Epidemiology and In Vitro Activity of Ceftazidime/Avibactam, Meropenem/Vaborbactam and Imipenem/Relebactam against <i>KPC</i>-Producing <i>K. pneumoniae</i> Collected from Bacteremic Patients, 2018 to 2020
The management of KPC-producing <i>K. pneumoniae</i> (KPC-Kp) in bloodstream infections (BSIs) represent a serious clinical challenge. In this study, the aim is to assess the incidence of resistance to novel β-lactams-β-lactamase inhibitor combinations (βL-βLICs), such as ceftazidime-avi...
| Main Authors: | , , , , |
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| Format: | Article |
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MDPI AG
2022-11-01
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| Series: | Antibiotics |
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| Online Access: | https://www.mdpi.com/2079-6382/11/11/1621 |
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| author | Federica Bovo Donatella Lombardo Tiziana Lazzarotto Simone Ambretti Paolo Gaibani |
| author_facet | Federica Bovo Donatella Lombardo Tiziana Lazzarotto Simone Ambretti Paolo Gaibani |
| author_sort | Federica Bovo |
| collection | DOAJ |
| description | The management of KPC-producing <i>K. pneumoniae</i> (KPC-Kp) in bloodstream infections (BSIs) represent a serious clinical challenge. In this study, the aim is to assess the incidence of resistance to novel β-lactams-β-lactamase inhibitor combinations (βL-βLICs), such as ceftazidime-avibactam (CAZ-AVI), meropenem-vaborbactam (MER-VAB) and imipenem-relebactam (IMI-REL), in KPC-Kp strains collected during a three-year period from patients with bacteremia. KPC-Kp strains resistant to βL-βLICs were selected for whole-genome sequencing. A total of 133 <i>K. pneumoniae</i> strains were isolated, and KPC-Kp strains were the most represented (87.2%). In 2018, resistance to CAZ-AVI and MER-VAB was 6.5% and 14.5%, respectively. In 2019, KPC-Kp resistance to CAZ-AVI and MER-VAB remained at low levels, with values of 12.9% and 3.2%, respectively. During 2020, CAZ-AVI resistance was detected in 2/23 of KPC-Kp strains (8.7%). IMI-REL was the most active βL-βLIC, inhibiting >98% of the isolates, while CAZ-AVI and MER-VAB inhibited 87–93% and 85–97% of the KPC producers, respectively. Correlations between genotypic traits and resistance to βL-βLICs showed that KPC-Kp strains resistant to CAZ-AVI harbored a mutation within the <i>bla</i><sub>KPC-3</sub> gene, while all KPC-Kp strains resistant to CAZ-AVI, MER-VAB and/or IMI-REL carried the <i>bla</i><sub>KPC-3</sub> gene. Moreover, genetic analysis of porin genes showed that 14/16 of KPC-Kp resistant isolates possessed a truncated OmpK35 and glycine (G) and aspartic acid (D) insertions at positions 134–135 within OmpK36, whereas 2/16 displayed truncated OmpK35 and OmpK36 porins. Novel βL-βLICs are promising agents against KPC-Kp infections; however, the emergence of resistance to these agents highlights the need for continuous surveillance and application of enhanced antimicrobial stewardship. |
| first_indexed | 2024-03-09T18:30:58Z |
| format | Article |
| id | doaj.art-24d6e9f7421a455aa3a668dd09a954c3 |
| institution | Directory Open Access Journal |
| issn | 2079-6382 |
| language | English |
| last_indexed | 2024-03-09T18:30:58Z |
| publishDate | 2022-11-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Antibiotics |
| spelling | doaj.art-24d6e9f7421a455aa3a668dd09a954c32023-11-24T07:30:46ZengMDPI AGAntibiotics2079-63822022-11-011111162110.3390/antibiotics11111621Epidemiology and In Vitro Activity of Ceftazidime/Avibactam, Meropenem/Vaborbactam and Imipenem/Relebactam against <i>KPC</i>-Producing <i>K. pneumoniae</i> Collected from Bacteremic Patients, 2018 to 2020Federica Bovo0Donatella Lombardo1Tiziana Lazzarotto2Simone Ambretti3Paolo Gaibani4Microbiology Unit, IRCCS Azienda Ospedaliero-Universitaria di Bologna, 40138 Bologna, ItalyMicrobiology Unit, IRCCS Azienda Ospedaliero-Universitaria di Bologna, 40138 Bologna, ItalyMicrobiology Unit, IRCCS Azienda Ospedaliero-Universitaria di