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Rifampin-Based Combination Therapy Is Active in Foreign-Body Osteomyelitis after Prior Rifampin Monotherapy
Cassandra L Brinkman1, Suzannah M Schmidt-Malan1, Jayawant N Mandrekar2
1Division of Clinical Microbiology, Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, Minnesota, USA.
Abstract:
Staphylococcal prosthetic joint infections (PJIs) are associated with biofilm formation, making them difficult to treat; if managed with debridement and implant retention, rifampin-based therapy is usually employed. Rifampin resistance potentially challenges PJI treatment. In investigating the effects of rifampin monotherapy on methicillin-resistant Staphylococcus aureus (MRSA) foreign-body osteomyelitis in rats, we previously demonstrated that rifampin resistance was selected but that it disappeared 14 days following rifampin monotherapy (1) and that rifampin resistance occurred less frequently following two rounds than following one round of rifampin monotherapy (2). Here, we compared rifampin monotherapy followed by rifampin-vancomycin combination therapy to rifampin-vancomycin combination therapy alone in experimental MRSA foreign-body osteomyelitis. Animals treated with rifampin monotherapy followed by rifampin-vancomycin combination therapy had decreased quantities of bacteria 14 days following treatment completion (P = 0.034) compared to those in animals treated with combination therapy alone. Additionally, some isolates recovered from animals treated with combination therapy alone, although still susceptible to rifampin, had higher MIC, minimum biofilm-inhibitory concentration (MBIC), and minimum biofilm-bactericidal concentration (MBBC) values than those of the inoculating strain. This suggests that rifampin may remain a feasible treatment option in foreign-body-associated orthopedic infections following the selection of rifampin resistance.
Insights
Rifampin-vancomycin combination therapy, following initial rifampin monotherapy, reduced bacterial load in MRSA osteomyelitis models. This suggests rifampin remains viable for prosthetic joint infections despite resistance development.
Area of Science:
- Infectious Diseases
- Orthopedic Surgery
- Microbiology
Background:
- Staphylococcal prosthetic joint infections (PJIs) are challenging due to biofilm formation.
- Rifampin is a key component in treating PJIs with debridement and implant retention.
- Rifampin resistance is a significant concern for PJI treatment efficacy.
Purpose of the Study:
- To compare rifampin monotherapy followed by rifampin-vancomycin combination therapy against rifampin-vancomycin combination therapy alone.
- To evaluate the effectiveness of different rifampin-based treatment strategies in a methicillin-resistant Staphylococcus aureus (MRSA) foreign-body osteomyelitis rat model.
- To assess the impact of prior rifampin exposure on treatment outcomes and resistance profiles.
Main Methods:
- Experimental MRSA foreign-body osteomyelitis was established in rats.
- Two treatment arms were compared: (1) rifampin monotherapy followed by rifampin-vancomycin combination therapy, and (2) rifampin-vancomycin combination therapy alone.
- Bacterial quantities were measured 14 days post-treatment completion.
Main Results:
- Animals receiving rifampin monotherapy followed by combination therapy showed significantly decreased bacterial quantities (P = 0.034) compared to those receiving combination therapy alone.
- Some isolates from the combination therapy alone group exhibited increased MIC, MBIC, and MBBC values, despite remaining rifampin-susceptible.
- These findings indicate a potential benefit of sequential therapy in reducing bacterial burden.
Conclusions:
- Sequential rifampin-vancomycin therapy may be more effective than vancomycin combination therapy alone in reducing bacterial load in MRSA osteomyelitis.
- Rifampin may retain its therapeutic utility in foreign-body-associated orthopedic infections, even after the selection of rifampin resistance.
- Further investigation into optimal treatment strategies for PJI is warranted.
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