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PubMed · 964768

[Amikacin].

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R Yeivin, T Sachs. 1976-06-15. [Amikacin].. https://pubmed.ncbi.nlm.nih.gov/964768/

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Investigation of in vitro susceptibility and resistance mechanisms to amikacin among diverse carbapenemase-producing Enterobacteriaceae.

OBJECTIVE: This study aims to assess the in vitro drug susceptibility of various Carbapenemase-Producing Enterobacteriaceae (CPE) genotypes and elucidate the underlying mechanisms of amikacin resistance. METHODS: A total of 72 unique CPE strains were collected from the Second Hospital of Jiaxing between 2019 and 2022, including 51 strains of Klebsiella pneumoniae, 11 strains of Escherichia coli, 6 strains of Enterobacter cloacae, 2 strains of Klebsiella aerogenes, 1 strain of Citrobacter freundii, and 1strain of Citrobacter werkmanii. Among these strains, 24 carried blaKPC gene, 20 carried blaNDM gene, 23 carried blaOXA-48-like gene, and 5 carried both blaKPC and blaNDM. We measured the in vitro activity of amikacin and other common antibiotics. Strains carrying blaOXA-48-like gene were selected for whole genome sequencing (WGS) via next-generation sequencing to identify genes related to antimicrobial resistance (AMR) and virulence factor (VF). RESULTS: Out of the 72 CPE strains tested, 41.7% exhibited resistance to amikacin. The drug resistance rates for K. pneumoniae, E. coli, and Enterobacter spp. were 51.0%, 27.3%, and 10.0%, respectively. The majority of the CPE strains (>&#x2009;90%) displayed resistance to cephalosporins and carbapenems, while most of them were sensitive to polymyxin B and tigecycline (97.2% and 94.4%). The amikacin resistance rate was 100% for strains carrying blaOXA-48, 20.8% for those with blaKPC, 5.0% for those with blaNDM, and 20.0% for those with both blaKPC and blaNDM. These differences were statistically significant (P&#x2009;<&#x2009;0.05). Through sequencing, we detected aminoglycoside resistance genes rmtF and aac(6')-Ib, VF genes iucABCD and rmpA2 in OXA-48-producing multidrug resistance and highly virulent strains. These genes were located on a IncFIB- and IncHI1B-type plasmid, respectively. Both plasmids were highly homologous to the plasmid from OXA-232 strains in Zhejiang province and Shanghai province. Integration of these resistance genes into the IncFIB plasmid, facilitated by the IS6 and/or Tn3 transposons, resulted in OXA232-producing K. pneumoniae with amikacin resistance. CONCLUSION: This study identified significant amikacin resistance in CPE strains, particularly in those carrying the blaOXA-48 gene. Resistance genes rmtF and aac(6')-Ib were identified on plasmids. These results highlight the need for careful monitoring of amikacin resistance.

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A new method for the analysis of amikacin using 6-aminoquinolyl-N-hydroxysuccinimidyl carbamate (AQC) derivatization and high-performance liquid chromatography with UV-detection.

A simple and sensitive reversed-phase liquid chromatographic method has been developed for the determination of amikacin (AMK) by derivatization. The method is based on the pre-column derivatization of AMK with 6-aminoquinolyl-N-hydroxysuccinimidyl carbamate (AQC). The derivatization reaction proceeds in aqueous solution at room temperature with a borate buffer of pH 8.0. The formation of the corresponding derivative of AMK is instantaneous and it is stable for more than 36 h. Detection was performed by UV-absorption instead of fluorescence. Several factors influencing the derivatization reaction yields were studied and optimized. The system offered the following analytical parameters: limit of detection (LOD) of 0.068 micro g ml(-1) (3sigma), linear correlation coefficient of 0.9998 and linear range response from 2 to 50 microg ml(-1). The precision of the method was <1%. As a preliminary application, the method has been successfully applied to the amikacin determination in parenteral pharmaceutical formulations.

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