A randomized prospective study. Ann Chir Gynaecol. 1998;87(3):224-8. PMID: 9825068.

• O’Connell CR, Kooda KJ, Sawyer MD, Wise KB, Mara KC, Skrupky LP. Evaluation of Piperacillin-Tazobactam for Antibiotic Prophylaxis in Traumatic Grade III Open Fractures. Surg Infect (Larchmt). 2021 Oct 5. doi: 10.1089/sur.2021.122. Epub ahead of print. PMID: 34612703.

• Shawar SK, Ly TV, Li J, Shirk MB, Reichert EM. Piperacillin/Tazobactam versus Tobramycin-Based Antibiotic Prophylaxis for Type III Open Fractures. Surg Infect (Larchmt). 2020 Feb;21(1):23-28. doi: 10.1089/sur.2019.064. Epub 2019 Aug 5. PMID: 31381489.

• Redfern J, Wasilko SM, Groth ME, McMillian WD, Bartlett CS 3rd. Surgical Site Infections in Patients With Type 3 Open Fractures: Comparing Antibiotic Prophylaxis With Cefazolin Plus Gentamicin Versus Piperacillin/Tazobactam. J Orthop Trauma. 2016 Aug;30(8):415-9. doi: 10.1097/BOT.0000000000000554. PMID: 26825490.

• Harper KD, Quinn C, Eccles J, Ramsey F, Rehman S. Administration of intravenous antibiotics in patients with open fractures is dependent on emergency room triaging. PLoS One. 2018;13(8):e0202013. Published 2018 Aug 14. doi:10.1371/journal.pone.0202013

• Patanwala AE, Radosevich JJ, Meshay I, Naderi M, Culver MA, Lee YG, Weinberg JA, Khobrani M, Nix DE. Cefazolin Monotherapy Versus Cefazolin Plus Aminoglycosides for Antimicrobial Prophylaxis of Type III Open Fractures. Am J Ther. 2019 Nov 25;28(3):e284-e291. doi: 10.1097/MJT.0000000000001121. PMID: 31789627.

• Depcinski SC, Nguyen KH, Ender PT. Cefazolin and an aminoglycoside compared with cefazolin alone for the antimicrobial prophylaxis of type III open orthopedic fractures. Int J Crit Illn Inj Sci. 2019 Jul-Sep;9(3):127-131. doi: 10.4103/IJCIIS.IJCIIS_7_19. Epub 2019 Sep 30. PMID: 31620351; PMCID: PMC6792399.

• Lou W, Zou K, Yu Z, Qin S, Wang K, Che B. Cefazolin sodium pentahydrate combined with vacuum sealing drainage in the treatment of open fracture complicated with soft tissue injury. Rev Assoc Med Bras (1992). 2020 Apr;66(4):430-436. doi: 10.1590/1806-9282.66.4.430. PMID: 32578775.

• Hopkins, Teri L. PharmD; Daley, Mitchell J. PharmD; Rose, Dusten T. PharmD; Jaso, Theresa C. PharmD; Brown, Carlos V.R. MD Presumptive antibiotic therapy for civilian trauma injuries, Journal of Trauma and Acute Care Surgery: October 2016 – Volume 81 – Issue 4 – p 765-774. doi: 10.1097/TA.0000000000001164 

• Chang Y, Bhandari M, Zhu KL, Mirza RD, Ren M, Kennedy SA, Negm A, Bhatnagar N, Naji FN, Milovanovic L, Fei Y, Agarwal A, Kamran R, Cho SM, Schandelmaier S, Wang L, Jin L, Hu S, Zhao Y, Lopes LC, Wang M, Petrisor B, Ristevski B, Siemieniuk RAC, Guyatt GH. Antibiotic Prophylaxis in the Management of Open Fractures: A Systematic Survey of Current Practice and Recommendations. JBJS Rev. 2019 Feb;7(2):e1. doi: 10.2106/JBJS.RVW.17.00197. PMID: 30724762.

• Messner J, Papakostidis C, Giannoudis PV, Kanakaris NK. Duration of Administration of Antibiotic Agents for Open Fractures: Meta-Analysis of the Existing Evidence. Surg Infect (Larchmt). 2017 Nov/Dec;18(8):854-867. doi: 10.1089/sur.2017.108. Epub 2017 Sep 28. PMID: 28956724.

