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Prevalence and mechanisms of linezolid resistance among staphylococcal clinical isolates from Egypt

European Journal of Clinical Microbiology & Infectious Diseases volume 40, pages 815–823 (2021)Cite this article

Abstract

The emergence of methicillin-resistant staphylococci necessitated the search for alternative agents as linezolid, introduced to treat infections due to multidrug-resistant bacteria. Linezolid resistance has since emerged, yet its global prevalence remains low. In Egypt, little is known about the situation. We investigated the prevalence and mechanisms of resistance among Egyptian staphylococcal clinical isolates. Linezolid resistance among 232 staphylococcal isolates obtained from Alexandria Main Hospitals between 2011 and 2016 was assessed using disc diffusion and minimum inhibitory concentration. Resistant isolates were checked for cfr presence using polymerase chain reaction. The V domain of different alleles of 23S rRNA gene was investigated for mutations. Selection for linezolid-resistant mutants was performed in vitro through serial passages in linezolid sub-inhibitory concentrations. Combinations of linezolid with imipenem or anti-inflammatory agents were investigated using time-kill and modified checkerboard assays. Three Staphylococcus haemolyticus isolates (1.3%) from 2015 to 2016 were linezolid-resistant. One isolate carried cfr which was plasmid-borne, and together with another isolate which had a G2603T point mutation in the V domain of 23S rRNA gene. Successive exposure to linezolid sub-inhibitory concentrations was selected for three resistant Staphylococcus aureus mutants out of ten susceptible isolates. These mutants were more resistant towards different antibiotic classes than their susceptible parents. Linezolid combinations with imipenem, ibuprofen, or aspirin were synergistic against the isolates and mutants. Despite unregulated use of linezolid, resistance remains fairly low among the Egyptian isolates. Strict antimicrobial stewardship guidelines are needed in hospitals and the community to guard against further evolution of resistant mutants.

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Data availability

All raw data are available from the corresponding author upon reasonable request.

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Acknowledgements

The authors would like to thank Dr. Marwa Naguib, Dr. Eva Adel, and Dr. Mustafa Alseqely for their help in isolate collection and PD Dr. med. Wilma Ziebuhr, Prof. Andrew Whitelaw Dr. Revathi Gunturu for their helpful insights.

Funding

This work was supported by the Academic Thesis Research Fund (ATRF), Faculty of Pharmacy, Alexandria University and DFG grant ZI665/3-1.

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Authors and Affiliations

  1. Department of Microbiology and Immunology, Faculty of Pharmacy, Alexandria University, 1 Khartoum Sq., Azarita, Alexandria, 21521, Egypt

    Lina Maarouf, Hoda Omar, Moustafa El-Nakeeb & Alaa Abouelfetouh

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  1. Lina Maarouf
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  2. Hoda Omar
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  3. Moustafa El-Nakeeb
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  4. Alaa Abouelfetouh
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Contributions

Lina Maarouf carried out the experimental part of the study, including data analysis, and participated in manuscript writing. Hoda Omar followed up the performance of the experiments, analysis of the data, and manuscript writing. Moustafa El-Nakeeb designed the study and followed the progress of the work and writing of the manuscript. Alaa Abouelfetouh designed the study, participated in data analysis, and manuscript writing. All authors approved of the final manuscript.

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Correspondence to Alaa Abouelfetouh.

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Maarouf, L., Omar, H., El-Nakeeb, M. et al. Prevalence and mechanisms of linezolid resistance among staphylococcal clinical isolates from Egypt. Eur J Clin Microbiol Infect Dis 40, 815–823 (2021). https://doi.org/10.1007/s10096-020-04045-w

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  • DOI: https://doi.org/10.1007/s10096-020-04045-w

Keywords

  • Cfr
  • V domain
  • 23S rRNA
  • CoNS
  • Antimicrobial combination