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Effect of in vivo neutralization of tumor necrosis alpha on the efficacy of antibiotic treatment in systemic Salmonella enterica infections

Immunity can co-operate with antibiotics, but can also antagonize drug efficacy by segregating the bacteria to areas of the body that are less accessible to antimicrobials, and by selecting for subpopulations with low division rates that are often difficult to eradicate. We studied the effect of an...

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Autores principales: Rossi, Omar, Grant, Andrew J., Mastroeni, Pietro
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Oxford University Press 2017
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5353993/
https://www.ncbi.nlm.nih.gov/pubmed/28087648
http://dx.doi.org/10.1093/femspd/ftx002
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author Rossi, Omar
Grant, Andrew J.
Mastroeni, Pietro
author_facet Rossi, Omar
Grant, Andrew J.
Mastroeni, Pietro
author_sort Rossi, Omar
collection PubMed
description Immunity can co-operate with antibiotics, but can also antagonize drug efficacy by segregating the bacteria to areas of the body that are less accessible to antimicrobials, and by selecting for subpopulations with low division rates that are often difficult to eradicate. We studied the effect of an anti-inflammatory/immunosuppressive anti-TNFα treatment, which accelerates bacterial growth in the tissues and inhibits or reverses the formation of granulomas, on the efficacy of ampicillin and ciprofloxacin during a systemic Salmonella enterica infection of the mouse. The anti-TNFα treatment neither precluded nor enhanced the efficacy of antibiotic treatment. However, the anti-TNFα treatment rendered the animals susceptible to the rapid relapse of the infection seen after cessation of the antibiotic treatment. Reactivation of an established infection, due to late administration of anti-TNFα antibodies, could be successfully controlled by antibiotics, but full clearance of the bacterial load from the tissues was not achieved. We conclude that the lack of TNFα does not preclude the efficacy of antibiotic treatment and must be monitored with care due to post-treatment relapses. Combinations of anti-cytokine compounds and antibiotic molecules may not be the best way to treat persistent infections with intracellular bacteria like Salmonella.
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spelling pubmed-53539932017-03-23 Effect of in vivo neutralization of tumor necrosis alpha on the efficacy of antibiotic treatment in systemic Salmonella enterica infections Rossi, Omar Grant, Andrew J. Mastroeni, Pietro Pathog Dis Research Article Immunity can co-operate with antibiotics, but can also antagonize drug efficacy by segregating the bacteria to areas of the body that are less accessible to antimicrobials, and by selecting for subpopulations with low division rates that are often difficult to eradicate. We studied the effect of an anti-inflammatory/immunosuppressive anti-TNFα treatment, which accelerates bacterial growth in the tissues and inhibits or reverses the formation of granulomas, on the efficacy of ampicillin and ciprofloxacin during a systemic Salmonella enterica infection of the mouse. The anti-TNFα treatment neither precluded nor enhanced the efficacy of antibiotic treatment. However, the anti-TNFα treatment rendered the animals susceptible to the rapid relapse of the infection seen after cessation of the antibiotic treatment. Reactivation of an established infection, due to late administration of anti-TNFα antibodies, could be successfully controlled by antibiotics, but full clearance of the bacterial load from the tissues was not achieved. We conclude that the lack of TNFα does not preclude the efficacy of antibiotic treatment and must be monitored with care due to post-treatment relapses. Combinations of anti-cytokine compounds and antibiotic molecules may not be the best way to treat persistent infections with intracellular bacteria like Salmonella. Oxford University Press 2017-01-13 2017-02 /pmc/articles/PMC5353993/ /pubmed/28087648 http://dx.doi.org/10.1093/femspd/ftx002 Text en © FEMS 2017. http://creativecommons.org/licenses/by/4.0/ This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted reuse, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle Research Article
Rossi, Omar
Grant, Andrew J.
Mastroeni, Pietro
Effect of in vivo neutralization of tumor necrosis alpha on the efficacy of antibiotic treatment in systemic Salmonella enterica infections
title Effect of in vivo neutralization of tumor necrosis alpha on the efficacy of antibiotic treatment in systemic Salmonella enterica infections
title_full Effect of in vivo neutralization of tumor necrosis alpha on the efficacy of antibiotic treatment in systemic Salmonella enterica infections
title_fullStr Effect of in vivo neutralization of tumor necrosis alpha on the efficacy of antibiotic treatment in systemic Salmonella enterica infections
title_full_unstemmed Effect of in vivo neutralization of tumor necrosis alpha on the efficacy of antibiotic treatment in systemic Salmonella enterica infections
title_short Effect of in vivo neutralization of tumor necrosis alpha on the efficacy of antibiotic treatment in systemic Salmonella enterica infections
title_sort effect of in vivo neutralization of tumor necrosis alpha on the efficacy of antibiotic treatment in systemic salmonella enterica infections
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5353993/
https://www.ncbi.nlm.nih.gov/pubmed/28087648
http://dx.doi.org/10.1093/femspd/ftx002
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