Antibiotic Therapy for Prosthetic Joint Infection

Posted by Carla Rothaus

How did 6 weeks of antibiotic therapy compare with 12 weeks for the treatment of prosthetic joint infection in the trial by Bernard et al.? 

Bernard et al. conducted the Duration of Antibiotic Treatment in Prosthetic Joint Infection (DATIPO) trial to compare the efficacy and safety of a short course of antibiotic treatment (6 weeks) with the efficacy and safety of a longer course (12 weeks) in patients with prosthetic joint infections that had been caused by various pathogens and managed with appropriate surgical procedures. Read the NEJM Original Article here.

Clinical Pearls

Q: How common is treatment failure among patients with prosthetic joint infection?

A: Prosthetic joint infections are associated with considerable morbidity. The treatment of this condition is challenging and costly. The management of prosthetic joint infection involves both surgery and antimicrobial therapy. The classic surgical options include one-stage or two-stage implant exchange, resection arthroplasty (with or without arthrodesis), or débridement with implant retention. Treatment failure occurs in 11 to 35% of patients.

Q: What are potential benefits of shortening the course of antibiotic treatment in patients with prosthetic joint infection?

A: The duration of antibiotic therapy in patients with prosthetic joint infection is primarily based on expert recommendations rather than evidence. Patients usually receive long courses of antibiotic therapy, which can be up to 6 months for staphylococcal infections. However, several studies suggest that shorter courses may be appropriate for most cases of prosthetic joint infection or osteomyelitis and may be associated with reductions in the duration of hospital stay, incidence of adverse events, and emergence of microbiologic resistance.

Morning Report Questions

Q: How did 6 weeks of antibiotic therapy compare with 12 weeks for the treatment of prosthetic joint infection in the trial by Bernard et al.?

A: The primary outcome of this trial was persistent infection within 2 years after the end of antibiotic therapy. Persistent infection occurred in 35 of 193 patients (18.1%) in the 6-week group and in 18 of 191 patients (9.4%) in the 12-week group. The difference in the risk of persistent infection (6-week group vs. 12-week group) was 8.7 percentage points (95% confidence interval [CI], 1.8 to 15.6), which did not meet the criterion for noninferiority. Noninferiority was also not shown in the per-protocol and sensitivity analyses. The results of the post hoc subgroup analyses consistently favored the 12-week group. The authors did not find clinically significant between-group differences with respect to serious adverse events, Clostridioides difficile infection, duration of hospital stay, or functional outcomes. A higher proportion of patients had nonserious adverse events in the 12-week group than in the 6-week group; the difference was mainly due to gastrointestinal side effects and mycosis.

Q: What were some of the limitations of the DATIPO trial?

A: First, most of the treatment failures in the 6-week group occurred among the patients who had undergone débridement with implant retention, although no heterogeneity was found in the subgroup analysis. Future studies should be directed at a single surgical procedure such as débridement with implant retention or prosthetic joint replacement but not both in the same trial. Second, this trial was open-label, but detection bias was minimized by adjudication of treatment failure by an independent committee whose members were unaware of the trial-group assignments. Because the choice of antibiotics was left to the treating physician, antibiotic treatment was not standardized, which led to the use of a wide variety of molecules, with different routes of administration. Prosthetic joint infection is typically managed with surgery and a prolonged course of antibiotics with an intravenous route of administration (U.S. standard), which has limited evidence of superiority over an oral route of administration. In this trial, the duration of intravenous antibiotic therapy was not standardized and was shorter than the U.S. standard.

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