Acinetobacter baumannii Resistance to Sulbactam/Durlobactam: A Systematic Review

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 considered “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.

Global Epidemiology and Mechanisms of Resistance of Acinetobacter baumannii-calcoaceticus Complex

“…included isolates recovered from various countries worldwide [ 107–111 ], whereas fewer entries are currently present for bla VEB and bla GES variants in Acinetobacter spp. Among these non-carbapenemase enzymes, bla PER reduced significantly the cefiderocol susceptibility but does not appear to affect sulbactam-durlobactam [ 112 , 113 ].…”

False-positive imipenemase detected by NG-Test CARBA-5 in carbapenem-resistant Acinetobacter baumannii

“…While that detecting carbapenemase in A. baumannii is generally not recommended due to the prevalence of class D carbapenemases, including OXA-23, OXA-24/40-like, OXA-51-like, and OXA-58 in the majority of CRAB that express a carbapenemase, metallo-β-lactamases (MBL), including imipenemase (IMP), New Delhi metallo-β-lactamase (NDM), and verona integron-mediated metallo-β-lactamse (VIM) are responsible for a small proportion of CRAB ( 4 , 8 ). Sulbactam-durlobactam was recently approved for use by the U.S. FDA, and it is intended to be used to treat CRAB pneumonia ( https://www.fda.gov/news-events/press-announcements/fda-approves-new-treatment-pneumonia-caused-certain-difficult-treat-bacteria ); however, CRABs with MBL are known to be resistant to sulbactam-durlobactam ( 9 ). Rapidly identifying an MBL, such as IMP, in an A. baumannii isolate using an immunoassay would preclude the empiric use of the sulbactam-durlobactam.…”

Antibiotic Treatment of Carbapenem-Resistant <em>Acinetobacter baumannii </em>Infections in View of the Newly Developed β-Lactams: A Narrative Review of the Existing Evidence

“…Furthermore, through PBP2 inhibition, it also showed a minimal intrinsic activity against the pathogen [14]. CRAB resistance to sulbactam/durlobactam was estimated to be 3.4%, mainly due to the substitution in the PBP3 determinant or the presence of New Delhi metallo-β-lactamase-1 (NDM-1); metallo β-lactamase (MBL)-producing strains are characterized by higher MIC values compared to other resistance mechanisms [15]. Although the current frequency of MBL-producing CRAB is relatively low [4,15], the commercialization of sulbactam/durlobactam may lead to an increase in the incidence of such strains, particularly NDM for which AB has been considered a reservoir [2].…”