NEW ORLEANS —Plazomicin was associated with lower all-cause mortality, fewer drug-related adverse events and a favorable safety profile compared with colistin in patients with carbapenem-resistant Enterobacteriaceae, or CRE, based on phase 3 data from the CARE study.
The results could support the use of plazomicin (Achaogen, Inc.) — a next-generation aminoglycoside — as a potential new treatment option for patients with serious infections caused by CRE, Lynn E. Connolly, MD, PhD, vice president and head of late development at Achaogen, Inc, told Infectious Disease News.
Connolly and colleagues assessed the safety and efficacy of plazomicin in two cohorts enrolled in the CARE study. The first cohort included patients with bloodstream infections (BSIs) or hospital-acquired/ventilator-associated bacterial pneumonia (HABP/VABP) who were randomly assigned to plazomicin (n = 18) or colistin (n = 21). The second, single arm cohort included BSI and HABP/VABP patients who were ineligible for enrollment in cohort one due to low APACHE II scores (< 15), known colistin-resistant CRE or polymicrobial infections involving additional, non-Enterobacteriaceae gram-negative pathogens, as well as patients with complicated urinary tract infections (cUTIs) or acute pyelonephritis (AP). All patients in cohort two (n = 30) received plazomicin.
In cohort one, in addition to adjunctive therapy, patients with BSI or HABP/VABP received either 15 mg/kg of once-daily IV plazomicin or a 300-mg loading dose of colistin followed by 5 mg/kg divided every 12 or 8 hours for 7 to 14 days. Patients with cUTIs or AP received plazomicin monotherapy for 4 to 7 days followed by optional oral therapy.
In cohort one, the rate of 28-day all-cause mortality or significant disease-related complications (SDRC) among the modified intent-to-treat (mMITT) population was 23.5% in the plazomicin arm (n = 17) vs. 50% in the colistin arm (n = 20). When assessing for 28-day mortality alone, the rate was 11.8% in the plazomicin arm vs. 40% in the colistin arm. Overall, plazomicin was associated with a 53% relative reduction in all-cause mortality or SDRC and a 70.5% relative reduction in all-cause mortality alone.
“In patients with BSIs due to CRE, the survival benefit associated with plazomicin vs. colistin was pronounced and represented an 82% relative reduction in 28-day all-cause mortality,” Connolly said.
During a presentation, Connolly reported that the survival benefit of plazomicin was sustained through day 60 among patients with BSIs in cohort one. A low 28-day all-cause mortality rate (14.3%) was also observed among patients with BSIs in cohort two, supporting the findings observed in cohort one, she said.
In cohort one, there were fewer drug-related adverse events (27.8% vs. 42.9%) and patients with an increase in serum creatinine greater than 0.5mg/dL (16.7% vs. 50.0%) in the plazomicin arm vs. the colistin arm. Drug-related serious adverse events occurred in one patient who received plazomicin and four who received colistin; however, no drug-related deaths or events of ototoxicity were reported. – by Stephanie Viguers
Connolly LE, et al. Plazomicin (PLZ) associated with improved survival and safety compared to colistin (CST) in serious carbapenem-resistant Enterobacteriaceae (CRE) infections: Results of the CARE study. Presented at: ASM Microbe; June 1-5, 2017; New Orleans.
Disclosure: Connolly is an employee of and stockholder in Achaogen, Inc.