OASIS Pooled Results: Omadacycline Safe and Efficacious in IVDU and non-IVDU
Investigators have presented the microbiological, efficacy, and safety results in the pooled intravenous drug use vs non-intravenous drug use patients in 2 phase 3 ABSSSI studies, OASIS-1 and 2.
Infections among patients who have a history of intravenous drug use (IVDU) are becoming more common and can present challenges to clinicians treating this population.
Omadacycline, a modern tetracycline with activity against a broad spectrum of bacteria including gram-positive, gram-negative, and drug-resistant strains, was approved by the US Food and Drug Administration in October 2018 for the treatment of both community-acquired bacterial pneumonia and acute skin and skin structure infections (ABSSSI). The antibiotic is permitted for once-daily intravenous (IV) and oral use.
In a presentation at the ASM/ESCMID Conference on Drug Development to Meet the Challenge of Antimicrobial Resistance, investigators presented the microbiology, efficacy, and safety results in the pooled IVDU vs non-IVDU patients in 2 phase 3 ABSSSI studies, OASIS-1 and 2.
The OASIS-1 study enrolled 655 patients who were randomized 1:1 to receive 100 mg of omadacycline IV every 12 hours twice followed by 100 mg of omadacycline IV every 24 hours, or to receive 600 mg of linezolid IV every 12 hours. After at least 3 days of therapy, patients could transition to 300 mg of oral omadacycline every 24 hours or 600 mg of oral linezolid every 12 hours.
In the OASIS-2 study, 735 patients were randomized 1:1 to receive either 450 mg of omadacycline orally every 24 hours for 2 doses, and then 300 mg of omadacycline orally every 24 hours or to receive 600 mg of linezolid 600 orally every 12 hours.
Duration of treatment was 7-14 days in both OASIS studies. The investigators evaluated efficacy 48 to 72 hours after the first dose, which is reported as early clinical response based upon the reduction of lesion size by at least 20%. The investigators also assessed efficacy 7 to 14 days following the last dose, which is reported as post therapy evaluations based on the investigators’ assessment of clinical response.
The research team also calculated 2-sided 95% confidence intervals for the difference between early clinical response and post therapy evaluations.
The investigators report that in OASIS-1 and 2, 820 IVDU and 527 non-IVDU patients were enrolled into the modified intent-to-treat population. Furthermore, wound infections were more frequently documented in IDCU patients (66%) and cellulitis/erysipelas was reported more often in non-IVDU patients (56%).
The most frequently isolated pathogens were gram-positive aerobes (82% vs 87%) and Staphylococcus aureus (66% vs 67%) in IVDU vs non-IVDU patients, respectively.
The investigators report that “early clinical response successes for omadacycline vs linezolid in IVDU patients was 87.4% vs 85.2% [D (difference) 2.2, 95% CI: -2.5, 7.0] and in non-IVDU was 84.4% VS 81.9% [D 2.5, 95% CI: -4.0, 8.9]. Post treatment efficacy successes for omadacycline vs linezolid in IVDU patients was 80.7% vs 80.0% [D 0.6, 95% CI: -4.8, 6.1] and in non-IVDU patients was 92.0% vs 85.3% [D 6.7, 95% CI: 1.2, 12.3].”
Overall, higher rates of treatment-emergent adverse events were observed in patients with IVDU patients (omadacycline 56.4%, linezolid 46.0%) vs non-IVDU patients (omadacycline 43.2%, linezolid 43.2%).
Rates of nausea and vomiting were found to be higher in omadacycline-treatment IVDU patients (26.3% and 14.1%) compared with omadacycline-treated non IVDU patients (15.4% and 7.5%)
The authors conclude that “S aureus is common in IVDU and non-IVDU ABSSSI and omadacycline showed similar efficacy and safety in IVDU and non-IVDU ABSSSI patients.”
The study, "Omadacycline Treatment of Acute Bacterial Skin and Skin Structure Infections in Intravenous Drug Users," was presented on Wednesday, September 4, 2019, at ASM ESCMID in Boston, Massachusetts.