Citation: Principe, L.; Di Bella, S.; Conti, J.; Perilli, M.; Piccirilli, A.; Mussini, C.; Decorti, G. Acinetobacter baumannii Resistance to Sulbactam/ Durlobactam: A Systematic Review. Antibiotics 2022, 11, 1793. https:// doi.org/10.3390/antibiotics11121793 Academic Editor: Masafumi Seki Received: 17 November 2022 Accepted: 7 December 2022 Published: 10 December 2022 Publisher’s Note: MDPI stays neutral with regard to jurisdictional claims in published maps and institutional affil- iations. Copyright: © 2022 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https:// creativecommons.org/licenses/by/ 4.0/). antibiotics Systematic Review Acinetobacter baumannii Resistance to Sulbactam/Durlobactam: A Systematic Review Luigi Principe 1, * , Stefano Di Bella 2 , Jacopo Conti 3 , Mariagrazia Perilli 4 , Alessandra Piccirilli 4 , Cristina Mussini 3 and Giuliana Decorti 2,5 1 Clinical Pathology and Microbiology Unit, “San Giovanni di Dio” Hospital, 88900 Crotone, Italy 2 Clinical University Department of Medical, Surgical and Health Sciences, University of Trieste, 34129 Trieste, Italy 3 AOU Policlinico di Modena, Università degli Studi di Modena e Reggio Emilia, 41121 Modena, Italy 4 Department of Biotechnological and Applied Clinical Sciences, University of L’Aquila, 67100 L’Aquila, Italy 5 Institute for Maternal & Child Health (I.R.C.C.S) Burlo Garofolo, 34129 Trieste, Italy * Correspondence: luigi.principe@gmail.com Abstract: Infections caused by carbapenem-resistant Acinetobacter baumannii (CRAB) have limited therapeutic options. Sulbactam-durlobactam is a combination of two βlactamase inhibitors with activity against CRAB under phase 3 clinical investigation. We performed a systematic review on in vitro studies reporting A. baumannii resistances against sulbactam/durlobactam. We consid- ered “resistant” species to be those with MIC ≥ 8 mg/L. Ten studies were included in the review (9754 tested isolates). Overall, 2.3% of A. baumannii were resistant to sulbactam/durlobactam, and this percentage rose to 3.4% among CRAB subgroups and to 3.7% among colistin-resistant strains. Resistance was 100% among metallo β-lactamase-producing strains. Overall, in 12.5% of cases, sulbactam/durlobactam resistance was associated with the production of NDM-1, in 31.7% of cases with the substitutions in the PBP3 determinants, and in the remaining cases the resistance mechanism was unknown. In conclusion, A. baumannii resistance towards sulbactam/durlobactam is limited, except for MBL-producing strains. Keywords: Acinetobacter; sulbactam/durlobactam; sulbactam-durlobactam; resistance; susceptibility; resistances; efficacy 1. Introduction Acinetobacter baumannii infections are among the most difficult bacterial infections to manage. The difficulty largely arises from the antibiotic resistance profile of the bacterium, which is one of the most resistant microorganisms encountered in clinics. Acinetobacter dis- plays multiple antibiotic resistance mechanisms (often coexisting) such as: enzymatic; non- enzymatic, involving efflux pumps and membrane permeability; and penicillin-binding proteins (PBPs) mutations [1,2]. Carbapenems have long been considered to be last-resort drugs for Acinetobacter infections, however during the last two decades we attended a global spread of carbapenem- resistant Acinetobacter baumannii (CRAB) strains that are at present in different countries around the world [3]. In the last few years, a number of new antibiotics against Gram-negative bacteria have been approved for human use. Most of them are β-lactam/β-lactamase inhibitor combi- nations (e.g., ceftazidime/avibactam, meropenem/vaborbactam, imipenem/relebactam) with no activity against CRAB [4]. Other new antibiotics are cefiderocol and eravacycline: these retain in vitro activity against CRAB, however cefiderocol experienced disappointing results in human studies [5] and the latter has virtually no human studies. In light of the above, CRAB remains the “big forgotten” in terms of therapeutic options. Antibiotics 2022, 11, 1793. https://doi.org/10.3390/antibiotics11121793 https://www.mdpi.com/journal/antibiotics