Evaluation of Aztreonam and Ceftazidime/Avibactam Synergism against <i>Klebsiella pneumoniae</i> by MALDI-TOF MS
Introduction: Resistance to carbapenems due to the co-production of NDM and ESBL or NDM and KPC is increasing. Therefore, combined therapy with aztreonam (ATM) plus ceftazidime/avibactam (CZA) has been recommended. Then, it is necessary to develop and evaluate fast and simple methods to determine sy...
| Main Authors: | , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
MDPI AG
2023-06-01
|
| Series: | Antibiotics |
| Subjects: | |
| Online Access: | https://www.mdpi.com/2079-6382/12/6/1063 |
| _version_ | 1797596421435686912 |
|---|---|
| author | Camila Mörschbächer Wilhelm Everton Inamine Andreza Francisco Martins Afonso Luís Barth |
| author_facet | Camila Mörschbächer Wilhelm Everton Inamine Andreza Francisco Martins Afonso Luís Barth |
| author_sort | Camila Mörschbächer Wilhelm |
| collection | DOAJ |
| description | Introduction: Resistance to carbapenems due to the co-production of NDM and ESBL or NDM and KPC is increasing. Therefore, combined therapy with aztreonam (ATM) plus ceftazidime/avibactam (CZA) has been recommended. Then, it is necessary to develop and evaluate fast and simple methods to determine synergism in vitro in microbiology laboratories. Objective: To develop a method to determine the synergism of ATM and CZA by MALDI-TOF MS (SynMALDI). Method: <i>Klebsiella pneumoniae</i> (n = 22) isolates with <i>bla</i><sub>NDM</sub> and/or <i>bla</i><sub>KPC</sub> genes were tested. The time–kill curve assay was performed for four isolates (three positives for <i>bla</i><sub>NDM</sub> and <i>bla</i><sub>KPC</sub> and one positive for <i>bla</i><sub>NDM</sub> only). For SynMALDI, each isolate was incubated for 3 h in 4 tubes containing brain–heart infusion broth with the following: (1) no antibiotic; (2) ATM at 64 mg/L; (3) CZA at 10/4 mg/L; and (4) ATM at 64 mg/L plus CZA at 10/4 mg/L. After incubation, the bacterial protein extract was analyzed by MALDI-TOF MS, and the relative growth (RG) was determined for each isolate, considering intensities of the peaks of the bacterium incubated with antibiotic (tubes 2, 3, and 4) to the same bacterium incubated without antibiotic (tube 1), as follows: RG = Intensity<sub>With antibiotic</sub>/Intensity<sub>Without antibiotic</sub>. The combination was determined as synergistic when there was an RG decrease of 0.3 in the antibiotic combination in relation to the RG of the most active antibiotic alone. Results: The combination of ATM plus CZA proved to be synergic by time–kill curve assay. All isolates tested with the SynMALDI method also presented synergism. Conclusions: Detection of synergism for ATM plus CZA combination can be determined by MALDI-TOF MS, providing fast results in order to improve patient treatment. |
| first_indexed | 2024-03-11T02:51:10Z |
| format | Article |
| id | doaj.art-db43fb7bf6b94c45abfab9b8b933c075 |
| institution | Directory Open Access Journal |
| issn | 2079-6382 |
| language | English |
| last_indexed | 2024-03-11T02:51:10Z |
| publishDate | 2023-06-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Antibiotics |
| spelling | doaj.art-db43fb7bf6b94c45abfab9b8b933c0752023-11-18T09:01:32ZengMDPI AGAntibiotics2079-63822023-06-01126106310.3390/antibiotics12061063Evaluation of Aztreonam and Ceftazidime/Avibactam Synergism against <i>Klebsiella pneumoniae</i> by MALDI-TOF MSCamila Mörschbächer Wilhelm0Everton Inamine1Andreza Francisco Martins2Afonso Luís Barth3Programa de Pós-Graduação em Ciências Farmacêuticas, Universidade Federal do Rio Grande do Sul, Porto Alegre 90610-000, BrazilLaboratório Carlos Franco Voegeli, Irmandade Santa Casa de Misericórdia de Porto Alegre, Porto Alegre 90050-170, BrazilPrograma de Pós-Graduação em Ciências Farmacêuticas, Universidade Federal do Rio Grande do Sul, Porto