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

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 hundr... Full description

Journal Title: European journal of clinical microbiology & infectious diseases 2021-08-31, Vol.41 (1), p.63-70
Main Author: Bianco, Gabriele
Other Authors: Boattini, Matteo , Comini, Sara , Iannaccone, Marco , Bondi, Alessandro , Cavallo, Rossana , Costa, Cristina
Format: Electronic Article Electronic Article
Language: English
Subjects:
Amikacin
Anti-Bacterial Agents - pharmacology
Antibiotics
Azabicyclo Compounds - pharmacology
Bacterial pneumonia
Bacterial Proteins - genetics
Bacterial Proteins - metabolism
beta-Lactamases - genetics
beta-Lactamases - metabolism
Biomedical and Life Sciences
Biomedicine
Breakpoints
Ceftazidime
Ceftazidime - pharmacology
Cephalosporins - pharmacology
Cross-resistance
Diffusion
Diffusion rate
Drug Combinations
Drug resistance in microorganisms
Drug Resistance, Bacterial
Drug Synergism
Enterobacterales
Enzymes
Evaluation
Humans
Imipenem
Infectious diseases
Internal Medicine
Klebsiella
Klebsiella Infections - drug therapy
Klebsiella Infections - microbiology
Klebsiella pneumoniae - drug effects
Klebsiella pneumoniae - genetics
Klebsiella pneumoniae - metabolism
Laboratories
Medical Microbiology
Meropenem
Microbial Sensitivity Tests
Original Article
Pneumonia
Quality control
Surveillance
Synergistic effect
β Lactamase
Publisher: Berlin/Heidelberg: Springer Berlin Heidelberg
ID: ISSN: 0934-9723
Link: https://www.ncbi.nlm.nih.gov/pubmed/34462816
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title: In vitro activity of cefiderocol against ceftazidime-avibactam susceptible and resistant KPC-producing Enterobacterales: cross-resistance and synergistic effects
format: Article
creator:
  • Bianco, Gabriele
  • Boattini, Matteo
  • Comini, Sara
  • Iannaccone, Marco
  • Bondi, Alessandro
  • Cavallo, Rossana
  • Costa, Cristina
subjects:
  • Amikacin
  • Anti-Bacterial Agents - pharmacology
  • Antibiotics
  • Azabicyclo Compounds - pharmacology
  • Bacterial pneumonia
  • Bacterial Proteins - genetics
  • Bacterial Proteins - metabolism
  • beta-Lactamases - genetics
  • beta-Lactamases - metabolism
  • Biomedical and Life Sciences
  • Biomedicine
  • Breakpoints
  • Ceftazidime
  • Ceftazidime - pharmacology
  • Cephalosporins - pharmacology
  • Cross-resistance
  • Diffusion
  • Diffusion rate
  • Drug Combinations
  • Drug resistance in microorganisms
  • Drug Resistance, Bacterial
  • Drug Synergism
  • Enterobacterales
  • Enzymes
  • Evaluation
  • Humans
  • Imipenem
  • Infectious diseases
  • Internal Medicine
  • Klebsiella
  • Klebsiella Infections - drug therapy
  • Klebsiella Infections - microbiology
  • Klebsiella pneumoniae - drug effects
  • Klebsiella pneumoniae - genetics
  • Klebsiella pneumoniae - metabolism
  • Laboratories
  • Medical Microbiology
  • Meropenem
  • Microbial Sensitivity Tests
  • Original Article
  • Pneumonia
  • Quality control
  • Surveillance
  • Synergistic effect
  • β Lactamase
ispartof: European journal of clinical microbiology & infectious diseases, 2021-08-31, Vol.41 (1), p.63-70
description: 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  
language: eng
source:
identifier: ISSN: 0934-9723
fulltext: no_fulltext
issn:
  • 0934-9723
  • 1435-4373
url: Link


