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General Orthopaedics

EFFICACY AND SAFETY OF INTRAVENOUS FOSFOMYCIN IN PATIENTS WITH PERIPROSTHETIC JOINT INFECTION: PRELIMINARY RESULTS FROM THE PROOF STUDY. A PROSPECTIVE MULTICENTRE STUDY

European Bone and Joint Infection Society (EBJIS) meeting, Antwerp, Belgium, September 2019.



Abstract

Aim

We evaluated the efficacy and safety of treatment regimens in a pathogen and surgery specific mode according to a standardized algorithm for the treatment of periprosthetic joint infection (PJI) based on combinations with 15g/d intravenous fosfomycin followed by oral antibiotics for totally 12 weeks.

Method

Consecutive patients with PJI caused by at least one of the following isolates were prospectively included: staphylococci (MIC ≤32 mg/l), streptococci (MIC ≤128 mg/l), enterococci (MIC ≤128 mg/l), Enterobacteriaceae (MIC ≤32 mg/l) and Pseudomonas spp. (MIC ≤128 mg/l). PJI was defined by the proposed European Bone and Joint Infection Society (EBJIS) criteria. Follow up with clinical (joint function and quality of life scores), laboratory and radiological evaluation at 3, 12 and 24 months after last surgery is performed. Infection outcome was assessed as the proportion of infection-free patients. The probability of infection-free survival was estimated using the Kaplan-Meier survival method.

Results

50 patients were screened for eligibility, of which 2 were excluded due to intolerance or allergy to fosfomycin, 1 due to isolation of fosfomycin resistant pathogen and 2 patients died due to unrelated cause to infection. The remaining 45 patients were included. Due to persistence of infection, 3 patients underwent prosthesis explantation after initial debridement and retention, 1 patient underwent debridement of Girdlestone-situation; all 4 infections were caused by S. aureus. At 2 patients debridement of hematoma after Girdlestone approach was performed. 41 patients were infection-free (91%) after a median follow-up of 6 month (range, 1 – 14 months). Nausea (n=14) and hypokalemia (n=13) were the most frequent adverse events and resolved after fosfomycin discontinuation; 5 patients had diarrhea and vomiting was observed in 2 patients. Isolated pathogens were staphylococci (n=30), streptococci (n=3), enterococci (n=5) and gram-negative rods (n=2). Cultures were negative in 9 patients and polymicrobial in 2 patients. The infection occurred postoperatively in 31 patients (69%) and hematogenously in 14 (31%). Two-stage exchange was performed in 27 (60%), debridement with retention in 13 (29%) and one-stage exchange in 5 patients (11%).

Conclusions

The applied PJI treatment algorithm including intravenous fosfomycin in the initial postoperative period was associated with infection-free outcome of 91% after a median follow-up of 6 month. The Kaplan-Meier survival method showed the probability of infection-free survival of 88.5% after 1 year. Adverse events occurred in 21 patients (46%) mostly nausea and hypokalemia were reported. Adverse events were mild and resolved completely.


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