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Suppressive Antibiotic Therapy after Debridement, Antibiotics, and Implant Retention (DAIR) is Well-Tolerated Without Inducing Resistance: A Multicenter Study

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Abstract
Background Suppressive antibiotic therapy (SAT) after total joint arthroplasty (TJA) debridement, antibiotics, and implant retention (DAIR) maximizes reoperation-free survival. Our aims were to evaluate SAT after DAIR of acutely infected primary TJA regarding: 1) adverse drug reaction (ADR)/intolerance; 2) reoperation for infection; and 3) antibiotic resistance. Methods Patients who underwent total knee arthroplasty (TKA) or total hip arthroplasty (THA) DAIR for acute PJI at two academic medical centers from 2015 to 2020 were identified (n = 115). Data were collected on patient demographics, infecting organisms, antibiotics, ADR/intolerances, reoperations, and antibiotic resistances. Median SAT duration was 11 months. Stepwise multivariate logistic regressions were used to identify covariates significantly associated with outcomes of interest. Results There were 11.1% and 16.3% of TKA and THA DAIR patients, respectively, who had ADR/intolerance to SAT. Patients prescribed trimethoprim/sulfamethoxazole (TMP-SMZ) (P = 0.0014) or combination antibiotic therapy (P = 0.0169) after TKA DAIR had increased risk of ADR/intolerance. There was no difference in reoperation-free survival between TKA (83.3%) and THA (65.1%) DAIR (P = 0.5900) at mean 2.8-year follow-up. Risk of reoperation for infection was higher among TKA Staphylococcus aureus infections (P = 0.0004) and lower with increased SAT duration (P < 0.0450). The optimal duration of SAT was nearly 2 years. No cases of antibiotic resistance developed due to SAT. Conclusion One should consider SAT after TJA DAIR due to improved reoperation-free survival and favorable safety profile. Prolonged SAT did not induce antibiotic resistance. Use TMP-SMZ with caution because of the increased likelihood of ADR/intolerance.
Publication
The Journal of Arthroplasty
Date
9/2023
DOI
10.1016/j.arth.2023.09.004
URL
https://linkinghub.elsevier.com/retrieve/pii/S0883540323009257
Notes

Key Question: What is the effectiveness and safety of suppressive antibiotic therapy (SAT) after debridement, antibiotics, and implant retention (DAIR) for acute periprosthetic joint infection (PJI) following total knee arthroplasty (TKA) or total hip arthroplasty (THA)?

Key Findings:

  • 11.1% of TKA and 16.3% of THA patients had adverse drug reactions (ADR) or intolerance to SAT requiring change or discontinuation of therapy. Use of trimethoprim-sulfamethoxazole and combination antibiotic therapy increased risk of ADR/intolerance after TKA DAIR.
  • Reoperation-free survival was 83.3% for TKA and 65.1% for THA at mean 2.8 years after DAIR. Increased duration of SAT decreased risk of reoperation for infection in both groups. The optimal duration was nearly 2 years.
  • No cases of antibiotic resistance developed due to SAT.

Clinical Implications:

  • SAT should be considered after DAIR for acute PJI in TKA and THA given improved reoperation-free survival rates and generally favorable safety profile.
  • Use trimethoprim-sulfamethoxazole cautiously due to increased ADR/intolerance.
  • Prolonged SAT for nearly 2 years provides maximum benefit in reducing reoperations, without increasing risk of antibiotic resistance.

Strengths:

  • Multicenter retrospective cohort design with adequate sample size
  • Strict inclusion/exclusion criteria
  • Primary outcomes of ADR/intolerance and reoperation for infection recurrence clearly defined
  • Use of appropriate statistical analyses, including multivariate regression, to identify factors associated with outcomes

Limitations:

  • Retrospective design relies on accuracy/completeness of available data
  • Single geographic region limits generalizability
  • Moderate follow-up duration; unknown if longer follow-up would change observations
  • Unable to evaluate changes in patient microbiome due to SAT

Level of Evidence: Moderate

Rationale: Well-designed retrospective cohort study, provides better evidence than case series alone. Prospective comparative study would further strengthen evidence.

Citation
1.
Nandi S, Doub JB, DePalma BJ, et al. Suppressive Antibiotic Therapy after Debridement, Antibiotics, and Implant Retention (DAIR) is Well-Tolerated Without Inducing Resistance: A Multicenter Study. The Journal of Arthroplasty. Published online 2023:S0883540323009257.
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