Characterization of <i>Enterobacter cloacae</i> and <i>Citrobacter freundii</i> Species Complex Isolates with Decreased Susceptibility to Cephalosporins from United States Hospitals and Activity of Aztreonam–Avibactam and Comparator Agents (2019–2023)
Background: <i>Citrobacter freundii</i> (CFC) and <i>Enterobacter cloacae</i> (ECLC) species complexes represent important causes of hospital-associated infections, frequently are related to outbreaks, and have a great ability to develop antimicrobial resistance. We evaluated...
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2025-04-01
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| author | Helio S. Sader Timothy B. Doyle John H. Kimbrough Rodrigo E. Mendes Mariana Castanheira |
| author_facet | Helio S. Sader Timothy B. Doyle John H. Kimbrough Rodrigo E. Mendes Mariana Castanheira |
| author_sort | Helio S. Sader |
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| description | Background: <i>Citrobacter freundii</i> (CFC) and <i>Enterobacter cloacae</i> (ECLC) species complexes represent important causes of hospital-associated infections, frequently are related to outbreaks, and have a great ability to develop antimicrobial resistance. We evaluated a large collection of CFC and ECLC isolates with decreased susceptibility to broad-spectrum cephalosporins (Ceph-DS) from United States (US) hospitals. Methods: A total of 43,325 Enterobacterales (1/patient) were collected in 2019–2023 and susceptibility tested by broth microdilution; among those, 5106 (11.8%) were CFC (<i>n</i> = 1374) or ECLC (<i>n</i> = 3732). Ceph-DS CFC (<i>n</i> = 379) and ECLC isolates (<i>n</i> = 1065), defined as isolates with ceftazidime MICs ≥ 16 mg/L and/or cefepime MICs ≥ 2 mg/L, were screened for β-lactamase genes by whole genome sequencing. Results: The most common ESBLs were CTX-M type (<i>n</i> = 98; 47.6% of ESBL producers), SHV type (<i>n</i> = 94; 45.6%), and OXA type (<i>n</i> = 78; 37.9%); ≥2 ESBLs were identified in 65 isolates (31.6%), mainly OXA-1/30 plus a CTX-M. A carbapenemase was identified in 55 of 64 (85.9%) carbapenem-resistant (CB-R) isolates, including KPC type (40 isolates; 62.5% of CB-R) and NDM-1 (16; 23.4% of CB-R). Aztreonam–avibactam was active against 99.6% of Ceph-DS and 100.0% of ESBL producers and CB-R isolates, including NDM producers. Ceftazidime–avibactam and meropenem–vaborbactam were active against 100.0% of ESBL producers (excluding carbapenemase co-producers) and 70.3–71.9% of CB-R isolates. Cefiderocol was active against 82.8% of CB-R isolates but only 46.7% of MBL producers. Conclusions: Aztreonam–avibactam was highly active against cephalosporin-nonsusceptible ECLC and CFC, including MBL producers. The activities of ceftazidime–avibactam, meropenem–vaborbactam, and cefiderocol were compromised against CB-R isolates due to the high frequency of NDM producers. |
| format | Article |
| id | doaj-art-90135e61cbe24b4d8b4145ea99900465 |
| institution | OA Journals |
| issn | 2079-6382 |
| language | English |
| publishDate | 2025-04-01 |
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| spelling | doaj-art-90135e61cbe24b4d8b4145ea999004652025-08-20T02:17:25ZengMDPI AGAntibiotics2079-63822025-04-0114438210.3390/antibiotics14040382Characterization of <i>Enterobacter cloacae</i> and <i>Citrobacter freundii</i> Species Complex Isolates with Decreased Susceptibility to Cephalosporins from United States Hospitals and Activity of Aztreonam–Avibactam and Comparator Agents (2019–2023)Helio S. Sader0Timothy B. Doyle1John H. Kimbrough2Rodrigo E. Mendes3Mariana Castanheira4Element Iowa City (JMI Laboratories), 345 Beaver Kreek Centre, Suite A, North Liberty, IA 52317, USAElement Iowa City (JMI Laboratories), 345 Beaver Kreek Centre, Suite A, North Liberty, IA 52317, USAElement Iowa City (JMI Laboratories), 345 Beaver Kreek Centre, Suite A, North Liberty, IA 52317, USAElement Iowa City (JMI Laboratories), 345 Beaver Kreek Centre, Suite A, North Liberty, IA 52317, USAElement Iowa City (JMI Laboratories), 345 Beaver Kreek Centre, Suite A, North Liberty, IA 52317, USABackground: <i>Citrobacter freundii</i> (CFC) and <i>Enterobacter