Abstract

Abstract Background Infections caused by Achromobacter spp. and Burkholderia spp. have limited clinical treatment options due to the intrinsic resistance of these non-fermenters to several antimicrobial agents. These pathogens are known to cause severe nosocomial infections such as bloodstream infections and pneumonia in immunocompromised patients. Cefiderocol (CFDC) is a siderophore cephalosporin antibiotic approved in the US and Europe, with potent activity against Gram-negative bacteria including carbapenem-resistant strains. We evaluated the in vitro activity of CFDC and comparator agents against Achromobacter spp. and Burkholderia spp. clinical isolates, collected from hospitalized patients in US medical centers as part of the SENTRY Antimicrobial Surveillance Program. Methods Susceptibility testing for CFDC and comparators were performed by broth microdilution according to the CLSI guidance. CFDC was tested in iron-depleted cation-adjusted Mueller Hinton broth. The susceptibilities of CFDC and comparators against a total of 78 strains of Achromobacter spp. and a total of 99 strains of Burkholderia spp. isolated in the US between 2020 to 2021 were analyzed. CLSI breakpoints were used where available. Isolate identification was provided by the submitting site and confirmed at JMI Laboratories using MALDI-TOF. Results The minimum inhibitory concentration (MIC) range, MIC50/90, and susceptible rate for CFDC and comparators for Achromobacter spp. and Burkholderia spp. are shown in the Table 1 and 2, respectively. CFDC inhibited the growth of all 78 Achromobacter spp. isolates tested at ≤4 µg/mL and showed MIC90 of 0.5 μg/mL. CFDC inhibited the growth of 96% (95/99) of Burkholderia spp. isolates tested at ≤4 µg/mL and showed MIC90 of 1 μg/mL. There were 4 strains with high CFDC MIC (≥16 µg/mL), 3 of which were Burkholderia gladioli and 1 was Burkholderia multivorans. Table 1Activity of cefiderocol and comparator antimicrobial agents tested against 78 Achromobacter spp. isolates collected from medical centers in the US during 2020 and 2021Table 2Activity of cefiderocol and comparator antimicrobial agents tested against 99 Burkholderia spp. isolates collected from medical centers in the US during 2020 and 2021 Conclusion CFDC demonstrated potent in vitro activity against Achromobacter spp. and Burkholderia spp. collected in the US between 2020 and 2021, indicating that CFDC has high potential for treating infections caused by these pathogens. Disclosures Miki Takemura, n/a, Shionogi: Employee Dee Shortridge, PhD, AbbVie: Grant/Research Support|JMI Laboratory: Employee|Melinta: Grant/Research Support|Menarini: Grant/Research Support|Shionogi: Grant/Research Support Christine M. Slover, PharmD, Shionogi: Employee Christopher M. Longshaw, PhD, Shionogi: Employee Roger Echols, MD, Shionogi: Advisor/Consultant Roger Echols, MD, Shionogi: Advisor/Consultant Roger Echols, MD, Shionogi: Advisor/Consultant Yoshinori Yamano, PhD, Shionogi: Employee.

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