Meropenem-Vaborbactam Activity against U.S. Multidrug-Resistant Enterobacterales Strains, Including Carbapenem-Resistant Isolates
ABSTRACT Carbapenems are a common first-line therapy for serious Gram-negative infections, but carbapenem-resistant Enterobacterales (CRE) isolates have become an urgent health concern. Klebsiella pneumoniae serine carbapenemases (KPCs) now have been disseminated worldwide and are endemic in many ho...
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| Format: | Article |
| Language: | English |
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American Society for Microbiology
2023-02-01
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| Series: | Microbiology Spectrum |
| Subjects: | |
| Online Access: | https://journals.asm.org/doi/10.1128/spectrum.04507-22 |
| _version_ | 1811164408780423168 |
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| author | Dee Shortridge Valerie Kantro Mariana Castanheira |
| author_facet | Dee Shortridge Valerie Kantro Mariana Castanheira |
| author_sort | Dee Shortridge |
| collection | DOAJ |
| description | ABSTRACT Carbapenems are a common first-line therapy for serious Gram-negative infections, but carbapenem-resistant Enterobacterales (CRE) isolates have become an urgent health concern. Klebsiella pneumoniae serine carbapenemases (KPCs) now have been disseminated worldwide and are endemic in many hospitals globally. Isolates producing metallo-β-lactamases (MBLs) or class D OXA-48 carbapenemases are also increasingly common in Europe, although they are less common in the United States. Meropenem-vaborbactam is a combination of the carbapenem meropenem and vaborbactam, which is a β-lactamase inhibitor with activity against serine carbapenemases, including KPC-producing isolates. We examined the susceptibility of U.S. multidrug-resistant (MDR) isolates to meropenem-vaborbactam. A total of 1,697 MDR Enterobacterales isolates were collected in 31 U.S. medical centers in 2016 to 2020. Susceptibility testing was performed using the Clinical and Laboratory Standards Institute (CLSI) broth microdilution method. Whole-genome sequencing was performed for all CRE strains (MIC values of >2 mg/L for imipenem or meropenem). The rate of susceptibility of all MDR Enterobacterales strains to meropenem-vaborbactam was 99.1%, and 86.2% of the isolates were susceptible to meropenem. There were 222 CRE isolates (13.1%). KPC was the most common carbapenemase (81.1%). Thirteen CRE isolates produced NDM (n = 7), VIM (n = 3), and/or OXA-48-like (n = 4) carbapenemases; 29 CRE isolates (13.1%) had no detected carbapenemase. The rate of susceptibility of all CRE strains to meropenem-vaborbactam was 93.2%, and the rate of susceptibility of the KPC-producing isolates to meropenem-vaborbactam was 98.9%. The primary carbapenemase in the United States continues to be KPC, while MBL and OXA-48-like carbapenemases remain uncommon. Overall, the rate of susceptibility of these U.S. MDR organisms to meropenem-vaborbactam was 99.1%, indicating that meropenem-vaborbactam is a valuable treatment option for Gram-negative infections caused by U.S. MDR organisms. IMPORTANCE Carbapenems are a common first-line therapy for serious Gram-negative infections, but CRE isolates have become an urgent health concern. Meropenem-vaborbactam is a combination of the carbapenem meropenem and vaborbactam, which is a β-lactamase inhibitor with activity against serine carbapenemases, including KPC-producing isolates. We examined the susceptibility of U.S. MDR Gram-negative isolates to meropenem-vaborbactam. A total of 1,697 U.S. MDR Enterobacterales isolates collected in 2016 to 2020 were tested. Susceptibility testing was performed using the CLSI broth microdilution method. Whole-genome sequencing was performed for all CRE strains (MIC values of >2 mg/L for imipenem or meropenem). The rate of susceptibility of all MDR Enterobacterales strains to meropenem-vaborbactam was 99.1%, and 86.2% of the isolates were susceptible to meropenem. A total of 13.1% of the isolates were CRE strains, and KPC was the most common carbapenemase. Overall, the rate of susceptibility of these U.S. MDR organisms to meropenem-vaborbactam indicates that meropenem-vaborbactam is a valuable treatment option for Gram-negative infections caused by U.S. MDR Gram-negative pathogens. |
| first_indexed | 2024-04-10T15:22:07Z |
| format | Article |
| id | doaj.art-ee92ea0033ff46c8ad9dd5ef629d770c |
| institution | Directory Open Access Journal |
| issn | 2165-0497 |
| language | English |
| last_indexed | 2024-04-10T15:22:07Z |
| publishDate | 2023-02-01 |
| publisher | American Society for Microbiology |
| record_format | Article |
| series | Microbiology Spectrum |