Alegre 90610-000, BrazilPrograma de Pós-Graduação em Ciências Farmacêuticas, Universidade Federal do Rio Grande do Sul, Porto Alegre 90610-000, BrazilIntroduction: Resistance to carbapenems due to the co-production of NDM and ESBL or NDM and KPC is increasing. Therefore, combined therapy with aztreonam (ATM) plus ceftazidime/avibactam (CZA) has been recommended. Then, it is necessary to develop and evaluate fast and simple methods to determine synergism in vitro in microbiology laboratories. Objective: To develop a method to determine the synergism of ATM and CZA by MALDI-TOF MS (SynMALDI). Method: <i>Klebsiella pneumoniae</i> (n = 22) isolates with <i>bla</i><sub>NDM</sub> and/or <i>bla</i><sub>KPC</sub> genes were tested. The time–kill curve assay was performed for four isolates (three positives for <i>bla</i><sub>NDM</sub> and <i>bla</i><sub>KPC</sub> and one positive for <i>bla</i><sub>NDM</sub> only). For SynMALDI, each isolate was incubated for 3 h in 4 tubes containing brain–heart infusion broth with the following: (1) no antibiotic; (2) ATM at 64 mg/L; (3) CZA at 10/4 mg/L; and (4) ATM at 64 mg/L plus CZA at 10/4 mg/L. After incubation, the bacterial protein extract was analyzed by MALDI-TOF MS, and the relative growth (RG) was determined for each isolate, considering intensities of the peaks of the bacterium incubated with antibiotic (tubes 2, 3, and 4) to the same bacterium incubated without antibiotic (tube 1), as follows: RG = Intensity<sub>With antibiotic</sub>/Intensity<sub>Without antibiotic</sub>. The combination was determined as synergistic when there was an RG decrease of 0.3 in the antibiotic combination in relation to the RG of the most active antibiotic alone. Results: The combination of ATM plus CZA proved to be synergic by time–kill curve assay. All isolates tested with the SynMALDI method also presented synergism. Conclusions: Detection of synergism for ATM plus CZA combination can be determined by MALDI-TOF MS, providing fast results in order to improve patient treatment.https://www.mdpi.com/2079-6382/12/6/1063synergismMALDI-TOF MSrelative growthaztreonamceftazidime/avibactam |
| spellingShingle | Camila Mörschbächer Wilhelm Everton Inamine Andreza Francisco Martins Afonso Luís Barth Evaluation of Aztreonam and Ceftazidime/Avibactam Synergism against <i>Klebsiella pneumoniae</i> by MALDI-TOF MS Antibiotics synergism MALDI-TOF MS relative growth aztreonam ceftazidime/avibactam |
| title | Evaluation of Aztreonam and Ceftazidime/Avibactam Synergism against <i>Klebsiella pneumoniae</i> by MALDI-TOF MS |
| title_full | Evaluation of Aztreonam and Ceftazidime/Avibactam Synergism against <i>Klebsiella pneumoniae</i> by MALDI-TOF MS |
| title_fullStr | Evaluation of Aztreonam and Ceftazidime/Avibactam Synergism against <i>Klebsiella pneumoniae</i> by MALDI-TOF MS |
| title_full_unstemmed | Evaluation of Aztreonam and Ceftazidime/Avibactam Synergism against <i>Klebsiella pneumoniae</i> by MALDI-TOF MS |
| title_short | Evaluation of Aztreonam and Ceftazidime/Avibactam Synergism against <i>Klebsiella pneumoniae</i> by MALDI-TOF MS |
| title_sort | evaluation of aztreonam and ceftazidime avibactam synergism against i klebsiella pneumoniae i by maldi tof ms |
| topic | synergism MALDI-TOF MS relative growth aztreonam ceftazidime/avibactam |
| url | https://www.mdpi.com/2079-6382/12/6/1063 |
| work_keys_str_mv | AT camilamorschbacherwilhelm evaluationofaztreonamandceftazidimeavibactamsynergismagainstiklebsiellapneumoniaeibymalditofms AT evertoninamine evaluationofaztreonamandceftazidimeavibactamsynergismagainstiklebsiellapneumoniaeibymalditofms AT andrezafranciscomartins evaluationofaztreonamandceftazidimeavibactamsynergismagainstiklebsiellapneumoniaeibymalditofms AT afonsoluisbarth evaluationofaztreonamandceftazidimeavibactamsynergismagainstiklebsiellapneumoniaeibymalditofms |