Top

European Journal of Clinical Microbiology & Infectious Diseases

Published in:

01-04-2022 | Carbapenem Antibiotic | Brief Report

Co-resistance to ceftazidime-avibactam and cefiderocol in clinical isolates producing KPC variants

Authors: Laurent Poirel, Mustafa Sadek, Ayda Kusaksizoglu, Patrice Nordmann

Published in: European Journal of Clinical Microbiology & Infectious Diseases | Issue 4/2022

Abstract

Cefiderocol (FDC) and ceftazidime-avibactam (CZA) are among the latest generation of commercialized antibiotics against carbapenem-resistant Gram negatives. However, emergence of CZA resistance is being increasingly reported, involving different KPC variants in Enterobacterales. By analyzing two CZA-resistant KPC-3 clinical variants, KPC-41 and KPC-50, we showed that KPC-41, and to a lesser extent KPC-50, may also have an impact on susceptibility to FDC leading to a cross-resistance. This feature highlights that a susceptibility testing to FDC is mandatory prior any clinical use of FDC for treating infections due to KPC producers.

Munoz-Price LS, Poirel L, Bonomo RA et al (2013) Clinical epidemiology of the global expansion of Klebsiella pneumoniae carbapenemases. Lancet Infect Dis 13(9):785–796. https://doi.org/10.1016/S1473-3099(13)70190-7CrossRefPubMedPubMedCentral

Kazmierczak KM, Biedenbach DJ, Hackel M et al (2016) Global dissemination of bla_KPC into bacterial species beyond Klebsiella pneumoniae and in vitro susceptibility to ceftazidime-avibactam and aztreonam-avibactam. Antimicrob Agents Chemother 60(8):4490–4500. https://doi.org/10.1128/AAC.00107-16CrossRefPubMedPubMedCentral

Zhanel GG, Lawson CD, Adam H et al (2013) Ceftazidime-avibactam: a novel cephalosporin/β-lactamase inhibitor combination. Drugs 73(2):159–177. https://doi.org/10.1007/s40265-013-0013-7CrossRefPubMed

Sharma R, Park TE, Moy S (2016) Ceftazidime-avibactam: a novel cephalosporin/β-lactamase inhibitor combination for the treatment of resistant Gram-negative organisms. Clin Ther 38(3):431–444. https://doi.org/10.1016/j.clinthera.2016.01.018CrossRefPubMed

Barnes MD, Winkler ML, Taracila MA et al (2017) Klebsiella pneumoniae carbapenemase-2 (KPC-2), substitutions at ambler position Asp179, and resistance to ceftazidime-avibactam: unique antibiotic-resistant phenotypes emerge from β-lactamase protein engineering. MBio 8(5):e00528-e617. https://doi.org/10.1128/mBio.00528-17CrossRefPubMedPubMedCentral

Hemarajata P, Humphries RM (2019) Ceftazidime/avibactam resistance associated with L169P mutation in the omega loop of KPC-2. J Antimicrob Chemother 74(5):1241–1243. https://doi.org/10.1093/jac/dkz026CrossRefPubMed

Di Pilato V, Aiezza N, Viaggi V et al (2020) KPC-53, a KPC-3 Variant of clinical origin associated with reduced susceptibility to ceftazidime-avibactam. Antimicrob Agents Chemother 65(1):e01429-e1520. https://doi.org/10.1128/AAC.01429-20CrossRefPubMedPubMedCentral

Livermore DM, Warner M, Jamrozy D et al (2015) In vitro selection of ceftazidime-avibactam resistance in Enterobacteriaceae with KPC-3 carbapenemase. Antimicrob Agents Chemother 59(9):5324–5330. https://doi.org/10.1128/AAC.00678-15CrossRefPubMedPubMedCentral

Shields RK, Chen L, Cheng S et al (2017) Emergence of ceftazidime-avibactam resistance due to plasmid-borne bla_KPC-3 mutations during treatment of carbapenem-resistant Klebsiella pneumoniae infections. Antimicrob Agents Chemother 61(3):e02097-e2116. https://doi.org/10.1128/AAC.02097-16CrossRefPubMedPubMedCentral

10.

