Vancomycin-Rifampin Combination Therapy Has Enhanced Efficacy against an Experimental Staphylococcus aureus Prosthetic Joint Infection

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Published inAntimicrobial Agents and Chemotherapy Vol. 57; no. 10; pp. 5080 - 5086
Main Authors Niska, Jared A., Shahbazian, Jonathan H., Ramos, Romela Irene, Francis, Kevin P., Bernthal, Nicholas M., Miller, Lloyd S.
Format Journal Article
LanguageEnglish
Published Washington, DC American Society for Microbiology 01.10.2013
Subjects
Animals
Anti-Bacterial Agents
Anti-Bacterial Agents - administration & dosage
Anti-Bacterial Agents - therapeutic use
Antibiotics. Antiinfectious agents. Antiparasitic agents
Bacterial diseases
Biological and medical sciences
Diseases of the osteoarticular system
Drug Therapy, Combination
Experimental Therapeutics
Human bacterial diseases
Infectious diseases
Male
Medical sciences
Mice
Mice, Inbred C57BL
Miscellaneous. Osteoarticular involvement in other diseases
Pharmacology. Drug treatments
Prosthesis-Related Infections
Prosthesis-Related Infections - drug therapy
Rifampin
Rifampin - administration & dosage
Rifampin - therapeutic use
Staphylococcal Infections
Staphylococcal Infections - drug therapy
Staphylococcal infections, streptococcal infections, pneumococcal infections
Staphylococcus aureus
Staphylococcus aureus - drug effects
Staphylococcus aureus - pathogenicity
Vancomycin
Vancomycin - administration & dosage
Vancomycin - therapeutic use
Drug combination
Peptides
Prosthesis
Treatment efficiency
Diseases of the osteoarticular system
Arthritis
Vancomycin
Infection
Antibiotic
Rifampicin
Glycopeptide
Polypeptide
Bacteriosis
Bacteria
Micrococcales
Micrococcaceae
Antituberculous agent
Combined treatment
Protein synthesis inhibitor
Antibacterial agent
Staphylococcal infection
Staphylococcus aureus
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Abstract Classifications Services AAC Citing Articles Google Scholar PubMed Related Content Social Bookmarking CiteULike Delicious Digg Facebook Google+ Mendeley Reddit StumbleUpon Twitter current issue AAC About AAC Subscribers Authors Reviewers Advertisers Inquiries from the Press Permissions & Commercial Reprints ASM Journals Public Access Policy AAC RSS Feeds 1752 N Street N.W. • Washington DC 20036 202.737.3600 • 202.942.9355 fax • journals@asmusa.org Print ISSN: 0066-4804 Online ISSN: 1098-6596 Copyright © 2014 by the American Society for Microbiology.   For an alternate route to AAC .asm.org, visit: AAC       
AbstractList Treatment of prosthetic joint infections often involves a two-stage exchange, with implant removal and antibiotic spacer placement followed by systemic antibiotic therapy and delayed reimplantation. However, if antibiotic therapy can be improved, one-stage exchange or implant retention may be more feasible, thereby decreasing morbidity and preserving function. In this study, a mouse model of prosthetic joint infection was used in which Staphylococcus aureus was inoculated into a knee joint containing a surgically placed metallic implant extending from the femur. This model was used to evaluate whether combination therapy of vancomycin plus rifampin has increased efficacy compared with vancomycin alone against these infections. On postoperative day 7, vancomycin with or without rifampin was administered for 6 weeks with implant retention. In vivo bioluminescence imaging, ex vivo CFU enumeration, X-ray imaging, and histologic analysis were carried out. We found that there was a marked therapeutic benefit when vancomycin was combined with rifampin compared with vancomycin alone. Taken together, our results suggest that the mouse model used could serve as a valuable in vivo preclinical model system to evaluate and compare efficacies of antibiotics and combinatory therapy for prosthetic joint infections before more extensive studies are carried out in human subjects.
Treatment of prosthetic joint infections often involves a two-stage exchange, with implant removal and antibiotic spacer placement followed by systemic antibiotic therapy and delayed reimplantation. However, if antibiotic therapy can be improved, one-stage exchange or implant retention may be more feasible, thereby decreasing morbidity and preserving function. In this study, a mouse model of prosthetic joint infection was used in which Staphylococcus aureus was inoculated into a knee joint containing a surgically placed metallic implant extending from the femur. This model was used to evaluate whether combination therapy of vancomycin plus rifampin has increased efficacy compared with vancomycin alone against these infections. On postoperative day 7, vancomycin with or without rifampin was administered for 6 weeks with implant retention. In vivo bioluminescence imaging, ex vivo CFU enumeration, X-ray imaging, and histologic analysis were carried out. We found that there was a marked therapeutic benefit when vancomycin was combined with rifampin compared with vancomycin alone. Taken together, our results suggest that the mouse model used could serve as a valuable in vivo preclinical model system to evaluate and compare efficacies of antibiotics and combinatory therapy for prosthetic joint infections before more extensive studies are carried out in human subjects.
