Activity of Imipenem, Meropenem, Cefepime, and Sulbactam in Combination with the β-Lactamase Inhibitor LN-1-255 against <i>Acinetobacter</i> spp.

• Main Authors: Cristina Lasarte-Monterrubio (Author), Juan C. Vázquez-Ucha (Author), Maria Maneiro (Author), Jorge Arca-Suárez (Author), Isaac Alonso (Author), Paula Guijarro-Sánchez (Author), John D. Buynak (Author), Germán Bou (Author), Concepción González-Bello (Author), Alejandro Beceiro (Author)
• Format: Book
• Published: MDPI AG, 2021-02-01T00:00:00Z.
• Subjects: article
• Online Access: Connect to this object online.
• Notes: 10.3390/antibiotics10020210; 2079-6382
• Keywords: <i>Acinetobacter</i> spp.; <i>Acinetobacter baumannii</i>; β-lactam antibiotic resistance; β-lactamase inhibitors; LN-1-255; imipenem; Therapeutics. Pharmacology; RM1-950
• Source: Antibiotics, Vol 10, Iss 2, p 210 (2021)

Treatment of infections caused by <i>Acinetobacter</i> spp., particularly <i>A. baumannii</i>, is a major clinical problem due to its high rates of antibiotic resistance. New strategies must be developed; therefore, restoration of β-lactam efficacy through the use of β-lactamase inhibitors is paramount. Activities of the antibiotics imipenem, meropenem, cefepime, and sulbactam in combination with the penicillin-sulfone inhibitor LN-1-255 were tested by microdilution against 148 isolates of <i>Acinetobacter</i> spp. collected in 14 hospitals in Spain in 2020. Relevantly, the MIC₉₀ (i.e., minimum concentration at which 90% of isolates were inhibited) of antibiotics in combination with LN-1-255 decreased 4- to 8-fold for all of the <i>Acinetobacter</i> isolates. Considering only the carbapenem-resistant <i>A. baumannii</i> isolates, which produce carbapenem-hydrolyzing class D β-lactamases, the addition of LN-1-255 decreased the resistance rates from 95.1% to 0% for imipenem, from 100% to 9.8% for meropenem, from 70.7% to 7.3% for cefepime, and sulbactam resistance rates from 9.8% to 0% and intermediate susceptibility rates from 53.7% to 2.4%. The inhibitor also decreased the minimum inhibitory concentrations (MICs) when tested against non-carbapenem-resistant <i>Acinetobacter</i> spp. isolates. In conclusion, combining LN-1-255 with imipenem, meropenem, cefepime, and sulbactam to target <i>A. baumannii</i>, and especially carbapenem-resistant isolates, represents an attractive option that should be developed for the treatment of infections caused by this pathogen.