In vitro activities of omadacycline, eravacycline, cefiderocol, apramycin, and comparator antibiotics against Acinetobacter baumannii causing bloodstream infections in Greece, 2020-2021: a multicenter study

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.

Keywords: Acinetobacter baumannii; Apramycin; ArmA; Cefiderocol; Eravacycline; IC II; OXA-23.

Fig. 1

Geographical map showing the location of the19 participating hospitals providing Acinetobacter baumannii blood isolates, Greece, 2020–2021, and the percentage of the prevailing clone

Fig. 2

Cefiderocol 30μg disk diameter distribution. The dashed line in blue represents the CLSI susceptibility breakpoint, and the dashed line in red separates the zone diameters of ≥17 mm, which according to EUCAST, correspond to MIC values below the PK-PD breakpoint of S ≤ 2 mg/L

Fig. 3

Third-generation tetracyclines MIC distributions, compared to minocycline. The dashed lines represent the CLSI clinical breakpoints for minocycline (S ≤ 4 mg/L; R ≥ 16 mg/L)

Fig. 4

Aminoglycosides MIC distribution. The dashed line represents the preliminary apramycin (EBL-1003) epidemiological cut-off value (ECOFF) [13]