• Ondari JN, Masika MM, Ombachi RB, Ating’a JE. Unblinded randomized control trial on prophylactic antibiotic use in gustilo II open tibia fractures at Kenyatta National Hospital, Kenya. Injury. 2016 Oct;47(10):2288-2293. doi: 10.1016/j.injury.2016.07.014. Epub 2016 Jul 19. PMID: 27492064.

• Saveli CC, Morgan SJ, Belknap RW, Ross E, Stahel PF, Chaus GW, Hak DJ, Biffl WL, Knepper B, Price CS. Prophylactic antibiotics in open fractures: a pilot randomized clinical safety study. J Orthop Trauma. 2013 Oct;27(10):552-7. doi: 10.1097/BOT.0b013e31828d92ee. PMID: 23446823.

• Atwan, Yousif MDa,∗; Miclau, Theodore MDb; Schemitsch, Emil H. MD, FRCSCa; Teague, David MDc Antibiotic utilization in open fractures, OTA International: March 2020 – Volume 3 – Issue 1 – p e071 doi: 10.1097/OI9.0000000000000071

• Thompson McMurtrie, John Prather, Ryan Cone, Tyler Montgomery, Chirag Patel, Gerald McGwin, and Clay Spitler.Surgical Infections.Sep 2021.662-667.http://doi.org/10.1089/sur.2020.300

• Samai K, Vilella A. Update in Therapeutics: Prophylactic Antibiotics in Open Fractures. J Trauma Nurs. 2018 Mar/Apr;25(2):83-86. doi: 10.1097/JTN.0000000000000348. PMID: 29521772.

• Backes M, Dingemans SA, Dijkgraaf MGW, van den Berg HR, van Dijkman B, Hoogendoorn JM, Joosse P, Ritchie ED, Roerdink WH, Schots JPM, Sosef NL, Spijkerman IJB, Twigt BA, van der Veen AH, van Veen RN, Vermeulen J, Vos DI, Winkelhagen J, Goslings JC, Schepers T; WIFI Collaboration Group. Effect of Antibiotic Prophylaxis on Surgical Site Infections Following Removal of Orthopedic Implants Used for Treatment of Foot, Ankle, and Lower Leg Fractures: A Randomized Clinical Trial. JAMA. 2017 Dec 26;318(24):2438-2445. doi: 10.1001/jama.2017.19343. Erratum in: JAMA. 2018 Mar 13;319(10 ):1051. PMID: 29279933; PMCID: PMC5820713.

• When Sticks & Stones Expose Your Bones Will Gentamicin Save You?Evaluating the Need for Expanded Gram-Negative Coverage in Prophylaxis of Grade III Open Fractures by  Amber N. Welborn, Pharm.D.

• DeBaun, Malcolm R. MDa,b; Lai, Cara BSc; Sanchez, Mark BSc; Chen, Michael J. MDb; Goodnough, L. Henry MD, PhDa,b; Chang, Amy MDd; Bishop, Julius A. MDb; Gardner, Michael J. MDb,∗ Antibiotic resistance: still a cause of concern?, OTA International: June 2021 – Volume 4 – Issue 3S – p e104 doi: 10.1097/OI9.0000000000000104

• Frank, Matt MD; Francis, Jeffrey BS; Bender, Mark DC; Roberts, Michael BS; Watson, David MD; Shah, Anjan MD; Maxson, Ben DO; Infante, Anthony DO; Sanders, Roy MD; Mir, Hassan R. MD, MBA, FACS∗ Multidose prophylactic IV antibiotics do not lower the risk of surgical site infection for isolated closed ankle fractures, OTA International: December 2019 – Volume 2 – Issue 4 – p e035 doi: 10.1097/OI9.0000000000000035

Other Interventions on Open Fracture Antibiotics

1. Antibiotic-Coated Nail

• Metsemakers WJ, Reul M, Nijs S. The use of gentamicin-coated nails in complex open tibia fracture and revision cases: A retrospective analysis of a single centre case series and review of the literature. Injury. 2015 Dec;46(12):2433-7. doi: 10.1016/j.injury.2015.09.028. Epub 2015 Oct 8. PMID: 26477343.
• Kulkarni, Govind Shivram MS, MS, FRCSa,∗; Kulkarni, Sunil MBBS, MS, (ortho), D (ortho)b; Babhulkar, Sushrut MS, Orth, MCh, Orthc Cement beads and cement spacers: indications, techniques, and clinical results, OTA International: June 2021 – Volume 4 – Issue 3S – p e118 doi: 10.1097/OI9.0000000000000118

2. PMMA Bead Chains

• Seligson D, Berling S. Antibiotic-laden PMMA bead chains for the prevention of infection in compound fractures: current state of the art. Eur J Orthop Surg Traumatol. 2015 Aug;25(6):969-74. doi: 10.1007/s00590-015-1652-z. Epub 2015 Jun 9. PMID: 26055399.

