Fig. 1 The duration of the holiday period was not significantly associated with reinfection; however, the duration of the spacer implantation was.
Courtesy of Timothy Tan, MD

AAOS Now

Published 11/1/2017
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Maureen Leahy

Two-stage Exchange Arthroplasty and the Antibiotic Holiday

Study finds that duration of the antibiotic-free period between stages does not affect treatment outcomes
Study results presented at the Musculoskeletal Infection Society (MSIS) annual meeting indicate that the duration of the antibiotic-free period often associated with two-stage exchange arthroplasty—the current gold standard for treating periprosthetic joint infection (PJI) following total joint arthroplasty—does not significantly affect reinfection rates following reimplantation.

Two-stage exchange arthroplasty involves resection of the infected implant and insertion of an interim antibiotic-impregnated spacer. After a period of time, a new prosthesis is implanted. However, there are no clear metrics for determining the optimal timing of reimplantation after spacer insertion, according to Timothy Tan, MD, who presented the data. Dr. Tan noted that many surgeons determine when to reimplant based on serum inflammatory markers trends, joint aspiration, or an antibiotic holiday period.

"The rationale of the antibiotic holiday period is to mitigate the influence of antibiotics. Clinical improvement of the patient during the holiday period signifies infection eradication, while deterioration suggests possible recurrence or persistence of infection," he explained. "Because there is little evidence to support this practice, the goal of our study was to determine the optimal duration of the antibiotic holiday period and to elucidate its clinical significance on treatment outcomes."

Study methods
The researchers retrospectively reviewed a multi-institutional database to identify patients who had undergone two-stage exchange arthroplasty for the treatment of PJI between 2000 and 2015. Patients whose PJIs met MSIS criteria, had a minimum of 1-year follow-up, and underwent reimplantation without any surgeries between stages were included in the analysis. Patients with the following were excluded:

  • no available antibiotic information
  • megaprostheses
  • spacer exchange or surgery prior to reimplantation
  • prolonged antibiotic holiday period (> 60 days)

A total of 409 patients (mean age: 64 years; mean body mass index [BMI]: 31) met the inclusion and exclusion criteria. Of the 409 patients, 211 (51 percent) were male; 282 (68.9 percent) of the procedures had been performed for PJI following total knee arthroplasty.

During the first stage of the procedures, static and dynamic spacers containing dual antibiotics were inserted after all prosthetic components were removed and extensive synovectomy and débridement had been performed. Patients then received a 4- to 8-week course of antibiotics. The duration of the antibiotic holiday period and the timing of reimplantation were at the surgeons' discretion.

Treatment success was defined using the following Delphi Consensus Criteria:

  • infection eradication, characterized by a healed wound without fistula, drainage, pain, or infection recurrence caused by the same organism strain
  • no subsequent surgical intervention for infection after reimplantation surgery
  • no occurrence of PJI-related mortality

Antibiotic-resistant organisms were defined as methicillin-resistant Staphylococcus aureus and vancomycin-resistant Enterococcus.

Duration of holiday period does not affect reinfection rates
The average duration of the holiday period was 29.8 days. Overall, treatment failed in 15.6 percent of the two-stage arthroplasties (64/409). The researchers found no differences in the treatment failure rate among PJIs reimplanted within an antibiotic holiday period of 1 week (odds ratio [OR] 1.45, 95 percent confidence interval [CI] 0.63-3.31, P = 0.38), 2 weeks (OR 1.46, 95 percent CI 0.78-2.74, P = 0.23), or 4 weeks (OR 1.06, 95 percent CI 0.62-1.82, P = 0.83).

Multivariate analysis was performed to determine the influence of the holiday period on treatment success and controlled for joint involvement, age, gender, resistant organisms, BMI, Charlson comorbidity index, and spacer implantation duration. The analysis revealed that the duration of the antibiotic holiday period was not significantly associated with reinfection following reimplantation (OR 0.94 per week, 95 percent CI 0.83-1.07, P = 0.38), suggesting no optimal threshold for its duration. "However, we did find that the duration of the spacer implantation was significantly associated with reinfection," Dr. Tan said (Fig. 1).

The researchers also analyzed 94 patients who underwent surgery in the interim stage for persistent or recurrent infection. "We found that 41.5 percent of patients who failed in the interim stage did so while on antibiotics, and 58.5 percent failed during the antibiotic holiday period at a mean of 26.1 days. Furthermore, 14 percent occurred within 14 days of antibiotic discontinuation," he said.

Dr. Tan noted that the study had several limitations. "In addition to being a retrospective study, the number of surgeons involved may account for widespread heterogeneity in treatment, results may be due to individual surgeon protocol, and it is possible that patients with worse infections were monitored with a longer holiday period," he said.

Based on the study's results, the authors conclude that the duration of the antibiotic-free period does not appear to significantly influence treatment failure after reimplantation. "However, many patients did fail during the holiday period and many failed 2 weeks after antibiotic discontinuation. Further prospective studies are needed to determine the optimal timing of reimplantation and duration of the antibiotic holiday period for two-stage exchange arthroplasty for PJI," Dr. Tan concluded.

Dr. Timothy Tan's coauthors of "Determining the Role and Duration of the 'Antibiotic Holiday' Period" are Michael M. Kheir, MD; Alexander J. Rondon MD, MBA; Javad Parvizi MD, FRCS; Jaiben George, MBBS; Carlos Higuera, MD; and Antonia D. Chen, MD, MBA.

Maureen Leahy is assistant managing editor of AAOS Now. She can be reached at leahy@aaos.org.

Bottom Line

  • No clear metrics exist to guide timing of reimplantation after spacer insertion during two-stage arthroplasty for PJI.
  • One method surgeons use to determine timing of reimplantation is an antibiotic holiday period between stages.
  • This study examined the clinical role of the antibiotic holiday period and attempted to determine its optimal duration.
  • The results indicate that the duration of the antibiotic holiday period does not significantly affect the PJI rate after reimplantation.
  • Further studies are needed to determine the optimal timing of reimplantation and duration of the antibiotic holiday period.

Reference:
Restrepo C, Schmitt S, Backstein D, Alexander BT, Babic M, Brause BD, et al: Antibiotic treatment and timing of reimplantation. J Orthop Res Off Publ Orthop Res Soc 2014;32 Suppl 1:S136-140. doi:10.1002/jor.22557.