Clinical Experience with Omadacycline for the Treatment of Diabetic Foot Infections and Acute Osteomyelitis

Diabetic foot infections (DFIs), frequently complicated by acute osteomyelitis (AOM), are associated with substantial morbidity and are increasingly difficult to manage due to antimicrobial resistance and treatment-related toxicities. Omadacycline is a broad-spectrum aminomethylcycline with favorable safety characteristics and oral bioavailability, but real-world data in DFI and AOM are limited. We conducted a prospective, open-label, two-center study evaluating omadacycline for hospitalized adults with moderate-to-severe DFI with or without AOM who were at high risk for adverse events from standard therapy. Outcomes were compared with a 2:1 matched historical cohort treated with standard of care. The primary endpoint was clinical success at end of therapy (EOT); secondary endpoints included clinical success at test-of-cure (TOC), safety outcomes, and healthcare utilization. A TOTAL OF 14 patients received omadacycline and were matched to 28 historical controls. AOM was present in 64.3% of patients in both groups, while systemic inflammatory response syndrome was more common in the omadacycline group. Clinical success at EOT was achieved in 90% of omadacycline-treated patients versus 85.7% of controls (p = 0.999). TOC success rates were similar (60% vs. 64.3%, p = 0.999). All omadacycline patients transitioned to oral therapy and none required central venous catheter placement, compared with 71.4% of controls (p < 0.001). Serious adverse drug events occurred in no omadacycline patients versus 25% of controls. In this real-world analysis, there was no observed difference in efficacy between omadacycline and standard care for DFI, including cases complicated by AOM, with few adverse events observed. These findings support continued evaluation and potential use of omadacycline in treating select patients with DFIs. ClinicalTrials.gov identifier, NCT04714411. Diabetic foot infections are common complications of diabetes and can result in substantial illness, particularly when the infection involves bone, known as acute osteomyelitis. Treatment may be challenging in patients who are at increased risk for adverse effects from standard antibiotic therapies or who require prolonged intravenous treatment. Omadacycline is a broad-spectrum antibiotic that can be administered orally, potentially allowing treatment without the need for intravenous access. However, clinical experience with omadacycline for diabetic foot infections remains limited. This study evaluated the effectiveness and safety of omadacycline in hospitalized adults with moderate-to-severe diabetic foot infections, with or without acute osteomyelitis, who were considered at high risk for adverse events from standard treatment. A total of 14 patients treated prospectively with omadacycline were compared with 28 similar patients who had previously received standard-of-care antibiotics. Acute osteomyelitis was present in approximately two-thirds of patients in both groups. Clinical outcomes were similar between treatment groups. At the end of therapy, clinical success was achieved in 90% of patients receiving omadacycline compared with 85.7% of those receiving standard care. At follow-up after treatment, clinical success was also similar (60% vs. 64.3%). All patients treated with omadacycline were able to transition to oral therapy, and none required placement of a central venous catheter, compared with 71.4% of patients receiving standard care. Serious adverse drug events occurred in none of the omadacycline-treated patients compared with 25% of patients receiving standard care. These early real-world findings suggest that omadacycline may be a useful treatment option for select patients with diabetic foot infections, including those with acute osteomyelitis. Larger comparative studies are needed to further evaluate the effectiveness and safety of omadacycline in this population.