1272. Cefiderocol In Vitro Activity Against Molecularly Characterized Acinetobacter baumannii-calcoaceticus Complex and Pseudomonas aeruginosa Clinical Isolates Causing Infection in United States Hospitals (2020)
Authors: Mendes Rodrigo E , Doyle Timothy B , Shortridge Dee , Sader Helio S , Streit Jennifer M , Castanheira Mariana , Castanheira Mariana 
Published: December 2021

Abstract

Background
Cefiderocol (CFDC) is a novel siderophore-conjugated cephalosporin with broad activity against aerobic, nonfastidious Gram-negative bacteria. CFDC and comparator activities were analyzed against molecularly characterized A. baumannii-calcoaceticus complex (ACB) and P. aeruginosa (PSA), as a part of the SENTRY Antimicrobial Surveillance Program in the USA.

Methods
248 ACB and 1,069 PSA were consecutively collected from 30 sites in 2020. Susceptibility was performed by broth microdilution and CFDC testing used iron-depleted media. FDA and CLSI breakpoints were used for CFDC. CLSI criteria were applied to comparators, except for imipenem-relebactam (IMR) that used FDA breakpoints. ACB and PSA with imipenem and/or meropenem (MER) MIC ≥4 μg/mL or ceftazidime (CAZ) and/or cefepime MIC ≥16 μg/mL were subjected to next-generation genome sequencing for screening for acquired extended-spectrum β-lactamase (ESBL) and carbapenemase genes.

Results
33.0% of PSA met the MIC screening criteria, and ESBL or carbapenemase genes were not detected among these isolates, except for 1 strain with blaIMP-1. CFDC (97.7-100% susceptible [S]) had similar MIC50 (0.12 μg/mL) and MIC90 (0.25-0.5 μg/mL) values against both PSA populations, as did IMR (91.8-100%S). An MIC of 1 μg/mL was noted for CFDC against the single blaIMP-1-carrying isolate, whereas other agents had MIC values &gt;8 μg/mL (Table). CFDC (MIC50/90, 0.25/2 μg/mL) had the lowest MIC against ACB that met the MIC screening criteria, whereas CFDC, IMR, MER and CAZ were active (99.2-100%S) against MIC screen negative ACB. CFDC (MIC50/90, 0.25/2 μg/mL; 86.7-96.7%S) and IMR (MIC50/90, 0.25/1 μg/mL; 90.0%S) were the most active agents against ACB where only blaOXA-51 and variant genes were noted. CFDC was the only agent active (93.9-100%S; CLSI criteria) against ACB carrying blaOXA-23 (MIC50/90, 0.5/4 μg/mL), blaOXA-24 (MIC50/90, 0.25/1 μg/mL) or other genes (MIC50, 1 μg/mL).

Conclusion
Acquired ESBL and carbapenemase genes remained rare among multidrug-resistant PSA in USA hospitals, whereas acquired blaOXA carbapenemase were prevalent among ACB. CFDC showed potent activity against PSA subsets, as well as across molecularly characterized subsets of ACB, where treatment options were limited.