cloacae</i> (ECLC) species complexes represent important causes of hospital-associated infections, frequently are related to outbreaks, and have a great ability to develop antimicrobial resistance. We evaluated a large collection of CFC and ECLC isolates with decreased susceptibility to broad-spectrum cephalosporins (Ceph-DS) from United States (US) hospitals. Methods: A total of 43,325 Enterobacterales (1/patient) were collected in 2019–2023 and susceptibility tested by broth microdilution; among those, 5106 (11.8%) were CFC (<i>n</i> = 1374) or ECLC (<i>n</i> = 3732). Ceph-DS CFC (<i>n</i> = 379) and ECLC isolates (<i>n</i> = 1065), defined as isolates with ceftazidime MICs ≥ 16 mg/L and/or cefepime MICs ≥ 2 mg/L, were screened for β-lactamase genes by whole genome sequencing. Results: The most common ESBLs were CTX-M type (<i>n</i> = 98; 47.6% of ESBL producers), SHV type (<i>n</i> = 94; 45.6%), and OXA type (<i>n</i> = 78; 37.9%); ≥2 ESBLs were identified in 65 isolates (31.6%), mainly OXA-1/30 plus a CTX-M. A carbapenemase was identified in 55 of 64 (85.9%) carbapenem-resistant (CB-R) isolates, including KPC type (40 isolates; 62.5% of CB-R) and NDM-1 (16; 23.4% of CB-R). Aztreonam–avibactam was active against 99.6% of Ceph-DS and 100.0% of ESBL producers and CB-R isolates, including NDM producers. Ceftazidime–avibactam and meropenem–vaborbactam were active against 100.0% of ESBL producers (excluding carbapenemase co-producers) and 70.3–71.9% of CB-R isolates. Cefiderocol was active against 82.8% of CB-R isolates but only 46.7% of MBL producers. Conclusions: Aztreonam–avibactam was highly active against cephalosporin-nonsusceptible ECLC and CFC, including MBL producers. The activities of ceftazidime–avibactam, meropenem–vaborbactam, and cefiderocol were compromised against CB-R isolates due to the high frequency of NDM producers.https://www.mdpi.com/2079-6382/14/4/382aztreonam–avibactamCREmetallo-beta-lactamaseNDMESBL |
| spellingShingle | Helio S. Sader Timothy B. Doyle John H. Kimbrough Rodrigo E. Mendes Mariana Castanheira Characterization of <i>Enterobacter cloacae</i> and <i>Citrobacter freundii</i> Species Complex Isolates with Decreased Susceptibility to Cephalosporins from United States Hospitals and Activity of Aztreonam–Avibactam and Comparator Agents (2019–2023) Antibiotics aztreonam–avibactam CRE metallo-beta-lactamase NDM ESBL |
| title | Characterization of <i>Enterobacter cloacae</i> and <i>Citrobacter freundii</i> Species Complex Isolates with Decreased Susceptibility to Cephalosporins from United States Hospitals and Activity of Aztreonam–Avibactam and Comparator Agents (2019–2023) |
| title_full | Characterization of <i>Enterobacter cloacae</i> and <i>Citrobacter freundii</i> Species Complex Isolates with Decreased Susceptibility to Cephalosporins from United States Hospitals and Activity of Aztreonam–Avibactam and Comparator Agents (2019–2023) |
| title_fullStr | Characterization of <i>Enterobacter cloacae</i> and <i>Citrobacter freundii</i> Species Complex Isolates with Decreased Susceptibility to Cephalosporins from United States Hospitals and Activity of Aztreonam–Avibactam and Comparator Agents (2019–2023) |
| title_full_unstemmed | Characterization of <i>Enterobacter cloacae</i> and <i>Citrobacter freundii</i> Species Complex Isolates with Decreased Susceptibility to Cephalosporins from United States Hospitals and Activity of Aztreonam–Avibactam and Comparator Agents (2019–2023) |
| title_short | Characterization of <i>Enterobacter cloacae</i> and <i>Citrobacter freundii</i> Species Complex Isolates with Decreased Susceptibility to Cephalosporins from United States Hospitals and Activity of Aztreonam–Avibactam and Comparator Agents (2019–2023) |
| title_sort | characterization of i enterobacter cloacae i and i citrobacter freundii i species complex isolates with decreased susceptibility to cephalosporins from united states hospitals and activity of aztreonam avibactam and comparator agents 2019 2023 |
| topic | aztreonam–avibactam CRE metallo-beta-lactamase NDM ESBL |
| url | https://www.mdpi.com/2079-6382/14/4/382 |
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