• Shiels SM, Tennent DJ, Akers KS, Wenke JC. Determining potential of PMMA as a depot for rifampin to treat recalcitrant orthopaedic infections. Injury. 2017 Oct;48(10):2095-2100. doi: 10.1016/j.injury.2017.08.021. Epub 2017 Aug 16. PMID: 28842287.

• Poi MJ, Pisimisis G, Barshes NR, Darouiche RO, Lin PH, Kougias P, Bechara CF. Evaluating effectiveness of antibiotic polymethylmethacrylate beads in achieving wound sterilization and graft preservation in patients with early and late vascular graft infections. Surgery. 2013 May;153(5):673-82. doi: 10.1016/j.surg.2012.10.011. Epub 2012 Dec 24. PMID: 23270968.

• Opalko M, Bösebeck H, Vogt S. Properties and clinical application safety of antibiotic-loaded bone cement in kyphoplasty. J Orthop Surg Res. 2019 Jul 27;14(1):238. doi: 10.1186/s13018-019-1200-3. PMID: 31351477; PMCID: PMC6660699.

3. Local Antibiotic Delivery via Bioabsorbable Gel

• Penn-Barwell JG, Murray CK, Wenke JC. Local antibiotic delivery by a bioabsorbable gel is superior to PMMA bead depot in reducing infection in an open fracture model. J Orthop Trauma. 2014 Jun;28(6):370-5. doi: 10.1097/BOT.0b013e3182a7739e. PMID: 23948961.

4. Negative Pressure Wound Therapy

• Large TM, Douglas G, Erickson G, Grayson JK. Effect of negative pressure wound therapy on the elution of antibiotics from polymethylmethacrylate beads in a porcine simulated open femur fracture model. J Orthop Trauma. 2012 Sep;26(9):506-11. doi: 10.1097/BOT.0b013e31825354ce. PMID: 22549033.

5. Impregnated Beads

• Henry SL, Ostermann PA, Seligson D. The prophylactic use of antibiotic impregnated beads in open fractures. J Trauma. 1990 Oct;30(10):1231-8. doi: 10.1097/00005373-199010000-00007. PMID: 2213931.

6. Topical Antibiotics

• Burbank, Kimberly M. BSa; Schauer, Steven G. DO, MSa,b,c,d,e; De Lorenzo, Robert A. MD, MSM, MSCIe; Wenke, Joseph C. PhDa Early application of topical antibiotic powder in open-fracture wounds, OTA International: December 2020 – Volume 3 – Issue 4 – p e091 doi: 10.1097/OI9.0000000000000091

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Review Articles

• Hauser CJ, Adams CA Jr, Eachempati SR; Council of the Surgical Infection Society. Surgical Infection Society guideline: prophylactic antibiotic use in open fractures: an evidence-based guideline. Surg Infect (Larchmt). 2006 Aug;7(4):379-405. doi: 10.1089/sur.2006.7.379. PMID: 16978082.

• Garner MR, Sethuraman SA, Schade MA, Boateng H. Antibiotic Prophylaxis in Open Fractures: Evidence, Evolving Issues, and Recommendations. J Am Acad Orthop Surg. 2020 Apr 15;28(8):309-315. doi: 10.5435/JAAOS-D-18-00193. PMID: 31851021. 

• Warrender WJ, Lucasti CJ, Chapman TR, Ilyas AM. Antibiotic Management and Operative Debridement in Open Fractures of the Hand and Upper Extremity: A Systematic Review. Hand Clin. 2018 Feb;34(1):9-16. doi: 10.1016/j.hcl.2017.09.001. PMID: 29169601.

• Hannigan GD, Pulos N, Grice EA, Mehta S. Current Concepts and Ongoing Research in the Prevention and Treatment of Open Fracture Infections. Adv Wound Care (New Rochelle). 2015 Jan 1;4(1):59-74. doi: 10.1089/wound.2014.0531. PMID: 25566415; PMCID: PMC4281849.

• Godfrey J, Pace JL. Type I Open Fractures Benefit From Immediate Antibiotic Administration But Not Necessarily Immediate Surgery. J Pediatr Orthop. 2016 Jun;36 Suppl 1:S6-S10. doi: 10.1097/BPO.0000000000000766. PMID: 27100039.

