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                <forename type="first">Víctor</forename>
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            <funder>The authors thank CIBER de Enfermedades Infecciosas (CIBERINFEC) for providing us the Citrobacter collection strains. V.V. is supported by the Río Hortega Program from the Instituto de Salud Carlos III. A.C.L. is supported by the Atracción de Talento Program of the Community of Madrid. This project was funded by MPY380/18, awarded to M.J.M. from Instituto de Salud Carlos III.</funder>
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              <date type="whenSubmitted">2025-11-06 18:39:13</date>
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            <idno type="halRefHtml">&lt;i&gt;Journal of Global Antimicrobial Resistance&lt;/i&gt;, 2025, 44, pp.366-370. &lt;a target="_blank" href="https://dx.doi.org/10.1016/j.jgar.2025.07.020"&gt;&amp;#x27E8;10.1016/j.jgar.2025.07.020&amp;#x27E9;&lt;/a&gt;</idno>
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                <title xml:lang="en">Activity of LpxC inhibitors on carbapenemase producing Citrobacter spp. clinical isolates</title>
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                    <forename type="first">Andrés</forename>
                    <surname>Corral-Lugo</surname>
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                    <forename type="first">Michael</forename>
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                  <idno type="idhal" notation="numeric">1577365</idno>
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                <title level="j">Journal of Global Antimicrobial Resistance</title>
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                <term xml:lang="en">Carbapenemase</term>
                <term xml:lang="en">Citrobacter spp.</term>
                <term xml:lang="en">Clinical isolates</term>
                <term xml:lang="en">LpxC inhibitors</term>
                <term xml:lang="en">Strain collection</term>
                <term xml:lang="en">Antibiotic resistance</term>
                <term xml:lang="en">Escherichia coli</term>
                <term xml:lang="en">Enterobacteriaceae</term>
                <term xml:lang="en">Citrobacter</term>
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              <p>Objective: Citrobacter spp. are commonly found in the human intestine and can cause antibiotic-resistant infections. Inhibitors of LpxC, an enzyme involved in the synthesis of lipid A, have demonstrated potent activity against multiple Gram-negative species, but their activity in Citrobacter spp. has not been well-characterised. The objective of the present study was to evaluate the antimicrobial activity of LpxC inhibitors against carbapenemase-producing Citrobacter spp. clinical isolates.Methods: The MICs of LpxC-2, LpxC-4, and CHIR-090 LpxC inhibitors were determined for 61 clinical isolates with high genetic diversity. Time-kill assays with the three LpxC inhibitors were performed with two Citrobacter spp. strains, with low (Cit 52) and high (Cit 110) LpxC inhibitor MIC values.Results: LpxC-4 was shown to be the most potent inhibitor (MIC90 = 0.5 mg/L). In general, the three LpxC inhibitors demonstrated similar activity between Citrobacter spp. isolates harbouring type A (n = 11 isolates), B (n = 39 isolates), and D (n = 11 isolates) carbapenemases. All LpxC inhibitors showed bactericidal activity at concentrations 4× the MIC and no activity at ¼× the MIC at 24 h for the two Citrobacter spp. strains analysed.Conclusions: Although LpxC-4 had a lower MIC90 value compared with CHIR-090, CHIR-090 showed a bactericidal effect at short times and prevented the regrowth of both isolates in the time-kill assays. In terms of cross-resistance, all three structurally similar LpxC inhibitors showed a moderate positive correlation between their activity.</p>
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