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Molecular Characterization of Intermediate Susceptible Typhoidal Salmonella to Ciprofloxacin, and its Impact

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Abstract

Background and Objective

Extensive use of ciprofloxacin to treat Salmonella typhi infections has led to the emergence of resistance, resulting in clinical failure and delayed treatment response. Interpretative breakpoints for ciprofloxacin were revised by the Clinical and Laboratory Standards Institute (CLSI) and the European Committee on Antimicrobial Susceptibility Testing (EUCAST) in 2012. Since the majority of S. typhi isolates fall under the category of ‘intermediate susceptible’ as per CLSI criteria, we undertook molecular characterization to better define the susceptibility of these isolates.

Methods

Of 113 typhoidal Salmonella isolates collected during 2014, 33 (27 S. typhi and 6 S. paratyphi A) were randomly selected to determine the presence of chromosomal (gyrA, gyrB and parC), plasmid (qnrA, qnrB, qnrS and aac(6′)-lb-cr), and efflux-mediated fluoroquinolone resistance.

Results

To the best of our knowledge, the parC mutation Glu(84)-Gly was observed for the first time in S. typhi in India. Of 33 isolates, only one harbored the qnrB gene, which is responsible for plasmid-mediated resistance. No significant change in efflux pump activity was observed for ciprofloxacin, except one that showed a fivefold decrease. Ninety-six percent of isolates with intermediate minimum inhibitory concentration to ciprofloxacin (CLSI) had mutations in the gyrA and parC genes, which might translate to possible/probable clinical failure in patients if treated with ciprofloxacin. In contrast, the EUCAST criteria define these isolates as resistant and may result in appropriate therapy with reduced morbidity.

Conclusion

It was clear that the molecular mechanism of ciprofloxacin resistance correlates better with the EUCAST criteria than the CLSI criteria, which is also in agreement with the pefloxacin results, suggesting it as a surrogate marker for identifying fluoroquinolone susceptibility.

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Acknowledgments

The authors gratefully acknowledge Dr. Kamini Walia, Scientist E, Division of Epidemiology and Communicable Diseases, Indian Council of Medical Research (ICMR), New Delhi, and the ICMR council for providing the grant for this research, as well as the Institutional Review Board of the Christian Medical College, Vellore (83-i/11/13). The authors also thank Dr. Arti Kapil, Professor, Department of Microbiology, All India Institute of Medical Sciences (AIIMS), New Delhi, for sharing the Multilocus sequence typing (MLST) data undertaken as part of the ICMR-funded S. typhi surveillance.

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Authors and Affiliations

  1. Department of Clinical Microbiology, Christian Medical College, 8th Floor, Asha Building, Vellore, 632 004, Tamil Nadu, India

    Balaji Veeraraghavan, Shalini Anandan, Dhiviya Prabaa Muthuirulandi Sethuvel, Nivetha Puratchiveeran & Naveen Kumar Devanga Ragupathi

  2. Division of Epidemiology and Communicable Diseases, Indian Council of Medical Research, Ansari Nagar, New Delhi, 110 029, India

    Kamini Walia

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  1. Balaji Veeraraghavan
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  2. Shalini Anandan
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  6. Naveen Kumar Devanga Ragupathi
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Correspondence to Balaji Veeraraghavan.

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Conflict of interest

Balaji Veeraraghavan, Shalini Anandan, Dhiviya Prabaa Muthuirulandi Sethuvel, Nivetha Puratchiveeran, Kamini Walia and Naveen Kumar Devanga Ragupathi declare that there are no conflict of interest.

Funding

This study was funded by the ICMR, New Delhi, India (Ref. No. AMR/TF/55/13ECDII, dated 23 October 2013).

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Veeraraghavan, B., Anandan, S., Muthuirulandi Sethuvel, D.P. et al. Molecular Characterization of Intermediate Susceptible Typhoidal Salmonella to Ciprofloxacin, and its Impact. Mol Diagn Ther 20, 213–219 (2016). https://doi.org/10.1007/s40291-016-0191-6

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  • DOI: https://doi.org/10.1007/s40291-016-0191-6

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