ABSTRACT
Resistance of Acinetobacter baumannii to multiple clinically important antimicrobials has increased to very high rates in Greece, rendering most of them obsolete. The aim of this study was to determine the molecular epidemiology and susceptibilities of A. baumannii isolates collected from different hospitals across Greece. Single-patient A. baumannii strains isolated from blood cultures (n = 271), from 19 hospitals, in a 6-month period (November 2020-April 2021) were subjected to minimum inhibitory concentration determination and molecular testing for carbapenemase, 16S rRNA methyltransferase and mcr gene detection and epidemiological evaluation. 98.9% of all isolates produced carbapenemase OXA-23. The vast majority (91.8%) of OXA-23 producers harbored the armA and were assigned mainly (94.3%) to sequence group G1, corresponding to IC II. Apramycin (EBL-1003) was the most active agent inhibiting 100% of the isolates at ≤16 mg/L, followed by cefiderocol which was active against at least 86% of them. Minocycline, colistin and ampicillin-sulbactam exhibited only sparse activity (S <19%), while eravacycline was 8- and 2-fold more active than minocycline and tigecycline respectively, by comparison of their MIC50/90 values. OXA-23-ArmA producing A. baumannii of international clone II appears to be the prevailing epidemiological type of this organism in Greece. Cefiderocol could provide a useful alternative for difficult to treat Gram-negative infections, while apramycin (EBL-1003), the structurally unique aminoglycoside currently in clinical development, may represent a highly promising agent against multi-drug resistant A. baumanni infections, due to its high susceptibility rates and low toxicity.
Subject(s)
Acinetobacter baumannii , Sepsis , Humans , Anti-Bacterial Agents/pharmacology , Minocycline , Greece/epidemiology , RNA, Ribosomal, 16S , Microbial Sensitivity Tests , Drug Resistance, Multiple, Bacterial , CefiderocolSubject(s)
Anti-Bacterial Agents/pharmacology , Bacterial Proteins/genetics , Klebsiella Infections/drug therapy , Klebsiella Infections/epidemiology , Klebsiella pneumoniae/drug effects , Klebsiella pneumoniae/enzymology , beta-Lactamases/genetics , Anti-Bacterial Agents/therapeutic use , Drug Resistance, Bacterial/genetics , Greece/epidemiology , Humans , Klebsiella Infections/diagnosis , Klebsiella Infections/microbiology , Klebsiella pneumoniae/genetics , Klebsiella pneumoniae/isolation & purification , Microbial Sensitivity Tests , Polymerase Chain Reaction , PrevalenceSubject(s)
Amikacin/administration & dosage , Anti-Bacterial Agents/administration & dosage , Central Nervous System Infections/drug therapy , Colistin/administration & dosage , Vancomycin/administration & dosage , Amikacin/adverse effects , C-Reactive Protein/analysis , Central Nervous System Infections/blood , Colistin/adverse effects , Humans , Injections, Intraventricular , Injections, Spinal , Intensive Care Units , Neurosurgical Procedures , Retrospective Studies , Vancomycin/adverse effectsABSTRACT
A new efficient synthetic approach to the natural coumarins 5-hydroxyseselin (5), 5-methoxyseselin (3), and (+/-) cis-grandmarin (9) is described as well as the synthesis of some new derivatives in the 5-methoxyseselin series (10-15). The natural coumarins 7-hydroxyalloxanthyletin (6), alloxanthoxyletin (8), and dipetalolactone (7) have also been obtained as secondary products. The type of fusion of the pyrano ring in all cases has been established by 2D NMR spectroscopy. The compounds have been studied for their in vitro antibacterial activity, which has been compared with that of some previously synthesized seselin derivatives. The most active compounds were 3, 7, 8, 11, and 14. Some structure-activity relationships are discussed.
