A New Twist: The Combination of Sulbactam/Avibactam Enhances Sulbactam Activity against Carbapenem-Resistant <i>Acinetobacter baumannii</i> (CRAB) Isolates
Fernando Pasteran,
Jose Cedano,
Michelle Baez,
Ezequiel Albornoz,
Melina Rapoport,
Jose Osteria,
Sabrina Montaña,
Casin Le,
Grace Ra,
Robert A. Bonomo,
Marcelo E. Tolmasky,
Mark Adams,
Alejandra Corso,
Maria Soledad Ramirez
Affiliations
Fernando Pasteran
National/Regional Reference Laboratory for Antimicrobial Resistance (NRL), Servicio Antimicrobianos, Instituto Nacional de Enfermedades Infecciosas, ANLIS “Dr. Carlos G. Malbrán”, C1282AFF Buenos Aires, Argentina
Jose Cedano
Center for Applied Biotechnology Studies, Department of Biological Science, College of Natural Sciences and Mathematics, California State University Fullerton, Fullerton, CA 92831-3599, USA
Michelle Baez
Center for Applied Biotechnology Studies, Department of Biological Science, College of Natural Sciences and Mathematics, California State University Fullerton, Fullerton, CA 92831-3599, USA
Ezequiel Albornoz
National/Regional Reference Laboratory for Antimicrobial Resistance (NRL), Servicio Antimicrobianos, Instituto Nacional de Enfermedades Infecciosas, ANLIS “Dr. Carlos G. Malbrán”, C1282AFF Buenos Aires, Argentina
Melina Rapoport
National/Regional Reference Laboratory for Antimicrobial Resistance (NRL), Servicio Antimicrobianos, Instituto Nacional de Enfermedades Infecciosas, ANLIS “Dr. Carlos G. Malbrán”, C1282AFF Buenos Aires, Argentina
Jose Osteria
Center for Applied Biotechnology Studies, Department of Biological Science, College of Natural Sciences and Mathematics, California State University Fullerton, Fullerton, CA 92831-3599, USA
Sabrina Montaña
Laboratorio de Bacteriología Clínica, Departamento de Bioquímica Clínica, Hospital de Clínicas José de San Martín, Facultad de Farmacia y Bioquímica, C1120 Buenos Aires, Argentina
Casin Le
Center for Applied Biotechnology Studies, Department of Biological Science, College of Natural Sciences and Mathematics, California State University Fullerton, Fullerton, CA 92831-3599, USA
Grace Ra
Center for Applied Biotechnology Studies, Department of Biological Science, College of Natural Sciences and Mathematics, California State University Fullerton, Fullerton, CA 92831-3599, USA
Robert A. Bonomo
Research Service and GRECC, Louis Stokes Cleveland Department of Veterans Affairs Medical Center, Cleveland, OH 44106, USA
Marcelo E. Tolmasky
Center for Applied Biotechnology Studies, Department of Biological Science, College of Natural Sciences and Mathematics, California State University Fullerton, Fullerton, CA 92831-3599, USA
Mark Adams
The Jackson Laboratory, Farmington, CT 06032, USA
Alejandra Corso
National/Regional Reference Laboratory for Antimicrobial Resistance (NRL), Servicio Antimicrobianos, Instituto Nacional de Enfermedades Infecciosas, ANLIS “Dr. Carlos G. Malbrán”, C1282AFF Buenos Aires, Argentina
Maria Soledad Ramirez
Center for Applied Biotechnology Studies, Department of Biological Science, College of Natural Sciences and Mathematics, California State University Fullerton, Fullerton, CA 92831-3599, USA
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.
