1068. Antimicrobial Activity of Aztreonam-Avibactam and Comparator Agents against Gram-Negative Bacteria Isolated from Bloodstream and Complicated Urinary Tract Infections in Europe, Asia, and Latin America (2019-2020)
Authors: Sader Helio S , Mendes Rodrigo E , Carvalhaes Cecilia G , Doyle Timothy B , Castanheira Mariana , Castanheira Mariana 
Published: December 2021

Abstract

Background
Aztreonam (ATM) is a monobactam stable to hydrolysis by metallo-β-lactamases (MBLs). Avibactam (AVI) is a non-β-lactam β-lactamase inhibitor that inhibits serine β-lactamases (BLs) such as ESBLs, KPCs, AmpC, and some OXAs. ATM-AVI is under clinical development for the treatment of serious infections caused by gram-negative bacteria (GNB), including MBL-producers. We evaluated ATM-AVI activity against GNB causing bloodstream (BSI) and complicated urinary tract infections (cUTI).

Methods
10,103 GNB isolates (5,314 from BSI and 4,789 from cUTI) were consecutively collected (1/patient) from 66 medical centers located in Western Europe (W-EU; n=5,238; 25 centers in 10 countries), Eastern Europe (E-EU; n=1,729; 13 centers in 10 countries), the Asia-Pacific region (APAC; n=1,817; 17 centers in 9 countries), and Latin America (LATAM; n=1,319; 11 centers in 7 countries) in 2019 (n=5,030) and 2020 (n=5,073). Susceptibility (S) testing was performed by reference broth microdilution methods in a central laboratory.

Results
Overall, 99.9% of Enterobacterales (ENT; MIC50/90, ≤0.03/0.12 mg/L), including 99.7% of carbapenem-resistant ENT (CRE; MIC50/90, 0.25/0.5 mg/L), were inhibited at an ATM-AVI MIC of ≤8 mg/L (Table). CRE rates among BSI/cUTI isolates were 2.3%/0.6% in W-EU, 9.5%/6.1% in E-EU, 3.3%/2.8% in APAC, and 8.1%/5.2% in LATAM (4.2%/2.7% overall). ATM-AVI was very active against MDR (MIC50/90, 0.06/0.5 mg/L; 99.6% inhibited at ≤8 mg/L) and XDR (MIC50/90, 0.25/0.5 mg/L; highest MIC, 2 mg/L) ENT. Among P. aeruginosa, the percentage of isolates inhibited at ≤8 mg/L of ATM-AVI (78.3%) was similar to the S rates for piperacillin-tazobactam (78.8%), meropenem (79.1%), and ceftazidime (80.6%). Among S. maltophilia isolates, 100.0% were inhibited at ≤8mg/L of ATM-AVI and 95.4% were S to cotrimoxazole. ATM-AVI was highly active against Aeromonas spp. (highest MIC, 0.25 mg/L) and showed good activity against B. cepacia (MIC50/90, 4/16 mg/L).

Conclusion
ATM-AVI exhibited potent and consistent activity against ENT (including CRE, MDR, and XDR isolates) from W-EU, E-EU, APAC, and LATAM. Our results support clinical development of ATM-AVI to treat BSI and cUTI caused by ENT, P. aeruginosa, S. maltophilia, B. cepacia and Aeromonas spp.
Table

Disclosures
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) 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) Cecilia G. Carvalhaes, MD, PhD, AbbVie (formerly Allergan) (Research Grant or Support)Cidara Therapeutics, Inc. (Research Grant or Support)Cipla Therapeutics (Research Grant or Support)Cipla USA Inc. (Research Grant or Support)Melinta Therapeutics, LLC (Research Grant or Support)Pfizer, Inc. (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) 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. (Individual(s) Involved: Self): Research Grant or Support; Curza (Individual(s) Involved: Self): Research Grant or Support; CXC7 (Individual(s) Involved: Self): Research Grant or Support; Entasis (Individual(s) Involved: Self): Research Grant or Support; Fedora Pharmaceutical (Individual(s) Involved: Self): Research Grant or Support; Fimbrion Therapeutics (Individual(s) Involved: Self): Research Grant or Support; Fox Chase (Individual(s) Involved: Self): Research Grant or Support; GlaxoSmithKline (Individual(s) Involved: Self): Research Grant or Support; Guardian Therapeutics (Individual(s) Involved: Self): Research Grant or Support; Hardy Diagnostics (Individual(s) Involved: Self): Research Grant or Support; IHMA (Individual(s) Involved: Self): Research Grant or Support; Janssen Research & Development (Individual(s) Involved: Self): Research Grant or Support; Johnson & Johnson (Individual(s) Involved: Self): Research Grant or Support; Kaleido Biosceinces (Individual(s) Involved: Self): Research Grant or Support; KBP Biosciences (Individual(s) Involved: Self): Research Grant or Support; Luminex (Individual(s) Involved: Self): Research Grant or Support; Matrivax (Individual(s) Involved: Self): Research Grant or Support; Mayo Clinic (Individual(s) Involved: Self): Research Grant or Support; Medpace (Individual(s) Involved: Self): Research Grant or Support; Meiji Seika Pharma Co., Ltd. (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