In Vitro Antimicrobial Activity of the Siderophore Cephalosporin Cefiderocol against Acinetobacter baumannii Strains Recovered from Clinical Samples

Abstract

Background: Cefiderocol is a siderophore cephalosporin that exhibits antimicrobial activity against most multi-drug resistant Gram-negative bacteria, including Enterobacterales, Pseudomonas aeruginosa, Acinetobacter baumannii, and Stenotrophomonas maltophilia. Methods: A total of 20 multidrug-resistant A. baumannii strains were isolated from 2020 to 2021, molecularly characterized and tested to assess the in vitro antibacterial activity of cefiderocol. Thirteen strains were carbapenem-hydrolysing oxacillinase OXA-23-like producers, while seven were non-OXA-23-like producers. Minimum inhibitory concentrations (MICs) were determined by broth microdilution, considered as the gold standard method. Disk diffusion test was also carried out using iron-depleted CAMHB plates for cefiderocol. Results: Cefiderocol MICs ranged from 0.5 to 1 mg/L for OXA-23-like non-producing A. baumannii strains and from 0.25 to >32 mg/L for OXA-23-like producers, using the broth microdilution method. Cefiderocol MIC90 was 8 mg/L. Diameter of inhibition zone of cefiderocol ranged from 18 to 25 mm for OXA-23-like non-producers and from 15 to 36 mm for OXA-23-like producers, using the diffusion disk method. A large variability and a low reproducibility were observed during the determination of diameter inhibition zone. Molecular characterization showed that all isolates presented the ISAba1 genetic element upstream the blaOXA-51. Among OXA-23-like non-producers, four were blaOXA-58 positive and two were negative for all the resistance determinants analyzed. Conclusions: Cefiderocol showed in vitro antimicrobial activity against both carbapenem-susceptible and non-susceptible A. baumannii strains, although some OXA-23-like producers were resistant. Further clinical studies are needed to consolidate the role of cefiderocol as an antibiotic against MDR A. baumannii.

In Vitro Activity of Sulbactam–Durlobactam against Carbapenem-Resistant Acinetobacter baumannii Clinical Isolates: A Multicentre Report from Italy

“…However, in addition to β-lactamases, other mechanisms of resistance to carbapenems, including overexpression of efflux pumps, the reduction or inactivation of the expression of porins and the modification in the expression or synthesis of new PBPs, are found in A. baumannii isolates [ 10 ]. In the 141 A. baumannii analyzed in the present study, class C and D β-lactamases such as OXA-23, OXA-58, OXA-66 (OXA-51-like enzyme), OXA-82 (OXA-51-like enzyme) and ADC-25 were previously identified [ 36 , 37 , 38 , 39 , 40 , 41 , 42 , 43 , 44 , 45 , 46 , 47 ]. The bla OXA -types are, usually, flanked by one or two copies of the insertion sequences (i.e., IS Aba1 , IS Aba125 ) which are located in opposite orientations.…”

“…A total of 141 non duplicate CR Ab strains, which were previously characterized for their mechanisms of resistance, were included in this study [ 36 , 37 , 38 , 39 , 40 , 41 , 42 , 43 , 44 , 45 , 46 , 47 ]. In particular, we retrospectively selected 64 XDR and 77 PDR previously characterized CR Ab clinical isolates collected in six centers from Italy.…”

“…In these A. baumannii strains, the carbapenem resistance was mainly mediated by the presence of OXA-23 (80 isolates), OXA-58 (48 isolates), OXA-66 (4 isolates) and OXA-82 (4 isolates). The simultaneous presence of OXA-23 and OXA-58 was found in 11 isolates and, in addition, ADC-25, a chromosomal AmpC enzyme, was also identified [ 36 , 37 , 38 , 39 , 40 , 41 , 42 , 43 , 44 , 45 , 46 , 47 ].…”

New Antimicrobial Options in the Clinical Practice of Infections Caused by Difficult-to-Treat Pathogens: A Global Opportunity for Public Health

“…A. baumannii is usually an XDR pathogen, mostly susceptible only to colistin. This study highlights the potential role of cefiderocol as an anti- Acinetobacter antibiotic, showing activity against both carbapenem-susceptible and non-susceptible strains [ 1 ].…”

“…This Special Issue considers all aspects of infections related to difficult-to-treat pathogens and new antimicrobial options. In particular, regarding new antimicrobial alternatives, the paper of Carcione et al reports the antimicrobial activity of the most promising commercially available antibiotic, cefiderocol, against molecularly characterized A. baumannii clinical isolates, most of which were OXA-23 producers [ 1 ]. Cefiderocol MICs ranged from 0.5 to 1 mg/L for OXA-23 non-producing strains and from 0.25 to >32 mg/L for OXA-23 producers using the broth microdilution method.…”