• Gaudias J. Antibiotic prophylaxis in orthopedics-traumatology. Orthop Traumatol Surg Res. 2021 Feb;107(1S):102751. doi: 10.1016/j.otsr.2020.102751. Epub 2020 Dec 11. PMID: 33316449.

• Trimaille A, Kerfant N, Henry AS, Ta P, Rouanet M, Le Nen D, Stindel E, Ansart S, Hu W. Multidisciplinary management of the bone and joint infection complicating treatment of an open fracture of the lower limb. Ann Chir Plast Esthet. 2020 Nov;65(5-6):380-393. doi: 10.1016/j.anplas.2020.05.012. Epub 2020 Aug 13. PMID: 32800464.

• Craig J, Fuchs T, Jenks M, Fleetwood K, Franz D, Iff J, Raschke M. Systematic review and meta-analysis of the additional benefit of local prophylactic antibiotic therapy for infection rates in open tibia fractures treated with intramedullary nailing. Int Orthop. 2014 May;38(5):1025-30. doi: 10.1007/s00264-014-2293-2. Epub 2014 Feb 15. PMID: 24531401; PMCID: PMC3997785.

• Metcalfe D, Aquilina AL, Hedley HM. Prophylactic antibiotics in open distal phalanx fractures: systematic review and meta-analysis. J Hand Surg Eur Vol. 2016 May;41(4):423-30. doi: 10.1177/1753193415601055. Epub 2015 Sep 1. PMID: 26329883.

• Carver DC, Kuehn SB, Weinlein JC. Role of Systemic and Local Antibiotics in the Treatment of Open Fractures. Orthop Clin North Am. 2017 Apr;48(2):137-153. doi: 10.1016/j.ocl.2016.12.005. Epub 2017 Jan 30. PMID: 28336038

• Isaac SM, Woods A, Danial IN, Mourkus H. Antibiotic Prophylaxis in Adults With Open Tibial Fractures: What Is the Evidence for Duration of Administration? A Systematic Review. J Foot Ankle Surg. 2016 Jan-Feb;55(1):146-50. doi: 10.1053/j.jfas.2015.07.012. Epub 2015 Sep 11. PMID: 26364701.

• Chang Y, Kennedy SA, Bhandari M, Lopes LC, Bergamaschi CC, Carolina de Oliveira E Silva M, Bhatnagar N, Mousavi SM, Khurshid S, Petrisor B, Ren M, Sodhi SK, Mirza RD, Guyatt GH. Effects of Antibiotic Prophylaxis in Patients with Open Fracture of the Extremities: A Systematic Review of Randomized Controlled Trials. JBJS Rev. 2015 Jun 9;3(6):e2. doi: 10.2106/JBJS.RVW.N.00088. PMID: 27490013.

• Olinger CR, Carver DC, Nolan VG, Weinlein JC. The Effect of Under-Dosing Prophylactic Antibiotics in the Care of Open Tibial Fractures. J Orthop Trauma. 2018 Jul;32(7):322-326. doi: 10.1097/BOT.0000000000001171. PMID: 29634602.

• Zalavras CG. Prevention of Infection in Open Fractures. Infect Dis Clin North Am. 2017 Jun;31(2):339-352. doi: 10.1016/j.idc.2017.01.005. Epub 2017 Mar 11. PMID: 28292542.

• Rupp M, Popp D, Alt V. Prevention of infection in open fractures: Where are the pendulums now? Injury. 2020 May;51 Suppl 2:S57-S63. doi: 10.1016/j.injury.2019.10.074. Epub 2019 Oct 25. PMID: 31679836.

• Ketonis C, Dwyer J, Ilyas AM. Timing of Debridement and Infection Rates in Open Fractures of the Hand: A Systematic Review. Hand (N Y). 2017 Mar;12(2):119-126. doi: 10.1177/1558944716643294. Epub 2016 Jul 8. PMID: 28344521; PMCID: PMC5349411.

• Morgenstern M, Vallejo A, McNally MA, Moriarty TF, Ferguson JY, Nijs S, Metsemakers WJ. The effect of local antibiotic prophylaxis when treating open limb fractures: A systematic review and meta-analysis. Bone Joint Res. 2018 Aug 4;7(7):447-456. doi: 10.1302/2046-3758.77.BJR-2018-0043.R1. PMID: 30123494; PMCID: PMC6076360.

• Whitehouse MR, McDaid C, Kelly MB, Moran CG, Costa ML. The effect of timing of antibiotic delivery on infection rates related to open limb fractures: a systematic review. Emerg Med J. 2017 Sep;34(9):613-620. doi: 10.1136/emermed-2016-205900. Epub 2016 Sep 15. PMID: 27633346.

