Introduction 

The rise of multidrug resistance (MDR) Enterobacterales has become a major concern and it limits the choice of optimal antibiotic treatment. Patients with this infection are thrice more likely to receive inappropriate antibiotics, longer hospital stays, higher hospitalization costs, and a higher risk of septic shock and death. Aminoglycoside antibiotics are preferred for MDR Enterobacteriaceae infections. Plazomicin, a novel aminoglycoside antibiotic,  is approved for treatment of complex urinary tract infections (cUTIs). It has shown rapid bactericidal effect and strong activity against MDR Enterobacterales in in vitro studies; however, clinical studies are limited. 

Aim

To compare the efficacy and safety of plazomicin with other antibiotics in the treatment of infections caused by Enterobacterales.

Studies Included  

• Three randomized controlled trials (RCTs) consisting of 761 patients with Enterobacterales infection
• Two studies compared plazomicin with levofloxacin or meropenem in cUTIs and the third one compared plazomicin with colistin in investigated bloodstream infections (BSIs) or hospital-acquired pneumonia (HAP)

Method

Study Design

Endpoints

Results 

Efficacy 

• Plazomicin had a similar clinical remission rate to that of comparator group in the modified intention-to-treat (MITT) population (odds ratio, OR 1.02) in this pooled analysis of the 3 studies
• Similar clinical relapse rates were noted between plazomicin and comparators in the clinically evaluable MITT population in the pooled analysis of the 2 studies of cUTIs (OR 0.60)
• Overall microbiologic eradication rate with plazomicin in the microbiological MITT population was similar to that of the comparators group (OR 1.46)
• Plazomicin was associated with significantly lower microbiologic recurrence rate of Enterobacterales than that in the comparator group in the microbiologically evaluable MITT population in the pooled analysis of the 2 studies of cUTIs (OR 0.38; P = 0.02)

Safety   

• No significant differences were found between plazomicin and comparators for the risk of any adverse events (OR 0.78), serious AEs (OR 0.49), or AEs related to study drug (OR 0.58)
• No significant difference was noted between plazomicin and comparators in terms of renal function (OR 1.36) or vestibular and cochlear function (OR 1.10)

Conclusion 

The clinical efficacy and tolerance of plazomicin was non-inferior to that of comparator group in the treatment of MDR Enterobacterales infections

Open Forum Infect Dis 2022; 9(9): ofac429