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Treatment of Methicillin-resistant Staphylococcus aureus experimental Osteomyelitis with bone-targeted Vancomycin
INTRODUCTION: Methicillin-resistant S. aureus (MRSA) is a common cause of bone and joint infection. BT2-peg2-vancomycin is an investigational bone-targeted formulation of vancomycin which we hypothesized would have increased antimicrobial activity compared to conventional vancomycin in a chronic exp...
Autores principales: | , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Springer International Publishing
2013
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4320154/ https://www.ncbi.nlm.nih.gov/pubmed/25674391 http://dx.doi.org/10.1186/2193-1801-2-329 |
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author | Karau, Melissa J Schmidt-Malan, Suzannah M Greenwood-Quaintance, Kerryl E Mandrekar, Jayawant Cai, Jian Pierce, William M Merten, Kevyn Patel, Robin |
author_facet | Karau, Melissa J Schmidt-Malan, Suzannah M Greenwood-Quaintance, Kerryl E Mandrekar, Jayawant Cai, Jian Pierce, William M Merten, Kevyn Patel, Robin |
author_sort | Karau, Melissa J |
collection | PubMed |
description | INTRODUCTION: Methicillin-resistant S. aureus (MRSA) is a common cause of bone and joint infection. BT2-peg2-vancomycin is an investigational bone-targeted formulation of vancomycin which we hypothesized would have increased antimicrobial activity compared to conventional vancomycin in a chronic experimental MRSA osteomyelitis model. METHODS: We tested bone affinity using an hydroxyapatite (HA) binding assay, assessed the in vitro antimicrobial susceptibility of 30 MRSA isolates, and compared vancomycin and BT2-peg2-vancomycin in a rat experimental osteomyelitis model. RESULTS: Vancomycin did not bind to hydroxyapatite (HA binding index = 0), whereas BT2-peg2-vancomycin showed appreciable binding (HA binding index = 57). The MIC(50) was 1 μg/ml and the MIC(90) was 2 μg/ml for both vancomycin and BT2-peg2-vancomycin. The MBC(90) was 16 and 4 μg/ml for vancomycin and BT2-peg2-vancomycin, respectively. Treatment with 50 mg/kg of vancomycin every 12 hours (median, 4.73 log(10) cfu/g), 63.85 mg/kg (equivalent to 50 mg/kg vancomycin) of BT2-peg2-vancomycin every 12 hours (median, 3.93 log(10) cfu/g) or 63.85 mg/kg of BT2-peg2-vancomycin once per week (median, 5.00 log(10) cfu/g) was more active than no treatment (median, 5.22 log(10) cfu/g) (P =0.0481). Treatment with 63.85 mg/kg of BT2-peg2-vancomycin every 12 hours was more active than all other treatment regimens evaluated (P≤0.0150), but was associated with high plasma BT2-peg2-vancomycin levels, decreased animal weight, increased kidney size, creatinine and BUN, and leukocytosis with tubulointerstitial nephritis. CONCLUSION: With optimization of pharmacokinetic parameters to prevent toxicity, BT2-peg2-vancomycin may be useful in the treatment of MRSA osteomyelitis. |
format | Online Article Text |
id | pubmed-4320154 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2013 |
publisher | Springer International Publishing |
record_format | MEDLINE/PubMed |
spelling | pubmed-43201542015-02-11 Treatment of Methicillin-resistant Staphylococcus aureus experimental Osteomyelitis with bone-targeted Vancomycin Karau, Melissa J Schmidt-Malan, Suzannah M Greenwood-Quaintance, Kerryl E Mandrekar, Jayawant Cai, Jian Pierce, William M Merten, Kevyn Patel, Robin Springerplus Research INTRODUCTION: Methicillin-resistant S. aureus (MRSA) is a common cause of bone and joint infection. BT2-peg2-vancomycin is an investigational bone-targeted formulation of vancomycin which we hypothesized would have increased antimicrobial activity compared to conventional vancomycin in a chronic experimental MRSA osteomyelitis model. METHODS: We tested bone affinity using an hydroxyapatite (HA) binding assay, assessed the in vitro antimicrobial susceptibility of 30 MRSA isolates, and compared vancomycin and BT2-peg2-vancomycin in a rat experimental osteomyelitis model. RESULTS: Vancomycin did not bind to hydroxyapatite (HA binding index = 0), whereas BT2-peg2-vancomycin showed appreciable binding (HA binding index = 57). The MIC(50) was 1 μg/ml and the MIC(90) was 2 μg/ml for both vancomycin and BT2-peg2-vancomycin. The MBC(90) was 16 and 4 μg/ml for vancomycin and BT2-peg2-vancomycin, respectively. Treatment with 50 mg/kg of vancomycin every 12 hours (median, 4.73 log(10) cfu/g), 63.85 mg/kg (equivalent to 50 mg/kg vancomycin) of BT2-peg2-vancomycin every 12 hours (median, 3.93 log(10) cfu/g) or 63.85 mg/kg of BT2-peg2-vancomycin once per week (median, 5.00 log(10) cfu/g) was more active than no treatment (median, 5.22 log(10) cfu/g) (P =0.0481). Treatment with 63.85 mg/kg of BT2-peg2-vancomycin every 12 hours was more active than all other treatment regimens evaluated (P≤0.0150), but was associated with high plasma BT2-peg2-vancomycin levels, decreased animal weight, increased kidney size, creatinine and BUN, and leukocytosis with tubulointerstitial nephritis. CONCLUSION: With optimization of pharmacokinetic parameters to prevent toxicity, BT2-peg2-vancomycin may be useful in the treatment of MRSA osteomyelitis. Springer International Publishing 2013-07-18 /pmc/articles/PMC4320154/ /pubmed/25674391 http://dx.doi.org/10.1186/2193-1801-2-329 Text en © Karau et al.; licensee Springer. 2013 This article is published under license to BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. |
spellingShingle | Research Karau, Melissa J Schmidt-Malan, Suzannah M Greenwood-Quaintance, Kerryl E Mandrekar, Jayawant Cai, Jian Pierce, William M Merten, Kevyn Patel, Robin Treatment of Methicillin-resistant Staphylococcus aureus experimental Osteomyelitis with bone-targeted Vancomycin |
title | Treatment of Methicillin-resistant Staphylococcus aureus experimental Osteomyelitis with bone-targeted Vancomycin |
title_full | Treatment of Methicillin-resistant Staphylococcus aureus experimental Osteomyelitis with bone-targeted Vancomycin |
title_fullStr | Treatment of Methicillin-resistant Staphylococcus aureus experimental Osteomyelitis with bone-targeted Vancomycin |
title_full_unstemmed | Treatment of Methicillin-resistant Staphylococcus aureus experimental Osteomyelitis with bone-targeted Vancomycin |
title_short | Treatment of Methicillin-resistant Staphylococcus aureus experimental Osteomyelitis with bone-targeted Vancomycin |
title_sort | treatment of methicillin-resistant staphylococcus aureus experimental osteomyelitis with bone-targeted vancomycin |
topic | Research |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4320154/ https://www.ncbi.nlm.nih.gov/pubmed/25674391 http://dx.doi.org/10.1186/2193-1801-2-329 |
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