L. Bernard, C. Arvieux, B. Brunschweiler, S. Touchais, S. Ansart, J.-P. Bru, E. Oziol, C. Boeri, G. Gras, J. Druon, P. Rosset, E. Senneville, H. Bentayeb, D. Bouhour, G. Le Moal, J. Michon, H. Aumaître, E. Forestier, J.-M. Laffosse, T. Begué, C. Chirouze, F.-A. Dauchy, E. Devaud, B. Martha, D. Burgot, D. Boutoille, E. Stindel, A. Dinh, P. Bemer, B. Giraudeau, B. Issartel, and A. Caille
N Engl J Med 2021;384:1991-2001.
DOI: 10.1056/NEJMoa2020198
Summary by Colin Baker, BS
Prosthetic joint infection (PJI) remains a devastating complication following total joint arthroplasty. PJI is often managed with a combination of surgical intervention and oral or intravenous (IV) antimicrobial therapy. Surgical procedures may include extensive debridement, 1-stage, or 2-stage exchange arthroplasty. The choice of antibiotic therapy often depends on results obtained from cultures and susceptibility of the causative organism [1]. Although systemic antibiotics are commonly used for treatment of PJI, the optimal duration of therapy is undefined.
In this study, Bernard et al. compared the efficacy and safety of antibiotic therapy for the treatment of PJI when administered for either 6 weeks or 12 weeks. Four hundred ten patients at 28 sites across France were randomized 1:1 to receive either 6 or 12 weeks of antibiotic therapy. Prior to antibiotic therapy, patients underwent appropriate surgical intervention at the discretion of the treating surgeon. Patients who had at a minimum of one clinical symptom of PJI with at least two distinct cultures demonstrating the same pathogen were considered eligible for the study. Six patients withdrew from the study, leaving 203 patients in the 6-week group and 201 in the 12-week group. Patients were followed for 2 years after the end of antibiotic therapy.
Debridement with retention of implant components was performed in 40.4% of patients in the 6-week group and 42.3% in the 12-week group. Furthermore, 37.9% of the 6-week group and 36.3% of the 12-week group underwent 1-stage exchange while 21.7% and 21.4% underwent 2-stage exchange, respectively. Rifampin (n=267) and fluoroquinolone (n=260) were the most frequent oral antibiotic agents; 194 patients received both. Methicillin or cephalosporin were the initial intravenous antibiotic for 136 of 221 patients with PJI due to methicillin-susceptible staphylococci. Persistent infection with the initial causative pathogen occurred in 18.1% of patients who received 6-weeks of antibiotic therapy compared to 9.4% in the 12-week group; the risk difference of 8.7% had a 95% confidence interval of 1.8-15.6%. However, 6.8% of the 6-week group and 10.6% of the 12-week group developed a new infection following treatment. No significant difference in incidence of serious adverse events, C. difficile infection, or hospital length of stay was observed.
This trial was not without limitations. First, the majority of patients in the 6-week group who failed treatment were treated with debridement and implant retention, indicating a possible confounding variable. Second, the unblinded design of the trial may lend itself to unintended bias. Lastly, antibiotic treatment was not standardized which allowed for variability in the chosen treatment regimens.
The authors concluded that 6-weeks of antibiotic therapy for PJI was not shown to be noninferior to a 12-week duration of treatment. Patients receiving 6-weeks of therapy experienced a higher incidence of unfavorable outcomes. Additionally, in an exploratory subgroup analysis, the difference in risk for persistent infection between the 6-week and 12-week groups among patients who underwent 1 or 2-stage exchange was less than those who underwent debridement alone, indicating a need for further exploration.
Reference:
- Gehrke T, Alijanipour P, Parvizi J. The management of an infected total knee arthroplasty. The Bone & Joint Journal 2015;97-B:20–9. https://doi.org/10.1302/0301-620X.97B10.36475.