Ceftolozane/tazobactam as good as meropenem for nosocomial pneumonia
The combination of the antipseudomonal cephalosporin, ceftolozane, and an extended-spectrum β-lactamase inhibitor, tazobactam (ceftolozane/tazobactam), is noninferior to meropenem in the treatment of adults with ventilated nosocomial pneumonia (VNP), phase 3 data from the ASPECT-NP* trial have shown.
“Patients with a serious medical condition or a compromised immune system, especially those who require intrusive treatment with tubes, are at high risk for contracting nosocomial pneumonia,” said primary investigator Dr Ignacio Martin-Loeches, vice chair of intensive care medicine at St. James University Hospital in Dublin, Ireland. “Ceftolozane/tazobactam was found to be noninferior to meropenem for the primary endpoint of 28-day all-cause mortality.”
In the intent-to-treat (ITT) population (n=726 patients), all-cause mortality rate was 24 percent for the combination drug vs 25.3 for meropenem. As for the secondary endpoint of clinical cure at 7–14 days post therapy, ceftolozane/tazobactam was, again, noninferior to meropenem at 54.4 percent vs 53.3 percent cure rate. [ECCMID 2019, abstract 302]
Nosocomial pneumonia is a lower respiratory infection that presents clinically two or more days after hospitalization and is associated with high rates of death, yet only few data exist for this patient population. Novel treatment options are desperately needed, said Martin-Loeches.
Ceftolozane/tazobactam has demonstrated both safety and efficacy in treating medically vulnerable patients. In ASPECT-NP study, patients with VNP were randomized to ceftolozane/tazobactam 3 g or meropenem 1 g through intravenous infusion over 1 hour every 8 hours for 8–14 days.
Clinical and microbiologic response rates for ceftolozane/tazobactam were also comparable to meropenem for gram-negative respiratory tract pathogens in the analysis of outcomes for each pathogen. In the 233 patients in the microbiologically evaluable (ME) population with a gram-negative pathogen at baseline, clinical cure rates were 75.2 percent and 66.7 percent and microbiologic response rates were 69.9 percent and 62.4 percent for ceftolozane/tazobactam and meropenem, respectively.
The findings were consistent even among 511 patients in the microbiologic ITT population, with clinical cure rates of 73 percent and 67.9 percent for ceftolozane/tazobactam and meropenem, respectively.
“The ceftolozane/tazobactam 3-gram dose regimen is an efficacious and well-tolerated treatment option for critically ill patients with ventilated, gram-negative nosocomial pneumonia,” said Martin-Loeches and team.
Drug-related adverse events occurred in 11 percent of ceftolozane/tazobactam recipients and 8 percent of meropenem recipients. Across the study, 2 percent and 1 percent, respectively, experienced serious adverse events, but drug discontinuation due to adverse events only occurred in 1 percent of patients in each arm.
Ceftolozane/tazobactam is approved in the US for adults with complicated urinary tract infections (UTIs), including pyelonephritis, caused by Escherichia coli, Klebsiella pneumoniae, Proteus mirabilis, and Pseudomonas aeruginosa, and in combination with metronidazole to treat adults with complicated intra-abdominal infections, but not for VNP.
The ASPECT-NP trial results may pave the way for a US Food and Drug Administration supplemental approval of ceftolozane/tazobactam for VNP in the days ahead.