Introduction

Carbapenem-resistant  Enterobacteriaceae (CRE) infected patients have limited management options and are associated with a high risk of mortality. The CARE trial (Combating Antibiotic-Resistant Enterobacteriaceae) assessed the treatment options in these patients.

Aim

To assess the efficacy and safety of plazomicin as compared with colistin as part of a combination therapy regimen for serious carbapenem-resistant Enterobacteriaceae (CRE) infections

Patient Profile

• 37 patients with bloodstream infection or hospital-acquired or ventilator-associated bacterial pneumonia caused by CRE

Method

Study Design

• Multicenter, randomized, open-label trial
• Patients were randomised to either plazomicin (15 mg/kilogram of body weight once daily) or colistin (5 mg/kilogram/day), in combination with adjunctive meropenem or tigecycline, for 7 to 14 days of therapy

Endpoints

• Primary end point: composite of death from any cause at 28 days or clinically

significant disease-related complications

Results

Efficacy

• Plazomicin treatment was associated with lower risk of composite of death from any cause at 28 days or clinically significant disease related complications as compared to colistin (24% vs. 50%; difference, −26 percentage points) in the overall study population (Figure 1)
• In the subgroup of patients with bloodstream infection, plazomicin had lower risk of primary endpoint as compared to those who received colistin (14% vs. 53%, difference, −39 percentage points)
• A lower risk of mortality was seen with plazomicin treatment at day 14, which was persistent till day 60 in a secondary analysis of time to death

Figure 1: Effect of plazomicin on the primary endpoint

Safety 

• Plazomicin treatment was less frequently associated with serious adverse events as compared to colistin (50% vs. 81%)
• An increase in serum creatinine levels (≥0.5 mg/dL) occurred in fewer patients on plazomicin treatment versus colistin treatment

Conclusion

The CARE trial results supported the use of plazomicin in patients with serious infections caused by multidrug-resistant Enterobacteriaceae who have limited treatment options 

NEJM 2019; 380: 791-3