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

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 <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.

Cost of off-label antibiotic therapy for bone and joint infections: a 6-year prospective monocentric observational cohort study in a referral centre for management of complex osteo-articular infections

“…Generic drugs are defined as bio-equivalent replicas of brand name drugs, containing the same active molecules, with identical quality, safety, and efficacy profiles. Only inactive ingredients, like colouring, flavouring, and stabilizing agents can differ (Wouters et al, 2017). Generic drugs can be approved for sale when relevant patents and legal exclu-sivities have expired (generally 20 years) or when the patent owner waives their rights (Gulsen Oner and Polli, 2018).…”

“…Unfortunately, these results do not represent what is has been achieved in other countries. In Switzerland, the proportion of prescriptions filled with generic drugs is only about 17 % to 23 %, while in France it is about 30 % to 40 % -far from Germany and Great Britain, with 80 % to 82 % and 83 % to 85 %, respectively (Wouters et al, 2017;Decollogny et al, 2011; Organisation for Economic Co-Operation and Development (OECD), 2019). Nevertheless, without the generic molecules of daptomycin and linezolid, the costs associated with ETs during the study period could not have been stable and would have increased dramatically, especially in 2019 with the use of tedizolid, ceftolozane-tazobactam, and ceftazidime-avibactam.…”

Proposed empiric antibiotic therapy for prosthetic joint infections: an analysis of the Prosthetic Joint Infection in Australia and New Zealand, Observational (PIANO) cohort

“…As well as the risks of unnecessarily broad‐spectrum therapy (such as dysbiosis and individual and community risk of multi‐resistant organism acquisition), there is the direct risk of adverse effects in the individual patient. Vancomycin is associated with an increased risk of acute kidney injury when used as empiric therapy for PJI 16,17 . This is one reason we recommend cefazolin rather than vancomycin as empiric therapy for late acute infections.…”

“…Vancomycin is associated with an increased risk of acute kidney injury when used as empiric therapy for PJI. 16,17 This is one reason we recommend cefazolin rather than vancomycin as empiric therapy for late acute infections.…”

Lowered Risk of Nephrotoxicity through Intervention against the Combined Use of Vancomycin and Tazobactam/Piperacillin: A Retrospective Cohort Study

“…Based on the findings of a previous study, that is, an AKI risk of 25.8% and 6.7% with the combination and comparator, respectively ( 37 ), with an assumed detection power of 0.8, the sample size was calculated as 63 participants in each group for the primary endpoint.…”