Nephrotoxicity Incidence Compared for Two Beta-Lactam Antibiotics

Nafcillin was associated with greater acute kidney injury and in-hospital mortality vs. cefazolin.

NEW ORLEANS, LA—Nafcillin was associated with greater acute kidney injury and in-hospital mortality vs. cefazolin, W. Cliff Rutter, PharmD, from University of Kentucky HealthCare, Lexington, KY, presented at IDWeek 2016.

For methicillin-sensitive Staphylococcus aureus (MSSA) infections, treatment with antistaphylococcal beta-lactam antibiotics are standard. Nafcillin is associated with significant adverse events such as acute kidney injury and cefazolin has been associated with treatment failures in high bacterial burden infections (eg, endocarditis, osteomyelitis). Dr. Rutter and researchers evaluated the incidence of acute kidney injury and in-hospital mortality in patients treated with nafcillin vs. cefazolin. They obtained electronic medical record data from the University of Kentucky Center for Clinical and Translational Science Enterprise Data Trust between 9/1/2007 to 10/1/2015.  

Patients receiving nafcillin or cefazolin for ≥48 hours were included; patients who were pregnant, had chronic kidney disease, baseline CrCl <30mL/min or vancomycin therapy were excluded. The RIFLE criteria was used to assess AKI and comparative statistics and multivariate logistic regression were performed. Patients were also matched on baseline renal function, concomitant nephrotoxins, and comorbidities predisposing to acute kidney injury. 

A total of 518 patient receiving nafcillin and 3.433 patients receiving cefazolin were included for the analysis. The nafcillin group had higher baseline renal function (101 vs. 92mL/min; P<0.0001). Acute kidney injury was observed in 29.2% of nafcillin treated patients vs. 14.8% of cefazolin-treated patients (P<0.0001). Also, nafcillin-treated patients were more likely to experience in-hospital mortality (14.3% vs. 4.9%; P<0.0001) but this trend was not evident when stratified by endocarditis, osteomyelitis or bacteremia. 

After patient matching, the rate of acute kidney injury for nafcillin-treated patients stayed at 29.2% and the rate in cefazolin patients was 21.6% (P=0.007). Receiving nafcillin was associated with an adjusted odds ratio [OR] or 1.59 (95% CI: 1.19–2.14; P=0.002) for acute kidney injury vs. cefazolin. 

“Mortality was more common in patients treated with nafcillin but infection-specific mortality was not different in the matched cohort, suggesting nafcillin patients were more ill at baseline,” noted Dr. Rutter.

Factors that increased the likelihood of acute kidney injury were exposure to loop diuretics (OR 2.38, 95% CI: 1.76–3.23; P<0.001) or hypotension (OR 2.17, 95% CI: 1.6–2.97; P<0.001). The length of hospitalization was similar between the groups, the study authors added. 

Based on the study’s findings, the authors concluded that cefazolin may be a reasonable alternative treatment to nafcillin.