A Matched Cohort Study Evaluating the Comparative Incidence of Adverse Renal Outcomes in Patients Receiving Vancomycin and Piperacillin-Tazobactam in Combination or as Monotherapy

Background: This study evaluated the comparative incidence of adverse renal outcomes in patients treated with Vancomycin monotherapy (VAN), Piperacillin-Tazobactam monotherapy (PTZ) and concurrent VAN and PTZ (COMBO).

Methods: Retrospective matched cohort comparing the incidence of acute kidney injury (AKI) and nephrotoxicity (NT) between 3 groups (VAN, PTZ, and COMBO). Inclusion criteria: admitted between 9/2013 and 8/2014, age ≥ 18 y, received IV VAN, PTZ or COMBO for ≥ 2 days. Exclusion criteria: pregnant, ANC < 1000/mm³, AKI on admission, and cystic fibrosis. VAN, PTZ and COMBO were matched 1:1:1 on exact combination of 4 risk factor categories. Outcomes assessment was blinded and included: NT (≥ 2 serum creatinine [SCr] levels ≥ 0.5 mg/dL or ≥ 50% [whichever was greater] above baseline) and AKI (increase in SCr ≥ 0.3 mg/dL above baseline or reduction in urine output to < 0.5 mL/kg/hr for ≥ 6 hours).

Results: 213 subjects were matched. Baseline characteristics were similar between groups with the exceptions of age, creatinine clearance, and initial admittance to the ICU (Table 1). Risk factor prevalence was 18.3% VAN ≥ 4 g/day or weight ≥ 110 kg, 1.4% vasopressors, 39.4% nephrotoxins, 38.0% history of AKI or baseline SCr ≥ 1.3 mg/dL. Incidence of NT was 0% vs. 0% vs 12.7% in VAN, PTZ, and COMBO, respectively (P < 0.001). Incidence of AKI was 7.0% vs 8.5% vs 26.8% in VAN, PTZ, and COMBO, respectively (P = 0.001) (Figure 1). In multivariable logistic regression, variables found to be associated with AKI included COMBO (aOR =4.54 [95% CI: 1.49 – 13.83]), ICU length of stay (aOR = 1.17 [95% CI: 1.04 – 1.32]), and initial VAN trough (aOR = 1.09 [95% CI: 1.01 – 1.18]).

Conclusion: In this matched cohort study, COMBO appears to have an increased risk of AKI as compared to VAN or PTZ. Further prospective studies are needed to clearly define the attributable risk of combination therapy.

 

Table 1 – Patient Characteristics	Vanco (n = 71)	Pip-Tazo (n = 71)	Combo (n = 71)	P- value
Age (y)	56 (46-68)	65(49-81)	58 (47 – 69)	<0.01
Male Sex	41 (57.7)	37 (52.1)	45 (63.4)	0.40
Initially Admitted to ICU	6 (8.5)	20 (28.2)	5 (7.0)	0.001
CrCl (ml/min)	76(55 -107)	62 (43 -87)	79 (57 -100)	0.003
Charlson Score	1 (0 -2)	1 (0 -2)	1 (0 -2)	0.18
Initial VAN Trough (mg/L)	10.0 (7.7 – 13.0)	N/A	11.0 (8.9 – 15.4)	0.10
Data are n (%) or median (IQR)