A New Twist: The Combination of Sulbactam/Avibactam Enhances Sulbactam Activity against Carbapenem-Resistant Acinetobacter baumannii (CRAB) Isolates

Antibiotics

卷:10

Jose Osteria¹  Jose Cedano¹  Grace Ra¹  Michelle Baez¹  MarceloE. Tolmasky¹  Casin Le¹  MariaSoledad Ramirez¹  Sabrina Montaña²  Ezequiel Albornoz³  Alejandra Corso³  Melina Rapoport³  Fernando Pasteran³  RobertA. Bonomo⁴  Mark Adams⁵ 

[1] Center for Applied Biotechnology Studies, Department of Biological Science, College of Natural Sciences and Mathematics, California State University Fullerton, Fullerton, CA 92831-3599, USA;

[2] Laboratorio de Bacteriología Clínica, Departamento de Bioquímica Clínica, Hospital de Clínicas José de San Martín, Facultad de Farmacia y Bioquímica, C1120 Buenos Aires, Argentina;

[3] National/Regional Reference Laboratory for Antimicrobial Resistance (NRL), Servicio Antimicrobianos, Instituto Nacional de Enfermedades Infecciosas, ANLIS “Dr. Carlos G. Malbrán”, C1282AFF Buenos Aires, Argentina;

[4] Research Service and GRECC, Louis Stokes Cleveland Department of Veterans Affairs Medical Center, Cleveland, OH 44106, USA;

[5] The Jackson Laboratory, Farmington, CT 06032, USA;

关键词: Acinetobacter;    carbapenem-resistance;    sulbactam;    avibactam;    relebactam;   

DOI  :  10.3390/antibiotics10050577

来源: DOAJ

【 摘 要 】

An increasing number of untreatable infections are recorded every year. Many studies have focused their efforts on developing new β-lactamase inhibitors to treat multi-drug resistant (MDR) isolates. In the present study, sulbactam/avibactam and sulbactam/relebactam combination were tested against 187 multi-drug resistant (MDR) Acinetobacter clinical isolates; both sulbactam/avibactam and sulbactam/relebactam restored sulbactam activity. A decrease ≥2 dilutions in sulbactam MICs was observed in 89% of the isolates when tested in combination with avibactam. Sulbactam/relebactam was able to restore sulbactam susceptibility in 40% of the isolates. In addition, the susceptibility testing using twenty-three A. baumannii AB5075 knockout strains revealed potential sulbactam and/or sulbactam/avibactam target genes. We observed that diazabicyclooctanes (DBOs) β-lactamase inhibitors combined with sulbactam restore sulbactam susceptibility against carbapenem-resistant Acinetobacter clinical isolates. However, relebactam was not as effective as avibactam when combined with sulbactam. Exploring novel combinations may offer new options to treat Acinetobacter spp. infections, especially for widespread oxacillinases and metallo-β-lactamases (MBLs) producers.

【 授权许可】

Unknown