Shields RK, Nguyen MH, Chen L et al (2018) Pneumonia and renal replacement therapy are risk factors for ceftazidime-avibactam treatment failures and resistance among patients with carbapenem-resistant Enterobacteriaceae infections. Antimicrob Agents Chemother 62(5):e02497-e2517. https://doi.org/10.1128/AAC.02497-17CrossRefPubMedPubMedCentral

11.

Venditti C, Nisii C, D’Arezzo S et al (2019) Molecular and phenotypical characterization of two cases of antibiotic-driven ceftazidime-avibactam resistance in bla_KPC-3-harboring Klebsiella pneumoniae. Infect Drug Resist 12:1935–1940. https://doi.org/10.2147/IDR.S207993CrossRefPubMedPubMedCentral

12.

Mueller L, Masseron A, Prod’Hom G et al (2019) Phenotypic, biochemical and genetic analysis of KPC-41, a KPC-3 variant conferring resistance to ceftazidime-avibactam and exhibiting reduced carbapenemase activity. Antimicrob Agents Chemother 63(12):e01111-e1119. https://doi.org/10.1128/AAC.01111-19CrossRefPubMedCentral

13.

Poirel L, Vuillemin X, Juhas M et al (2020) KPC-50 confers resistance to ceftazidime-avibactam associated with reduced carbapenemase activity. Antimicrob Agents Chemother 64(8):e00321-e420. https://doi.org/10.1128/AAC.00321-20CrossRefPubMedPubMedCentral

14.

Findlay J, Poirel L, Juhas M, Nordmann P (2021) KPC-mediated resistance to ceftazidime-avibactam and collateral effects in Klebsiella pneumoniae. Antimicrob Agents Chemother 65(9):e0089021. https://doi.org/10.1128/AAC.00890-21CrossRefPubMed

15.

Kohira N, West J, Ito A et al (2015) In vitro antimicrobial activity of a siderophore cephalosporin, S-649266, against enterobacteriaceae clinical isolates, including carbapenem-resistant strains. Antimicrob Agents Chemother 60(2):729–734. https://doi.org/10.1128/AAC.01695-15CrossRefPubMed

16.

Hackel MA, Tsuji M, Yamano Y et al (2018) In vitro activity of the siderophore cephalosporin, cefiderocol, against carbapenem-nonsusceptible and multidrug-resistant isolates of Gram-negative bacilli collected worldwide in 2014 to 2016. Antimicrob Agents Chemother 62(2):e01968-e2017. https://doi.org/10.1128/AAC.01968-17CrossRefPubMedPubMedCentral

17.

Sato T, Yamawaki K (2019) Cefiderocol: discovery, chemistry, and in vivo profiles of a novel siderophore cephalosporin. Clin Infect Dis 69(Suppl 7):S538–S543. https://doi.org/10.1093/cid/ciz826CrossRefPubMedPubMedCentral

18.

Kohira N, Hackel MA, Ishioka Y et al (2020) Reduced susceptibility mechanism to cefiderocol, a siderophore cephalosporin, among clinical isolates from a global surveillance programme (SIDERO-WT-2014). J Glob Antimicrob Resist 22:738–741. https://doi.org/10.1016/j.jgar.2020.07.009CrossRefPubMed

19.

Poirel L, Sadek M, Nordmann P (2021) Contribution of PER-type and NDM-type β-lactamases to cefiderocol resistance in Acinetobacter baumannii. Antimicrob Agents Chemother 65(10):e0087721. https://doi.org/10.1128/AAC.00877-21CrossRefPubMed

20.

Hobson CA, Cointe A, Jacquier H et al (2021) Cross-resistance to cefiderocol and ceftazidime-avibactam in KPC β-lactamase mutants and the inoculum effect. Clin Microbiol Infect 27(8):1172.e7-1172.e10. https://doi.org/10.1016/j.cmi.2021.04.016CrossRef

21.

