In Vivo
 Development of Aztreonam Resistance in Meropenem-Resistant Pseudomonas aeruginosa Owing to Overexpression of the
 bla
 PDC-16

Sun, Yue; Zhang, Yizhuo; Shen, Shuling; Hu, Fupin

doi:10.1128/spectrum.03080-22

Microbiol Spectr

2023

DOI: 10.1128/spectrum.03080-22

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In Vivo Development of Aztreonam Resistance in Meropenem-Resistant Pseudomonas aeruginosa Owing to Overexpression of the bla _PDC-16

Yue Sun

Yizhuo Zhang

Shuling Shen

et al.

Abstract: Pseudomonas aeruginosa is notorious for being highly resistant to antimicrobial agents. In this study, two P. aeruginosa strains isolated from the same patient with different susceptibility to aztreonam were used to illustrate the within-host resistance evolution process of P. aeruginosa .

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Cited by 2 publications

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Synthesis of peptidomimetics as antibiotic adjuvants for combination with aztreonam to combat MDR Pseudomonas aeruginosa

Ma,

Guo,

Zhu

et al. 2023

European Journal of Medicinal Chemistry

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Synthesis of peptidomimetics as antibiotic adjuvants for combination with aztreonam to combat MDR Pseudomonas aeruginosa

Ma,

Guo,

Zhu

et al. 2023

European Journal of Medicinal Chemistry

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In vitro resistance development gives insights into molecular resistance mechanisms against cefiderocol

Kriz,

Spettel,

Pichler

et al. 2024

J Antibiot

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Cefiderocol, a novel siderophore cephalosporin, demonstrates promising in vitro activity against multidrug-resistant Gram-negative bacteria, including carbapenemase-producing strains. Nonetheless, only a few reports are available regarding the acquisition of resistance in clinical settings, primarily due to its recent usage. This study aimed to investigate cefiderocol resistance using an in vitro resistance development model to gain insights into the underlying molecular resistance mechanisms. Cefiderocol susceptible reference strains (Escherichia coli, Klebsiella pneumoniae, Pseudomonas aeruginosa) and a clinical Acinetobacter baumannii complex isolate were exposed to increasing cefiderocol concentrations using a high-throughput resistance development model. Cefiderocol susceptibility testing was performed using broth microdilution. Whole-genome sequencing was employed to identify newly acquired resistance mutations. Our in vitro resistance development model led to several clones of strains exhibiting cefiderocol resistance, with MIC values 8-fold to 512-fold higher than initial levels. In total, we found 42 different mutations in 26 genes, of which 35 could be described for the first time. Putative loss-of-function mutations were detected in the envZ, tonB, and cirA genes in 13 out of 17 isolates, leading to a decrease in cefiderocol influx. Other potential resistance mechanisms included multidrug efflux pumps (baeS, czcS, nalC), antibiotic-inactivating enzymes (ampR, dacB), and target mutations in penicillin-binding-protein genes (mrcB). This study reveals new insights into underlying molecular resistance mechanisms against cefiderocol. While mutations leading to reduced influx via iron transporters was the most frequent resistance mechanism, we also detected several other novel resistance mutations causing cefiderocol resistance.

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In Vivo Development of Aztreonam Resistance in Meropenem-Resistant Pseudomonas aeruginosa Owing to Overexpression of the bla _PDC-16

Abstract: Pseudomonas aeruginosa is notorious for being highly resistant to antimicrobial agents. In this study, two P. aeruginosa strains isolated from the same patient with different susceptibility to aztreonam were used to illustrate the within-host resistance evolution process of P. aeruginosa .

Cited by 2 publications

References 29 publications

Synthesis of peptidomimetics as antibiotic adjuvants for combination with aztreonam to combat MDR Pseudomonas aeruginosa

Synthesis of peptidomimetics as antibiotic adjuvants for combination with aztreonam to combat MDR Pseudomonas aeruginosa

In vitro resistance development gives insights into molecular resistance mechanisms against cefiderocol

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In Vivo Development of Aztreonam Resistance in Meropenem-Resistant Pseudomonas aeruginosa Owing to Overexpression of the bla PDC-16

Cited by 2 publications

References 29 publications

Synthesis of peptidomimetics as antibiotic adjuvants for combination with aztreonam to combat MDR Pseudomonas aeruginosa

Synthesis of peptidomimetics as antibiotic adjuvants for combination with aztreonam to combat MDR Pseudomonas aeruginosa

In vitro resistance development gives insights into molecular resistance mechanisms against cefiderocol

Contact Info

Product

Resources

About

In Vivo Development of Aztreonam Resistance in Meropenem-Resistant Pseudomonas aeruginosa Owing to Overexpression of the bla _PDC-16