Acute kidney injury during treatment with high-dose cloxacillin A report of 23 cases and literature review

Aurélie Lavergne (1) , Cécile Vigneau (2, 1) , Elisabeth Polard (1) , Louise Triquet (1) , Nathalie Rioux-Leclercq (2, 1) , Pierre Tattevin (2) , Léonard Golbin (1)

1 Centre Hospitalier Universitaire de Rennes [CHU Rennes] = Rennes University Hospital [Ponchaillou]
2 Irset - Institut de recherche en santé, environnement et travail

Background - International guidelines recommend high-dose cloxacillin for endocarditis or osteoarticular infections due to methicillin-susceptible staphylococci. However, data on the tolerability of these regimens are scarce.Methods - We used the computerized registry of suspected drug-related adverse events in our institution. Cases of acute kidney injury (AKI), as defined by KDIGO, in patients receiving high-dose cloxacillin were retrospectively reviewed. Data were collected from medical charts on a standardized questionnaire.Results - From 2009 to 2015, 23 consecutive patients (16 men, 7 women) with a median age of 75 years (interquartile range [IQR], 66-80) fulfilled inclusion criteria. By the time of AKI diagnosis, patients were treated with a median cloxacillin dose of 12 g/day (IQR, 10-12) after a median duration of 7 days (IQR, 4-10). Most patients (n=20) fulfilled RIFLE criteria for failure, with a median peak serum creatinine concentration of 339 µmol/L (IQR, 249-503). Urinalysis was indicative of tubular disease in 7 patients, 3 had hypereosinophilia and 8 had abnormal liver function tests. All patients presented at least one risk factor for AKI, including concomitant nephrotoxic drugs: gentamicin (n=19), diuretics (n=15), angiotensin-converting enzyme inhibitors (n=8) and angiotensin II receptor-blockers (n=6). Thirteen patients (57%) had cloxacillin plasma concentrations >50 µg/mL. Thirteen patients (57%) had complete recovery of renal function.Conclusions - AKI during high-dose cloxacillin treatment mostly occurs in elderly patients taking concomitant nephrotoxic drugs. The outcome is usually favourable after cloxacillin discontinuation. Therapeutic drug monitoring may decrease the risk of AKI in patients treated with high-dose cloxacillin.

Mots clés: Cloxacillin; High-dose; Therapeutic drug monitoring; Nephrotoxicity; Acute kidney injury

Domaines: Sciences pharmaceutiques; Urologie et Néphrologie

Aurélie Lavergne, Cécile Vigneau, Elisabeth Polard, Louise Triquet, Nathalie Rioux-Leclercq, et al.. Acute kidney injury during treatment with high-dose cloxacillin A report of 23 cases and literature review. International Journal of Antimicrobial Agents, 2018, 52 (3), pp.344-349. ⟨10.1016/j.ijantimicag.2018.04.007⟩. ⟨hal-01795802⟩