Abstract

BackgroundElevated resistance rates have been reported in ICUs. Aztreonam (ATM) combined with avibactam (AVI) is being developed for use against drug-resistant Enterobacterales (Ebact), including metallo-β-lactamase (MBL)-positive isolates. We examined the activity of ATM-AVI and comparators against Ebact isolates collected from geriatric patients in ICU and non-ICU wards as part of the ATLAS surveillance program.Methods23754 non-duplicate Ebact isolates were collected in 53 countries in Asia/Pacific (excluding mainland China and India), Europe, Latin America, and Middle East/Africa from patients ≥65 years with lower respiratory tract (LRTI), urinary tract (UTI), skin and soft tissue (SSTI), intra-abdominal (IAI), and bloodstream (BSI) infections. Susceptibility testing was performed by CLSI broth microdilution and values interpreted using CLSI 2021 breakpoints. PCR and sequencing were used to determine the β-lactamase genes present in isolates with meropenem MIC >1 µg/mL, and Escherichia coli, Klebsiella spp. and Proteus mirabilis with ATM or ceftazidime MIC >1 µg/mL.ResultsSusceptibility of the studied comparator agents was generally slightly lower among Ebact from BSI than other infection types (Table). Susceptibility was also generally lower among Ebact from ICU than non-ICU wards by up to 10 percentage points, and MIC90 values were up to 32-fold higher. ATM-AVI MIC90 values were within one doubling-dilution across all studied strata (0.12-0.25 µg/mL), were comparable to or lower than for meropenem in all strata, and were 2 to ≥9 dilutions lower than all other tested comparators. MBL-positive Ebact were found in 1.5% of LRTI (n=91), 1.2% of UTI (n=70), 1.1% of SSTI (n=52), 1.3% of BSI (n=49), and 0.7% of IAI isolates (n=22). MBL-positive rates were higher among ICU (1.7%, n=101) than non-ICU isolates (1.0%, n=183). ATM-AVI MIC90 values were 0.5 µg/mL against MBL-positive isolates from all ward and infection types except SSTI (MIC90 0.25 µg/mL) and BSI (MIC90 1 µg/mL), 2-4 dilutions lower than tigecycline and at least 5-10 dilutions lower than the other comparators.Results Table ConclusionATM-AVI could provide a valuable therapeutic option for treatment of infections caused by Ebact in patients ≥65 years old in both ICU and non-ICU wards.Disclosures Sibylle Lob, PhD, IHMA (Employee)Pfizer, Inc. (Independent Contractor) Krystyna Kazmierczak, PhD, IHMA (Employee)Pfizer, Inc. (Independent Contractor) Francis Arhin, PhD, Pfizer, Inc. (Employee) Daniel F. Sahm, PhD, IHMA (Employee)Pfizer, Inc. (Independent Contractor)

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