Bologna, 40138 Bologna, ItalyMicrobiology Unit, IRCCS Azienda Ospedaliero-Universitaria di Bologna, 40138 Bologna, ItalyMicrobiology Unit, IRCCS Azienda Ospedaliero-Universitaria di Bologna, 40138 Bologna, ItalyThe management of KPC-producing <i>K. pneumoniae</i> (KPC-Kp) in bloodstream infections (BSIs) represent a serious clinical challenge. In this study, the aim is to assess the incidence of resistance to novel β-lactams-β-lactamase inhibitor combinations (βL-βLICs), such as ceftazidime-avibactam (CAZ-AVI), meropenem-vaborbactam (MER-VAB) and imipenem-relebactam (IMI-REL), in KPC-Kp strains collected during a three-year period from patients with bacteremia. KPC-Kp strains resistant to βL-βLICs were selected for whole-genome sequencing. A total of 133 <i>K. pneumoniae</i> strains were isolated, and KPC-Kp strains were the most represented (87.2%). In 2018, resistance to CAZ-AVI and MER-VAB was 6.5% and 14.5%, respectively. In 2019, KPC-Kp resistance to CAZ-AVI and MER-VAB remained at low levels, with values of 12.9% and 3.2%, respectively. During 2020, CAZ-AVI resistance was detected in 2/23 of KPC-Kp strains (8.7%). IMI-REL was the most active βL-βLIC, inhibiting >98% of the isolates, while CAZ-AVI and MER-VAB inhibited 87–93% and 85–97% of the KPC producers, respectively. Correlations between genotypic traits and resistance to βL-βLICs showed that KPC-Kp strains resistant to CAZ-AVI harbored a mutation within the <i>bla</i><sub>KPC-3</sub> gene, while all KPC-Kp strains resistant to CAZ-AVI, MER-VAB and/or IMI-REL carried the <i>bla</i><sub>KPC-3</sub> gene. Moreover, genetic analysis of porin genes showed that 14/16 of KPC-Kp resistant isolates possessed a truncated OmpK35 and glycine (G) and aspartic acid (D) insertions at positions 134–135 within OmpK36, whereas 2/16 displayed truncated OmpK35 and OmpK36 porins. Novel βL-βLICs are promising agents against KPC-Kp infections; however, the emergence of resistance to these agents highlights the need for continuous surveillance and application of enhanced antimicrobial stewardship.https://www.mdpi.com/2079-6382/11/11/1621BL-BLICsresistanceenterobacterialeswhole-genome sequencing |
| spellingShingle | Federica Bovo Donatella Lombardo Tiziana Lazzarotto Simone Ambretti Paolo Gaibani Epidemiology and In Vitro Activity of Ceftazidime/Avibactam, Meropenem/Vaborbactam and Imipenem/Relebactam against <i>KPC</i>-Producing <i>K. pneumoniae</i> Collected from Bacteremic Patients, 2018 to 2020 Antibiotics BL-BLICs resistance enterobacteriales whole-genome sequencing |
| title | Epidemiology and In Vitro Activity of Ceftazidime/Avibactam, Meropenem/Vaborbactam and Imipenem/Relebactam against <i>KPC</i>-Producing <i>K. pneumoniae</i> Collected from Bacteremic Patients, 2018 to 2020 |
| title_full | Epidemiology and In Vitro Activity of Ceftazidime/Avibactam, Meropenem/Vaborbactam and Imipenem/Relebactam against <i>KPC</i>-Producing <i>K. pneumoniae</i> Collected from Bacteremic Patients, 2018 to 2020 |
| title_fullStr | Epidemiology and In Vitro Activity of Ceftazidime/Avibactam, Meropenem/Vaborbactam and Imipenem/Relebactam against <i>KPC</i>-Producing <i>K. pneumoniae</i> Collected from Bacteremic Patients, 2018 to 2020 |
| title_full_unstemmed | Epidemiology and In Vitro Activity of Ceftazidime/Avibactam, Meropenem/Vaborbactam and Imipenem/Relebactam against <i>KPC</i>-Producing <i>K. pneumoniae</i> Collected from Bacteremic Patients, 2018 to 2020 |
| title_short | Epidemiology and In Vitro Activity of Ceftazidime/Avibactam, Meropenem/Vaborbactam and Imipenem/Relebactam against <i>KPC</i>-Producing <i>K. pneumoniae</i> Collected from Bacteremic Patients, 2018 to 2020 |
| title_sort | epidemiology and in vitro activity of ceftazidime avibactam meropenem vaborbactam and imipenem relebactam against i kpc i producing i k pneumoniae i collected from bacteremic patients 2018 to 2020 |
| topic | BL-BLICs resistance enterobacteriales whole-genome sequencing |
| url | https://www.mdpi.com/2079-6382/11/11/1621 |
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