F S Sinkeler, I J E Kouijzer, N G L Jager, J Ten Oever, E Leegwater, J Gisolf, D Reuling, Z M Spoel, M P M Hensgens, R J Brüggemann
Flucloxacillin was associated with increased AKI risk compared with cefazolin, with most AKI episodes occurring early after index blood culture and recovery decreasing with increasing AKI severity. Lower flucloxacillin doses were not associated with reduced AKI risk, suggesting that dose reduction alone may not mitigate flucloxacillin-associated nephrotoxicity.
BACKGROUND AND OBJECTIVES: Staphylococcus aureus bacteraemia (SAB) is associated with high mortality and frequent complications, including acute kidney injury (AKI). Although flucloxacillin has been associated with higher AKI rates than cefazolin, the clinical characteristics of AKI, including severity, timing, recovery and the potential influence of dosing, remain unclear.
METHODS: We conducted a retrospective multicentre cohort study across three hospitals in the Netherlands, including adults with SAB treated with cefazolin or flucloxacillin. AKI incidence and severity were compared using adjusted regression analyses. Time-to-event and cumulative incidence analyses were used to evaluate AKI timing and renal recovery. Among flucloxacillin-treated patients, the association between initial dose and AKI was evaluated.
RESULTS: Among 1408 patients, 483 (34.3%) developed AKI. Most AKI episodes occurred early after index blood culture (median 1.3 days), and recovery within 30 days decreased with increasing AKI severity (81.7% in Stage 1 versus 50.5% in Stage 3). AKI occurred more frequently among patients treated with flucloxacillin than cefazolin (466/1324 [35.2%] versus 17/84 [20.2%], P = 0.004). After multivariable adjustment, flucloxacillin remained associated with higher AKI risk (adjusted OR 2.37, 95% CI 1.30-4.55). Among patients with AKI, severity distribution did not differ between treatments (P = 0.599). Initial flucloxacillin dose was not associated with AKI occurrence, timing or severity.
CONCLUSIONS: Flucloxacillin was associated with increased AKI risk compared with cefazolin, with most AKI episodes occurring early after index blood culture and recovery decreasing with increasing AKI severity. Lower flucloxacillin doses were not associated with reduced AKI risk, suggesting that dose reduction alone may not mitigate flucloxacillin-associated nephrotoxicity.