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In Vitro and In Vivo Synergism of Fosfomycin in Combination with Meropenem or Polymyxin B against KPC-2-Producing Klebsiella pneumoniae Clinical Isolates
Fosfomycin disodium is a potential therapeutic option to manage difficult-to-treat infections, especially when combined with other antimicrobials. In this study, we evaluated the activity of fosfomycin in combination with meropenem or polymyxin B against contemporaneous KPC-2-producing K. pneumoniae...
Autores principales: | , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
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MDPI
2023
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9952190/ https://www.ncbi.nlm.nih.gov/pubmed/36830148 http://dx.doi.org/10.3390/antibiotics12020237 |
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author | Ribeiro, Aghata Cardoso da Silva Chikhani, Yohanna Carvalho dos Santos Aoun Valiatti, Tiago Barcelos Valêncio, André Kurihara, Mariana Neri Lucas Santos, Fernanda Fernandes Minarini, Luciene Andrade da Rocha Gales, Ana Cristina |
author_facet | Ribeiro, Aghata Cardoso da Silva Chikhani, Yohanna Carvalho dos Santos Aoun Valiatti, Tiago Barcelos Valêncio, André Kurihara, Mariana Neri Lucas Santos, Fernanda Fernandes Minarini, Luciene Andrade da Rocha Gales, Ana Cristina |
author_sort | Ribeiro, Aghata Cardoso da Silva |
collection | PubMed |
description | Fosfomycin disodium is a potential therapeutic option to manage difficult-to-treat infections, especially when combined with other antimicrobials. In this study, we evaluated the activity of fosfomycin in combination with meropenem or polymyxin B against contemporaneous KPC-2-producing K. pneumoniae clinical isolates (KPC-KPN). Synergistic activity was assessed by checkerboard (CKA) and time–kill (TKA) assays. TKA was performed using serum peak and trough concentrations. The activity of these combinations was also assessed in the Galleria mellonella model. Biofilm disruption was assessed by the microtiter plate technique. CKA resulted in an 8- to 2048-fold decrease in meropenem MIC, restoring meropenem activity for 82.4% of the isolates when combined with fosfomycin. For the fosfomycin + polymyxin B combination, a 2- to 128-fold reduction in polymyxin B MIC was achieved, restoring polymyxin B activity for 47% of the isolates. TKA resulted in the synergism of fosfomycin + meropenem (3.0–6.7 log(10) CFU/mL decrease) and fosfomycin + polymyxin B (6.0–6.2 log(10) CFU/mL decrease) at peak concentrations. All larvae treated with fosfomycin + meropenem survived. Larvae survival rate was higher with fosfomycin monotherapy (95%) than that observed for fosfomycin + polymyxin B (75%) (p-value < 0.0001). Finally, a higher biofilm disruption was observed under exposure to fosfomycin + polymyxin B (2.4–3.4-fold reduction). In summary, we observed a synergistic effect of fosfomycin + meropenem and fosfomycin + polymyxin B combinations, in vitro and in vivo, against KPC-KPN, as well as biofilm disruption. |
format | Online Article Text |
id | pubmed-9952190 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-99521902023-02-25 In Vitro and In Vivo Synergism of Fosfomycin in Combination with Meropenem or Polymyxin B against KPC-2-Producing Klebsiella pneumoniae Clinical Isolates Ribeiro, Aghata Cardoso da Silva Chikhani, Yohanna Carvalho dos Santos Aoun Valiatti, Tiago Barcelos Valêncio, André Kurihara, Mariana Neri Lucas Santos, Fernanda Fernandes Minarini, Luciene Andrade da Rocha Gales, Ana Cristina Antibiotics (Basel) Article Fosfomycin disodium is a potential therapeutic option to manage difficult-to-treat infections, especially when combined with other antimicrobials. In this study, we evaluated the activity of fosfomycin in combination with meropenem or polymyxin B against contemporaneous KPC-2-producing K. pneumoniae clinical isolates (KPC-KPN). Synergistic activity was assessed by checkerboard (CKA) and time–kill (TKA) assays. TKA was performed using serum peak and trough concentrations. The activity of these combinations was also assessed in the Galleria mellonella model. Biofilm disruption was assessed by the microtiter plate technique. CKA resulted in an 8- to 2048-fold decrease in meropenem MIC, restoring meropenem activity for 82.4% of the isolates when combined with fosfomycin. For the fosfomycin + polymyxin B combination, a 2- to 128-fold reduction in polymyxin B MIC was achieved, restoring polymyxin B activity for 47% of the isolates. TKA resulted in the synergism of fosfomycin + meropenem (3.0–6.7 log(10) CFU/mL decrease) and fosfomycin + polymyxin B (6.0–6.2 log(10) CFU/mL decrease) at peak concentrations. All larvae treated with fosfomycin + meropenem survived. Larvae survival rate was higher with fosfomycin monotherapy (95%) than that observed for fosfomycin + polymyxin B (75%) (p-value < 0.0001). Finally, a higher biofilm disruption was observed under exposure to fosfomycin + polymyxin B (2.4–3.4-fold reduction). In summary, we observed a synergistic effect of fosfomycin + meropenem and fosfomycin + polymyxin B combinations, in vitro and in vivo, against KPC-KPN, as well as biofilm disruption. MDPI 2023-01-23 /pmc/articles/PMC9952190/ /pubmed/36830148 http://dx.doi.org/10.3390/antibiotics12020237 Text en © 2023 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Article Ribeiro, Aghata Cardoso da Silva Chikhani, Yohanna Carvalho dos Santos Aoun Valiatti, Tiago Barcelos Valêncio, André Kurihara, Mariana Neri Lucas Santos, Fernanda Fernandes Minarini, Luciene Andrade da Rocha Gales, Ana Cristina In Vitro and In Vivo Synergism of Fosfomycin in Combination with Meropenem or Polymyxin B against KPC-2-Producing Klebsiella pneumoniae Clinical Isolates |
title | In Vitro and In Vivo Synergism of Fosfomycin in Combination with Meropenem or Polymyxin B against KPC-2-Producing Klebsiella pneumoniae Clinical Isolates |
title_full | In Vitro and In Vivo Synergism of Fosfomycin in Combination with Meropenem or Polymyxin B against KPC-2-Producing Klebsiella pneumoniae Clinical Isolates |
title_fullStr | In Vitro and In Vivo Synergism of Fosfomycin in Combination with Meropenem or Polymyxin B against KPC-2-Producing Klebsiella pneumoniae Clinical Isolates |
title_full_unstemmed | In Vitro and In Vivo Synergism of Fosfomycin in Combination with Meropenem or Polymyxin B against KPC-2-Producing Klebsiella pneumoniae Clinical Isolates |
title_short | In Vitro and In Vivo Synergism of Fosfomycin in Combination with Meropenem or Polymyxin B against KPC-2-Producing Klebsiella pneumoniae Clinical Isolates |
title_sort | in vitro and in vivo synergism of fosfomycin in combination with meropenem or polymyxin b against kpc-2-producing klebsiella pneumoniae clinical isolates |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9952190/ https://www.ncbi.nlm.nih.gov/pubmed/36830148 http://dx.doi.org/10.3390/antibiotics12020237 |
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