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Characterization of Transferrable Mechanisms of Quinolone Resistance (TMQR) among Quinolone-resistant Escherichia coli and Klebsiella pneumoniae causing Urinary Tract Infection in Nepalese Children

BACKGROUND: Transferrable mechanisms of quinolone resistance (TMQR) can lead to fluoroquinolone non-susceptibility in addition to chromosomal mechanisms. Some evidence suggests that fluoroquinolone resistance is increasing among the pediatric population. We sought to determine the occurrence of TMQR...

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Autores principales: Shrestha, Raj Kumar, Thapa, Ashmita, Shrestha, Dhruba, Pokhrel, Sabi, Aryal, Anubhav, Adhikari, Rupika, Shrestha, Nipun, Dhoubhadel, Bhim Gopal, Parry, Christopher M
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10498618/
https://www.ncbi.nlm.nih.gov/pubmed/37704964
http://dx.doi.org/10.1186/s12887-023-04279-5
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author Shrestha, Raj Kumar
Thapa, Ashmita
Shrestha, Dhruba
Pokhrel, Sabi
Aryal, Anubhav
Adhikari, Rupika
Shrestha, Nipun
Dhoubhadel, Bhim Gopal
Parry, Christopher M
author_facet Shrestha, Raj Kumar
Thapa, Ashmita
Shrestha, Dhruba
Pokhrel, Sabi
Aryal, Anubhav
Adhikari, Rupika
Shrestha, Nipun
Dhoubhadel, Bhim Gopal
Parry, Christopher M
author_sort Shrestha, Raj Kumar
collection PubMed
description BACKGROUND: Transferrable mechanisms of quinolone resistance (TMQR) can lead to fluoroquinolone non-susceptibility in addition to chromosomal mechanisms. Some evidence suggests that fluoroquinolone resistance is increasing among the pediatric population. We sought to determine the occurrence of TMQR genes among quinolone-resistant E. coli and K. pneumoniae causing urinary tract infections among Nepalese outpatient children (< 18 years) and identify molecular characteristics of TMQR-harboring isolates. METHODS: We performed antimicrobial susceptibility testing, phenotypic extended-spectrum β-lactamase (ESBL) and modified carbapenem inactivation method tests, and investigated the presence of six TMQR genes (qnrA, qnrB, qnrS, aac(6’)-Ib-cr, oqxAB, qepA), three ESBL genes (bla(CTX−M), bla(TEM), bla(SHV)), and five carbapenemase genes (bla(NDM), bla(OXA−48), bla(KPC), bla(IMP), bla(VIM)). The quinolone resistance-determining region (QRDR) of gyrA and parC were sequenced for 35 TMQR-positive isolates. RESULTS: A total of 74/147 (50.3%) isolates were TMQR positive by multiplex PCR [aac(6’)-Ib-cr in 48 (32.7%), qnrB in 23 (15.7%), qnrS in 18 (12.3%), qnrA in 1 (0.7%), and oqxAB in 1 (0.7%) isolate]. The median ciprofloxacin minimum inhibitory concentration of TMQR-positive isolates (64 µg/mL) was two-fold higher than those without TMQR (32 µg/mL) (p = 0.004). Ser-83→Leu and Asp-87→Asn in GyrA and Ser-80→Ile in ParC were the most common QRDR mutations (23 of 35). In addition, there was a statistically significant association between TMQR and two β-lactamase genes; bla(CTX−M) (p = 0.037) and bla(TEM) (p = 0.000). CONCLUSION: This study suggests a high prevalence of TMQR among the quinolone-resistant E. coli and K. pneumoniae isolates causing urinary tract infection in children in this area of Nepal and an association with the carriage of ESBL gene. This is a challenge for the management of urinary infections in children. Comprehensive prospective surveillance of antimicrobial resistance in these common pathogens will be necessary to devise strategies to mitigate the emergence of further resistance. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12887-023-04279-5.
