Lasarte-Monterrubio Cristina, Vázquez-Ucha Juan C, Maneiro Maria, Arca-Suárez Jorge, Alonso Isaac, Guijarro-Sánchez Paula, Buynak John D, Bou Germán, González-Bello Concepción, Beceiro Alejandro
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.
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.
Antibiotics (Basel). 2021 Feb 20;10(2):210. doi: 10.3390/antibiotics10020210.
Treatment of infections caused by spp., particularly , 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 spp. collected in 14 hospitals in Spain in 2020. Relevantly, the MIC (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 isolates. Considering only the carbapenem-resistant 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 spp. isolates. In conclusion, combining LN-1-255 with imipenem, meropenem, cefepime, and sulbactam to target , and especially carbapenem-resistant isolates, represents an attractive option that should be developed for the treatment of infections caused by this pathogen.
由[具体菌名]菌引起的感染，尤其是[具体菌名]菌感染，因其高抗生素耐药率而成为一个主要的临床问题。必须制定新的策略；因此，通过使用β-内酰胺酶抑制剂来恢复β-内酰胺的疗效至关重要。2020年，在西班牙14家医院收集了148株[具体菌名]菌，通过微量稀释法测试了亚胺培南、美罗培南、头孢吡肟和舒巴坦与青霉素砜抑制剂LN-1-255联合使用时的抗菌活性。相关地，对于所有[具体菌名]菌分离株，抗生素与LN-1-255联合使用时的MIC（即90%分离株被抑制的最低浓度）降低了4至8倍。仅考虑产生碳青霉烯水解D类β-内酰胺酶的耐碳青霉烯[具体菌名]菌分离株，添加LN-1-255后，亚胺培南的耐药率从95.1%降至0%，美罗培南从100%降至9.8%，头孢吡肟从70.7%降至7.3%，舒巴坦的耐药率从9.8%降至0%，中介敏感率从53.7%降至2.4%。当针对非耐碳青霉烯[具体菌名]菌分离株进行测试时，该抑制剂也降低了最低抑菌浓度（MIC）。总之，将LN-1-255与亚胺培南、美罗培南、头孢吡肟和舒巴坦联合用于治疗[具体菌名]菌感染，尤其是耐碳青霉烯分离株感染，是一个有吸引力的选择，应进一步开发用于治疗由该病原体引起的感染。
