Comparative Rates of Nephrotoxicity in Patients Treated with Piperacillin-tazobactam and Meropenem: a Retrospective Cohort Study.

Background: Studies show an increase in acute kidney injury (AKI) in patients treated with piperacillin-tazobactam (PTZ) compared to those treated with cefepime. It is not known whether meropenem (MEM) increases the risk of AKI similarly. This study evaluated the incidence of AKI in patients treated with MEM or PTZ.

Methods: Data were collected from the University of Kentucky Center for Clinical and Translational Science Enterprise Data Trust from September 2007 through October 2015. Adults without previous renal disease, who received MEM or PTZ for at least 2 days were examined. Patients were matched on severity of illness, nephrotoxin exposure, and specific comorbidities.

Results: There were 15554 patients who met inclusion criteria, 776 received MEM and 14778 received PTZ. The MEM patients were younger (44[27-60] v 55 [42-66] years, p<0.0001), more likely to be female (54% v 44%, p<0.0001),  were slightly more ill (Charlson comorbidity index 4 [2-5.25] v 3 [1-7], p=0.003), and had higher baseline renal function (114 [79-153] v 91 [66-122] mL/min, p <0.0001). More MEM patients had cystic fibrosis (29.5% v 2.4%, p<0.0001). AKI occurred more frequently in the PTZ group (22.5% v 13.5%, p < 0.0001). The PTZ population receiving vancomycin (VAN) experienced more AKI than those receiving PTZ alone (27.5 v 11.8%, p <0.0001). MEM+VAN had higher AKI rates than MEM alone (16.4% vs 10.6%, p=0.02). Following matching, the AKI rates were 22.8% in PTZ patients compared to 13.6% in MEM patients (p<0.0001). Table 1 shows AKI rates in relation to VAN exposure. MEM+VAN was associated with an adjusted OR of 1.68 (1.1-2.6) for AKI incidence when compared to MEM alone. PTZ alone compared to MEM alone also increased the odds of AKI (aOR 1.5 [1.05-2.21]). PTZ+VAN patients had higher odds of AKI compared to MEM+VAN patients (aOR 2.19 [1.64-2.97]). Other independent predictors of AKI were baseline creatinine clearance ≥ 90 mL/min, and unknown BMI or BMI ≥30 kg/m².

Conclusion: PTZ with and without VAN was associated with more frequent AKI compared to MEM. The interaction of VAN and ß-lactams warrants further research.

Table 1: AKI rates (%) stratified by group and VAN exposure

	Unmatched	Matched
MEM	13.5	13.6
MEM alone	10.6	10.7
MEM+VAN	16.4	16.4
PTZ	22.5	22.8
PTZ alone	11.8	14.8
PTZ+VAN	27.5	30.2