Cargando…

1539. Dalbavancin, Vancomycin, and Daptomycin Alone and in Combination with Cefazolin Against Vancomycin Intermediate-Resistant (VISA) and Daptomycin Non-Susceptible (DNS) Staphylococcus aureus

BACKGROUND: Glycopeptides and lipopeptides, more specifically vancomycin (VAN) and daptomycin (DAP) have been principally utilized in treating MRSA infections. Due to continued use, MRSA strains have developed resistance to these antibiotics including vancomycin intermediate susceptible Staphylococc...

Descripción completa

Detalles Bibliográficos
Autores principales: Abdul-Mutakabbir, Jacinda, Kebriaei, Razieh, Stamper, Kyle, Maassen, Philip, Rybak, Michael J
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Oxford University Press 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6808787/
http://dx.doi.org/10.1093/ofid/ofz360.1403
_version_ 1783461821172154368
author Abdul-Mutakabbir, Jacinda
Kebriaei, Razieh
Stamper, Kyle
Maassen, Philip
Rybak, Michael J
author_facet Abdul-Mutakabbir, Jacinda
Kebriaei, Razieh
Stamper, Kyle
Maassen, Philip
Rybak, Michael J
author_sort Abdul-Mutakabbir, Jacinda
collection PubMed
description BACKGROUND: Glycopeptides and lipopeptides, more specifically vancomycin (VAN) and daptomycin (DAP) have been principally utilized in treating MRSA infections. Due to continued use, MRSA strains have developed resistance to these antibiotics including vancomycin intermediate susceptible Staphylococcus aureus (VISA) and daptomycin non-susceptible strains (DNS). Lipoglycopeptides; notably dalbavancin (DAL), have been employed due to their ease of administration and enhanced activity against highly resistant S. aureus. As previously demonstrated, the use of β-lactams, specifically cefazolin (CFZ) in combination with anti-MRSA drug therapy has been effective in eradicating S. aureus complicated by increased resistance. The objective of this study was to evaluate the activity of DAL, VAN, and DAP, alone and in combination with CFZ in a pharmacokinetic/pharmacodynamic (PK/PD) model. METHODS: The well-characterized DNS-VISA strain, D712, was evaluated in eight different regimens in duplicate via a one-compartment 7-day PK/PD model. The experimental regimens were as follows: D712 growth control, DAL 1500 mg given on day 1, VAN 2 g given every 12 hours, DAP 10 mg/kg once-daily, CFZ 2 g given every 8 hours and DAL, DAP, and VAN in combination with CFZ. RESULTS: The combinations of DAL+CFZ, VAN+CFZ, and DAP+CFZ demonstrated a significant log(10) CFU/mL reduction (more than 5 log (10) CFU/mL and up to detection limit), compared with each drug used as monotherapy (P < 0.001). Neither DAP nor VAN demonstrated sustained bactericidal activity, (represented by a >3-log(10) CFU/mL reduction from baseline) and resulted in significant regrowth, when administered alone. However, the DAP +CFZ, and VAN+CFZ combination models demonstrated bactericidal activity at 4 hours and 24 hours, respectively. While DAL alone did demonstrate bactericidal activity, the DAL+CFZ combination was more rapidly bactericidal, achieving a > 3-log reduction from baseline in 8 hours vs. 48 hours (P < 0.05). CONCLUSION: The combination of DAL, VAN, or DAP with CFZ demonstrated significantly improved activity against this multiple drug-resistant S. aureus strain. Further research is warranted, both in vivo and in vitro, to explore the synergistic capabilities of anti-MRSA drug therapy in combination with β-lactams. DISCLOSURES: All authors: No reported disclosures.
format Online
Article
Text
id pubmed-6808787
institution National Center for Biotechnology Information
language English
publishDate 2019
publisher Oxford University Press
record_format MEDLINE/PubMed
spelling pubmed-68087872019-10-28 1539. Dalbavancin, Vancomycin, and Daptomycin Alone and in Combination with Cefazolin Against Vancomycin Intermediate-Resistant (VISA) and Daptomycin Non-Susceptible (DNS) Staphylococcus aureus Abdul-Mutakabbir, Jacinda Kebriaei, Razieh Stamper, Kyle Maassen, Philip Rybak, Michael J Open Forum Infect Dis Abstracts BACKGROUND: Glycopeptides and lipopeptides, more specifically vancomycin (VAN) and daptomycin (DAP) have been principally utilized in treating MRSA infections. Due to continued use, MRSA strains have developed resistance to these antibiotics including vancomycin intermediate susceptible Staphylococcus aureus (VISA) and daptomycin non-susceptible strains (DNS). Lipoglycopeptides; notably dalbavancin (DAL), have been employed due to their ease of administration and enhanced activity against highly resistant S. aureus. As previously demonstrated, the use of β-lactams, specifically cefazolin (CFZ) in combination with anti-MRSA drug therapy has been effective in eradicating S. aureus complicated by increased resistance. The objective of this study was to evaluate the activity of DAL, VAN, and