P35 Heteroresistance to cefiderocol in clinical Gram-negative isolates

نویسندگان

چکیده

Abstract Background Heteroresistance is a phenotype in which clinically susceptible bacterial isolate contains less subpopulations. Unexpectedly high levels of treatment failure for cefiderocol, novel antibiotic designed to treat multidrug-resistant infections, have been attributed this phenomenon. Objectives To determine prevalence cefiderocol heteroresistance amongst clinical isolates at North London tertiary care centre and study the population dynamics upon exposure antibiotic. Methods Gram-negative (n = 146) were screened susceptibility by standard disc diffusion Etest assays. Isolates classified based on EUCAST breakpoints susceptibility. was confirmed performing modified-population analysis profile (mPAP) assay iron-depleted Mueller Hinton II agar. MIC values determined broth microdilution (BMD) as per guidelines. The heteroresistant their corresponding subpopulations serially passaged media with sub-inhibitory concentrations well cefiderocol-free medium. changes frequency and/or subpopulation detected using mPAP. Results Eleven (7.53%) twenty-two resistant (15.06%) identified. Cefiderocol after five passages medium partially reverted that parent population. However, phenomenon not observed cohort first cefiderocol-containing before When populations 0.25× values, no serial passages; however, proportion increased 1.2 log10 one out isolates. Nevertheless, when pressure removed passaging further passages, colonies within 80% In isolate, sub-population >32-fold while 1.0 another. Conclusions around 7% phenotypes unstable unless exposed cefiderocol. Such may also increase cells This amplification can continue even removal pressure. Developing methods detecting laboratories essential. Clinicians need take into account planning regimens optimize effectiveness invaluable addition antimicrobial armamentarium.

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ژورنال

عنوان ژورنال: JAC-antimicrobial resistance

سال: 2023

ISSN: ['2632-1823']

DOI: https://doi.org/10.1093/jacamr/dlad066.039