SLR - June 2020 - Anaida Abagyan-Stanczyk

Gram-Negative Antibiotic Coverage in Gustillo-Anderson Type-III Open Fractures

Reference: Hand TL, Hand EO, Welborn A, Zelle BA. Gram-Negative Antibiotic Coverage in Gustillo-Anderson Type-III Open Fractures. J Bone Joint Surg Am. 2020 Apr 20. doi: 10.2106/JBJS.19.01358

Scientific Literature Review

Reviewed By: Anaida Abagyan-Stanczyk, DPM
Residency Program: New York Presbyterian Queens – Queens, NY

Podiatric Relevance: Gustillo-Anderson Type-III fractures carry a significant risk of mortality and morbidity. Antibiotic treatment guidelines have not changed for decades, even though antibiotic resistance and negative effects of broad spectrum antibiotics have emerged. No guidelines exist from the American Academy of Orthopedic Surgeons or the Orthopedic Trauma Association, and the current guidelines from Eastern Association for the Surgery of Trauma (EAST) and Surgical Infection Society (SIS) differ in their recommendation. The EAST guidelines include gram-negative coverage in addition to gram-positive coverage, while SIS recommends gram-positive monotherapy. Gustillo-Anderson Type III antibiotic recommendation classically includes the addition of expanded gram-negative coverage, specifically aminoglycosides, to the gram-positive coverage. The purpose of this article is to review historical basis for the use of aminoglycosides, use of non-aminoglycoside gram-negative therapy and evidence for 1st generation cephalosporin monotherapy.

Methods: The authors reviewed prior research on antibiotic prophylaxis of Gustillo-Anderson type-III fractures and outcome measures of infection from historical studies in the beginning of the 20th century until 2000s. This article evaluated for infection with regard to timing of antibiotic administration, duration of prophylaxis, use of aminoglycoside, use of Zosyn and use of cephalosporin monotherapy.

Results: The optimal timing for antibiotic administration is unknown. Current evidence (level III studies), however, suggest early initiation to be beneficial. As for the duration of treatment, research is not specific to Gustillo-Anderson Type-III fractures and is equivocal in short term (24 hours) versus long term (24 hours to 10 days) treatment. Recent research has not shown aminoglycosides, when added to cephalosporins, to be effective in the prevention of infections caused by gram-negative bacilli, P. aeruginosa and Enterobacter. Zosyn monotherapy has been shown to be non-inferior to cefazolin with gentamycin combination therapy in a small (level of evidence?) study. Most recent studies evaluating infection rates between cefazolin monotherapy versus the addition of gentamicin to the treatment show no statistical difference or advantage in the gentamicin group against gram negative bacilli. These articles also highlight the potential complications of aminoglycosides, mainly acute kidney injury, supporting the use of cephalosporin monotherapy.  

Conclusions: Historically aminoglycosides have been used in Gustillo-Anderson Type-III fractures in an effort to prevent gram-negative bacilli infections, although current evidence shows no therapeutic benefit over cephalosporin monotherapy. Clinical practice guidelines are shifting away from aminoglycosides use altogether due to insufficient benefits and increased risk of renal toxicity and antibiotics resistance. Further research needs to be conducted for a reliable alternative for gram-negative antibiotic prophylaxis in Type-III open fractures. Meanwhile, cefazolin holds Grade B level of evidence and can be used as monotherapy prophylaxis even in Type-III open fractures. 

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