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Open Fracture Management: Antibiotics

Introduction

  1. Open fracture wounds are considered high energy injuries that come with a high risk of infection due to the potential exposure of bone and tissue to environmental pathogens.
  2. The Gustilo- Anderson classification system grades open fractures and can be utilized to guide antimicrobial prophylaxis.
  3. For Type I fractures, which are clean wounds less than 1 centimeter long, gram positive coverage is recommended; cefazolin is usually the agent of choice.
  4. For Type II factures, which are wounds greater than 1 centimeter long without extensive soft tissue damage, gram positive coverage is recommended; cefazolin is usually the agent of choice.
  5. For Type III fractures, which are open segmental fractures that have extensive soft tissue damage, gram negative coverage is recommended, in addition to gram positive coverage. Aminoglycosides such as gentamicin formerly were the gram-negative agent of choice, to be given in addition to an agent such as cefazolin. However, more recently monotherapies such as ceftriaxone and piperacillin-tazobactam have been studied as a potential alternative. Type III fractures may carry an infection risk up to 50%.
  6. For injuries involving fecal or clostridial contamination such as farm-related injuries, high dose penicillin should be added as well. For injuries with saltwater contamination, the addition of doxycycline should also be considered.

Pharmacology
 CeftriaxoneCefazolinGentamicin
Dose2 grams2 grams (3 grams if >120 kg)5 mg/kg
AdministrationIV as a bolus over 3 to 5 minutesIV as a bolus over 3 to 5 minutesIV infusion over 30 to 120 minutes
PK/PDVd: ~6 to 14 L T1/2: ~5 to 9 hoursVd: 0.193 ± 0.064 L/kg T1/2: 1.8 hours Time to peak: within 5 minsVd: 0.2 to 0.3 L/kg T1/2: 2 hours Time to peak: 30 minutes after 30 min infusion
Adverse EffectsSkin rash; GI ADEsSkin rash; GI ADEsNephrotoxicity; neurotoxicity (including ototoxicity)
Drug Interactions and warningsDrug interactions: aminoglycosides, warfarin, probenecidWarnings: may elevate INRDrug interactions: aminoglycosides, warfarin, fosphenytoin, rifampin, probenecidWarnings: may elevate INR; cause in caution with penicillin allergyDrug interactions: other nephrotoxic agents; neuromuscular blockersWarnings: may cause irreversible renal damage; may cause neuromuscular blockade and respiratory paralysis; may cause irreversible neurotoxicity
CompatibilityCompatible with NS, D5W Not compatible with LRCompatible with LR, NS, D5WCompatible with LR, NS

 Overview of Evidence 
Author, yearDesign/ sample sizeIntervention & ComparisonOutcome
O’Connell, 2022Single-center retrospective cohort study (n=120) in type III open fracturesPiperacillin-tazobactam (PT) vs cefazolin with or without aminoglycosidePer univariate analysis, more infections in PT group (23.7% vs. 4.3%; p = 0.042), however per multivariate analysis, antibiotic choice was not a predictor of infection (OR, 5.81 [95% CI, 0.73–46.25; p = 0.096])
Shawar, 2020Single-center retrospective cohort study (n=82) in type III open fracturesHigh dose tobramycin with either cefazolin or clindamycin vs PTFaster time to admin: 179 mins vs 77 mins (p<0.05) with PT   Fewer surgical site infections (SSI) at 30 days: 27.5% vs 4.3% (p = 0.033) and at 60 days: 32% vs 4.3% (p = 0.009) with PT
Depcinski, 2019Single-center retrospective cohort study (n=68) in type III open fracturesCefazolin alone vs cefazolin with an aminoglycosideGreater rates of infection in combination group: (40% vs 15.1%, P = 0.035)
Patanwala, 2019Single-center retrospective cohort study (n=134) in type III open fracturesCefazolin alone vs cefazolin with an aminoglycosideNo difference in rate of infection: (15% vs 16%, P = 1.000)
Redfern, 2016Single-center retrospective study (n=72) in type III open fracturesCefazolin with gentamicin vs PTNo difference in rate of SSI at 30 days (21.69% vs 11.4%; p = 0.246) or 1 year (32.4% vs 31.4%; p = 1.000)
Rodriguez, 2014Single-center retrospective study (n=174) in open fracturesPre-protocol (grade I-II cefazolin, grade III cefazolin plus gentamicin) vs post-protocol (cefazolin for grade I-II, ceftriaxone for grade III)No difference in rate of SSI (20.8% vs 24.7%; p = 0.58)
Patzakis, 1974Single center retrospective study (n=310) in open fracturesPenicillin plus streptomycin vs cephalothin vs no antibioticsRate of infection: 9.7% v 2.3% vs 13.9%
Gustilo, 1976Retrospective (n= 673) and prospective (n=352) analysis in open fracturesIn retrospective study, from 1955-1960, patients given penicillin and streptomycin; from 1961- 1967, patients given penicillin and chloramphenicol   In prospective study, patients given oxacillin-ampicillin before surgeryRetrospective infection rate: from 1955-1960, 12% vs from 1961-1968, 5% Prospective infection rate: 2.5% For type III open fractures specifically, infection rates 44% in retrospective study; 9% in prospective study

Conclusions

Antimicrobial prophylaxis is an important component of open fracture management; without appropriate antibiotic selection, infection rates may be up to 50%. For grade I and II fractures, gram positive coverage is needed, and cefazolin is a reasonable agent of choice. For grade III fractures, broadened coverage included gram negatives is recommended. Emerging evidence suggest ceftriaxone or piperacillin-tazobactam may be reasonable agents of choice.

References

  1. Ceftriaxone. Micromedex [Electronic version].Greenwood Village, CO: Truven Health Analytics. Retrieved February 10, 2022, from http://www.micromedexsolutions.com/
  2. Cefazolin. Micromedex [Electronic version].Greenwood Village, CO: Truven Health Analytics. Retrieved February 10, 2022, from http://www.micromedexsolutions.com/
  3. Gentacicin (systemic). Micromedex [Electronic version].Greenwood Village, CO: Truven Health Analytics. Retrieved February 10, 2022, from http://www.micromedexsolutions.com/
  4. 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). 2022 Feb;23(1):41-46. doi: 10.1089/sur.2021.122. Epub 2021 Oct 5. PMID: 34612703.
  5. 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.
  6. 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.
  7. 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.
  8. 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.
  9. 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.
  10. Patzakis MJ, Harvey JP Jr, Ivler D. The role of antibiotics in the management of open fractures. J Bone Joint Surg Am. 1974 Apr;56(3):532-41.
  11. 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.

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