In Vitro Activity of New β-Lactamase Inhibitor Combinations against <i>bla</i><sub>NDM</sub>, <i>bla</i><sub>KPC</sub>, and ESBL-Producing Enterobacteriales Uropathogens

Antibiotic resistance in uropathogens has increased substantially and severely affected treatment of urinary tract infections (UTIs). Lately, some new formulations, including meropenem/vaborbactam (MEV), ceftazidime/avibactam (CZA), and ceftolozane/tazobactam (C/T) have been introduced to treat infe...

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Main Authors: Lubna Razaq, Fakhur Uddin, Shahzad Ali, Shah Muhammad Abbasi, Muhammad Sohail, Nabila E. Yousif, Hala M. Abo-Dief, Zeinhom M. El-Bahy
Format: Article
Language:English
Published: MDPI AG 2023-09-01
Series:Antibiotics
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Online Access:https://www.mdpi.com/2079-6382/12/10/1481
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author Lubna Razaq
Fakhur Uddin
Shahzad Ali
Shah Muhammad Abbasi
Muhammad Sohail
Nabila E. Yousif
Hala M. Abo-Dief
Zeinhom M. El-Bahy
author_facet Lubna Razaq
Fakhur Uddin
Shahzad Ali
Shah Muhammad Abbasi
Muhammad Sohail
Nabila E. Yousif
Hala M. Abo-Dief
Zeinhom M. El-Bahy
author_sort Lubna Razaq
collection DOAJ
description Antibiotic resistance in uropathogens has increased substantially and severely affected treatment of urinary tract infections (UTIs). Lately, some new formulations, including meropenem/vaborbactam (MEV), ceftazidime/avibactam (CZA), and ceftolozane/tazobactam (C/T) have been introduced to treat infections caused by drug-resistant pathogens. This study was designed to screen Enterobacteriales isolates from UTI patients and to assess their antimicrobial resistance pattern, particularly against the mentioned (new) antibiotics. Phenotypic screening of extended-spectrum β-lactamase (ESBL) and carbapenem resistance was followed by inhibitor-based assays to detect <i>K. pneumoniae</i> carbapenemase (KPC), metallo-β-lactamase (MBL), and class D oxacillinases (OXA). Among 289 Enterobacteriales, <i>E. coli</i> (66.4%) was the most predominant pathogen, followed by <i>K. pneumoniae</i> (13.8%) and <i>P. mirabilis</i> (8.3%). The isolates showed higher resistance to penicillins and cephalosporins (70–87%) than to non-β-lactam antimicrobials (33.2–41.5%). NDM production was a common feature among carbapenem-resistant (CR) isolates, followed by KPC and OXA. ESBL producers were susceptible to the tested new antibiotics, but NDM-positive isolates appeared resistant to these combinations. KPC-producers showed resistance to only C/T. ESBLs and carbapenemase encoding genes were located on plasmids and most of the genes were successfully transferred to recipient cells. This study revealed that MEV and CZA had significant activity against ESBL and KPC producers.
