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Oral rifampin plus azithromycin or clarithromycin to treat osteomyelitis in rabbits
M E Shirtliff1, J T Mader, J Calhoun
1Department of Internal Medicine, University of Texas Medical Branch, Galveston 77555-1019, USA.
Abstract:
A rabbit model for Staphylococcus aureus osteomyelitis was used to compare 28-day combination antibiotic therapy using oral rifampin (40 mg/kg, twice daily) plus oral azithromycin (50 mg/kg, once per day), oral clarithromycin (80 mg/kg, twice daily), or parenteral nafcillin (30 mg/kg, four times daily). The left tibial metaphysis of New Zealand White rabbits was infected with Staphylococcus aureus. Grades 3 to 4 osteomyelitis (according to the Cierny-Mader classification system) development in the rabbits was confirmed radiographically. After antibiotic therapy regimens of 28 days, all tibias from controls that were infected but left untreated (n = 10) revealed positive cultures for Staphylococcus aureus at a mean concentration of 2.8 x 10(4) colony forming units/g bone. The rifampin plus clarithromycin (n = 15) and rifampin plus azithromycin (n = 15) groups showed significantly lower percentages of positive Staphylococcus aureus infection (20% and 13.3%, respectively) and bacterial concentrations (3.5 x 10(1) and 1.75 x 10(1) colony forming units/g bone, respectively). The osteomyelitic tibias of the nafcillin plus rifampin treated group (n = 7) showed no detectable Staphylococcus aureus infection (significantly lower than controls). The differences observed for bone bacterial concentrations and sterilization percentages between the antibiotic treated groups were not statistically significant. Although fluoroquinolones (including ofloxacin and ciprofloxacin) are the agents usually prescribed with rifampin, increasing resistance has been observed. Although macrolides traditionally are not used in the treatment of osteomyelitis, the results of this study indicate that azithromycin and clarithromycin may be attractive partners for rifampin for the treatment of Staphylococcus aureus osteomyelitis in humans.
Insights
Rifampin combined with azithromycin or clarithromycin effectively treated Staphylococcus aureus osteomyelitis in rabbits. This macrolide combination therapy shows promise for treating bone infections, offering alternatives to traditional treatments.
Area of Science:
- Infectious Diseases
- Pharmacology
- Orthopedic Surgery
Background:
- Staphylococcus aureus is a leading cause of osteomyelitis.
- Rifampin is a key component in treating osteomyelitis, but resistance to fluoroquinolones, often used with rifampin, is increasing.
- Macrolides like azithromycin and clarithromycin are not traditionally used for osteomyelitis.
Purpose of the Study:
- To evaluate the efficacy of 28-day combination antibiotic therapy for Staphylococcus aureus osteomyelitis in a rabbit model.
- To compare rifampin combined with azithromycin, clarithromycin, or nafcillin against untreated controls.
Main Methods:
- A rabbit model of Staphylococcus aureus osteomyelitis was established in the tibial metaphysis.
- Rabbits received 28-day combination therapy: oral rifampin plus oral azithromycin, oral clarithromycin, or parenteral nafcillin.
- Radiographic confirmation of osteomyelitis (Grades 3-4) and post-treatment bone cultures were performed.
Main Results:
- Untreated controls showed high bacterial concentrations (2.8 x 10(4) CFU/g bone).
- Rifampin plus clarithromycin and rifampin plus azithromycin groups had significantly lower infection rates (20% and 13.3%) and bacterial loads.
- Rifampin plus nafcillin achieved sterile bone, but differences between treated groups were not statistically significant.
Conclusions:
- Combination therapy with rifampin and macrolides (azithromycin or clarithromycin) significantly reduced bacterial burden in Staphylococcus aureus osteomyelitis.
- These macrolide combinations demonstrate potential as effective treatments for human osteomyelitis.
- This study suggests azithromycin and clarithromycin as viable alternatives when combined with rifampin for Staphylococcus aureus osteomyelitis.