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Erschienen in: European Journal of Clinical Microbiology & Infectious Diseases 1/2022

31.08.2021 | Original Article

In vitro activity of cefiderocol against ceftazidime-avibactam susceptible and resistant KPC-producing Enterobacterales: cross-resistance and synergistic effects

verfasst von: Gabriele Bianco, Matteo Boattini, Sara Comini, Marco Iannaccone, Alessandro Bondi, Rossana Cavallo, Cristina Costa

Erschienen in: European Journal of Clinical Microbiology & Infectious Diseases | Ausgabe 1/2022

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Abstract

Purpose

To assess the in vitro activity of cefiderocol (CFDC) against a collection of both ceftazidime-avibactam (CZA) susceptible and resistant KPC-producing Enterobacterales (KPC-EB) isolates. Secondly, to assess its synergistic activity in combination with different antibiotics.

Methods

One hundred KPC-EB isolates were tested: 60 CZA susceptible and 40 CZA resistant. Among them, 17 pairs of CZA susceptible and resistant KPC-producing Klebsiella pneumoniae (KPC-Kp) isolates were collected from 17 distinct patients before and after CZA treatment, respectively.
CFDC susceptibility was evaluated by both broth microdilution (lyophilized panels; Sensititre; Thermo Fisher) and disk diffusion testing. Results were interpreted using EUCAST breakpoints. Synergistic activity of CFDC in combination with CZA, meropenem-vaborbactam, imipenem, and amikacin against six characterized KPC-Kp strains, before and after acquisition of CZA resistance, was evaluated using gradient diffusion strip crossing method.

Results

CFDC resistance rate was significantly higher in CZA resistant EB subset than in the susceptible one (p < 0.001): 82.5% vs 6.7%. MIC50 and MIC90 values were 0.25 and 2 mg/L, 8 and 64 mg/L in CZA-susceptible and CZA-resistant subset, respectively. KPC-Kp isolates harboring KPC-D179Y or KPC-Δ242-GT-243 variants showed CFDC MICs ranging from 4 to 64 mg/L. CFDC showed in vitro synergistic effect mostly with CZA, against both CZA susceptible and resistant isolates, resulting in a synergy rate of 66.7%.

Conclusions

CZA resistance mechanisms in KPC-EB impair the in vitro activity of CFDC, often leading to co-resistance. CFDC in combination with the new β-lactamases inhibitors might represent a strategy to enhance its activity.
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Literatur
5.
Zurück zum Zitat Tamma PD, Aitken SL, Bonomo RA, Mathers AJ, van Duin D, Clancy CJ (2020) Infectious Diseases Society of America Guidance on the Treatment of Extended-Spectrum β-lactamase Producing Enterobacterales (ESBL-E), Carbapenem-Resistant Enterobacterales (CRE), and Pseudomonas aeruginosa with Difficult-to-Treat Resistance (DTR-P. aeruginosa). Clin Infect Dis ciaa1478. https://doi.org/10.1093/cid/ciaa1478 Tamma PD, Aitken SL, Bonomo RA, Mathers AJ, van Duin D, Clancy CJ (2020) Infectious Diseases Society of America Guidance on the Treatment of Extended-Spectrum β-lactamase Producing Enterobacterales (ESBL-E), Carbapenem-Resistant Enterobacterales (CRE), and Pseudomonas aeruginosa with Difficult-to-Treat Resistance (DTR-P. aeruginosa). Clin Infect Dis ciaa1478. https://​doi.​org/​10.​1093/​cid/​ciaa1478
9.
Zurück zum Zitat Bianco G, Boattini M, Iannaccone M, Cavallo R, Costa C (2020) Bloodstream infection by two subpopulations of Klebsiella pneumoniae ST1685 carrying KPC-33 or KPC-14 following ceftazidime/avibactam treatment: considerations regarding acquired heteroresistance and choice of carbapenemase detection assay. J Antimicrob Chemother. https://doi.org/10.1093/jac/dkaa283 Bianco G, Boattini M, Iannaccone M, Cavallo R, Costa C (2020) Bloodstream infection by two subpopulations of Klebsiella pneumoniae ST1685 carrying KPC-33 or KPC-14 following ceftazidime/avibactam treatment: considerations regarding acquired heteroresistance and choice of carbapenemase detection assay. J Antimicrob Chemother. https://​doi.​org/​10.​1093/​jac/​dkaa283
11.
15.
Zurück zum Zitat Kazmierczak KM, Tsuji M, Wise MG, Hackel M, Yamano Y, Echols R et al (2019) In vitro activity of cefiderocol, a siderophore cephalosporin, against a recent collection of clinically relevant carbapenem-non-susceptible Gram-negative bacilli, including serine carbapenemase- and metallo-β-lactamase-producing isolates (SIDERO-WT-2014 Study). Int J Antimicrob Agents 53:177–184. https://doi.org/10.1016/j.ijantimicag.2018.10.007CrossRefPubMed Kazmierczak KM, Tsuji M, Wise MG, Hackel M, Yamano Y, Echols R et al (2019) In vitro activity of cefiderocol, a siderophore cephalosporin, against a recent collection of clinically relevant carbapenem-non-susceptible Gram-negative bacilli, including serine carbapenemase- and metallo-β-lactamase-producing isolates (SIDERO-WT-2014 Study). Int J Antimicrob Agents 53:177–184. https://​doi.​org/​10.​1016/​j.​ijantimicag.​2018.​10.​007CrossRefPubMed
16.
Zurück zum Zitat Jacobs MR, Abdelhamed AM, Good CE, Rhoads DD, Hujer KM, Hujer AM et al (2018) ARGONAUT-I: activity of cefiderocol (S-649266), a siderophore cephalosporin, against gram-negative bacteria, including carbapenem-resistant nonfermenters and Enterobacteriaceae with defined extended-spectrum β-lactamases and carbapenemases. Antimicrob Agents Chemother 63:e01801-e1818. https://doi.org/10.1128/AAC.01801-18CrossRefPubMedPubMedCentral Jacobs MR, Abdelhamed AM, Good CE, Rhoads DD, Hujer KM, Hujer AM et al (2018) ARGONAUT-I: activity of cefiderocol (S-649266), a siderophore cephalosporin, against gram-negative bacteria, including carbapenem-resistant nonfermenters and Enterobacteriaceae with defined extended-spectrum β-lactamases and carbapenemases. Antimicrob Agents Chemother 63:e01801-e1818. https://​doi.​org/​10.​1128/​AAC.​01801-18CrossRefPubMedPubMedCentral
Metadaten
Titel
In vitro activity of cefiderocol against ceftazidime-avibactam susceptible and resistant KPC-producing Enterobacterales: cross-resistance and synergistic effects
verfasst von
Gabriele Bianco
Matteo Boattini
Sara Comini
Marco Iannaccone
Alessandro Bondi
Rossana Cavallo
Cristina Costa
Publikationsdatum
31.08.2021
Verlag
Springer Berlin Heidelberg
Erschienen in
European Journal of Clinical Microbiology & Infectious Diseases / Ausgabe 1/2022
Print ISSN: 0934-9723
Elektronische ISSN: 1435-4373
DOI
https://doi.org/10.1007/s10096-021-04341-z

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