Background: Plazomicin is a next-generation aminoglycoside that is currently under review at the United States Food and Drug Administration for complicated urinary tract infections (cUTIs), including acute pyelonephritis, and bloodstream infections (BSIs) due to certain Enterobacteriaceae (ENT) in patients who have limited or no alternative treatment options. We evaluated the activity of plazomicin and aminoglycosides against ENT isolates collected in US hospitals during 2014 to 2017 by site of infection.
Methods: A total of 8,510 ENT isolates were collected from BSIs (2,133), pneumonia in hospitalized patients (PIHP; 1,826), skin and skin structure infections (SSSIs; 1,155), intra-abdominal infections (IAIs; 731), UTIs (2,508), and other or unknown infection sites (others; 157) in 71 US hospitals during 2014 to 2017. Isolates were susceptibility (S) tested by reference broth microdilution methods and results were interpreted using CLSI breakpoints.
Results: Plazomicin (MIC50/90 ranges, 0.250.5/12 µg/mL) inhibited 98.899.9% of the ENT isolates at ≤4 µg/mL across all infection types (Figure). At ≤4 µg/mL, plazomicin inhibited 93.8100% of the carbapenem-resistant ENT (CRE) isolates stratified by infection type. The S rates for amikacin ranged from 98.799.7% against ENT isolates overall. However, amikacin S rates for CRE ranged from 53.1% for UTI to 100% for IAI isolates. Gentamicin (89.293.6%S) and tobramycin (88.894.3%S) were slightly less active than plazomicin and amikacin against the ENT isolates stratified by infection source. Gentamicin S rates against CRE isolates ranged from 43.866.7% while tobramycin inhibited <45% of the CRE isolates from the different infection sources.
Conclusion: The activity of plazomicin and amikacin was similar against ENT isolates from US hospitals and did not vary by infection type; however, amikacin activity against CRE isolates varied by infection source while plazomicin remained active against CRE isolates regardless of infection source. These results highlight the potential role of plazomicin for treating serious infections caused by CRE.
This project was partially funded under BARDA Contract No. HHSO100201000046C.
A. W. Serio, Achaogen: Employee , Salary .
K. M. Krause, Achaogen: Employee , Salary .
R. K. Flamm, Achaogen: Research Contractor , Research support .