Disclosures
Rodrigo E. Mendes, PhD, AbbVie (Research Grant or Support)AbbVie (formerly Allergan) (Research Grant or Support)Cipla Therapeutics (Research Grant or Support)Cipla USA Inc. (Research Grant or Support)ContraFect Corporation (Research Grant or Support)GlaxoSmithKline, LLC (Research Grant or Support)Melinta Therapeutics, Inc. (Research Grant or Support)Melinta Therapeutics, LLC (Research Grant or Support)Nabriva Therapeutics (Research Grant or Support)Pfizer, Inc. (Research Grant or Support)Shionogi (Research Grant or Support)Spero Therapeutics (Research Grant or Support) Timothy B. Doyle, AbbVie (formerly Allergan) (Research Grant or Support)Bravos Biosciences (Research Grant or Support)GlaxoSmithKline (Research Grant or Support)Melinta Therapeutics, Inc. (Research Grant or Support)Pfizer, Inc. (Research Grant or Support)Shionogi (Research Grant or Support)Spero Therapeutics (Research Grant or Support) Dee Shortridge, PhD, AbbVie (formerly Allergan) (Research Grant or Support)Melinta Therapeutics, Inc. (Research Grant or Support)Melinta Therapeutics, LLC (Research Grant or Support)Shionogi (Research Grant or Support) Helio S. Sader, MD, PhD, FIDSA, AbbVie (formerly Allergan) (Research Grant or Support)Basilea Pharmaceutica International, Ltd. (Research Grant or Support)Cipla Therapeutics (Research Grant or Support)Cipla USA Inc. (Research Grant or Support)Department of Health and Human Services (Research Grant or Support, Contract no. HHSO100201600002C)Melinta Therapeutics, LLC (Research Grant or Support)Nabriva Therapeutics (Research Grant or Support)Pfizer, Inc. (Research Grant or Support)Shionogi (Research Grant or Support)Spero Therapeutics (Research Grant or Support) Jennifer M. Streit, BS, GlaxoSmithKline, LLC (Research Grant or Support)Melinta Therapeutics, LLC (Research Grant or Support)Shionogi (Research Grant or Support)Spero Therapeutics (Research Grant or Support) Mariana Castanheira, PhD, AbbVie (formerly Allergan) (Research Grant or Support)Bravos Biosciences (Research Grant or Support)Cidara Therapeutics, Inc. (Research Grant or Support)Cipla Therapeutics (Research Grant or Support)Cipla USA Inc. (Research Grant or Support)GlaxoSmithKline (Research Grant or Support)Melinta Therapeutics, Inc. (Research Grant or Support)Melinta Therapeutics, LLC (Research Grant or Support)Pfizer, Inc. (Research Grant or Support)Qpex Biopharma (Research Grant or Support)Shionogi (Research Grant or Support)Spero Therapeutics (Research Grant or Support) Mariana Castanheira, PhD, Affinity Biosensors (Individual(s) Involved: Self): Research Grant or Support; Allergan (Individual(s) Involved: Self): Research Grant or Support; Amicrobe, Inc (Individual(s) Involved: Self): Research Grant or Support; Amplyx Pharma (Individual(s) Involved: Self): Research Grant or Support; Artugen Therapeutics USA, Inc. (Individual(s) Involved: Self): Research Grant or Support; Astellas (Individual(s) Involved: Self): Research Grant or Support; Basilea (Individual(s) Involved: Self): Research Grant or Support; Beth Israel Deaconess Medical Center (Individual(s) Involved: Self): Research Grant or Support; BIDMC (Individual(s) Involved: Self): Research Grant or Support; bioMerieux Inc. (Individual(s) Involved: Self): Research Grant or Support; BioVersys Ag (Individual(s) Involved: Self): Research Grant or Support; Bugworks (Individual(s) Involved: Self): Research Grant or Support; Cidara (Individual(s) Involved: Self): Research Grant or Support; Cipla (Individual(s) Involved: Self): Research Grant or Support; Contrafect (Individual(s) Involved: Self): Research Grant or Support; Cormedix (Individual(s) Involved: Self): Research Grant or Support; Crestone, Inc. 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(Individual(s) Involved: Self): Research Grant or Support; Melinta (Individual(s) Involved: Self): Research Grant or Support; Menarini (Individual(s) Involved: Self): Research Grant or Support; Merck (Individual(s) Involved: Self): Research Grant or Support; Meridian Bioscience Inc. (Individual(s) Involved: Self): Research Grant or Support; Micromyx (Individual(s) Involved: Self): Research Grant or Support; MicuRx (Individual(s) Involved: Self): Research Grant or Support; N8 Medical (Individual(s) Involved: Self): Research Grant or Support; Nabriva (Individual(s) Involved: Self): Research Grant or Support; National Institutes of Health (Individual(s) Involved: Self): Research Grant or Support; National University of Singapore (Individual(s) Involved: Self): Research Grant or Support; North Bristol NHS Trust (Individual(s) Involved: Self): Research Grant or Support; Novome Biotechnologies (Individual(s) Involved: Self): Research Grant or Support; Paratek (Individual(s) Involved: Self): Research Grant or Support; Pfizer (Individual(s) Involved: Self): Research Grant or Support; Prokaryotics Inc. (Individual(s) Involved: Self): Research Grant or Support; QPEX Biopharma (Individual(s) Involved: Self): Research Grant or Support; Rhode Island Hospital (Individual(s) Involved: Self): Research Grant or Support; RIHML (Individual(s) Involved: Self): Research Grant or Support; Roche (Individual(s) Involved: Self): Research Grant or Support; Roivant (Individual(s) Involved: Self): Research Grant or Support; Salvat (Individual(s) Involved: Self): Research Grant or Support; Scynexis (Individual(s) Involved: Self): Research Grant or Support; SeLux Diagnostics (Individual(s) Involved: Self): Research Grant or Support; Shionogi (Individual(s) Involved: Self): Research Grant or Support; Specific Diagnostics (Individual(s) Involved: Self): Research Grant or Support; Spero (Individual(s) Involved: Self): Research Grant or Support; SuperTrans Medical LT (Individual(s) Involved: Self): Research Grant or Support; T2 Biosystems (Individual(s) Involved: Self): Research Grant or Support; The University of Queensland (Individual(s) Involved: Self): Research Grant or Support; Thermo Fisher Scientific (Individual(s) Involved: Self): Research Grant or Support; Tufts Medical Center (Individual(s) Involved: Self): Research Grant or Support; Universite de Sherbrooke (Individual(s) Involved: Self): Research Grant or Support; University of Iowa (Individual(s) Involved: Self): Research Grant or Support; University of Iowa Hospitals and Clinics (Individual(s) Involved: Self): Research Grant or Support; University of Wisconsin (Individual(s) Involved: Self): Research Grant or Support; UNT System College of Pharmacy (Individual(s) Involved: Self): Research Grant or Support; URMC (Individual(s) Involved: Self): Research Grant or Support; UT Southwestern (Individual(s) Involved: Self): Research Grant or Support; VenatoRx (Individual(s) Involved: Self): Research Grant or Support; Viosera Therapeutics (Individual(s) Involved: Self): Research Grant or Support; Wayne State University (Individual(s) Involved: Self): Research Grant or Support