The ASPECT-NP trial compared a new 3-gram dose regimen of ceftolozane/tazobactam versus meropenem in the treatment of ventilated nosocomial pneumonia.
As antibacterial resistance rates are on the rise among gram-negative bacteria such as Pseudomonas aeruginosa, novel treatment options are needed to treat infections such as nosocomial pneumonia.
Ceftolozane/tazobactam (Zerbaxa) is a combination treatment of an anti-pseudomonal cephalosporin, ceftolozane, and an extended-spectrum β-lactamase inhibitor, tazobactam.
Ceftolozane/tazobactam is approved by the US Food and Drug Administration and is indicated for the treatment of adult patients with complicated urinary tract infections, including pyelonephritis, caused by particular gram-negative organisms. When used in combination with metronidazole, it is indicated for the treatment of complicated intra-abdominal infections cause by specific gram-negative and gram-positive microogranisms.
But now, a team of investigators has conducted a multicenter, randomized, controlled, double-blind, phase 3, non-inferiority trial to evaluate the efficacy and safety of ceftolozane/tazobactam for the treatment of nosocomial pneumonia.
The findings of the study were presented in a poster presentation at the European Congress for Clinical Microbiology and Infectious Diseases (ECCMID 2019).
Contagion® spoke to the poster presenter Marin Kollef, MD, a professor in the Department of Internal Medicine, Pulmonary, and Critical Care at Washington University in St. Louis, Missouri, to learn more about the findings of the study (see video).
The study, which compared a new 3-gram dose regimen of ceftolozane/tazobactam with meropenem, enrolled patients who were mechanically ventilated with hospital-acquired/ventilator-associated bacterial pneumonia (vHABP/VABP). A total of 726 participants were enrolled into the trial and were randomized 1:1 to 3 g ceftolozane/tazobactam or 1 g meropenem, both by intravenous (IV) infusion over 1 hour every 8 hours for 8-14 days, stratified by age and diagnosis (vHABP vs VABP).
The investigators collected lower respiratory tract (LRT) specimens for Gram stain and quantitative culture ≤36 hours prior to administering the first dose. Additionally, the participants received adjunctive empiric linezolid (and optional amikacin, in <30% of patients) until baseline pathogen susceptibility was confirmed.
At randomization, 362 participants were enrolled in the ceftolozane/tazobactam arm, and 364 into the meropenem arm, which were included in the intent-to-treat population. The investigators report that 72% of the participants had VABP and 44% of the participants were ≥65 years old. Further details indicate that 33% of the participants had APACHE-II scores ≥20, 14% had creatinine clearance ≤50 mL/min and 18% ≥150 mL/min, and 13% had previous failed antibacterial therapy for ventilated nosocomial pneumonia.
Prior to enrollment, 77% of participants had been hospitalized for ≥5 days and 49% ventilated for ≥5 days. The study investigators state that baseline characteristics were balanced between treatment arms.
In patients with positive lower respiratory tract cultures (70%), at baseline causative gram-negative pathogens were predominately Enterobacteriaceae (74%) and P aeruginosa (25%).
The primary endpoint was 28-day all-cause mortality (10% non-inferiority margin) and the secondary endpoint was clinical response at test-of-cure (7-14 days after end-of-therapy; 12.5% non-inferiority margin) in the intent-to-treat population (all randomized patients).
Ceftolozane/tazobactam was found to be non-inferior to meropenem for the primary and key secondary endpoints. Mortality was reported to be the highest in meropenem-treated patients with vHABP.
Adverse events deemed drug-related by the investigators (DRAEs) occurred in 11% of ceftolozane/tazobactam and 8% of meropenem patients. Across the study, 2% and 1%, respectively, experienced serious adverse events, but drug discontinuation due to adverse events only occurred in 1% of patients per arm.
Based on the findings, the investigators concluded that the ceftolozane/tazobactam 3-gram dose regimen was efficacious and well-tolerated in this study. Therefore, the regimen should be a viable treatment option for patients with ventilated, gram-negative nosocomial pneumonia.
The study, “ASPECT-NP: A randomized, double-blind, phase 3 trial comparing efficacy and safety of ceftolozane/tazobactam versus meropenem in patients with ventilated nosocomial pneumonia,” was presented in a poster presentation on April 15, 2019, at ECCMID 2019 in Amsterdam, the Netherlands.