Activity of Aztreonam-avibactam and other β-lactamase inhibitor combinations against Gram-negative bacteria isolated from patients hospitalized with pneumonia in United States medical centers (2020–2022)
Abstract Background Initial antimicrobial therapy for pneumonia is frequently empirical and resistance to antimicrobial agents represents a great challenge to the treatment of patients hospitalized with pneumonia. We evaluated the frequency and antimicrobial susceptibility of Gram-negative bacteria...
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BMC
2025-01-01
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| Series: | BMC Pulmonary Medicine |
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| Online Access: | https://doi.org/10.1186/s12890-025-03500-8 |
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| author | Helio S. Sader Rodrigo E. Mendes S. J. Ryan Arends Timothy B. Doyle Mariana Castanheira |
| author_facet | Helio S. Sader Rodrigo E. Mendes S. J. Ryan Arends Timothy B. Doyle Mariana Castanheira |
| author_sort | Helio S. Sader |
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| description | Abstract Background Initial antimicrobial therapy for pneumonia is frequently empirical and resistance to antimicrobial agents represents a great challenge to the treatment of patients hospitalized with pneumonia. We evaluated the frequency and antimicrobial susceptibility of Gram-negative bacteria causing pneumonia in US hospitals. Methods Bacterial isolates were consecutively collected (1/patient) from patients hospitalized with pneumonia and the susceptibility of Gram-negative bacilli (3,911 Enterobacterales and 2,753 non-fermenters) was evaluated by broth microdilution in a monitoring laboratory. Isolates were collected in 69 medical centers in 2020–2022. Aztreonam-avibactam was tested with avibactam at fixed 4 mg/L and a pharmacokinetic/pharmacodynamic susceptible (S) breakpoint of ≤ 8 mg/L was applied for comparison. Carbapenem-resistant Enterobacterales (CRE; isolates with MIC values of > 2 mg/L for imipenem and/or meropenem) isolates were screened for carbapenemases by whole genome sequencing. Results Gram-negative bacilli represented 71.1% of organisms. The most common Gram-negative species were Pseudomonas aeruginosa (22.4% of organisms), Klebsiella pneumoniae (8.8%), Escherichia coli (6.6%), Serratia marcescens (6.2%), Stenotrophomonas maltophilia (4.9%), and Enterobacter cloacae complex (4.8%). Aztreonam-avibactam inhibited 100.0% of Enterobacterales at ≤ 8 mg/L and 99.9% at ≤ 4 mg/L and showed potent activity against CRE (MIC50/90, 0.25/1 mg/L). Ceftazidime-avibactam and meropenem-vaborbactam were active against 89.4% and 88.5% of CREs, respectively. Aztreonam-avibactam retained activity against Enterobacterales non-susceptible to ceftazidime-avibactam and/or meropenem-vaborbactam (n = 19; MIC50/90, 0.25/4 mg/L). The most common carbapenemases were KPC (69.2% of CREs), NDM (9.6%), and SME (4.8%). A carbapenemase gene was not identified in 16.3% of CREs. Ceftazidime-avibactam and meropenem-vaborbactam were highly active against KPC and SME producers but showed limited activity against MBL producers. The most active comparators against CRE were tigecycline (95.2%S), amikacin (73.1%S), and gentamicin (60.6%S). Among Pseudomonas aeruginosa, 79.1% were inhibited at ≤ 8 mg/L of aztreonam-avibactam, 77.2% were meropenem susceptible, and 77.2% were piperacillin-tazobactam susceptible. Aztreonam-avibactam was highly active against S. maltophilia, inhibiting 99.5% of isolates at ≤ 8 mg/L. Conclusions Aztreonam-avibactam displayed potent in vitro activity against a large collection of contemporary Gram-negative organisms isolated from patients hospitalized with pneumonia, including CRE isolates resistant to ceftazidime-avibactam and/or meropenem-vaborbactam. Results of surveillance programs are valuable for planning empiric antimicrobial therapy guidelines and infection control measures. |
| format | Article |
| id | doaj-art-d32669634bf24bb69fa587281d74b03b |
| institution | Kabale University |
| issn | 1471-2466 |
| language | English |
| publishDate | 2025-01-01 |
| publisher | BMC |
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| series | BMC Pulmonary Medicine |
