Comparison of Ceftolozane/Tazobactam vs Polymyxin/Amingoglycoside for Treatment of MDR/XDR Pseudomonas aeruginosa

Ceftolozane/tazobactam (C/T) is a novel agent that has demonstrated in vitro activity against Pseudomonas aeruginosa. The agent is currently indicated for complicated urinary tract infections and complicated intra-abdominal infections and being reviewed for ventilator-associated bacterial pneumonia; however real-world data that compare C/T to agents that have historically been used to treat P aeruginosa are lacking.

In a Poster Abstract Session at ID Week 2018 in San Francisco, California, Jason Pogue, PharmD, BCPS-AQID, presented the data of a retrospective, multi-site cohort study that analyzed the treatment of multidrug-resistant (MDR) or extensively-drug resistant (XDR) P aeruginosa infection with C/T in comparison with a polymyxin- or aminoglycoside- (Poly/AG) based regimen.

In an exclusive interview with Contagion®, Dr. Pogue discussed the need for real-world data on C/T (see video).

“One of the limitations of the [previously completed study] data is that there is no comparison group,” Dr. Pogue explained, “And so, you get a success rate with C/T, but you really can’t compare it to anything…If we’re really going to make the sell that we should use this therapy over another therapy, or perhaps even the opposite, you really need to know how people who get treated with other agents fair as well.”

Dr. Pogue and his team set out to assess the rates of clinical care and acute kidney injury in patients with MDR/XDR P aeruginosa treated with either C/T or a Poly/AG.

Patients with MDR/XDR P aeruginosa infections who received C/T or Poly/AG for >48 hours were included. Patients with creatine clearance of <20 mL/min or those who required renal replacement therapy at baseline were excluded from the study.

A total of 117 patients from 5 medical centers across Michigan and Ohio were included. In total, 57 patients received C/T and 60 received Poly/AG.

Baseline characteristics, infection source, severity of illness and time to appropriate therapy were similar between treatment groups, according to the study abstract.

The mean age of participants was 58.6 + 15.1 years and 70% of the patients were male. Common comorbidities in the study participants included diabetes (35%), congestive heart failure (28%), and the median Charlson Comorbidity Index was 3 (1-4).

Additionally, the authors indicate that 42% of the population presented with severe sepsis or septic shock, and 68% were in the intensive care unit at onset of infection. The most common infections observed were ventilator-associated pneumonia (54%) or hospital-acquired pneumonia (17%).

The authors observed that combination therapy was more frequently used in the Poly/AG group (72% vs 12% p < 0.001).

Results indicate that treatment with C/T was associated with a higher rate of clinical cure (79% vs 62%; p=0.046) and a lower incidence of acute kidney injury (7% vs 33%; p<0.001) compared with Poly/AG based therapy.

Dr. Pogue discussed the results of the study and what the future of C/T with Contagion® (see video).

“What was interesting was we found that clinical cure was actually about 20% better and it was statistically significant as well with C/T in our study,” Dr. Pogue explained. “In addition to just being safer, it improved the clinical outcomes in our patients as well.”

No patients receiving C/T had hypersensitivity reactions, neurological adverse events, or Clostridium difficile infections, according to the abstract.

The in-hospital mortality rates were similar across groups (28% vs 37%; p=0.33). According to Dr. Pogue, while these rates were noted, mortality was not a central focus of the study.

The authors conclude that this study provides needed real-world data that demonstrates that use of C/T can improve outcomes in invasive infections due to MDR/XDR P aeruginosa in comparison with Poly/AG.

More research focusing on real-world data on C/T is needed, according to Dr. Pogue, along with getting results for randomized control trials for the disease state of HABP/VABP.