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titleIn vitro activity of cefiderocol against ceftazidime-avibactam susceptible and resistant KPC-producing Enterobacterales: cross-resistance and synergistic effects
creatorBianco, Gabriele ; Boattini, Matteo ; Comini, Sara ; Iannaccone, Marco ; Bondi, Alessandro ; Cavallo, Rossana ; Costa, Cristina
creatorcontribBianco, Gabriele ; Boattini, Matteo ; Comini, Sara ; Iannaccone, Marco ; Bondi, Alessandro ; Cavallo, Rossana ; Costa, Cristina
descriptionPurpose 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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1EISSN: 1435-4373
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languageeng
publisherBerlin/Heidelberg: Springer Berlin Heidelberg
subjectAmikacin ; Anti-Bacterial Agents - pharmacology ; Antibiotics ; Azabicyclo Compounds - pharmacology ; Bacterial pneumonia ; Bacterial Proteins - genetics ; Bacterial Proteins - metabolism ; beta-Lactamases - genetics ; beta-Lactamases - metabolism ; Biomedical and Life Sciences ; Biomedicine ; Breakpoints ; Ceftazidime ; Ceftazidime - pharmacology ; Cephalosporins - pharmacology ; Cross-resistance ; Diffusion ; Diffusion rate ; Drug Combinations ; Drug resistance in microorganisms ; Drug Resistance, Bacterial ; Drug Synergism ; Enterobacterales ; Enzymes ; Evaluation ; Humans ; Imipenem ; Infectious diseases ; Internal Medicine ; Klebsiella ; Klebsiella Infections - drug therapy ; Klebsiella Infections - microbiology ; Klebsiella pneumoniae - drug effects ; Klebsiella pneumoniae - genetics ; Klebsiella pneumoniae - metabolism ; Laboratories ; Medical Microbiology ; Meropenem ; Microbial Sensitivity Tests ; Original Article ; Pneumonia ; Quality control ; Surveillance ; Synergistic effect ; β Lactamase
ispartofEuropean journal of clinical microbiology & infectious diseases, 2021-08-31, Vol.41 (1), p.63-70
rights
0The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature 2021
12021. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.
2COPYRIGHT 2022 Springer
3The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature 2021.
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0Bianco, Gabriele
1Boattini, Matteo
2Comini, Sara
3Iannaccone, Marco
4Bondi, Alessandro
5Cavallo, Rossana
6Costa, Cristina
title
0In vitro activity of cefiderocol against ceftazidime-avibactam susceptible and resistant KPC-producing Enterobacterales: cross-resistance and synergistic effects
1European journal of clinical microbiology & infectious diseases
addtitle
0Eur J Clin Microbiol Infect Dis
1Eur J Clin Microbiol Infect Dis
descriptionPurpose 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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0Amikacin
1Anti-Bacterial Agents - pharmacology
2Antibiotics
3Azabicyclo Compounds - pharmacology
4Bacterial pneumonia
5Bacterial Proteins - genetics
6Bacterial Proteins - metabolism
7beta-Lactamases - genetics
8beta-Lactamases - metabolism
9Biomedical and Life Sciences
10Biomedicine
11Breakpoints
12Ceftazidime
13Ceftazidime - pharmacology
14Cephalosporins - pharmacology
15Cross-resistance
16Diffusion
17Diffusion rate
18Drug Combinations
19Drug resistance in microorganisms
20Drug Resistance, Bacterial
21Drug Synergism
22Enterobacterales
23Enzymes
24Evaluation
25Humans
26Imipenem
27Infectious diseases
28Internal Medicine
29Klebsiella
30Klebsiella Infections - drug therapy
31Klebsiella Infections - microbiology
32Klebsiella pneumoniae - drug effects
33Klebsiella pneumoniae - genetics
34Klebsiella pneumoniae - metabolism
35Laboratories
36Medical Microbiology
37Meropenem
38Microbial Sensitivity Tests
39Original Article
40Pneumonia
41Quality control
42Surveillance
43Synergistic effect
44β Lactamase
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3Iannaccone, Marco
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5Cavallo, Rossana
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titleIn vitro activity of cefiderocol against ceftazidime-avibactam susceptible and resistant KPC-producing Enterobacterales: cross-resistance and synergistic effects
authorBianco, Gabriele ; Boattini, Matteo ; Comini, Sara ; Iannaccone, Marco ; Bondi, Alessandro ; Cavallo, Rossana ; Costa, Cristina
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0Amikacin
1Anti-Bacterial Agents - pharmacology
2Antibiotics
3Azabicyclo Compounds - pharmacology
4Bacterial pneumonia
5Bacterial Proteins - genetics
6Bacterial Proteins - metabolism
7beta-Lactamases - genetics
8beta-Lactamases - metabolism
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10Biomedicine
11Breakpoints
12Ceftazidime
13Ceftazidime - pharmacology
14Cephalosporins - pharmacology
15Cross-resistance
16Diffusion
17Diffusion rate
18Drug Combinations
19Drug resistance in microorganisms
20Drug Resistance, Bacterial
21Drug Synergism
22Enterobacterales
23Enzymes
24Evaluation
25Humans
26Imipenem
27Infectious diseases
28Internal Medicine
29Klebsiella
30Klebsiella Infections - drug therapy
31Klebsiella Infections - microbiology
32Klebsiella pneumoniae - drug effects
33Klebsiella pneumoniae - genetics
34Klebsiella pneumoniae - metabolism
35Laboratories
36Medical Microbiology
37Meropenem
38Microbial Sensitivity Tests
39Original Article
40Pneumonia
41Quality control
42Surveillance
43Synergistic effect
44β Lactamase
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1Boattini, Matteo
2Comini, Sara
3Iannaccone, Marco
4Bondi, Alessandro
5Cavallo, Rossana
6Costa, Cristina
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1Boattini, Matteo
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atitleIn vitro activity of cefiderocol against ceftazidime-avibactam susceptible and resistant KPC-producing Enterobacterales: cross-resistance and synergistic effects
jtitleEuropean journal of clinical microbiology & infectious diseases
stitleEur J Clin Microbiol Infect Dis
addtitleEur J Clin Microbiol Infect Dis
date2021-08-31
risdate2021
volume41
issue1
spage63
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issn0934-9723
eissn1435-4373
abstractPurpose 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.
copBerlin/Heidelberg
pubSpringer Berlin Heidelberg
pmid34462816
doi10.1007/s10096-021-04341-z