Penetration of Parenterally Administered Rifampicin into Bone Tissue

Roth, Bianca

doi:10.1159/000238294

Cited by 26 publications

(15 citation statements)

References 11 publications

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“…In child cases, administration of the recommended dose of 10-12 mg/kg/day of rifampicin achieved maximum serum concentrations of 3.3-3.8 pg/ ml [16,26]. In another study, 3 h after intravenous infusion of 600 mg rifampicin, the drug concentrations in the bone reached 1.4-8.8 pg/g [24]. These studies indicate that the range of drug concentrations which occurs clinically in serum and bone overlaps the concentrations of rifampicin which, in the present study, had significant inhibitory effects on osteoblasts.…”

Section: Discussionmentioning

confidence: 99%

Toxic effect of rifampicin on human osteoblast‐like cells

Isefuku

Joyner

Simpson

2001

Journal Orthopaedic Research

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We examined the effects of rifampicin on osteoblast-like cells derived from adult human bone in vitro. Cancellous bone was collected from five different individuals during elective orthopaedic operations and cultured in antibiotic-free media. Total DNA, 'H-thymidine incorporation and alkaline phosphatase (ALP) activity were measured after the cells were cultured for 4 days in media containing concentrations of rifampicin ranging from 0 to 1000 pg/ml. Mean total DNA was decreased at concentrations of 10 pglml and above in the cultures obtained from four out of five individuals but these decreases were significant in the cultures from only two individuals. 'H-thymidine incorporation, a more sensitive indicator of change in cell proliferation, and ALP activity were significantly decreased ( P < 0.05) in all of the cultures containing 3 and 7 pginil, respectively. In the clinical setting, serum concentrations of rifampicin often exceed 10 pglml after systemic administration. The present study has shown that rifampicin, at these concentrations. can inhibit the proliferation of osteoblast-like cells in vitro. Further studies should be carried out to assess whether rifampicin is detrimental to the bone repair process in vivo.

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Section: Discussionmentioning

confidence: 99%

Toxic effect of rifampicin on human osteoblast‐like cells

Isefuku

Joyner

Simpson

2001

Journal Orthopaedic Research

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“…For the following incubation for 20h or 40h at 37°C and 5% CO 2 10 μg/ml tigecyclin, 10 μg/ml gentamicin, 7 μg/ml rifampicin or the combinations tigecyclin/gentamicin or tigecyclin/rifampicin are added. The antibiotic concentrations were chosen according to high level doses that can be reached after intravenous application in serum and tissue [31-33]. Both S .…”

Section: Methodsmentioning

confidence: 99%

Therapy of intracellular Staphylococcus aureus by tigecyclin

et al. 2013

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BackgroundIn the fields of traumatology and orthopaedics staphylococci are the most frequently isolated pathogens. Staphylococcus aureus and Staphylococcus epidermidis are known to be the major causative agents of osteomyelitis. The increasing number of multiresistant Staphylococcus aureus and resistant coagulase-negative staphylococci as a trigger of complicated osteomyelitis and implant-associated infections is a major problem. Antibiotic therapy fails in 20% of cases. Therefore the development of novel antibiotics becomes necessary.MethodsThis study analyses tigecyclin, the first antibiotic of the glycylines, as a potential therapy for osteomyelitis caused by multiresistant Staphylococcus aureus. Therefore its intracellular activity and the potential use in polymethylmetacrylate-bone cement are examined. The intracellular activity of tigecyclin is determined by a human osteoblast infection model. The investigation of the biomechanical characteristics is conducted concerning the ISO 5833-guidelines.ResultsTigecyclin shows in vitro an intracellular activity that ranges between the antimicrobial activity of gentamicin and rifampicin. A significant negative effect on the biomechanical characteristics with an impaired stability is detected after adding tigecyclin to polymethylmetacrylate-bone cement with a percentage of 1.225% per weight.ConclusionsThis study shows that tigecyclin might be a potent alternative for the systemic therapy of osteomyelitis and implant-associated infections whereas the local application has to be reconsidered individually.

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“…Several studies shown that after oral administration of rifampicin, the rifampicin concentration in bone and in the joint tuberculosis focus was lower than the effective bactericidal concentration (Roth, 1984;Widmer et al, 1992;Mahajan et al, 1997;Zimmerli et al, 1998;Isefuku et al, 2001). Therefore, the topical application of rifampicin on tuberculosis foci has been considered as an approach worth investigating.…”

Section: Introductionmentioning

confidence: 99%

Effects of rifampicin on osteogenic differentiation and proliferation of human mesenchymal stem cells in the bone marrow

et al. 2014

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ABSTRACT. This study was designed to investigate the effect of different concentrations of rifampicin on osteogenic differentiation and proliferation of mesenchymal stem cells (MSCs) in human bone marrow. Rifampicin treatment at 0, 4, 8, 16, 32, 64, and 128 mg/mL was applied throughout the whole process, from stromal cells purified from human bone marrow to differentiated bone cells. The effect of rifampicin on MSC proliferation was determined using the MTT assay. The effect of rifampicin on the expressions of type I collagen (COL1A1), osteopontin/ bone Gla protein (OPN/BGP), and alkaline phosphatase (ALP) in human osteoblast cells were determined by real-time polymerase chain reaction, and the expressions of COL1A1, OPN/BGP, and the runt-related transcription factor (RUNX2) were determined by Western blot. Results showed that the proliferation of MSCs was significantly inhibited when the rifampicin concentration exceeded 32 mg/mL. In addition, increased rifampicin concentrations inhibited the formation of calcium nodules, OPN/BGP, and COL1A1 in osteoblasts after 28 days of induction. The RNA expressions of OPN/BGP, COL1A1, and ALP were significantly downregulated compared to those of the control group in osteoblasts 6399 ©FUNPEC-RP www.funpecrp.com.br Genetics and Molecular Research 13 (3): 6398-6410 (2014) Rifampicin and MSC proliferation and differentiation after induction. The protein expressions of RUNX2, COL1A1, and OPN/BGP were also significantly downregulated compared to those of the control group after induction. In conclusion, rifampicin at exorbitant concentration exerts adverse effects on the proliferation of MSCs in human bone marrow and the differentiation of osteoblasts.

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Penetration of Parenterally Administered Rifampicin into Bone Tissue

Cited by 26 publications

References 11 publications

Toxic effect of rifampicin on human osteoblast‐like cells

Toxic effect of rifampicin on human osteoblast‐like cells

Therapy of intracellular Staphylococcus aureus by tigecyclin

Effects of rifampicin on osteogenic differentiation and proliferation of human mesenchymal stem cells in the bone marrow

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