Ceftolozane/Tazobactam: Real-World Treatment Patterns & Associated Outcomes

As antibiotic resistance continues to rise, the treatment of patients with gram-negative infections resistant to front-line agents has become increasingly more difficult.

Ceftolozane/tazobactam, an antipseudomonal agent with broad activity against gram-negative pathogens, is a newer option that is currently indicated for patients with complicated urinary tract infections and complicated intra-abdominal infections.

Recently, a team of investigators performed a real-world evaluation of ceftolozane/tazobactam to observe patterns and outcomes associated with the treatment. They found that in spite of the complex nature of the patients in which the treatment was used, they experienced positive outcomes.

The data was presented today, October 6, 2018, in a Poster Abstract Session at ID Week 2018 held this year in San Francisco, California, by Thomas Lodise, PharmD, PhD, professor at the Albany College of Pharmacy and an investigator on the study.

In an exclusive interview with Contagion^®, Dr. Lodise discussed the need for data separate from clinical trials in order to provide real-world evidence to clinicians about the capabilities of ceftolozane/tazobactam (see video).

“Many times, these trials have very strict inclusion and exclusion criteria, and due to this, the patients enrolled in the trial are not necessarily the patients that we use the drug [for] in practice. With all new drugs, I think it’s critical to evaluate how the drug is used post-approval,” he said, highlighting the reason his team set out to conduct the study.

To collect real-world evidence, Dr. Lodise and his team performed a retrospective cohort study of hospitalized patients in the Premier Healthcare Database from January 1, 2015, to June 30, 2017, who received >2 consecutive days of ceftolozane/tazobactam. The database contains data from over 500 hospitals, 20% of which contained microbiology data, which allowed for the investigators to analyze length of stay, 30-day mortality, and readmissions.

The retrospective cohort study looked at data from 1490 patients across 253 hospitals throughout the United States. The mean age of the patients was 59.1 ± 17.5 years, 57% were male, and 65% were Caucasian. More than half of the patients were admitted to the intensive care unit and 49% were mechanically ventilated.

A number of comorbidities were observed in the patients, including chronic pulmonary disease (36%), renal disease (34%), and congestive heart failure (25%). Additionally, 27% of the patients had been hospitalized previously in the past 30 days.

Microbiology data available for 259 of the patients pinpointed Pseudomonas aeruginosa as the most prevalent pathogen identified. Dr. Lodise discussed this finding with Contagion® and indicated that over 40% of Pseudomonas infections were beta-lactam resistant (see video).

“When we think about treating infections like Pseudomonas aeruginosa, the rule of thumb is to use a beta-lactam if a beta-lactam is available. And so, in these patients with extensively beta-lactam resistant infections, that’s where we saw a lot of [ceftolozane/tazobactam] use among culture positive individuals,” Dr. Lodise explained.

The investigators observed that the median number of days from the date of admission to first treatment with ceftolozane/tazobactam was 6 days (2-15). The median number of days for the course of treatment was 7 (4-11). The median length of stay following the first dose of ceftolozane was 10 (6-18) days. The 30-day mortality rate was 9% and all-cause and infection-related readmissions were 17% and 9%, respectively.

The investigators concluded that even though the patients treated in the study belonged to critically ill populations, the outcomes were positive and provided real-world evidence of the efficacy of ceftolozane /tazobactam.

DISCLOSURES

L. Puzniak, Merck: Employee and Shareholder, Salary; R. Fu, Merck: Research Contractor, Research grant; J. Gundrum, Merck: Research Contractor, Research grant; T. P. Lodise Jr., Motif BioSciences: Board Member, Consulting fee.