Abstract
Cefiderocol is a catechol-substituted siderophore cephalosporin combining rapid penetration into the periplasmic space with increased stability against β-lactamases. This study provides additional data on the in vitro antimicrobial activity of cefiderocol and commercially available comparators against an epidemiologically diverse collection of Acinetobacter baumannii clinical isolates. Antimicrobial susceptibility was tested using pre-prepared frozen 96-well microtiter plates containing twofold serial dilutions of: cefepime, ceftazidime/avibactam, imipenem/relebactam, ampicillin/sulbactam, meropenem, meropenem/vaborbactam, ciprofloxacin, minocycline, tigecycline, trimethoprim/sulfamethoxazole and colistin using the standard broth microdilution procedure in cation-adjusted Mueller–Hinton broth (CAMHB). For cefiderocol, iron-depleted CAMHB was used. A collection of 113 clinical strains of A. baumannii isolated from Argentina, Azerbaijan, Croatia, Greece, Italy, Morocco, Mozambique, Peru and Spain were included. The most active antimicrobial agents against our collection were colistin and cefiderocol, with 12.38% and 21.23% of non-susceptibility, respectively. A high proportion of multidrug-resistant (76.77%) and carbapenem-resistant (75.28%) A. baumannii isolates remained susceptible to cefiderocol, which was clearly superior to novel β-lactam/β-lactamase inhibitor combinations. Cefiderocol-resistance was higher among carbapenem-resistant isolates and isolates belonging to ST2, but could not be associated with any particular resistance mechanism or clonal lineage. Our data suggest that cefiderocol is a good alternative to treat infections caused by MDR A. baumanni, including carbapenem-resistant strains.
Highlights
The emergence of bacteria resistant to currently available antibiotics is steadily increasing but the development of new therapies to combat infections caused by these microorganisms are not following at an appropriate pace
The present study comprised a collection of 113 bacterial isolates of A. baumannii recovered from several countries all over the world including both carbapenem-resistant and carbapenem-susceptible isolates
Upon testing the antimicrobial susceptibility to a selected panel of antibacterial agents, the lowest MIC50 values reported among all 113 isolates tested corresponded to cefiderocol and colistin (MIC50 = 0.5 μg/mL), closely followed by tigecycline and minocycline (MIC50 = 2 and 4 μg/mL, respectively)
Summary
The emergence of bacteria resistant to currently available antibiotics is steadily increasing but the development of new therapies to combat infections caused by these microorganisms are not following at an appropriate pace. Current therapeutic options for the treatment of carbapenem-resistant A. baumannii infections are limited and suboptimal, being restricted to available antibiotics including colistin, tigecycline, minocycline, amikacin and sulbactam. These antimicrobials are administered either alone or in combination, despite the occurrence of pharmacokinetic issues and high toxicity in some cases, as it is the case for colistin and amikacin [5]
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