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Article

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

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Servicio de Microbiología, Instituto de Investigación Biomédica de A Coruña (INIBIC-CICA), Complejo Hospitalario Universitario A Coruña (CHUAC), As Xubias 84, 15006 A Coruña, Spain
2
Centro Singular de Investigación en Química Biolóxica e Materiais Moleculares (CIQUS), Departamento de Química Orgánica, Universidade de Santiago de Compostela, Jenaro de la Fuente s/n, 15782 Santiago de Compostela, Spain
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Servicio de Microbiología, Hospital Provincial Pontevedra, Loureiro Crespo 2, 36002 Pontevedra, Spain
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Department of Chemistry, Southern Methodist University, Dallas, TX 75275, USA
*
Authors to whom correspondence should be addressed.
Cristina Lasarte-Monterrubio and Juan C. Vázquez-Ucha contributed equally to the study.
Academic Editors: Maria Tomas, Clara Ballesté-Delpierre and Maria Eugenia Pachón-Ibáñez
Antibiotics 2021, 10(2), 210; https://doi.org/10.3390/antibiotics10020210
Received: 27 January 2021 / Revised: 12 February 2021 / Accepted: 14 February 2021 / Published: 20 February 2021
(This article belongs to the Special Issue Non-antimicrobial Agents as Adjuvants against Bacterial Infections)
Treatment of infections caused by Acinetobacter spp., particularly A. baumannii, 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 Acinetobacter 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 Acinetobacter isolates. Considering only the carbapenem-resistant A. baumannii 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 Acinetobacter spp. isolates. In conclusion, combining LN-1-255 with imipenem, meropenem, cefepime, and sulbactam to target A. baumannii, and especially carbapenem-resistant isolates, represents an attractive option that should be developed for the treatment of infections caused by this pathogen. View Full-Text
Keywords: Acinetobacter spp.; Acinetobacter baumannii; β-lactam antibiotic resistance; β-lactamase inhibitors; LN-1-255; imipenem; meropenem; cefepime; sulbactam; carbapenem-hydrolyzing class D β-lactamases (CHDLs) Acinetobacter spp.; Acinetobacter baumannii; β-lactam antibiotic resistance; β-lactamase inhibitors; LN-1-255; imipenem; meropenem; cefepime; sulbactam; carbapenem-hydrolyzing class D β-lactamases (CHDLs)
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MDPI and ACS Style

Lasarte-Monterrubio, C.; Vázquez-Ucha, J.C.; Maneiro, M.; Arca-Suárez, J.; Alonso, I.; Guijarro-Sánchez, P.; Buynak, J.D.; Bou, G.; González-Bello, C.; Beceiro, A. Activity of Imipenem, Meropenem, Cefepime, and Sulbactam in Combination with the β-Lactamase Inhibitor LN-1-255 against Acinetobacter spp. Antibiotics 2021, 10, 210. https://doi.org/10.3390/antibiotics10020210

AMA Style

Lasarte-Monterrubio C, Vázquez-Ucha JC, Maneiro M, Arca-Suárez J, Alonso I, Guijarro-Sánchez P, Buynak JD, Bou G, González-Bello C, Beceiro A. Activity of Imipenem, Meropenem, Cefepime, and Sulbactam in Combination with the β-Lactamase Inhibitor LN-1-255 against Acinetobacter spp. Antibiotics. 2021; 10(2):210. https://doi.org/10.3390/antibiotics10020210

Chicago/Turabian Style

Lasarte-Monterrubio, Cristina, Juan C. Vázquez-Ucha, Maria Maneiro, Jorge Arca-Suárez, Isaac Alonso, Paula Guijarro-Sánchez, John D. Buynak, Germán Bou, Concepción González-Bello, and Alejandro Beceiro. 2021. "Activity of Imipenem, Meropenem, Cefepime, and Sulbactam in Combination with the β-Lactamase Inhibitor LN-1-255 against Acinetobacter spp." Antibiotics 10, no. 2: 210. https://doi.org/10.3390/antibiotics10020210

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