| spelling | doaj-art-d32669634bf24bb69fa587281d74b03b2025-01-26T12:13:05ZengBMCBMC Pulmonary Medicine1471-24662025-01-012511810.1186/s12890-025-03500-8Activity of Aztreonam-avibactam and other β-lactamase inhibitor combinations against Gram-negative bacteria isolated from patients hospitalized with pneumonia in United States medical centers (2020–2022)Helio S. Sader0Rodrigo E. Mendes1S. J. Ryan Arends2Timothy B. Doyle3Mariana Castanheira4Element Iowa City (JMI Laboratories)Element Iowa City (JMI Laboratories)Element Iowa City (JMI Laboratories)Element Iowa City (JMI Laboratories)Element Iowa City (JMI Laboratories)Abstract Background Initial antimicrobial therapy for pneumonia is frequently empirical and resistance to antimicrobial agents represents a great challenge to the treatment of patients hospitalized with pneumonia. We evaluated the frequency and antimicrobial susceptibility of Gram-negative bacteria causing pneumonia in US hospitals. Methods Bacterial isolates were consecutively collected (1/patient) from patients hospitalized with pneumonia and the susceptibility of Gram-negative bacilli (3,911 Enterobacterales and 2,753 non-fermenters) was evaluated by broth microdilution in a monitoring laboratory. Isolates were collected in 69 medical centers in 2020–2022. Aztreonam-avibactam was tested with avibactam at fixed 4 mg/L and a pharmacokinetic/pharmacodynamic susceptible (S) breakpoint of ≤ 8 mg/L was applied for comparison. Carbapenem-resistant Enterobacterales (CRE; isolates with MIC values of > 2 mg/L for imipenem and/or meropenem) isolates were screened for carbapenemases by whole genome sequencing. Results Gram-negative bacilli represented 71.1% of organisms. The most common Gram-negative species were Pseudomonas aeruginosa (22.4% of organisms), Klebsiella pneumoniae (8.8%), Escherichia coli (6.6%), Serratia marcescens (6.2%), Stenotrophomonas maltophilia (4.9%), and Enterobacter cloacae complex (4.8%). Aztreonam-avibactam inhibited 100.0% of Enterobacterales at ≤ 8 mg/L and 99.9% at ≤ 4 mg/L and showed potent activity against CRE (MIC50/90, 0.25/1 mg/L). Ceftazidime-avibactam and meropenem-vaborbactam were active against 89.4% and 88.5% of CREs, respectively. Aztreonam-avibactam retained activity against Enterobacterales non-susceptible to ceftazidime-avibactam and/or meropenem-vaborbactam (n = 19; MIC50/90, 0.25/4 mg/L). The most common carbapenemases were KPC (69.2% of CREs), NDM (9.6%), and SME (4.8%). A carbapenemase gene was not identified in 16.3% of CREs. Ceftazidime-avibactam and meropenem-vaborbactam were highly active against KPC and SME producers but showed limited activity against MBL producers. The most active comparators against CRE were tigecycline (95.2%S), amikacin (73.1%S), and gentamicin (60.6%S). Among Pseudomonas aeruginosa, 79.1% were inhibited at ≤ 8 mg/L of aztreonam-avibactam, 77.2% were meropenem susceptible, and 77.2% were piperacillin-tazobactam susceptible. Aztreonam-avibactam was highly active against S. maltophilia, inhibiting 99.5% of isolates at ≤ 8 mg/L. Conclusions Aztreonam-avibactam displayed potent in vitro activity against a large collection of contemporary Gram-negative organisms isolated from patients hospitalized with pneumonia, including CRE isolates resistant to ceftazidime-avibactam and/or meropenem-vaborbactam. Results of surveillance programs are valuable for planning empiric antimicrobial therapy guidelines and infection control measures.https://doi.org/10.1186/s12890-025-03500-8Nosocomial pneumoniaEnterobacteralesCREPseudomonas aeruginosaStenotrophomonas maltophiliaMetallo-beta-lactamase |
| spellingShingle | Helio S. Sader Rodrigo E. Mendes S. J. Ryan Arends Timothy B. Doyle Mariana Castanheira Activity of Aztreonam-avibactam and other β-lactamase inhibitor combinations against Gram-negative bacteria isolated from patients hospitalized with pneumonia in United States medical centers (2020–2022) BMC Pulmonary Medicine Nosocomial pneumonia Enterobacterales CRE Pseudomonas aeruginosa Stenotrophomonas maltophilia Metallo-beta-lactamase |
| title | Activity of Aztreonam-avibactam and other β-lactamase inhibitor combinations against Gram-negative bacteria isolated from patients hospitalized with pneumonia in United States medical centers (2020–2022) |
| title_full | Activity of Aztreonam-avibactam and other β-lactamase inhibitor combinations against Gram-negative bacteria isolated from patients hospitalized with pneumonia in United States medical centers (2020–2022) |
| title_fullStr | Activity of Aztreonam-avibactam and other β-lactamase inhibitor combinations against Gram-negative bacteria isolated from patients hospitalized with pneumonia in United States medical centers (2020–2022) |
| title_full_unstemmed | Activity of Aztreonam-avibactam and other β-lactamase inhibitor combinations against Gram-negative bacteria isolated from patients hospitalized with pneumonia in United States medical centers (2020–2022) |
| title_short | Activity of Aztreonam-avibactam and other β-lactamase inhibitor combinations against Gram-negative bacteria isolated from patients hospitalized with pneumonia in United States medical centers (2020–2022) |
| title_sort | activity of aztreonam avibactam and other β lactamase inhibitor combinations against gram negative bacteria isolated from patients hospitalized with pneumonia in united states medical centers 2020 2022 |
| topic | Nosocomial pneumonia Enterobacterales CRE Pseudomonas aeruginosa Stenotrophomonas maltophilia Metallo-beta-lactamase |
| url | https://doi.org/10.1186/s12890-025-03500-8 |
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