Acinetobacter baumannii response to cefiderocol challenge in human urine

Area of Science:

• Microbiology
• Infectious Diseases
• Pharmacology

Background:

• Cefiderocol (CFDC) is a siderophore antibiotic for complicated urinary tract infections (cUTI) and pneumonia.
• Albumin-rich fluids increase bacterial resistance to CFDC by reducing iron uptake gene expression.
• Human urine (HU) has low albumin concentrations, prompting investigation into its effect on CFDC activity.

Purpose of the Study:

• To determine the impact of human urine (HU) on the antimicrobial activity of cefiderocol (CFDC) against carbapenem-resistant Acinetobacter baumannii.
• To analyze the effect of HU on the expression of iron uptake and beta-lactam resistance genes in Acinetobacter baumannii.

Main Methods:

• Minimum inhibitory concentrations (MICs) of CFDC were determined for Acinetobacter baumannii strains in the presence of HU.
• Gene expression levels (piuA, pirA, bauA, bfnH, pbp1, pbp3, blaOXA-51-like, blaADC, blaNDM-1) were quantified using qRT-PCR.

Main Results:

• HU did not modify CFDC MIC values for most tested carbapenem-resistant Acinetobacter baumannii strains.
• HU exposure enhanced the expression of iron uptake-related genes (piuA, pirA, bauA, bfnH) in Acinetobacter baumannii.
• The effect of HU on beta-lactam resistance genes, efflux pumps, and porins varied depending on the bacterial strain.

Conclusions:

• Unlike albumin-rich fluids, human urine (HU) does not negatively impact the antibacterial activity of cefiderocol (CFDC) against Acinetobacter baumannii.
• The low albumin and free iron content in HU contributes to its distinct effect on CFDC activity.
• Findings suggest CFDC may retain efficacy in urinary tract infections despite the presence of urine.