Renee Ackley, PharmD, BCPS: Comparing Agents for Treating CRE

At the Making a Difference in Infectious Diseases (MAD-ID 2019) annual meeting, Renee Ackley, PharmD, BCPS, PGY2 Infectious Diseases Pharmacy Resident, at Atrium Health, presented a research poster that compared meropenem/vaborbactam and ceftazidime/avibactam for the treatment of Carbapenem-resistant Enterobacteriaceae infections.

Ackley sat down with Contagion® to detail the findings of her research in an exclusive interview.

Interview transcript (modified slightly for readability):

So some of the historical regimens that were used prior to some of the new agents being brought to market were high dose combination therapy so this could include carbapenems, polymyxin B or colistin, tigecycline, etc. but in 2015 ceftazidime/avibactam was brought to market that has shown to be effective for KPC-producing CRE [Klebsiella pneumoniae carbapenemase-producing Carbapenem-Resistant-Enterobacteriaceae] and then in 2018 meropenem/vaborbactam and since then some newer agents as well have been approved such as plazomycin and eravacycline.

So, we wanted to look at the clinical outcomes between ceftazidime/avibactam and meropenem/vaborbactam for treatment of CRE infections because previous studies have shown that each agent is superior in terms of safety and efficacy for treatment of CRE, when compared to some of those older regimens that I talked about. But, direct comparison between the agents is lacking. In the TANGO 2 trial that showed meropenem/vaborbactam was safe and efficacious for CRE infections, there was only 1 patient that received ceftazidime/avibactam.

So, our primary endpoint was clinical success and some of our secondary endpoints were 30-, 90-day mortality, adverse events, hospital and ICU length of stay, and recurrence of CRE infections. In terms of clinical success, we didn't find any difference; both ceftazidime/avibactam and meropenem/vaborbactam had a clinical success rate around 60% and then we also didn't see any statistically significant differences in the secondary endpoints.

We did find a few surprising elements to our study, we did look at how often combination regimen was used in each arm and we found that ceftazidime avibactam was used in combination with other agents 63% of the time these are other agents included tigecycline, colistin, polymyxin B, and aminoglycosides, so as you can imagine are pretty toxic drugs and as a result we found a statistically significant increase in adverse events in ceftazidime/avibactam group and this was primarily driven by nephrotoxicity.

We concluded that although clinical success was similar between the two agents that meropenem/vaborbactam may be preferred as it can be used as monotherapy combination regimen as we saw with ceftazidime/avibactam does have an increased risk of adverse events.

The poster, “Meropenem/Vaborbactam versus Ceftazidime/Avibactam for the Treatment of Carbapenem/resistant Enterobacteriaceae Infections,” was presented on Thursday May 9, 2019, at MAD-ID 2019 in Orlando, Florida.