• Grote S, Polzer H, Prall WC, Gill S, Shafizadeh S, Banerjee M, Bouillon B, Bäthis H. Prävention von Infektionen bei offenen Frakturen heute: Ein evidenzbasierter systematischer Review [Prevention of infection in the current treatment of open fractures: an evidence-based systematic analysis]. Orthopade. 2012 Jan;41(1):32-42. German.

• Lin CA, O’Hara NN, Sprague S, O’Toole RV, Joshi M, Harris AD, Warner SJ, Johal H, Natoli RM, Hagen JE, Jeray KJ, Fowler JT, Phelps KD, Pilson HT, Gitajn IL, Bhandari M, Slobogean GP; PREP-IT Investigators. Low Adherence to Recommended Guidelines for Open Fracture Antibiotic Prophylaxis. J Bone Joint Surg Am. 2021 Apr 7;103(7):609-617. doi: 10.2106/JBJS.20.01229. PMID: 33411466.

• Cross WW 3rd, Swiontkowski MF. Treatment principles in the management of open fractures. Indian J Orthop. 2008;42(4):377-386. doi:10.4103/0019-5413.43373

• Sop JL, Sop A. Open Fracture Management. [Updated 2021 Aug 14]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2021 Jan-.

• Chukwulebe S, Hogrefe C. The Diagnosis and Management of Facial Bone Fractures. Emerg Med Clin North Am. 2019 Feb;37(1):137-151. doi: 10.1016/j.emc.2018.09.012. PMID: 30454777.

• Greco T, Vitiello R, Cazzato G, Cianni L, Malerba G, Maccauro G, Perisano C. Intramedullary antibiotic coated nail in tibial fracture: a systematic review. J Biol Regul Homeost Agents. 2020 May-Jun;34(3 Suppl. 2):63-69. ADVANCES IN MUSCULOSKELETAL DISEASES AND INFECTIONS – SOTIMI 2019. PMID: 32856442.

• De Meo D, Cannari FM, Petriello L, Persiani P, Villani C. Gentamicin-Coated Tibia Nail in Fractures and Nonunion to Reduce Fracture-Related Infections: A Systematic Review. Molecules. 2020 Nov 23;25(22):5471. doi: 10.3390/molecules25225471. PMID: 33238408; PMCID: PMC7700538.

• C L O, M M, N M J. Controversies in the management of open fractures. Open Orthop J. 2014;8:178-184. Published 2014 Jun 27. doi:10.2174/1874325001408010178

• Harvey S, Brad Hall A, Wilson K. Impact of an emergency medicine pharmacist on initial antibiotic prophylaxis for open fractures in trauma patients. Am J Emerg Med. 2018 Feb;36(2):290-293. doi: 10.1016/j.ajem.2017.10.039. Epub 2017 Oct 17. PMID: 29079370.

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Podcasts & Medical Blogs

• http://www.emdocs.net/em3am-open-fracture/#:~:text=The%20choice%20of%20antibiotic%20is,for%20gross%20contamination%20with%20soil.
• https://www.tamingthesru.com/blog/2021/3/2/open-breaks-antibiotics-for-open-fractures
• https://ota.org/sites/files/2021-06/General%20B2%20Open%20Fractures.pdf
• https://coreem.net/core/open-fractures/
• https://www.orthobullets.com/trauma/1004/open-fractures-management?section=topic

• Role Of Antibiotics In Open Fractures Of The Finger- https://www.emrap.org/episode/ema-1991-1/abstract22
• Evidence-based Protocol For Prophylactic Antibiotics In Open Fractures: Improved Antibiotic Stewardship With No Increase In Infection Rates- https://www.emrap.org/episode/ema-2015-2/abstract26
• Infections In Open Fractures Of The Hand – https://www.emrap.org/episode/ema-1991-6/abstract22
• The Use Of Prophylactic Flucloxacillin In Treatment Of Open Fractures Of The Distal Phalanx Within An Accident And Emergency Department – https://www.emrap.org/episode/ema-2004-3/abstract25
• Episode 41: Scratch the Gent! Antibiotics for Open Fractures with Rob O’Connell-  https://pharm-so-hard.com/2021/06/18/41/
• Open Fractures: Unique Techniques – Alexandra Schwartz, MD (OTFC 2019, 2.3)- https://www.orthobullets.com/video/view?id=102373