Ignacio Martin-Loeches, MD, PhD: ASPECT-NP Outcomes by Causative Agent

Pseudomonas aeruginosa and Enterobacteriaceae can be frequent causes of nosocomial pneumonia along with gram-negative bacteria isolates.

In a randomized, double blind study called the ASPECT-NP trial, a team of investigators across multiple institutions analyzed ceftolozane/tazobactam for the treatment of nosocomial pneumonia.

Ceftolozane/tazobactam, is a combination therapy that is approved for the treatment of complicated urinary tract infections and complicated intra-abdominal infections, by the US Food and Drug Administration.

The agent combines the antipseudomonal cephalosporin ceftolozane and the extended-spectrum β-lactamase (ESBL) inhibitor tazobactam, and has been proved to be active against many strains of multidrug-resistant P. aeruginosa and ESBL-producing Enterobacteriaceae.

In a poster presentation at the European Congress of Clinical Microbiology and Infectious Diseases (ECCMID 2019), investigators presented the efficacy outcomes by causative pathogen from the ASPECT-NP trial.

Contagion® sat down for an exclusive interview with the presenter of the poster Ignacio Martin-Loeches, MD, PhD, a consultant in intensive care medicine at St. James’s Hospital in Ireland (see video).

The phase 3 study enrolled mechanically ventilated patients with nosocomial pneumonia across multiple treatment centers. Patients were excluded from the trial if a respiratory of blood culture exhibited a gram-negative pathogen that was resistant to ceftolozane/tazobactam or meropenem within 15 days prior to the first dose.

The enrolled patients were randomized 1:1 to either receive 3 g ceftolozane/tazobactam or 1 g meropenem, both by IV infusion over 1 hour every 8 hours for 8-14 days.

The investigators note that quantitative lower respiratory tract (LRT) cultures were obtained from all patients prior to first dose via bronchoscopy or endotracheal aspirate. Additionally, pathogen identification and susceptibility were confirmed at a central laboratory.

The endpoints of the study were clinical and microbiologic response at test-of-cure (7-14 days after end-of-therapy) in the microbiologic intent-to-treat population (mITT) which consisted of all patients who received a study drug and had confirmed culture at baseline of a LRT pathogen susceptible to ≥1 study drug. Additionally, the investigators looked at the microbiologically evaluable population (ME), which consisted of mITT patients who met pre-defined quantitative LRT pathogen counts, adhered to the protocol and had evaluable clinical outcomes.

According to the results, the mITT population consisted of 511 patients 264 of which received ceftolozane/tazobactam and 247 received meropenem. In the ME population of 233 patients 115 received ceftolozane/tazobactam and 118 received meropenem.

The causative baseline LRT gram-negative pathogens in the mITT were mainly Enterobacteriaceae which was 74%; including Klebsiella pneumoniae (35%) and Escherichia coli (18%), P. aeruginosa (25%), and Haemophilus influenzae (7%); with 31% of all mITT patients reported to have ESBL-producing Enterobacteriaceae identified in their LRT cultures.

The investigators indicate that ceftolozane/tazobactam had clinical and microbiologic response rates that were compared to meropenem in patients with ventilated nosocomial pneumonia, regardless of the causative LRT pathogen.

Microbiologic eradication rates in ME patients with P. aeruginosa were 79.3% with ceftolozane/tazobactam and 55.3% with meropenem (difference: 24.0%; 95% CI: 1.11, 43.01). And for ME patients with ESBL-producing Enterobacteriaceae, eradication rates were 66.7% with ceftolozane/tazobactam and 69.2% with meropenem difference: -2.6%; 95% CI: -21.59, 17.14).

“These results lend additional support to the use of ceftolozane/tazobactam 3g [every 8 hours] as an efficacious treatment option for gram-negative nosocomial pneumonia,” the authors conclude.

The poster, “Clinical and microbiologic outcomes by causative pathogen in the ASPECT-NP randomised, controlled, phase III trial evaluating ceftolozane /tazobactam for treatment of ventilator-associated pneumonia,” was presented on April 13, 2019 at ECCMID 2019 in Amsterdam, the Netherlands.