Low-level amikacin resistance induced by AAC(6′)-Ib and AAC(6′)-Ib-cr in extended-spectrum β-lactamase (ESBL)-producing Enterobacterales isolated from urine in children

Amikacin is commonly used in children in combination with other agents as a last-resort treatment for severe infections caused by multidrug-resistant Gram-negative bacteria. Amikacin is also prescribed empirically in febrile neutropenia in children with cancer and in acute pulmonary exacerbations in...

وصف كامل

محفوظ في:
التفاصيل البيبلوغرافية
المؤلف الرئيسي: Hassan Al, Mana (author)
مؤلفون آخرون: Sundararaju, Sathyavathi (author), Eltai, Nahla O. (author), Al-Hadidi, Sara H. (author), Hasan, Mohammad Rubayet (author), Tang, Patrick (author), Pérez-López, Andrés (author)
التنسيق: article
منشور في: 2021
الموضوعات:
الوصول للمادة أونلاين:http://dx.doi.org/10.1016/j.jgar.2021.04.026
https://www.sciencedirect.com/science/article/pii/S2213716521001260
http://hdl.handle.net/10576/20677
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_version_ 1857415087346679808
author Hassan Al, Mana
author2 Sundararaju, Sathyavathi
Eltai, Nahla O.
Al-Hadidi, Sara H.
Hasan, Mohammad Rubayet
Tang, Patrick
Pérez-López, Andrés
author2_role author
author
author
author
author
author
author_facet Hassan Al, Mana
Sundararaju, Sathyavathi
Eltai, Nahla O.
Al-Hadidi, Sara H.
Hasan, Mohammad Rubayet
Tang, Patrick
Pérez-López, Andrés
author_role author
dc.creator.none.fl_str_mv Hassan Al, Mana
Sundararaju, Sathyavathi
Eltai, Nahla O.
Al-Hadidi, Sara H.
Hasan, Mohammad Rubayet
Tang, Patrick
Pérez-López, Andrés
dc.date.none.fl_str_mv 2021-06-16T11:15:07Z
2021-09-30
dc.format.none.fl_str_mv application/pdf
dc.identifier.none.fl_str_mv http://dx.doi.org/10.1016/j.jgar.2021.04.026
Mana, H. A., Sundararaju, S., Eltai, N. O., Al-Hadidi, S. H., Hasan, M. R., Tang, P., & Pérez-López, A. (2021). Low-level amikacin resistance induced by AAC (6')-Ib and AAC (6')-Ib-cr in ESBL-producing Enterobacterales isolated from urine in children. Journal of Global Antimicrobial Resistance.
22137165
https://www.sciencedirect.com/science/article/pii/S2213716521001260
http://hdl.handle.net/10576/20677
42-44
26
dc.language.none.fl_str_mv en
dc.publisher.none.fl_str_mv Elsevier
dc.rights.none.fl_str_mv http://creativecommons.org/licenses/by-nc-nd/4.0/
info:eu-repo/semantics/openAccess
dc.subject.none.fl_str_mv AMR
CTX-M
ESBL
Amikacin
Enterobacteriaceae
dc.title.none.fl_str_mv Low-level amikacin resistance induced by AAC(6′)-Ib and AAC(6′)-Ib-cr in extended-spectrum β-lactamase (ESBL)-producing Enterobacterales isolated from urine in children
dc.type.none.fl_str_mv Article
info:eu-repo/semantics/publishedVersion
info:eu-repo/semantics/article
description Amikacin is commonly used in children in combination with other agents as a last-resort treatment for severe infections caused by multidrug-resistant Gram-negative bacteria. Amikacin is also prescribed empirically in febrile neutropenia in children with cancer and in acute pulmonary exacerbations in cystic fibrosis patients. Over the past few years, however, amikacin has been increasingly used to treat urinary tract infections (UTIs) in children caused by Enterobacterales producing extended-spectrum β-lactamases (ESBLs), given the low resistance rates to this agent among ESBL-producing uropathogens worldwide. Resistance to amikacin in Enterobacterales can be caused by multiple mechanisms, including 16S rRNA methyltransferases. However, the most common cause is the aminoglycoside N-acetyltransferase AAC(6′)-Ib, which acetylates amikacin, tobramycin, kanamycin and netilmicin but spares gentamicin, while its bifunctional variant AAC(6′)-Ib-cr also modifies ciprofloxacin and norfloxacin . AAC(6′)-Ib-cr is frequently co-produced by CTX-M-type ESBL-producing isolates, particularly CTX-M-15, conferring low-level resistance to amikacin with minimum inhibitory concentrations (MICs) that do not exceed susceptible breakpoints. The study found that isolates carrying AAC(6′)-Ib-cr have on average a 2-fold higher amikacin MIC. The increased MIC may impact the ability to achieve a Cpeak/MIC > 8 assuming hypothetical peak concentrations between 20 mg/L and 30 mg/L, which could impact the antibiotic's efficacy as a theraputic agent.
eu_rights_str_mv openAccess
format article
id qu_4b19377347d2c8f3d3eb4c2405895350
identifier_str_mv Mana, H. A., Sundararaju, S., Eltai, N. O., Al-Hadidi, S. H., Hasan, M. R., Tang, P., & Pérez-López, A. (2021). Low-level amikacin resistance induced by AAC (6')-Ib and AAC (6')-Ib-cr in ESBL-producing Enterobacterales isolated from urine in children. Journal of Global Antimicrobial Resistance.
