Antimicrobial Susceptibility of Achromobacter spp. vs ASA spp

Clinical Center

Investigators

Abstract

Treatment of Achromobacter infections remains challenging due to intrinsic and acquired resistance to commonly used antibiotics and limited information regarding mechanisms of resistance. Additionally, clinical breakpoints are established for only a few antimicrobial agents. We attempted accurate species-level identification, and compared presence of genotypic resistance markers to phenotypic susceptibility patterns in retrospectively collected clinical isolates of Achromobacter spp. Our study revealed that A. xylosoxidans is the most prevalent species. Commercial matrix-assisted laser desorption ionization–time of flight (MALDI-TOF) systems cannot accurately identify all Achromobacter species due to limited inclusion of spectra in the databases particularly in the differentiation of A. ruhlandii and A. xylosoxidans. Phenotypic AST confirms resistance to majority of antibiotics tested. Newer agents like delafloxacin, plazomicin and omadacycline showed little or no activity, while minimum inhibitory concentrations were low for eravacycline, and beta-lactam/beta-lactamase inhibitor combinations. Genotypic analysis confirmed that A. xylosoxidans carries a high number of resistance genes, including multidrug efflux pump AxyXY-OprZ, several class D (OXA-type) and the Class A beta-lactamase blaAXC, while A. mucicolens has the lowest number, and no efflux pumps. Our results also indicate that some blaOXA plasmids such as the blaOXA-258 and blaOXA-243 may not be specific to certain Achromobacter spp. as previously suggested. This study concludes that there is significant genotypic and phenotypic diversity within the different species of Achromobacter which are important for identification of the species and for appropriate antimicrobial therapy. Intra-host evolved Achromobacter xylosoxidans isolates, NIH-010 and NIH-016, demonstrated the loss of flagella motility and variable cytotoxicity while exhibiting increased antibiotic resistance and enhanced biofilm formation. Sequence analysis suggests that NIH-016-3 has tyrosine to histidine mutation at position 330 (Y330H) near the FlhF Guanosine triphosphate (GTP)-binding domain that may affect flagellar assembly. Interestingly, virulence assays showed significant variation in the ability of different A. xylosoxidans isolates to induce cell death in in vitro models, suggesting its dynamic adaptation to the host. These findings highlight the complexity of this pathogen group and underscore the urgent need for further research into its mechanisms of antibiotic resistance and virulence.