Six Versus 4 Week Therapy for Osteomyelitis

According to research presented by Dr. Karim Gariani from the University of Zurich, three and six weeks of therapy give similar incidences of remission in diabetic foot osteomyelitis.

Diabetic foot infections are either bone or soft tissue infections below the malleoli. It is the most common issue that can come from having diabetes. It can lead to being hospitalized, and in more extreme cases, it can lead to amputation of an extremity. The most common pathogen that causes these infections is the staphylococcus species. Osteomyelitis can occur due to diabetic foot infections, which is one reason surgical intervention might be necessary. All patients who have diabetes should get their feet examined at least once a year to determine if ulcers are present. During these examinations, patients can be provided with proper foot care, blood pressure measurement and goals, smoking cessation, and glycemic control.

This trial sought to determine if differences between three and six weeks of antibiotic therapy exist and its impact on patients with diabetic foot infections. Dr. Gariani and her colleagues submitted this research to the Journal of Clinical Infectious Diseases to examine and summarize the benefits in this patient population. The study was an unblinded randomized controlled trial. Enrollment began in January 2017 and ended in October 2019. A total of 346 diabetic foot infections were identified, while 93 were included in the analysis of this study. Eligible patients were older than or equal to 18, diagnosis of diabetes, presence of diabetic foot osteomyelitis, and debridement of tissue. Ineligible patients were those with implants, those who received antibiotic therapy within the last 96 hours, amputation of necrotic tissue, and patients currently with endocarditis. Diabetic foot osteomyelitis was defined according to the Infectious Disease Society of America guidelines to include either microbiological, radiological, or clinical findings. Remission was defined as the absence of clinical and radiological findings after a minimum follow-up of two months. The primary outcome was remission after a follow-up of two months after the end of treatment. The secondary outcome was the incidence of adverse effects in each study arm. Adverse effects were defined as any medical occurrence during participation in the trial.

The results from this study used a binomial categorial, non-inferior design with a statistical significance of 0.05 and a power of 80 percent. For the non-inferior testing, they used a t-test with a confidence interval of 90 percent. The intention-to-treat consisted of all randomized episodes, and the per-protocol included all patients who completed the study. Of the 93 diabetic foot osteomyelitis episodes, 17 occurred in women. Forty-four patients were randomized to the three-week group, while 49 patients were added to the six-week group. They used 47 treatment regimens: augmentin, levofloxacin, clindamycin, co-trimoxazole, doxycycline, and rifampin. There were no differences in the incidences of clinical remission among the three-week group and the six-week group. Remission occurred in 37 of 44 patients in the three-week group and 36 of 49 patients in the six-week group. The number of adverse events that occurred in both groups was similar. These events occurred in 33 of 93 patients, with 14 being severe complications.

In conclusion, more studies should be done to determine how three weeks verse six weeks of antibiotic therapy impacts diabetic foot osteomyelitis. This study helped give more information on whether the duration of treatment truly affects outcomes in this patient population. According to Dr. Gariani, “in patients with diabetic foot osteomyelitis, short-course therapy of post-debridement antibiotic therapy was non-inferior to the standard duration of 6 weeks.” These results suggest the need for more randomized controlled trials to determine the generalizability of the findings. Limitations of this study include the sample size being relatively small. Another limitation of this study is that the follow-up period of two months is short compared to previous studies of 1 year. The third limitation of this study includes those with partial amputations being excluded from this study. Patients with partial amputations could not be adequately quantified. Lastly, 63 microbes cannot individually determine how they impacted the likelihood of remission.

Practice Pearls:

• Diabetic foot infections are either bone or soft tissue infections below the malleoli.
• Osteomyelitis can occur due to diabetic foot infections, which is one reason surgical intervention might be necessary.
• In diabetic foot osteomyelitis, short-course therapy of post-debridement antibiotic treatment was non-inferior to the standard duration of 6 weeks.

References

Gariani, Karim et al. “Three Weeks Versus Six Weeks of Antibiotic Therapy for Diabetic Foot Osteomyelitis: A Prospective, Randomized, Noninferiority Pilot Trial.” Clinical infectious diseases: an official publication of the Infectious Diseases Society of America vol. 73,7 (2021): e1539-e1545. doi:10.1093/cid/ciaa1758 link

 Lipsky, Benjamin A, and İlker Uçkay. “Treating Diabetic Foot Osteomyelitis: A Practical State-of-the-Art Update.” Medicina (Kaunas, Lithuania) vol. 57,4 339. 1 Apr. 2021, doi:10.3390/medicina57040339 link

Kmeone Kingdom, MPH, PharmD Candidate, South College School of Pharmacy