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spelling pubmed-104986182023-09-14 Characterization of Transferrable Mechanisms of Quinolone Resistance (TMQR) among Quinolone-resistant Escherichia coli and Klebsiella pneumoniae causing Urinary Tract Infection in Nepalese Children Shrestha, Raj Kumar Thapa, Ashmita Shrestha, Dhruba Pokhrel, Sabi Aryal, Anubhav Adhikari, Rupika Shrestha, Nipun Dhoubhadel, Bhim Gopal Parry, Christopher M BMC Pediatr Research BACKGROUND: Transferrable mechanisms of quinolone resistance (TMQR) can lead to fluoroquinolone non-susceptibility in addition to chromosomal mechanisms. Some evidence suggests that fluoroquinolone resistance is increasing among the pediatric population. We sought to determine the occurrence of TMQR genes among quinolone-resistant E. coli and K. pneumoniae causing urinary tract infections among Nepalese outpatient children (< 18 years) and identify molecular characteristics of TMQR-harboring isolates. METHODS: We performed antimicrobial susceptibility testing, phenotypic extended-spectrum β-lactamase (ESBL) and modified carbapenem inactivation method tests, and investigated the presence of six TMQR genes (qnrA, qnrB, qnrS, aac(6’)-Ib-cr, oqxAB, qepA), three ESBL genes (bla(CTX−M), bla(TEM), bla(SHV)), and five carbapenemase genes (bla(NDM), bla(OXA−48), bla(KPC), bla(IMP), bla(VIM)). The quinolone resistance-determining region (QRDR) of gyrA and parC were sequenced for 35 TMQR-positive isolates. RESULTS: A total of 74/147 (50.3%) isolates were TMQR positive by multiplex PCR [aac(6’)-Ib-cr in 48 (32.7%), qnrB in 23 (15.7%), qnrS in 18 (12.3%), qnrA in 1 (0.7%), and oqxAB in 1 (0.7%) isolate]. The median ciprofloxacin minimum inhibitory concentration of TMQR-positive isolates (64 µg/mL) was two-fold higher than those without TMQR (32 µg/mL) (p = 0.004). Ser-83→Leu and Asp-87→Asn in GyrA and Ser-80→Ile in ParC were the most common QRDR mutations (23 of 35). In addition, there was a statistically significant association between TMQR and two β-lactamase genes; bla(CTX−M) (p = 0.037) and bla(TEM) (p = 0.000). CONCLUSION: This study suggests a high prevalence of TMQR among the quinolone-resistant E. coli and K. pneumoniae isolates causing urinary tract infection in children in this area of Nepal and an association with the carriage of ESBL gene. This is a challenge for the management of urinary infections in children. Comprehensive prospective surveillance of antimicrobial resistance in these common pathogens will be necessary to devise strategies to mitigate the emergence of further resistance. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12887-023-04279-5. BioMed Central 2023-09-13 /pmc/articles/PMC10498618/ /pubmed/37704964 http://dx.doi.org/10.1186/s12887-023-04279-5 Text en © The Author(s) 2023 https://creativecommons.org/licenses/by/4.0/Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) . The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/ (https://creativecommons.org/publicdomain/zero/1.0/) ) applies to the data made available in this article, unless otherwise stated in a credit line to the data.
spellingShingle Research
Shrestha, Raj Kumar
Thapa, Ashmita
Shrestha, Dhruba
Pokhrel, Sabi
Aryal, Anubhav
Adhikari, Rupika
Shrestha, Nipun
Dhoubhadel, Bhim Gopal
Parry, Christopher M
Characterization of Transferrable Mechanisms of Quinolone Resistance (TMQR) among Quinolone-resistant Escherichia coli and Klebsiella pneumoniae causing Urinary Tract Infection in Nepalese Children
title Characterization of Transferrable Mechanisms of Quinolone Resistance (TMQR) among Quinolone-resistant Escherichia coli and Klebsiella pneumoniae causing Urinary Tract Infection in Nepalese Children
title_full Characterization of Transferrable Mechanisms of Quinolone Resistance (TMQR) among Quinolone-resistant Escherichia coli and Klebsiella pneumoniae causing Urinary Tract Infection in Nepalese Children
title_fullStr Characterization of Transferrable Mechanisms of Quinolone Resistance (TMQR) among Quinolone-resistant Escherichia coli and Klebsiella pneumoniae causing Urinary Tract Infection in Nepalese Children
title_full_unstemmed Characterization of Transferrable Mechanisms of Quinolone Resistance (TMQR) among Quinolone-resistant Escherichia coli and Klebsiella pneumoniae causing Urinary Tract Infection in Nepalese Children
title_short Characterization of Transferrable Mechanisms of Quinolone Resistance (TMQR) among Quinolone-resistant Escherichia coli and Klebsiella pneumoniae causing Urinary Tract Infection in Nepalese Children
title_sort characterization of transferrable mechanisms of quinolone resistance (tmqr) among quinolone-resistant escherichia coli and klebsiella pneumoniae causing urinary tract infection in nepalese children
topic Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10498618/
https://www.ncbi.nlm.nih.gov/pubmed/37704964
http://dx.doi.org/10.1186/s12887-023-04279-5
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