Tolerability of prosthetic joint infection empirical antimicrobial therapy: a prospective cohort study [PublishAheadOfPrint]

Objectives: The empirical use of vancomycin in combination with a broad-spectrum betalactam is currently recommended after the initial surgery of prosthetic joint infection (PJI). However, the tolerability of such high-dose intravenous regimens is poorly known.

Patient and methods: Adult patients receiving an empirical antimicrobial therapy (EAT) for a PJI were enrolled in a prospective cohort study (2011-2016). EAT-related adverse events (AE) were described according to the common terminology criteria for AE (CTCAE), and their determinants were assessed by logistic regression and Kaplan-Meier curve analysis.

Results: The EAT of the 333 included patients (median age, 69.8 (IQR, 59.3-79.1)) mostly relies on vancomycin (n=229, 68.8%), piperacillin/tazobactam (n=131, 39.3%) and/or 3^rdGC (n=50, 15%). Forty-two (12.6%) experienced an EAT-related AE. Ten (20.4%) AE were severe (CTCAE grade ≥3). The use of vancomycin (OR, 6.9; 95%CI, 2.1-22.9), piperacillin/tazobactam (OR, 3.7; 95%CI, 1.8-7.2) or the combination of both (OR, 4.1; 95%CI, 2.1-8.2) were the only AE predictors. Acute kidney injury (AKI) was the most frequent AE (n=25; 51.0% of AE), and was also associated with the use of the vancomycin and piperacillin/tazobactam combination (OR, 6.7; 95%CI, 2.6-17.3). A vancomycin plasma overexposure was noted in 9 (37.5%) of the vancomycin-related AKI, only. Other vancomycin-based therapies were significantly less at risk of AE and AKI.

Conclusions: The EAT of PJI is associated with an important rate of AE, linked with the use of the vancomycin and piperacillin/tazobactam combination. These results corroborate recent finding suggesting a synergic toxicity of these drugs in comparison with vancomycin-cefepime, which remain to be evaluated in PJI.

https://ift.tt/2mC9cwf