TY - JOUR
T1 - Cefiderocol retains antibiofilm activity in multidrug-resistant gram-negative pathogens
AU - Pybus, Christine A.
AU - Felder-Scott, Christina
AU - Obuekwe, Victor
AU - Greenberg, David E.
N1 - Funding Information:
MIC assays and MBEC biofilm tests were funded in David E. Greenberg's laboratory by Shionogi & Co., Ltd. (grant S-649266-EF-348-R). Shionogi & Co., Ltd., did not design or conduct assays or interpret the data. We thank Naoki Kohira for his role in supporting this project and Amila Nanayakkara for his thoughtful comments on the manuscript.
Funding Information:
MIC assays and MBEC biofilm tests were funded in David E. Greenberg’s laboratory by Shionogi & Co., Ltd. (grant S-649266-EF-348-R). Shionogi & Co., Ltd., did not design or conduct assays or interpret the data.
Publisher Copyright:
© 2021 Pybus et al. This is an open-access article distributed under the terms of the Creative Commons Attribution 4.0 International license.
PY - 2021/2
Y1 - 2021/2
N2 - Cefiderocol is a siderophore cephalosporin with potent antibacterial activity against a broad range of Gram-negative pathogens, including multidrug-resistant strains. Siderophore antibiotics bind ferric iron and utilize iron transporters to cross the cell membrane. In the biofilm setting, where antibiotic resistance is high but iron scavenging is important, cefiderocol may have advantageous antimicrobial properties. In this study, we compared the antimicrobial activity of cefiderocol to that of seven commonly used antibiotics in well-characterized multidrug-resistant pathogens and then determined their efficacy in the biofilm setting. MIC90 values for cefiderocol were consistently lower than those of other antibiotics (ceftolozane-tazobactam, ceftazidime-avibactam, ceftazidime, piperacillin-tazobactam, imipenem, and tobramycin) in all strains tested. Cefiderocol treatment displayed a reduction in the levels of Pseudomonas aeruginosa biofilm (93%, P, 0.0001) superior to that seen with the other antibiotics (49% to 82%). Cefiderocol was generally as effective as or superior to the other antibiotics, depending on the pathogen-antibiotic combination, in reducing biofilm in other pathogens. There was a trend toward greater biofilm reduction seen with increased antibiotic dose or with increased frequency of antibiotic treatment. We conclude that cefiderocol effectively reduces biofilm and is a potent inhibitor of planktonic growth across a range of Gram-negative medically important pathogens.
AB - Cefiderocol is a siderophore cephalosporin with potent antibacterial activity against a broad range of Gram-negative pathogens, including multidrug-resistant strains. Siderophore antibiotics bind ferric iron and utilize iron transporters to cross the cell membrane. In the biofilm setting, where antibiotic resistance is high but iron scavenging is important, cefiderocol may have advantageous antimicrobial properties. In this study, we compared the antimicrobial activity of cefiderocol to that of seven commonly used antibiotics in well-characterized multidrug-resistant pathogens and then determined their efficacy in the biofilm setting. MIC90 values for cefiderocol were consistently lower than those of other antibiotics (ceftolozane-tazobactam, ceftazidime-avibactam, ceftazidime, piperacillin-tazobactam, imipenem, and tobramycin) in all strains tested. Cefiderocol treatment displayed a reduction in the levels of Pseudomonas aeruginosa biofilm (93%, P, 0.0001) superior to that seen with the other antibiotics (49% to 82%). Cefiderocol was generally as effective as or superior to the other antibiotics, depending on the pathogen-antibiotic combination, in reducing biofilm in other pathogens. There was a trend toward greater biofilm reduction seen with increased antibiotic dose or with increased frequency of antibiotic treatment. We conclude that cefiderocol effectively reduces biofilm and is a potent inhibitor of planktonic growth across a range of Gram-negative medically important pathogens.
KW - Biofilms
KW - Cefiderocol
KW - Gram negatives
KW - Multidrug resistance
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U2 - 10.1128/AAC.01194-20
DO - 10.1128/AAC.01194-20
M3 - Article
C2 - 33199383
AN - SCOPUS:85099843491
SN - 0066-4804
VL - 65
JO - Antimicrobial agents and chemotherapy
JF - Antimicrobial agents and chemotherapy
IS - 2
M1 - e01194-20
ER -