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Low prevalence of tissue detection of cefepime and daptomycin used as empirical treatment during revision for periprosthetic joint infections: results of a prospective multicenter study

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Abstract

Data demonstrating that antibiotics administered intraoperatively in patients with surgical revision for periprosthetic joint infection achieve concentrations exceeding minimal inhibitory concentrations of the identified bacteria at the surgical site when the new implant is inserted are lacking. We prospectively included patients with periprosthetic joint infection operated with one- or two-stage replacement during which cefepime (2g)-daptomycin (10mg/kg) combination was administered intravenously as intraoperative empirical antibiotic treatment. Three biopsies (two bones and one synovial membrane) were taken from each patient just before the insertion of the new implant. Eighteen adults of median age 68 years were included. Knee was involved in 10 patients (55.6%) and surgery consisted in one-/two-stage replacement in 11/7 patients. A tourniquet was used during the intervention in the 10 patients with knee prosthesis. Among 54 tissue samples, cefepime and daptomycin were detected respectively in 35 (64.8%) and 21 (38.9%) cases (P=0.01). A total of 17 bacteria dominated by staphylococci (n=14) were identified in 10 patients; tissue inhibitory quotient calculated in 51 samples was >1 in 22 cases (43.1%) for cefepime and in 16 cases (31.4%) for daptomycin. The proportion of tissue samples with detectable antibiotic was significantly higher in hip versus knee prosthesis (P=0.03). The present study suggests that intraoperative empirical administration of cefepime-daptomycin combination during septic prosthetic joint replacement results in a high proportion of tissue samples in which at least one of the two antibiotics was not detected or at a low concentration despite satisfactory concomitant blood serum concentrations.

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Acknowledgements

We greatly thank the Research Unit of Tourcoing Hospital for the technical assistance.

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Authors and Affiliations

  1. Infectious Diseases Department, Gustave Dron Hospital, 135 rue du Président Coty, F-59200, Tourcoing, France

    O. Robineau & Eric Senneville

  2. Lille University, F-59000, Lille, France

    O. Robineau & Eric Senneville

  3. Laboratory of Microbiology, University Hospital of Strasbourg, F-67000, Strasbourg, France

    E. Talagrand-Reboulh, F. Jehl, A. Grillon & P. Boyer

  4. Department of Orthopedic Surgery, University Hospital of Amiens, F-80000, Amiens, France

    B. Brunschweiler

  5. Department of Orthopedic Surgery, Gustave Dron Hospital of Tourcoing, F-59000, Tourcoing, France

    E. Beltrand

  6. Laboratory of Microbiology, University Hospital of Amiens, F-80000, Amiens, France

    F. Rousseau

  7. Laboratory of Microbiology, Gustave Dron Hospital of Tourcoing, F-59000, Tourcoing, France

    N. Blondiaux

  8. Infectious Diseases Department, University Hospital of Amiens, F-80000, Amiens, France

    C. Joseph

  9. Department of Anesthesiology, Gustave Dron Hospital of Tourcoing, F-59000, Tourcoing, France

    P. Lambotte

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  1. O. Robineau
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from behalf of the G4 Bone and Joint infection study group

Contributions

ES, OR, and FJ participated in the design of the study; ES, ETR, FJ, and OR wrote the manuscript; EB and BB operated the patients; NB, FR, and AG performed the microbiological analysis; CJ, ES, and OR participated in the medical management of the patients; ETR, AG, PB, and FJ performed the dosages of cefepime and daptomycin; PL managed the anesthesiology part of the protocol.

Corresponding author

Correspondence to Eric Senneville.

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Ethics approval

The study was recorded in clinicaltrial.gov under the number NCT02860767, in the EudraCT database under the number 2013-000889-11 and was approved by the National Agency for Medicines and Health Products’ Safety on 27 October 2015 and by the French Nord-Ouest IV Committee of Protection of the People in Biomedical Research on 8 March 2016.

Consent to participate

All patients gave their written consent to participate in the study.

Conflict of interest

ES and FJ declare congress support, speaker invitation, and participation to scientific board with Novartis Pharma; OR declares speaker invitation and participation to scientific board with Gilead, ViiV, and MSD. Other co-authors do not declare any potential conflict of interest in relation with the present study.

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Robineau, O., Talagrand-Reboulh, E., Brunschweiler, B. et al. Low prevalence of tissue detection of cefepime and daptomycin used as empirical treatment during revision for periprosthetic joint infections: results of a prospective multicenter study. Eur J Clin Microbiol Infect Dis 40, 2285–2294 (2021). https://doi.org/10.1007/s10096-021-04277-4

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