SLR - February 2020 - Dixon H. Xu

Adjunctive Rifampin Therapy for Diabetic Foot Osteomyelitis in the Veterans Health Administration

Reference: Wilson BM, Bessesen MT, Doros G, Brown ST, Saade E, Hermos J, Perez F, Skalweit M, Spellberg B, Bonomo RA. Adjunctive Rifampin Therapy for Diabetic Foot Osteomyelitis in the Veterans Health Administration. JAMA Netw Open. 2019 Nov 1;2(11):e1916003.

Scientific Literature Review

Reviewed By: Dixon H. Xu, DPM
Residency Program: Scripps Mercy Kaiser Hospital – San Diego, CA

Podiatric Relevance: About 20-60 percent of all diabetic foot infections involve bone and result in a four-fold increased risk of lower extremity amputations. It is one of the most common conditions a podiatric physician treats in his or her career. Current antibiotic therapy for osteomyelitis from diabetic foot infections vary greatly. Rifampin is commonly prescribed in Europe for osteomyelitis for its ability to penetrate biofilms and osteoblasts while retaining intra-cellular antimicrobial activities. It has been shown in previous literature that the addition of rifampin as an adjunctive therapy showed reduced relapse rates from chronic osteomyelitis. In this study, the authors theorize that the use of rifampin as an adjunctive therapy for osteomyelitis from diabetic foot infection would result in a lower rate of amputations or mortalities.

Methods: The VA Northeast Ohio Healthcare System institutional review board approved the study. This is an observational cohort study including cases of diabetic foot or ankle osteomyelitis from January 2, 2009 to December 31, 2013. Patients initiating rifampin within six weeks of the diagnosis of osteomyelitis with a minimum therapy duration of 14 days within 90 days of diagnosis were included in the analysis. Patients who did not receive rifampin within 90 days after diagnosis of osteomyelitis were served as the comparator group. A combined end point of mortality or amputation within two years of diagnosis of osteomyelitis was analyzed. Differences in times to event were evaluated using long-rank tests and differences in event rates were compared using multivariable logistic regression.

Results: A significantly lower rate of a combined amputation or mortality end point was noted in the rifampin-treated group at 26.9 percent, compared to that of the group without rifampin therapy at 37 percent within two years after the diagnosis of osteomyelitis. Rifampin was most commonly combined with fluoroquinolones (47.7 percent), tetracyclines (28.5 percent), sulfa or trimethoprim (20.8 percent) and vancomycin (15.4 percent). Patients receiving rifampin therapy were also younger, had fewer medical comorbidities and more infectious disease involvement compared to the group without rifampin therapy.

Conclusions: This study showed that patients who have osteomyelitis from diabetic foot infections experienced a lower rate of death and lower extremity amputations than patients not treated with rifampin within two years of the diagnosis. Nonetheless, this same group of patients were also younger, had fewer medical comorbidities, more infectious disease specialty involvement with Staphylococcus aureus being the most common organism. These are confounding variables complicating the data analysis and results interpretation. One should interpret these results with caution, and not jump to the conclusion that rifampin should be considered in all cases of diabetic foot osteomyelitis, as this medication has multiple drug-drug interactions, which may in turn explain why the treatment group were younger and had fewer comorbidities. In a relatively younger and healthier population diagnosed with diabetic foot osteomyelitis, however, rifampin may have its implication in improving outcomes of limb salvage.

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