1278. Impact of Different Breakpoint Criteria on the Susceptibility Rates of Enterobacterales resistant Subsets to the Aminoglycosides
Authors: Sader Helio S , Arends S J Ryan , Gogtay Jaideep , Carvalhaes Cecilia G , Castanheira Mariana 
Published: January 2021

Abstract

Background
Plazomicin (PLZ) is an aminoglycoside recently approved by the United States (US) Food and Drug Administration (FDA) for the treatment of complicated urinary tract infections, including pyelonephritis. We evaluated the susceptibility (S) rates of PLZ, amikacin (AMK), gentamicin (GEN) and tobramycin (TOB) by applying current breakpoints published by different organizations.

Methods
A total of 9,303 Enterobacterales (ENT) isolates (1/patient) were collected in 2018-2019 from medical centers located in the US (n=3,899; 33 centers), Europe (n=3,782; 39 centers in 19 nations), Asia-Pacific (n=795; 13 centers in 7 nations [2018 only]), and Latin America (n=827; 10 centers in 6 nations [2018 only]). PLZ and comparator agents were S tested by reference broth microdilution methods at a central laboratory. Breakpoints for the following organizations were applied when available: CLSI, EUCAST, USCAST, and US FDA.

Results
PLZ was active against 95.5% and 98.0% of isolates as per US FDA (≤2 mg/L) and USCAST (≤4 mg/L) criteria, respectively. S rates as per US FDA and USCAST criteria were 97.4% and 90.2% for AMK, 86.4% and 85.6% for GEN, and 83.8% and 81.1% for TOB, respectively (Table). CLSI and US FDA breakpoints were identical for these three older aminoglycosides, and EUCAST breakpoints were identical for GEN and TOB and one doubling dilution higher for AMK when compared with USCAST. Per US FDA criteria, carbapenem-resistant ENT (CRE) S rates to PLZ and AMK were 71.5% and 58.3%, respectively. Differences in S rates between PLZ and AMK were higher when applying USCAST for resistant subsets, such as CRE (72.2% versus 38.5%, respectively), ESBL-phenotype (92.7% versus 72.4%, respectively), and multidrug-resistant isolates (n=1,348; 88.6% versus 59.6%, respectively). GEN and TOB exhibited limited activity against ENT resistant subsets.

Conclusion
PLZ retained potent activity against ENT, including resistant subsets. The discrepancies among the S rates for aminoglycosides were greater when applying breakpoints generated using the same stringent contemporary methods applied to determine PLZ breakpoints.
Table 1

Disclosures
Helio S. Sader, MD, PhD, A. Menarini Industrie Farmaceutiche Riunite S.R.L. (Research Grant or Support)Allergan (Research Grant or Support)Allergan (Research Grant or Support)Allergan (Research Grant or Support)Cipla Ltd. (Research Grant or Support)Cipla Ltd. (Research Grant or Support)Melinta (Research Grant or Support)Merck (Research Grant or Support)Merck (Research Grant or Support)Paratek Pharma, LLC (Research Grant or Support)Pfizer (Research Grant or Support) S. J. Ryan Arends, PhD, Allergan (Research Grant or Support)Cipla Ltd. (Research Grant or Support)GlaxoSmithKline (Research Grant or Support)Melinta Therapeutics, Inc. (Research Grant or Support) Jaideep Gogtay, n/a, Cipla Ltd. (Employee) Cecilia G. Carvalhaes, MD, PhD, A. Menarini Industrie Farmaceutiche Riunite S.R.L. (Research Grant or Support)Allergan (Research Grant or Support)Cidara Therapeutics (Research Grant or Support)Cipla Ltd. (Research Grant or Support)Fox Chase Chemical Diversity Center (Research Grant or Support)Melinta Therapeutics, Inc. (Research Grant or Support)Merck (Research Grant or Support)Merck (Research Grant or Support)Merck & Co, Inc. (Research Grant or Support)Pfizer (Research Grant or Support) Mariana Castanheira, PhD, 1928 Diagnostics (Research Grant or Support)A. Menarini Industrie Farmaceutiche Riunite S.R.L. (Research Grant or Support)Allergan (Research Grant or Support)Allergan (Research Grant or Support)Amplyx Pharmaceuticals (Research Grant or Support)Cidara Therapeutics (Research Grant or Support)Cidara Therapeutics (Research Grant or Support)Cipla Ltd. (Research Grant or Support)Cipla Ltd. (Research Grant or Support)Fox Chase Chemical Diversity Center (Research Grant or Support)GlaxoSmithKline (Research Grant or Support)Melinta Therapeutics, Inc. (Research Grant or Support)Melinta Therapeutics, Inc. (Research Grant or Support)Melinta Therapeutics, Inc. (Research Grant or Support)Merck (Research Grant or Support)Merck (Research Grant or Support)Merck & Co, Inc. (Research Grant or Support)Merck & Co, Inc. (Research Grant or Support)Paratek Pharma, LLC (Research Grant or Support)Pfizer (Research Grant or Support)Qpex Biopharma (Research Grant or Support)