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Front. Microbiol. | doi: 10.3389/fmicb.2019.01638

Amoxicillin Administration Regimen and Resistance Mechanisms of Staphylococcus aureus

  • 1Key Laboratory of Tropical Animal Breeding and Epidemic Disease Research of Hainan Province, Hainan University, China
  • 2Hainan University, China

Staphylococcus aureus is a zoonotic pathogen that causes various life-threatening diseases. Amoxicillin has strong antimicrobial activity against S. aureus, but its mechanisms of resistance development are unclear. In this study, we used a rabbit tissue cage infection model to evaluate the relationship between pharmacokinetic/pharmacodynamic (PK/PD) parameters and selective enrichment of resistant strains of S. aureus, and to elucidate the evolution of its resistance to amoxicillin. S. aureus was injected into the tissue cages at 1010 colony forming units (CFU)/mL. We injected different intramuscular concentrations of amoxicillin at doses of 5, 10, 20, and 30 mg/kg body weight once a day for 5 days and 5, 10, 20, and 30 mg/kg body weight twice a day for 2.5 days. Differences in gene expression between two differentially resistant strains and a sensitive strain were evaluated using Illumina sequencing followed by COG and KEGG analysis. RT-qPCR was carried out to validate the difference in protein translation levels. Our results demonstrated that the emergence of resistant bacteria was dose-dependent within a given time interval. In the same dosage group, the appearance of resistant bacteria increased as time progressed. The resistant bacteria showed cumulative growth, and the level of resistance rose over time. The resistant bacteria were completely inhibited when the cumulative percentage of time over a 24-h period that the drug concentration exceeded the mutant prevention concentration (MPC) (%T > MPC) was ≥ 52%. We also found that the expression of mecA and femX in S. aureus played a leading role in the development of resistance to amoxicillin. In conclusion, these data provide meaningful guidance for optimizing amoxicillin regimens to treat infections caused by S. aureus.

Keywords: Amoxicillin, Staphylococcus aureus, Administration regimen, resistance mechanisms, tissue cage infection model, resistant bacteria

Received: 15 Mar 2019; Accepted: 02 Jul 2019.

Edited by:

Miklos Fuzi, Semmelweis University, Hungary

Reviewed by:

Huanzhong Ding, South China Agricultural University, China
Yu-Feng Zhou, South China Agricultural University, China
Pritam K. Sidhu, Kansas State University, United States  

Copyright: © 2019 Yao, Gao, Xu, chen, Yang, Han, Tao, Li, Zhou and Yang. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

* Correspondence: Prof. Yuhui Yang, Key Laboratory of Tropical Animal Breeding and Epidemic Disease Research of Hainan Province, Hainan University, Haikou, Hainan Province, China, yanguniverse@sina.com