Comparison of testing methods assessing the in vitro efficacy of the combination of aztreonam with avibactam on multidrug-resistant Gram-negative bacilli.
Aztreonam
/ pharmacology
Azabicyclo Compounds
/ pharmacology
Microbial Sensitivity Tests
/ methods
Anti-Bacterial Agents
/ pharmacology
Humans
Drug Resistance, Multiple, Bacterial
Gram-Negative Bacteria
/ drug effects
Drug Combinations
Pseudomonas aeruginosa
/ drug effects
beta-Lactamases
/ metabolism
Enterobacteriaceae
/ drug effects
Bacterial Proteins
Gram-Negative Bacterial Infections
/ microbiology
Antibiotic combination
Antibiotic susceptibility testing
Carbapenemase
Metallo-β-lactamase
Aztreonam-avibactam
Journal
Annals of clinical microbiology and antimicrobials
ISSN: 1476-0711
Titre abrégé: Ann Clin Microbiol Antimicrob
Pays: England
ID NLM: 101152152
Informations de publication
Date de publication:
25 May 2024
25 May 2024
Historique:
received:
29
02
2024
accepted:
19
05
2024
medline:
26
5
2024
pubmed:
26
5
2024
entrez:
25
5
2024
Statut:
epublish
Résumé
Aztreonam-avibactam (ATM-AVI) combination shows promising effectiveness on most carbapenemase-producing Gram-negatives, yet standardized antibiotic susceptibility testing (AST) methods for evaluating the combination in clinical laboratories is lacking. We aimed to evaluate different ATM-AVI AST approaches. 96 characterized carbapenem-resistant clinical isolates belonging to 9 Enterobacterales (EB; n = 80) and P. aeruginosa (PA; n = 16) species, including 90 carbapenemase producers and 72 strains resistant to both CAZ-AVI and ATM, were tested. Paper disk elution (DE; Bio-Rad) and E-test gradient strips stacking (SS; bioMérieux) were performed for the ATM + CAZ-AVI combination. MIC Test Strip (MTS; Liofilchem) was evaluated for ATM-AVI MIC determination. Results were interpreted applying ATM clinical breakpoints of the EUCAST guidelines and compared to the broth microdilution method (Sensititre, Thermofisher). According to broth microdilution method, 93% of EB and 69% of PA were tested susceptible to ATM-AVI. The synergistic effect of ATM-AVI was of 95% for EB, but of only 17% for PA. The MTS method yielded higher categorical and essential agreement (CA/EA) rates for both EB (89%/91%) and PA (94%/94%) compared to SS, where the rates were 87%/83% for EB and 81%/81% for PA. MTS and SS yielded 2 and 3 major discrepancies, respectively, while 3 very major discrepancies each were observed for both methods. Concerning the DE method, CA reached 91% for EB and 81% for PA, but high number of very major discrepancies were observed for EB (n = 6; 8%) and for PA (n = 3; 19%). The ATM-AVI association displayed excellent in vitro activity against highly resistant clinical Enterobacterales strains. MTS method offers accurate ATM-AVI AST results, while the SS method might serve as better alternative then DE method in assessing the efficacy of ATM + CAZ-AVI combination. However, further investigation is needed to confirm the methods' ability to detect ATM-AVI resistance.
Sections du résumé
BACKGROUND
BACKGROUND
Aztreonam-avibactam (ATM-AVI) combination shows promising effectiveness on most carbapenemase-producing Gram-negatives, yet standardized antibiotic susceptibility testing (AST) methods for evaluating the combination in clinical laboratories is lacking. We aimed to evaluate different ATM-AVI AST approaches.
METHODS
METHODS
96 characterized carbapenem-resistant clinical isolates belonging to 9 Enterobacterales (EB; n = 80) and P. aeruginosa (PA; n = 16) species, including 90 carbapenemase producers and 72 strains resistant to both CAZ-AVI and ATM, were tested. Paper disk elution (DE; Bio-Rad) and E-test gradient strips stacking (SS; bioMérieux) were performed for the ATM + CAZ-AVI combination. MIC Test Strip (MTS; Liofilchem) was evaluated for ATM-AVI MIC determination. Results were interpreted applying ATM clinical breakpoints of the EUCAST guidelines and compared to the broth microdilution method (Sensititre, Thermofisher).
RESULTS
RESULTS
According to broth microdilution method, 93% of EB and 69% of PA were tested susceptible to ATM-AVI. The synergistic effect of ATM-AVI was of 95% for EB, but of only 17% for PA. The MTS method yielded higher categorical and essential agreement (CA/EA) rates for both EB (89%/91%) and PA (94%/94%) compared to SS, where the rates were 87%/83% for EB and 81%/81% for PA. MTS and SS yielded 2 and 3 major discrepancies, respectively, while 3 very major discrepancies each were observed for both methods. Concerning the DE method, CA reached 91% for EB and 81% for PA, but high number of very major discrepancies were observed for EB (n = 6; 8%) and for PA (n = 3; 19%).
CONCLUSIONS
CONCLUSIONS
The ATM-AVI association displayed excellent in vitro activity against highly resistant clinical Enterobacterales strains. MTS method offers accurate ATM-AVI AST results, while the SS method might serve as better alternative then DE method in assessing the efficacy of ATM + CAZ-AVI combination. However, further investigation is needed to confirm the methods' ability to detect ATM-AVI resistance.
Identifiants
pubmed: 38796461
doi: 10.1186/s12941-024-00708-0
pii: 10.1186/s12941-024-00708-0
doi:
Substances chimiques
Aztreonam
G2B4VE5GH8
Azabicyclo Compounds
0
Anti-Bacterial Agents
0
avibactam
7352665165
Drug Combinations
0
beta-Lactamases
EC 3.5.2.6
Bacterial Proteins
0
carbapenemase
EC 3.5.2.6
Types de publication
Journal Article
Comparative Study
Langues
eng
Sous-ensembles de citation
IM
Pagination
47Informations de copyright
© 2024. The Author(s).
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