Treatment of prosthetic joint infections often involves a two-stage exchange, with implant removal and antibiotic spacer placement followed by systemic antibiotic therapy and delayed reimplantation. However, if antibiotic therapy can be improved, one-stage exchange or implant retention may be more feasible, thereby decreasing morbidity and preserving function. In this study, a mouse model of prosthetic joint infection was used in which Staphylococcus aureus was inoculated into a knee joint containing a surgically placed metallic implant extending from the femur. This model was used to evaluate whether combination therapy of vancomycin plus rifampin has increased efficacy compared with vancomycin alone against these infections. On postoperative day 7, vancomycin with or without rifampin was administered for 6 weeks with implant retention. In vivo bioluminescence imaging, ex vivo CFU enumeration, X-ray imaging, and histologic analysis were carried out. We found that there was a marked therapeutic benefit when vancomycin was combined with rifampin compared with vancomycin alone. Taken together, our results suggest that the mouse model used could serve as a valuable in vivo preclinical model system to evaluate and compare efficacies of antibiotics and combinatory therapy for prosthetic joint infections before more extensive studies are carried out in human subjects.Treatment of prosthetic joint infections often involves a two-stage exchange, with implant removal and antibiotic spacer placement followed by systemic antibiotic therapy and delayed reimplantation. However, if antibiotic therapy can be improved, one-stage exchange or implant retention may be more feasible, thereby decreasing morbidity and preserving function. In this study, a mouse model of prosthetic joint infection was used in which Staphylococcus aureus was inoculated into a knee joint containing a surgically placed metallic implant extending from the femur. This model was used to evaluate whether combination therapy of vancomycin plus rifampin has increased efficacy compared with vancomycin alone against these infections. On postoperative day 7, vancomycin with or without rifampin was administered for 6 weeks with implant retention. In vivo bioluminescence imaging, ex vivo CFU enumeration, X-ray imaging, and histologic analysis were carried out. We found that there was a marked therapeutic benefit when vancomycin was combined with rifampin compared with vancomycin alone. Taken together, our results suggest that the mouse model used could serve as a valuable in vivo preclinical model system to evaluate and compare efficacies of antibiotics and combinatory therapy for prosthetic joint infections before more extensive studies are carried out in human subjects.
Classifications Services AAC Citing Articles Google Scholar PubMed Related Content Social Bookmarking CiteULike Delicious Digg Facebook Google+ Mendeley Reddit StumbleUpon Twitter current issue AAC About AAC Subscribers Authors Reviewers Advertisers Inquiries from the Press Permissions & Commercial Reprints ASM Journals Public Access Policy AAC RSS Feeds 1752 N Street N.W. • Washington DC 20036 202.737.3600 • 202.942.9355 fax • journals@asmusa.org Print ISSN: 0066-4804 Online ISSN: 1098-6596 Copyright © 2014 by the American Society for Microbiology.   For an alternate route to AAC .asm.org, visit: AAC       
Author Romela Irene Ramos
Jonathan H. Shahbazian
Jared A. Niska
Lloyd S. Miller
Nicholas M. Bernthal
Kevin P. Francis
Author_xml – sequence: 1
  givenname: Jared A.
  surname: Niska
  fullname: Niska, Jared A.
  organization: Orthopaedic Hospital Research Center, Orthopaedic Hospital Department of Orthopaedic Surgery, David Geffen School of Medicine at University of California, Los Angeles, Los Angeles, California, USA
– sequence: 2
  givenname: Jonathan H.
  surname: Shahbazian
  fullname: Shahbazian, Jonathan H.
  organization: Department of Dermatology, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA
– sequence: 3
  givenname: Romela Irene
  surname: Ramos
  fullname: Ramos, Romela Irene
  organization: Department of Medicine, David Geffen School of Medicine at University of California, Los Angeles, Los Angeles, California, USA
– sequence: 4
  givenname: Kevin P.
  surname: Francis
  fullname: Francis, Kevin P.
  organization: Caliper, a PerkinElmer Company, Alameda, California, USA
– sequence: 5
  givenname: Nicholas M.
  surname: Bernthal
  fullname: Bernthal, Nicholas M.
  organization: Orthopaedic Hospital Research Center, Orthopaedic Hospital Department of Orthopaedic Surgery, David Geffen School of Medicine at University of California, Los Angeles, Los Angeles, California, USA
– sequence: 6
  givenname: Lloyd S.
  surname: Miller
  fullname: Miller, Lloyd S.
  organization: Department of Dermatology, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA
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Keywords Drug combination
Peptides
Prosthesis
Treatment efficiency
Diseases of the osteoarticular system
Arthritis
Vancomycin
Infection
Antibiotic
Rifampicin
Glycopeptide
Polypeptide
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Staphylococcal infection
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Treatment of prosthetic joint infections often involves a two-stage exchange, with implant removal and antibiotic spacer placement followed by systemic...
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SubjectTerms Animals
Anti-Bacterial Agents
Anti-Bacterial Agents - administration & dosage
Anti-Bacterial Agents - therapeutic use
Antibiotics. Antiinfectious agents. Antiparasitic agents
Bacterial diseases
Biological and medical sciences
Diseases of the osteoarticular system
Drug Therapy, Combination
Experimental Therapeutics
Human bacterial diseases
Infectious diseases
Male
Medical sciences
Mice
Mice, Inbred C57BL
Miscellaneous. Osteoarticular involvement in other diseases
Pharmacology. Drug treatments
Prosthesis-Related Infections
Prosthesis-Related Infections - drug therapy
Rifampin
Rifampin - administration & dosage
Rifampin - therapeutic use
Staphylococcal Infections
Staphylococcal Infections - drug therapy
Staphylococcal infections, streptococcal infections, pneumococcal infections
Staphylococcus aureus
Staphylococcus aureus - drug effects
Staphylococcus aureus - pathogenicity
Vancomycin
Vancomycin - administration & dosage
Vancomycin - therapeutic use
Title Vancomycin-Rifampin Combination Therapy Has Enhanced Efficacy against an Experimental Staphylococcus aureus Prosthetic Joint Infection
URI http://aac.asm.org/content/57/10/5080.abstract
https://www.ncbi.nlm.nih.gov/pubmed/23917317
https://journals.asm.org/doi/10.1128/AAC.00702-13
https://www.proquest.com/docview/1433274198
https://www.proquest.com/docview/1443379258
https://pubmed.ncbi.nlm.nih.gov/PMC3811477
Volume 57
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