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spelling doaj.art-365046029f0d46cb95c30876b642beca2023-11-19T15:26:05ZengMDPI AGAntibiotics2079-63822023-09-011210148110.3390/antibiotics12101481In Vitro Activity of New β-Lactamase Inhibitor Combinations against <i>bla</i><sub>NDM</sub>, <i>bla</i><sub>KPC</sub>, and ESBL-Producing Enterobacteriales UropathogensLubna Razaq0Fakhur Uddin1Shahzad Ali2Shah Muhammad Abbasi3Muhammad Sohail4Nabila E. Yousif5Hala M. Abo-Dief6Zeinhom M. El-Bahy7Department of Microbiology, University of Karachi, Karachi 75270, PakistanDepartment of Microbiology, Basic Medical Sciences Institute (BMSI), Jinnah Postgraduate Medical Center (JPMC), Karachi 75510, PakistanDepartment of Urology, Jinnah Postgraduate Medical Center (JPMC), Karachi 75510, PakistanDepartment of Main Clinical Laboratory, Jinnah Postgraduate Medical Center (JPMC), Karachi 75510, PakistanDepartment of Microbiology, University of Karachi, Karachi 75270, PakistanDepartment of Science and Technology, University College-Ranyah, Taif University, P.O. Box 11099, Taif 21944, Saudi ArabiaDepartment of Science and Technology, University College-Ranyah, Taif University, P.O. Box 11099, Taif 21944, Saudi ArabiaDepartment of Chemistry, Faculty of Science, Al-Azhar University, Cairo 11884, EgyptAntibiotic resistance in uropathogens has increased substantially and severely affected treatment of urinary tract infections (UTIs). Lately, some new formulations, including meropenem/vaborbactam (MEV), ceftazidime/avibactam (CZA), and ceftolozane/tazobactam (C/T) have been introduced to treat infections caused by drug-resistant pathogens. This study was designed to screen Enterobacteriales isolates from UTI patients and to assess their antimicrobial resistance pattern, particularly against the mentioned (new) antibiotics. Phenotypic screening of extended-spectrum β-lactamase (ESBL) and carbapenem resistance was followed by inhibitor-based assays to detect <i>K. pneumoniae</i> carbapenemase (KPC), metallo-β-lactamase (MBL), and class D oxacillinases (OXA). Among 289 Enterobacteriales, <i>E. coli</i> (66.4%) was the most predominant pathogen, followed by <i>K. pneumoniae</i> (13.8%) and <i>P. mirabilis</i> (8.3%). The isolates showed higher resistance to penicillins and cephalosporins (70–87%) than to non-β-lactam antimicrobials (33.2–41.5%). NDM production was a common feature among carbapenem-resistant (CR) isolates, followed by KPC and OXA. ESBL producers were susceptible to the tested new antibiotics, but NDM-positive isolates appeared resistant to these combinations. KPC-producers showed resistance to only C/T. ESBLs and carbapenemase encoding genes were located on plasmids and most of the genes were successfully transferred to recipient cells. This study revealed that MEV and CZA had significant activity against ESBL and KPC producers.https://www.mdpi.com/2079-6382/12/10/1481meropenem/vaborbactamceftazidime/avibactam<i>Klebsiella pneumoniae</i> carbapenemaseNew Delhi metallo-β-lactamase
spellingShingle Lubna Razaq
Fakhur Uddin
Shahzad Ali
Shah Muhammad Abbasi
Muhammad Sohail
Nabila E. Yousif
Hala M. Abo-Dief
Zeinhom M. El-Bahy
In Vitro Activity of New β-Lactamase Inhibitor Combinations against <i>bla</i><sub>NDM</sub>, <i>bla</i><sub>KPC</sub>, and ESBL-Producing Enterobacteriales Uropathogens
Antibiotics
meropenem/vaborbactam
ceftazidime/avibactam
<i>Klebsiella pneumoniae</i> carbapenemase
New Delhi metallo-β-lactamase
title In Vitro Activity of New β-Lactamase Inhibitor Combinations against <i>bla</i><sub>NDM</sub>, <i>bla</i><sub>KPC</sub>, and ESBL-Producing Enterobacteriales Uropathogens
title_full In Vitro Activity of New β-Lactamase Inhibitor Combinations against <i>bla</i><sub>NDM</sub>, <i>bla</i><sub>KPC</sub>, and ESBL-Producing Enterobacteriales Uropathogens
title_fullStr In Vitro Activity of New β-Lactamase Inhibitor Combinations against <i>bla</i><sub>NDM</sub>, <i>bla</i><sub>KPC</sub>, and ESBL-Producing Enterobacteriales Uropathogens
title_full_unstemmed In Vitro Activity of New β-Lactamase Inhibitor Combinations against <i>bla</i><sub>NDM</sub>, <i>bla</i><sub>KPC</sub>, and ESBL-Producing Enterobacteriales Uropathogens
title_short In Vitro Activity of New β-Lactamase Inhibitor Combinations against <i>bla</i><sub>NDM</sub>, <i>bla</i><sub>KPC</sub>, and ESBL-Producing Enterobacteriales Uropathogens
title_sort in vitro activity of new β lactamase inhibitor combinations against i bla i sub ndm sub i bla i sub kpc sub and esbl producing enterobacteriales uropathogens
topic meropenem/vaborbactam
ceftazidime/avibactam
<i>Klebsiella pneumoniae</i> carbapenemase
New Delhi metallo-β-lactamase
url https://www.mdpi.com/2079-6382/12/10/1481
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