Short- versus standard-course intravenous antibiotics for peri-prosthetic joint infections managed with debridement and implant retention: a randomised pilot trial using a desirability of outcome ranking (DOOR) endpoint

Authors/contributors
Abstract
Background Peri-prosthetic joint infection (PJI) is a devastating complication of joint replacement surgery. Determining the optimal duration of intravenous (IV) antibiotics for PJI managed with debridement and implant retention (DAIR) is a research priority. Methods Patients undergoing DAIR for early and late-acute PJI of the hip or knee were randomised to receive 2 (short-course) or 6 (standard-course) weeks of IV antibiotics, with both groups completing 12 weeks of antibiotics in total. The primary endpoint of this pilot, open-label, randomised trial was a 7-point ordinal desirability of outcome ranking (DOOR) score, which accounted for mortality, clinical cure and treatment adverse events at 12 months. Duration of IV treatment was used as a tiebreaker, with shorter courses ranked higher. Outcome adjudication was performed by expert clinicians blinded to the allocated intervention (Australia and New Zealand Clinical Trials Registry ACTRN12617000127303). Results 60 patients were recruited; 31 and 29 were allocated to short- and standard-course treatment, respectively. All had an evaluable outcome at 12 months and were analysed by intention-to-treat. Clinical cure was demonstrated in 44 (73%) overall; 22 (71%) in the short-course group and 22 (76%) in the standard-care group (P=0.77). Using the DOOR approach, the probability that short- was better than standard-course treatment was 59.7% (95% confidence interval 45.1-74.3). Conclusions In selected patients with early and late-acute PJI managed with DAIR, shorter courses of IV antibiotics may be appropriate. Due to small sample size, these data accord with, but do not confirm, results from other international trials of early transition to oral antibiotics.
Publication
International Journal of Antimicrobial Agents
Date
07/2022
Notes

Key question: Among patients with early or late-acute peri-prosthetic joint infection (PJI) treated with debridement and implant retention (DAIR), is a short 2-week course of intravenous (IV) antibiotics non-inferior to a standard 6-week course?

Key findings:

  • In this open-label randomized pilot trial of 60 patients, the probability that short-course IV antibiotics resulted in a better desirability of outcome ranking (DOOR) score compared to standard course was 59.7%.
  • There were no significant differences in treatment failure rates, prosthesis removal, death, or Oxford knee/hip scores between the short and standard course groups.

Clinical implications:

  • In selected patients with early/late-acute PJI treated with DAIR, shorter 2-week courses of IV antibiotics may be appropriate compared to the standard 6-week course. However, this small pilot study does not provide definitive evidence.

Strengths:

  • Randomized trial design
  • Blinded outcome assessment
  • Novel DOOR endpoint incorporated mortality, cure, and adverse events
  • Per protocol and intention-to-treat analyses

Limitations:

  • Small sample size without power calculation
  • Open-label study
  • Highly selected patient population limits generalizability
  • Unable to control for surgical factors

Citation
1.
Manning L, Metcalf S, Dymock M, et al. Short- versus standard-course intravenous antibiotics for peri-prosthetic joint infections managed with debridement and implant retention: a randomised pilot trial using a desirability of outcome ranking (DOOR) endpoint. International Journal of Antimicrobial Agents. 2022;60(1):106598.