| spelling | doaj.art-ee92ea0033ff46c8ad9dd5ef629d770c2023-02-14T14:15:49ZengAmerican Society for MicrobiologyMicrobiology Spectrum2165-04972023-02-0111110.1128/spectrum.04507-22Meropenem-Vaborbactam Activity against U.S. Multidrug-Resistant Enterobacterales Strains, Including Carbapenem-Resistant IsolatesDee Shortridge0Valerie Kantro1Mariana Castanheira2JMI Laboratories, North Liberty, Iowa, USAJMI Laboratories, North Liberty, Iowa, USAJMI Laboratories, North Liberty, Iowa, USAABSTRACT Carbapenems are a common first-line therapy for serious Gram-negative infections, but carbapenem-resistant Enterobacterales (CRE) isolates have become an urgent health concern. Klebsiella pneumoniae serine carbapenemases (KPCs) now have been disseminated worldwide and are endemic in many hospitals globally. Isolates producing metallo-β-lactamases (MBLs) or class D OXA-48 carbapenemases are also increasingly common in Europe, although they are less common in the United States. Meropenem-vaborbactam is a combination of the carbapenem meropenem and vaborbactam, which is a β-lactamase inhibitor with activity against serine carbapenemases, including KPC-producing isolates. We examined the susceptibility of U.S. multidrug-resistant (MDR) isolates to meropenem-vaborbactam. A total of 1,697 MDR Enterobacterales isolates were collected in 31 U.S. medical centers in 2016 to 2020. Susceptibility testing was performed using the Clinical and Laboratory Standards Institute (CLSI) broth microdilution method. Whole-genome sequencing was performed for all CRE strains (MIC values of >2 mg/L for imipenem or meropenem). The rate of susceptibility of all MDR Enterobacterales strains to meropenem-vaborbactam was 99.1%, and 86.2% of the isolates were susceptible to meropenem. There were 222 CRE isolates (13.1%). KPC was the most common carbapenemase (81.1%). Thirteen CRE isolates produced NDM (n = 7), VIM (n = 3), and/or OXA-48-like (n = 4) carbapenemases; 29 CRE isolates (13.1%) had no detected carbapenemase. The rate of susceptibility of all CRE strains to meropenem-vaborbactam was 93.2%, and the rate of susceptibility of the KPC-producing isolates to meropenem-vaborbactam was 98.9%. The primary carbapenemase in the United States continues to be KPC, while MBL and OXA-48-like carbapenemases remain uncommon. Overall, the rate of susceptibility of these U.S. MDR organisms to meropenem-vaborbactam was 99.1%, indicating that meropenem-vaborbactam is a valuable treatment option for Gram-negative infections caused by U.S. MDR organisms. IMPORTANCE Carbapenems are a common first-line therapy for serious Gram-negative infections, but CRE isolates have become an urgent health concern. Meropenem-vaborbactam is a combination of the carbapenem meropenem and vaborbactam, which is a β-lactamase inhibitor with activity against serine carbapenemases, including KPC-producing isolates. We examined the susceptibility of U.S. MDR Gram-negative isolates to meropenem-vaborbactam. A total of 1,697 U.S. MDR Enterobacterales isolates collected in 2016 to 2020 were tested. Susceptibility testing was performed using the CLSI broth microdilution method. Whole-genome sequencing was performed for all CRE strains (MIC values of >2 mg/L for imipenem or meropenem). The rate of susceptibility of all MDR Enterobacterales strains to meropenem-vaborbactam was 99.1%, and 86.2% of the isolates were susceptible to meropenem. A total of 13.1% of the isolates were CRE strains, and KPC was the most common carbapenemase. Overall, the rate of susceptibility of these U.S. MDR organisms to meropenem-vaborbactam indicates that meropenem-vaborbactam is a valuable treatment option for Gram-negative infections caused by U.S. MDR Gram-negative pathogens.https://journals.asm.org/doi/10.1128/spectrum.04507-22CREU.S. surveillancemeropenem-vaborbactamsurveillance studies |
| spellingShingle | Dee Shortridge Valerie Kantro Mariana Castanheira Meropenem-Vaborbactam Activity against U.S. Multidrug-Resistant Enterobacterales Strains, Including Carbapenem-Resistant Isolates Microbiology Spectrum CRE U.S. surveillance meropenem-vaborbactam surveillance studies |
| title | Meropenem-Vaborbactam Activity against U.S. Multidrug-Resistant Enterobacterales Strains, Including Carbapenem-Resistant Isolates |
| title_full | Meropenem-Vaborbactam Activity against U.S. Multidrug-Resistant Enterobacterales Strains, Including Carbapenem-Resistant Isolates |
| title_fullStr | Meropenem-Vaborbactam Activity against U.S. Multidrug-Resistant Enterobacterales Strains, Including Carbapenem-Resistant Isolates |
| title_full_unstemmed | Meropenem-Vaborbactam Activity against U.S. Multidrug-Resistant Enterobacterales Strains, Including Carbapenem-Resistant Isolates |
| title_short | Meropenem-Vaborbactam Activity against U.S. Multidrug-Resistant Enterobacterales Strains, Including Carbapenem-Resistant Isolates |
| title_sort | meropenem vaborbactam activity against u s multidrug resistant enterobacterales strains including carbapenem resistant isolates |
| topic | CRE U.S. surveillance meropenem-vaborbactam surveillance studies |
| url | https://journals.asm.org/doi/10.1128/spectrum.04507-22 |
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