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. 2024 Mar 6;68(3):e0125823.
doi: 10.1128/aac.01258-23. Epub 2024 Jan 30.

In vitro activity of sulbactam-durlobactam against colistin-resistant and/or cefiderocol-non-susceptible, carbapenem-resistant Acinetobacter baumannii collected in U.S. hospitals

Alina Iovleva  1 , Christi L McElheny  1 , Erin L Fowler  1 , Eric Cober  2 , Erica S Herc  3 , Cesar A Arias  4   5   6 , Carol Hill  7 , Keri Baum  7 , Vance G Fowler Jr  7   8 , Henry F Chambers  9 , Kerryl E Greenwood-Quaintance  10 , Robin Patel  10   11 , David van Duin  12 , Robert A Bonomo  13   14   15   16   17   18   19   20 , Yohei Doi  1   21   22
Affiliations

In vitro activity of sulbactam-durlobactam against colistin-resistant and/or cefiderocol-non-susceptible, carbapenem-resistant Acinetobacter baumannii collected in U.S. hospitals

Alina Iovleva et al. Antimicrob Agents Chemother. .

Abstract

The activity of a novel β-lactamase inhibitor combination, sulbactam-durlobactam (SUL-DUR), was tested against 87 colistin-resistant and/or cefiderocol-non-susceptible carbapenem-resistant Acinetobacter baumannii clinical isolates collected from U.S. hospitals between 2017 and 2019. Among them, 89% and 97% were susceptible to SUL-DUR and imipenem plus SUL-DUR, with MIC50/MIC90 values of 2 µg/mL/8 µg/mL and 1 µg/mL/4 µg/mL, respectively. The presence of amino acid substitutions in penicillin-binding protein 3, including previously reported A515V or T526S, was associated with SUL-DUR non-susceptibility.

Keywords: antimicrobial resistance; diazabicyclooctane; surveillance.

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Conflict of interest statement

The authors thank Entasis Therapeutics Inc. for provision of durlobactam for the study.

Figures

Fig 1
Fig 1
Distruption of minimal inhibitory concentrations (MICs) for sulbactam-durlobactam (SUL-DUR) and imipenem with sulbactam-durlobactam (IPM-SUL-DUR) of colistin-resistant (A) and cefiderocol-non-susceptible (B) isolates. The numbers of isolates with each MIC are listed on top of the histogram bars. Susceptibility breakpoints to SUL-DUR are noted by dashed vertical lines.
See this image and copyright information in PMC

References

    1. Wang M, Ge L, Chen L, Komarow L, Hanson B, Reyes J, Cober E, Alenazi T, Zong Z, Xie Q, et al. . 2023. Clinical outcomes and bacterial characteristics of carbapenem-resistant Acinetobacter baumannii among patients from different global regions. Clin Infect Dis:ciad556. doi:10.1093/cid/ciad556 - DOI - PMC - PubMed
    1. Shapiro AB, Moussa SH, McLeod SM, Durand-Réville T, Miller AA. 2021. Durlobactam, a new diazabicyclooctane β-lactamase inhibitor for the treatment of Acinetobacter infections in combination with sulbactam. Front Microbiol 12:709974. doi:10.3389/fmicb.2021.709974 - DOI - PMC - PubMed
    1. Barnes MD, Kumar V, Bethel CR, Moussa SH, O’Donnell J, Rutter JD, Good CE, Hujer KM, Hujer AM, Marshall SH, Kreiswirth BN, Richter SS, Rather PN, Jacobs MR, Papp-Wallace KM, van den Akker F, Bonomo RA. 2019. Targeting multidrug-resistant Acinetobacter spp.: sulbactam and the diazabicyclooctenone β-lactamase inhibitor ETX2514 as a novel therapeutic agent. mBio 10:e00159-19. doi:10.1128/mBio.00159-19 - DOI - PMC - PubMed
    1. Kaye KS, Shorr AF, Wunderink RG, Du B, Poirier GE, Rana K, Miller A, Lewis D, O’Donnell J, Chen L, Reinhart H, Srinivasan S, Isaacs R, Altarac D. 2023. Efficacy and safety of sulbactam-durlobactam versus colistin for the treatment of patients with serious infections caused by Acinetobacter baumannii-calcoaceticus complex: a multicentre, randomised, active-controlled, phase 3, non-inferiority clinical trial (ATTACK). Lancet Infect Dis 23:1072–1084. doi:10.1016/S1473-3099(23)00184-6 - DOI - PubMed
    1. McLeod SM, Shapiro AB, Moussa SH, Johnstone M, McLaughlin RE, de Jonge BLM, Miller AA. 2018. Frequency and mechanism of spontaneous resistance to sulbactam combined with the novel β-lactamase inhibitor ETX2514 in clinical isolates of Acinetobacter baumannii. Antimicrob Agents Chemother 62:e01576-17. doi:10.1128/AAC.01576-17 - DOI - PMC - PubMed

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