gms | German Medical Science

German Congress of Orthopaedics and Traumatology (DKOU 2022)

25. - 28.10.2022, Berlin

Efficacy and safety of intravenous fosfomycin in patients with PJI: preliminary results from the PROOF study – a prospective multicenter study

Meeting Abstract

  • presenting/speaker Svetlana Karbysheva - Charité – Universitätsmedizin Berlin, Berlin, Germany
  • Paula Morovic - Charité – Universitätsmedizin Berlin, Berlin, Germany
  • Donara Margaryan - Charité – Universitätsmedizin Berlin, Berlin, Germany
  • Lilith Johannsen - Charité – Universitätsmedizin Berlin, Berlin, Germany
  • Antje Spranger - Charité – Universitätsmedizin Berlin, Berlin, Germany
  • Andrej Trampuz - Charité – Universitätsmedizin Berlin, Berlin, Germany

Deutscher Kongress für Orthopädie und Unfallchirurgie (DKOU 2022). Berlin, 25.-28.10.2022. Düsseldorf: German Medical Science GMS Publishing House; 2022. DocAB12-905

doi: 10.3205/22dkou018, urn:nbn:de:0183-22dkou0185

Published: October 25, 2022

© 2022 Karbysheva et al.
This is an Open Access article distributed under the terms of the Creative Commons Attribution 4.0 License. See license information at http://creativecommons.org/licenses/by/4.0/.


Outline

Text

Objectives: We evaluated 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.

Methods: Consecutive patients with hip, knee or shoulder 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<2 mg/l) and Pseudomonas spp. (MIC<128 mg/l). PJI was defined by the PRO-IMPLANT definition 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 was 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 and conclusion: 226 patients were included in the study, of whom 13 were excluded due to isolation of fosfomycin-resistant pathogens from intraoperative specimens (before fosfomycin treatment), 7 due to intolerance or allergy to fosfomycin, 4 patients due to unwillingness to participate in the study, and 16 patients due to other reasons according to exclusion criteria.Of the remaining 186 patients, two-stage exchange of the prosthesis was performed in 112 patients (60%), debridement with retention (DAIR) in 43 (23%), one-stage exchange in 27 (15%), and three-stage exchange in 4 patients (2%). Due to persistence of infection which was not related (n=23) or possibly related (n=1) to fosfomycin treatment, 6 patients underwent prosthesis explantation or one-stage exchange or change of mobile parts after initial DAIR, in 2 patients repeated one-stage exchange of the prosthesis was performed and 16 patients underwent debridement of Girdlestone or arthrodesis. In 5 patients repeated revision surgery was performed due to instability of the hip prosthesis or periprosthetic fracture. Isolated pathogens were mostly presented by staphylococci, followed by streptococci, enterococci and gram-negative rods. Cultures were negative in 23 patients and polymicrobial in 18 patients. The Kaplan-Meier analysis showed a probability of infection-free survival of 82% after 1 year and of 85% after 2 years. Nausea (n=28) and hypokalemia (n=44) were the most frequent adverse events and resolved after fosfomycin discontinuation; in 6 patients hypernatremia was observed, 8 patients had diarrhea and vomiting was documented in 10 patients.

In conclusion, PJI treatment regimens including intravenous fosfomycin in the initial therapy phase showed high efficacy (infection-free survival 85% after 2 years of follow-up). Fosfomycin-related adverse events were mostly mild and transitory, including nausea and hypokalemia.