Comparative activities of vancomycin, tigecycline and rifampin in a rat model of methicillin-resistant Staphylococcus aureus osteomyelitis

Paschalis Vergidis, Suzannah M. Schmidt-Malan, Jayawant Mandrekar, James M. Steckelberg, Robin Patel

Research output: Contribution to journalArticle

16 Citations (Scopus)

Abstract

Objectives: Implant-associated methicillin-resistant Staphylococcus aureus (MRSA) infections are challenging to treat. We compared antimicrobial activities in a rat model of chronic osteomyelitis in the context of retention of the foreign body without débridement. Methods: MRSA was inoculated into the proximal tibia and a wire implanted. Four weeks after infection, treatment with vancomycin 50mg/kg every 12h, tigecycline 14mg/kg every 12h, rifampin 25mg/kg every 12h, or the combination of vancomycin or tigecycline plus rifampin was administered intraperitoneally for 21 days. Results: MRSA was cultured from all tibias in the control group (median, 6.06 log<inf>10</inf>CFU/g bone). Median bacterial counts (log<inf>10</inf> CFU/g) at 48h post-treatment were 6.16 for vancomycin (p=0.753), 2.29 for vancomycin plus rifampin (p<0.001), 5.90 for tigecycline (p=0.270), 0.10 for tigecycline plus rifampin (p<0.001), and 0.91 for rifampin (p=0.044) treatment. Three deaths were observed in the tigecycline plus rifampin group. Median bacterial counts (log<inf>10</inf> CFU/g) at two weeks post-treatment were 5.65 for vancomycin (p = 0.6), 4.05 for vancomycin plus rifampin (p = 0.105), 5.68 for tigecycline (p = 0.401), 4.05 for tigecycline plus rifampin (p = 0.028), and 5.98 for rifampin (p = 0.297) treatment. Conclusions: Tigecycline plus rifampin resulted in a significant bacterial count decrease, an effect more prominent at 48 h than two weeks after treatment completion. Tigecycline was not well tolerated at the dose studied.

Original languageEnglish (US)
Pages (from-to)609-615
Number of pages7
JournalJournal of Infection
Volume70
Issue number6
DOIs
StatePublished - Jun 1 2015

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Osteomyelitis
Vancomycin
Rifampin
Methicillin-Resistant Staphylococcus aureus
Bacterial Load
Tibia
Foreign Bodies
Infection
tigecycline
Bone and Bones
Control Groups

Keywords

  • Osteomyelitis
  • Rifampin
  • Staphylococcus aureus
  • Tigecycline
  • Vancomycin

ASJC Scopus subject areas

  • Microbiology (medical)
  • Infectious Diseases

Cite this

Comparative activities of vancomycin, tigecycline and rifampin in a rat model of methicillin-resistant Staphylococcus aureus osteomyelitis. / Vergidis, Paschalis; Schmidt-Malan, Suzannah M.; Mandrekar, Jayawant; Steckelberg, James M.; Patel, Robin.

In: Journal of Infection, Vol. 70, No. 6, 01.06.2015, p. 609-615.

Research output: Contribution to journalArticle

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title = "Comparative activities of vancomycin, tigecycline and rifampin in a rat model of methicillin-resistant Staphylococcus aureus osteomyelitis",
abstract = "Objectives: Implant-associated methicillin-resistant Staphylococcus aureus (MRSA) infections are challenging to treat. We compared antimicrobial activities in a rat model of chronic osteomyelitis in the context of retention of the foreign body without d{\'e}bridement. Methods: MRSA was inoculated into the proximal tibia and a wire implanted. Four weeks after infection, treatment with vancomycin 50mg/kg every 12h, tigecycline 14mg/kg every 12h, rifampin 25mg/kg every 12h, or the combination of vancomycin or tigecycline plus rifampin was administered intraperitoneally for 21 days. Results: MRSA was cultured from all tibias in the control group (median, 6.06 log10CFU/g bone). Median bacterial counts (log10 CFU/g) at 48h post-treatment were 6.16 for vancomycin (p=0.753), 2.29 for vancomycin plus rifampin (p<0.001), 5.90 for tigecycline (p=0.270), 0.10 for tigecycline plus rifampin (p<0.001), and 0.91 for rifampin (p=0.044) treatment. Three deaths were observed in the tigecycline plus rifampin group. Median bacterial counts (log10 CFU/g) at two weeks post-treatment were 5.65 for vancomycin (p = 0.6), 4.05 for vancomycin plus rifampin (p = 0.105), 5.68 for tigecycline (p = 0.401), 4.05 for tigecycline plus rifampin (p = 0.028), and 5.98 for rifampin (p = 0.297) treatment. Conclusions: Tigecycline plus rifampin resulted in a significant bacterial count decrease, an effect more prominent at 48 h than two weeks after treatment completion. Tigecycline was not well tolerated at the dose studied.",
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AU - Schmidt-Malan, Suzannah M.