DAP, alone and in combination with CFZ in a pharmacokinetic/pharmacodynamic (PK/PD) model. METHODS: The well-characterized DNS-VISA strain, D712, was evaluated in eight different regimens in duplicate via a one-compartment 7-day PK/PD model. The experimental regimens were as follows: D712 growth control, DAL 1500 mg given on day 1, VAN 2 g given every 12 hours, DAP 10 mg/kg once-daily, CFZ 2 g given every 8 hours and DAL, DAP, and VAN in combination with CFZ. RESULTS: The combinations of DAL+CFZ, VAN+CFZ, and DAP+CFZ demonstrated a significant log(10) CFU/mL reduction (more than 5 log (10) CFU/mL and up to detection limit), compared with each drug used as monotherapy (P < 0.001). Neither DAP nor VAN demonstrated sustained bactericidal activity, (represented by a >3-log(10) CFU/mL reduction from baseline) and resulted in significant regrowth, when administered alone. However, the DAP +CFZ, and VAN+CFZ combination models demonstrated bactericidal activity at 4 hours and 24 hours, respectively. While DAL alone did demonstrate bactericidal activity, the DAL+CFZ combination was more rapidly bactericidal, achieving a > 3-log reduction from baseline in 8 hours vs. 48 hours (P < 0.05). CONCLUSION: The combination of DAL, VAN, or DAP with CFZ demonstrated significantly improved activity against this multiple drug-resistant S. aureus strain. Further research is warranted, both in vivo and in vitro, to explore the synergistic capabilities of anti-MRSA drug therapy in combination with β-lactams. DISCLOSURES: All authors: No reported disclosures. Oxford University Press 2019-10-23 /pmc/articles/PMC6808787/ http://dx.doi.org/10.1093/ofid/ofz360.1403 Text en © The Author(s) 2019. Published by Oxford University Press on behalf of Infectious Diseases Society of America. http://creativecommons.org/licenses/by-nc-nd/4.0/ This is an Open Access article distributed under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs licence (http://creativecommons.org/licenses/by-nc-nd/4.0/), which permits non-commercial reproduction and distribution of the work, in any medium, provided the original work is not altered or transformed in any way, and that the work is properly cited. For commercial re-use, please contact journals.permissions@oup.com
spellingShingle Abstracts
Abdul-Mutakabbir, Jacinda
Kebriaei, Razieh
Stamper, Kyle
Maassen, Philip
Rybak, Michael J
1539. Dalbavancin, Vancomycin, and Daptomycin Alone and in Combination with Cefazolin Against Vancomycin Intermediate-Resistant (VISA) and Daptomycin Non-Susceptible (DNS) Staphylococcus aureus
title 1539. Dalbavancin, Vancomycin, and Daptomycin Alone and in Combination with Cefazolin Against Vancomycin Intermediate-Resistant (VISA) and Daptomycin Non-Susceptible (DNS) Staphylococcus aureus
title_full 1539. Dalbavancin, Vancomycin, and Daptomycin Alone and in Combination with Cefazolin Against Vancomycin Intermediate-Resistant (VISA) and Daptomycin Non-Susceptible (DNS) Staphylococcus aureus
title_fullStr 1539. Dalbavancin, Vancomycin, and Daptomycin Alone and in Combination with Cefazolin Against Vancomycin Intermediate-Resistant (VISA) and Daptomycin Non-Susceptible (DNS) Staphylococcus aureus
title_full_unstemmed 1539. Dalbavancin, Vancomycin, and Daptomycin Alone and in Combination with Cefazolin Against Vancomycin Intermediate-Resistant (VISA) and Daptomycin Non-Susceptible (DNS) Staphylococcus aureus
title_short 1539. Dalbavancin, Vancomycin, and Daptomycin Alone and in Combination with Cefazolin Against Vancomycin Intermediate-Resistant (VISA) and Daptomycin Non-Susceptible (DNS) Staphylococcus aureus
title_sort 1539. dalbavancin, vancomycin, and daptomycin alone and in combination with cefazolin against vancomycin intermediate-resistant (visa) and daptomycin non-susceptible (dns) staphylococcus aureus
topic Abstracts
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6808787/
http://dx.doi.org/10.1093/ofid/ofz360.1403
work_keys_str_mv AT abdulmutakabbirjacinda 1539dalbavancinvancomycinanddaptomycinaloneandincombinationwithcefazolinagainstvancomycinintermediateresistantvisaanddaptomycinnonsusceptiblednsstaphylococcusaureus
AT kebriaeirazieh 1539dalbavancinvancomycinanddaptomycinaloneandincombinationwithcefazolinagainstvancomycinintermediateresistantvisaanddaptomycinnonsusceptiblednsstaphylococcusaureus
AT stamperkyle 1539dalbavancinvancomycinanddaptomycinaloneandincombinationwithcefazolinagainstvancomycinintermediateresistantvisaanddaptomycinnonsusceptiblednsstaphylococcusaureus
AT maassenphilip 1539dalbavancinvancomycinanddaptomycinaloneandincombinationwithcefazolinagainstvancomycinintermediateresistantvisaanddaptomycinnonsusceptiblednsstaphylococcusaureus
AT rybakmichaelj 1539dalbavancinvancomycinanddaptomycinaloneandincombinationwithcefazolinagainstvancomycinintermediateresistantvisaanddaptomycinnonsusceptiblednsstaphylococcusaureus