Outcomes in Participants with Renal Impairment from a Phase 3 Clinical Trial for Ceftolozane/Tazobactam Treatment of Nosocomial Pneumonia (ASPECT-NP).

In the phase 3 ASPECT-NP trial (NCT02070757), ceftolozane/tazobactam (C/T) was noninferior to meropenem for treatment of gram-negative ventilated hospital-acquired bacterial pneumonia and ventilator-associated bacterial pneumonia (vHABP/VABP). Here we report outcomes in participants from ASPECT-NP with renal impairment (RI). Participants were categorized by their baseline renal function: normal renal function (NRF; creatinine clearance [CLCR] ≥80 mL/min); mild RI (CLCR >50 to <80 mL/min); moderate RI (CLCR ≥30 to ≤50 mL/min); and severe RI (CLCR ≥15 to <30 mL/min). Dosing of both study drugs was adjusted based on renal function. The following C/T doses were administered every 8 h: NRF or mild RI, 3 g; moderate RI, 1.5 g; and severe RI, 0.75 g. The primary and key secondary endpoints were day 28 all-cause mortality (ACM) and clinical response at the test-of-cure visit in the intention-to-treat population, respectively. In the intention-to-treat population (ITT), day 28 ACM rates for the C/T arm versus the meropenem arm were 17.6% versus 19.1% (NRF), 36.6% versus 28.6% (mild RI), 31.4% versus 38.5% (moderate RI), and 35.3% versus 61.9% (severe RI), respectively. Rates of clinical cure in the ITT for the C/T arm vs the meropenem arm were 58.1% versus 58.5% (NRF), 54.9% versus 45.5% (mild RI), 37.1% versus 42.3% (moderate RI), and 41.2% versus 47.6% (severe RI), respectively. Small sample sizes in the RI groups resulted in large 95% CIs, limiting conclusive interpretation of the analysis. Both drugs were well tolerated across all renal function groups. Overall, these results support the use of the study dosing regimens of C/T for treatment of vHABP/VABP in patients with RI.