EUCAST (2021) The European Committee on antimicrobial susceptibility testing breakpoint tables for interpretation of MICs and zone diameters, version v11.0. 2021.https://www.eucast.org/fileadmin/src/media/PDFs/EUCAST_files/Breakpoint_tables/v_11.0_Breakpoint_Tables.pdf.

22.

Poirel L, Ortiz de la Rosa JM, Richard A, Aires-de-Sousa M, Nordmann P (2019) CTX-M-33, a CTX-M-15 derivative conferring reduced susceptibility to carbapenems. Antimicrob Agents Chemother 63(12):e01515-e1519. https://doi.org/10.1128/AAC.01515-19CrossRefPubMedCentral

23.

Ito A, Sato T, Ota M et al (2017) In vitro antibacterial properties of cefiderocol, a novel siderophore cephalosporin, against Gram-negative bacteria. Antimicrob Agents Chemother 62(1):e01454-e1517. https://doi.org/10.1128/AAC.01454-17CrossRefPubMedPubMedCentral

24.

Bianco G, Boattini M, Comini S et al (2021) In vitro activity of cefiderocol against ceftazidime-avibactam susceptible and resistant KPC-producing Enterobacterales: cross-resistance and synergistic effects [published online ahead of print, 2021 Aug 31]. Eur J Clin Microbiol Infect Dis. https://doi.org/10.1007/s10096-021-04341-z

25.

Tiseo G, Falcone M, Leonildi A et al (2021) Meropenem-vaborbactam as salvage therapy for ceftazidime-avibactam-, cefiderocol-resistant ST-512 Klebsiella pneumoniae-producing KPC-31, a D179Y variant of KPC-3. Open Forum Infect Dis 8(6):ofab141. https://doi.org/10.1093/ofid/ofab141

Title: Co-resistance to ceftazidime-avibactam and cefiderocol in clinical isolates producing KPC variants
Authors: Laurent Poirel
Mustafa Sadek
Ayda Kusaksizoglu
Patrice Nordmann
Publication date: 01-04-2022
Publisher: Springer Berlin Heidelberg
Keywords: Carbapenem Antibiotic
Ceftazidime
Published in: European Journal of Clinical Microbiology & Infectious Diseases / Issue 4/2022
Print ISSN: 0934-9723
Electronic ISSN: 1435-4373
DOI: https://doi.org/10.1007/s10096-021-04397-x

ACC 2024 Congress Coverage

Heart Failure Video

At a glance: The ONWARDS insulin icodec trials

Springer Medicine

Co-resistance to ceftazidime-avibactam and cefiderocol in clinical isolates producing KPC variants

Abstract

ACC 2024 Congress Coverage

Year in Review: Heart failure and cardiomyopathies

Semaglutide benefits people with type 2 diabetes and obesity-related heart failure

Incentivised to exercise

New intervention for STEMI-related cardiogenic shock

» View more highlights on the ACC 2024 congress hub page

At a glance: The ONWARDS insulin icodec trials

Springer Medicine

Abstract

Please log in to get access to this content

Other articles of this Issue 4/2022

Occurrence of multi-carbapenemases producers among carbapenemase-producing Enterobacterales and in vitro activity of combinations including cefiderocol, ceftazidime-avibactam, meropenem-vaborbactam, and aztreonam in the COVID-19 era

Mortality-associated factors of candidemia: a multi-center prospective cohort in Turkey

Epidemiology and outcome of occult bacteremia in patients discharged from emergency departments or ambulatory units: one-year study

Capnocytophaga zoonotic infections: a 10-year retrospective study (the French CANCAN study)

Assessing the diagnostic accuracy of the Xpert MTB/RIF assay in detecting epididymal tuberculosis

Pasteurella species bloodstream infections in Queensland, Australia, 2000–2019

ACC 2024 Congress Coverage

Year in Review: Heart failure and cardiomyopathies

Semaglutide benefits people with type 2 diabetes and obesity-related heart failure

Incentivised to exercise

New intervention for STEMI-related cardiogenic shock

» View more highlights on the ACC 2024 congress hub page