Tolerance and microbiological efficacy of cefepime or piperacillin/tazobactam in combination with vancomycin as empirical antimicrobial therapy of prosthetic joint infection: a propensity-matched cohort study
Authors: Triffault-Fillit C , Mabrut E , Corbin K , Braun E , Becker A , Goutelle S , Chaudier P , Fessy M H , Dupieux C , Laurent F , Gunst S , Lustig S , Chidiac C , Ferry T , Valour F ,   Lyon BJI Study Group, Ferry Tristan , Valour Florent , Perpoint Thomas , Miailhes Patrick , Ader Florence , Roux Sandrine , Becker Agathe , Triffault-Fillit Claire , Conrad Anne , Pouderoux Cécile , Benech Nicolas , Chauvelot Pierre , Perry Marielle , Daoud Fatiha , Lippman Johanna , Braun Evelyne , Chidiac Christian , Servien Elvire , Batailler Cécile , Gunst Stanislas , Schimdt Axel , Malatray Matthieu , Sappey-Marinier Eliott , Fessy Michel-Henry , Viste Anthony , Besse Jean-Luc , Chaudier Philippe , Louboutin Lucie , Ode Quentin , Van Haecke Adrien , Mercier Marcelle , Belgaid Vincent , Walch Arnaud , Martres Sébastien , Trouillet Franck , Barrey Cédric , Mojallal Ali , Brosset Sophie , Hanriat Camille , Person Hélène , Sigaux Nicolas , Céruse Philippe , Fuchsmann Carine , Aubrun Frédéric , Dziadzko Mikhail , Macabéo Caroline , Laurent Frederic , Beraut Laetitia , Roussel-Gaillard Tiphaine , Dupieux Céline , Kolenda Camille , Josse Jérôme , Craighero Fabien , Boussel Loic , Pialat Jean-Baptiste , Morelec Isabelle , Tod Michel , Gagnieu Marie-Claude , Goutelle Sylvain , Mabrut Eugénie 
Published: April 2020

Abstract

Background
The use of piperacillin/tazobactam with vancomycin as empirical antimicrobial therapy (EAT) for prosthetic joint infection (PJI) has been associated with an increased risk of acute kidney injury (AKI), leading us to propose cefepime as an alternative since 2017 in our reference centre.

Objectives
To compare microbiological efficacy and tolerance of these two EAT strategies.

Methods
All adult patients with PJI empirically treated with vancomycin+cefepime (n = 89) were enrolled in a prospective observational study and matched with vancomycin+piperacillin/tazobactam-treated historical controls (n = 89) according to a propensity score including age, baseline renal function and concomitant use of other nephrotoxic agents. The two groups were compared using Kaplan–Meier curve analysis, and non-parametric tests regarding the proportion of efficacious empirical regimen and the incidence of empirical therapy-related adverse events (AE).

Results
Among 146 (82.0%) documented infections, the EAT was considered efficacious in 77 (98.7%) and 65 (98.5%) of the piperacillin/tazobactam- and cefepime-treated patients, respectively (P = 1.000). The rate of AE, particularly AKI, was significantly higher in the vancomycin+piperacillin/tazobactam group [n = 27 (30.3%) for all AE and 23 (25.8%) for AKI] compared with the vancomycin+cefepime [n = 13 (14.6%) and 6 (6.7%)] group (P = 0.019 and &lt;0.001, respectively), leading to premature EAT discontinuation in 20 (22.5%) and 5 (5.6%) patients (P = 0.002). The two groups were not significantly different regarding their comorbidities, and AKI incidence was not related to vancomycin plasma overexposure.

Conclusions
Based on the susceptibility profile of bacterial isolates from included patients, microbiological efficacy of both strategies was expected to be similar, but vancomycin + cefepime was associated with a significantly lower incidence of AKI.