AU - Mandrekar, Jayawant

AU - Steckelberg, James M.

AU - Patel, Robin

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N2 - Objectives: Implant-associated methicillin-resistant Staphylococcus aureus (MRSA) infections are challenging to treat. We compared antimicrobial activities in a rat model of chronic osteomyelitis in the context of retention of the foreign body without débridement. Methods: MRSA was inoculated into the proximal tibia and a wire implanted. Four weeks after infection, treatment with vancomycin 50mg/kg every 12h, tigecycline 14mg/kg every 12h, rifampin 25mg/kg every 12h, or the combination of vancomycin or tigecycline plus rifampin was administered intraperitoneally for 21 days. Results: MRSA was cultured from all tibias in the control group (median, 6.06 log10CFU/g bone). Median bacterial counts (log10 CFU/g) at 48h post-treatment were 6.16 for vancomycin (p=0.753), 2.29 for vancomycin plus rifampin (p<0.001), 5.90 for tigecycline (p=0.270), 0.10 for tigecycline plus rifampin (p<0.001), and 0.91 for rifampin (p=0.044) treatment. Three deaths were observed in the tigecycline plus rifampin group. Median bacterial counts (log10 CFU/g) at two weeks post-treatment were 5.65 for vancomycin (p = 0.6), 4.05 for vancomycin plus rifampin (p = 0.105), 5.68 for tigecycline (p = 0.401), 4.05 for tigecycline plus rifampin (p = 0.028), and 5.98 for rifampin (p = 0.297) treatment. Conclusions: Tigecycline plus rifampin resulted in a significant bacterial count decrease, an effect more prominent at 48 h than two weeks after treatment completion. Tigecycline was not well tolerated at the dose studied.

AB - Objectives: Implant-associated methicillin-resistant Staphylococcus aureus (MRSA) infections are challenging to treat. We compared antimicrobial activities in a rat model of chronic osteomyelitis in the context of retention of the foreign body without débridement. Methods: MRSA was inoculated into the proximal tibia and a wire implanted. Four weeks after infection, treatment with vancomycin 50mg/kg every 12h, tigecycline 14mg/kg every 12h, rifampin 25mg/kg every 12h, or the combination of vancomycin or tigecycline plus rifampin was administered intraperitoneally for 21 days. Results: MRSA was cultured from all tibias in the control group (median, 6.06 log10CFU/g bone). Median bacterial counts (log10 CFU/g) at 48h post-treatment were 6.16 for vancomycin (p=0.753), 2.29 for vancomycin plus rifampin (p<0.001), 5.90 for tigecycline (p=0.270), 0.10 for tigecycline plus rifampin (p<0.001), and 0.91 for rifampin (p=0.044) treatment. Three deaths were observed in the tigecycline plus rifampin group. Median bacterial counts (log10 CFU/g) at two weeks post-treatment were 5.65 for vancomycin (p = 0.6), 4.05 for vancomycin plus rifampin (p = 0.105), 5.68 for tigecycline (p = 0.401), 4.05 for tigecycline plus rifampin (p = 0.028), and 5.98 for rifampin (p = 0.297) treatment. Conclusions: Tigecycline plus rifampin resulted in a significant bacterial count decrease, an effect more prominent at 48 h than two weeks after treatment completion. Tigecycline was not well tolerated at the dose studied.

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