22137165
42-44
26
language_invalid_str_mv en
network_acronym_str qu
network_name_str Qatar University repository
oai_identifier_str oai:qspace.qu.edu.qa:10576/20677
publishDate 2021
publisher.none.fl_str_mv Elsevier
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spelling Low-level amikacin resistance induced by AAC(6′)-Ib and AAC(6′)-Ib-cr in extended-spectrum β-lactamase (ESBL)-producing Enterobacterales isolated from urine in childrenHassan Al, ManaSundararaju, SathyavathiEltai, Nahla O.Al-Hadidi, Sara H.Hasan, Mohammad RubayetTang, PatrickPérez-López, AndrésAMRCTX-MESBLAmikacinEnterobacteriaceaeAmikacin is commonly used in children in combination with other agents as a last-resort treatment for severe infections caused by multidrug-resistant Gram-negative bacteria. Amikacin is also prescribed empirically in febrile neutropenia in children with cancer and in acute pulmonary exacerbations in cystic fibrosis patients. Over the past few years, however, amikacin has been increasingly used to treat urinary tract infections (UTIs) in children caused by Enterobacterales producing extended-spectrum β-lactamases (ESBLs), given the low resistance rates to this agent among ESBL-producing uropathogens worldwide. Resistance to amikacin in Enterobacterales can be caused by multiple mechanisms, including 16S rRNA methyltransferases. However, the most common cause is the aminoglycoside N-acetyltransferase AAC(6′)-Ib, which acetylates amikacin, tobramycin, kanamycin and netilmicin but spares gentamicin, while its bifunctional variant AAC(6′)-Ib-cr also modifies ciprofloxacin and norfloxacin . AAC(6′)-Ib-cr is frequently co-produced by CTX-M-type ESBL-producing isolates, particularly CTX-M-15, conferring low-level resistance to amikacin with minimum inhibitory concentrations (MICs) that do not exceed susceptible breakpoints. The study found that isolates carrying AAC(6′)-Ib-cr have on average a 2-fold higher amikacin MIC. The increased MIC may impact the ability to achieve a Cpeak/MIC > 8 assuming hypothetical peak concentrations between 20 mg/L and 30 mg/L, which could impact the antibiotic's efficacy as a theraputic agent.This work was funded by Sidra Internal Research Funding Grant [Project ID: SIRF_200040] to AP-L, and a Qatar University Grant [No. QUUG-BRC-2017-2] to NOE.Elsevier2021-06-16T11:15:07Z2021-09-30Articleinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articleapplication/pdfhttp://dx.doi.org/10.1016/j.jgar.2021.04.026Mana, H. A., Sundararaju, S., Eltai, N. O., Al-Hadidi, S. H., Hasan, M. R., Tang, P., & Pérez-López, A. (2021). Low-level amikacin resistance induced by AAC (6')-Ib and AAC (6')-Ib-cr in ESBL-producing Enterobacterales isolated from urine in children. Journal of Global Antimicrobial Resistance.22137165https://www.sciencedirect.com/science/article/pii/S2213716521001260http://hdl.handle.net/10576/2067742-4426enhttp://creativecommons.org/licenses/by-nc-nd/4.0/info:eu-repo/semantics/openAccessoai:qspace.qu.edu.qa:10576/206772024-11-20T10:16:40Z
spellingShingle Low-level amikacin resistance induced by AAC(6′)-Ib and AAC(6′)-Ib-cr in extended-spectrum β-lactamase (ESBL)-producing Enterobacterales isolated from urine in children
Hassan Al, Mana
AMR
CTX-M
ESBL
Amikacin
Enterobacteriaceae
status_str publishedVersion
title Low-level amikacin resistance induced by AAC(6′)-Ib and AAC(6′)-Ib-cr in extended-spectrum β-lactamase (ESBL)-producing Enterobacterales isolated from urine in children
title_full Low-level amikacin resistance induced by AAC(6′)-Ib and AAC(6′)-Ib-cr in extended-spectrum β-lactamase (ESBL)-producing Enterobacterales isolated from urine in children
title_fullStr Low-level amikacin resistance induced by AAC(6′)-Ib and AAC(6′)-Ib-cr in extended-spectrum β-lactamase (ESBL)-producing Enterobacterales isolated from urine in children
title_full_unstemmed Low-level amikacin resistance induced by AAC(6′)-Ib and AAC(6′)-Ib-cr in extended-spectrum β-lactamase (ESBL)-producing Enterobacterales isolated from urine in children
title_short Low-level amikacin resistance induced by AAC(6′)-Ib and AAC(6′)-Ib-cr in extended-spectrum β-lactamase (ESBL)-producing Enterobacterales isolated from urine in children
title_sort Low-level amikacin resistance induced by AAC(6′)-Ib and AAC(6′)-Ib-cr in extended-spectrum β-lactamase (ESBL)-producing Enterobacterales isolated from urine in children
topic AMR
CTX-M
ESBL
Amikacin
Enterobacteriaceae
url http://dx.doi.org/10.1016/j.jgar.2021.04.026
https://www.sciencedirect.com/science/article/pii/S2213716521001260
http://hdl.handle.net/10576/20677