In vitro activity of sulbactam in combination with other antimicrobial agents against extensively drug-resistant Acinetobacter baumannii

Abstract

Extensively drug-resistant (XDR) Acinetobacter baumannii infection has significant challenges due to limited treatment options. Although sulbactam (SUL) shows in vitro effectiveness against XDR A. baumannii, the efficacy of SUL-based combinations remains unclear. This investigation aimed to delineate the in vitro activity of SUL combined with various antimicrobial agents against XDR A. baumannii. Sixty-two clinical isolates of XDR A. baumannii were tested for minimal inhibitory concentrations (MICs) of SUL, amikacin (AMI), ciprofloxacin, colistin (COL), fosfomycin (FOS), gentamicin, meropenem (MER), rifampicin (RIF), sitafloxacin (SIT), and tigecycline (TIG) using broth microdilution. The checkerboard method, employing the fractional inhibitory concentration index, assessed in vitro synergy between the SUL-based combination. Time–kill analyses of selected isolates were conducted to measure log<inf>10</inf> colony-forming unit per milliliter growth changes over 24 hours between individual and combined agents. The SUL MICs ranged from <4 to 256 mg/L, with an MIC<inf>50</inf> of 64 mg/L. MIC ranges were lower for TIG (0.12–4.0 mg/L) and COL (0.5–2.0 mg/L), but higher for FOS (64–>512 mg/L). Synergism was evident in the combinations of SUL/FOS (41.9%), SUL/AMI (19.3%), SUL/MER (17.7%), SUL/RIF (14.5%), SUL/TIG (12.9%), SUL/COL (6.5%), and SUL/SIT (4.8%). Only 1.6%–3.2% of the combinations exhibited antagonism. In the time–kill assays, a combination of SUL/FOS/AMI/MER exhibited sustained bactericidal activity at 24 hours against the two isolates, whereas two- and three-agent combinations showed varying degrees of synergism. Combining SUL with available antimicrobial agents had varying degrees of synergistic effect against XDR A. baumannii. Notably, the clinical utility of SUL-based combination therapy for XDR A. baumannii infections requires further exploration.