126 Efficacy of Omadacycline in the Treatment of Acute Bacterial Skin and Skin Structure Infections in Patients With Cellulitis or Abscesses

Abstract

Patients with acute bacterial skin and skin structure infections (ABSSSI) are often admitted for intravenous (IV) antibiotic administration. Omadacycline (OMC) is a novel aminomethylcycline antibiotic, approved for community-acquired bacterial pneumonia and ABSSSI, with activity against key causative pathogens, notably methicillin-susceptible (MSSA) and resistant (MRSA) Staphylococcus aureus. We report pooled results from a post-hoc analysis in patients with cellulitis/erysipelas or major abscesses who were not people who inject drugs (PWID), from the Omadacycline in Acute Skin and Skin Structure Infections (OASIS)-1 and -2 studies. Patients with ABSSSI were randomized to OMC or linezolid (LZD), both IV-to-oral, in OASIS-1 (NCT02378480); and to once-daily oral OMC or twice-daily oral LZD in OASIS-2 (NCT02877927). Total therapy duration was 7-14 days. Populations included modified intent-to-treat (mITT, randomized patients without a sole Gram-negative pathogen); and micro-mITT (mITT patients with ≥1 identified Gram-positive causative pathogen). Primary endpoint: early clinical response (ECR) in the mITT population (survival with ≥20% reduction in lesion size, 48-72 h after first dose, without rescue therapy). Secondary endpoint: survival with infection resolution/improvement at post-treatment evaluation in the mITT population (PTE; 7-14 days after last dose). Baseline characteristics were generally similar between groups. In the mITT population, 294 patients had cellulitis/erysipelas (148 OMC, 146 LZD); 146 patients had major abscesses (77 OMC, 69 LZD). In the micro-mITT population, S. aureus was the primary baseline pathogen, detected in 111 (76%) of patients with cellulitis/erysipelas and in 94 (76%) of patients with major abscesses (Table). MRSA was detected in 46 (41%) patients with cellulitis/erysipelas and in 56 (60%) patients with major abscesses. ECR was achieved in 117 (79%) patients receiving OMC and 115 (79%) receiving LZD with cellulitis/erysipelas, and in 70 (91%) patients receiving OMC and 61 (88%) receiving LZD with major abscesses; these results were similar for patients who presented at baseline with low/high white blood cell counts, fever, and lesion sizes ≤300 cm2 (Table). Success at PTE was comparable between OMC and LZD across groups. When analyzed by baseline pathogen, high clinical success at PTE was observed with both OMC and LZD in patients with S. aureus for both infection types (cellulitis/erysipelas and major abscesses; Table). There were no new safety signals; nausea and vomiting were the most frequent treatment-emergent adverse events across groups. OMC is a once-daily, IV or oral option for inpatient and outpatient treatment of ABSSSI in patients with cellulitis or major abscesses, including those due to MRSA.TableTreatment efficacy at ECR and PTE in patients with cellulitis/erysipelas or major abscesses from the OASIS-1 and OASIS-2 clinical trials (mITT and micro-mITT populations)Cellulitis/erysipelas (N=294)Major abscess (N=146)OmadacyclineLinezolidDifference (95% CI)OmadacyclineLinezolidDifference (95% CI)mITT, n1481467769Success at ECR; n/N (%)117/148 (79)115/146 (79)0.3% (−9.1, 9.7)70/77 (91)61/69 (88)2.5% (−7.8, 13.4)WBC count ≥10,000 cells/mm3 or ≤4000 cells/mm3, n/N (%)44/60 (73.3)43/55 (78.2)−4.8% (−20.4, 11.1)26/29 (89.7)22/27 (81.5)8.2% (−11.3, 28.4)Fever >38.0°C, n/N (%)35/39 (89.7)32/43 (74.4)15.3% (−1.7, 31.9)17/20 (85.0)15/16 (93.8)-8.8% (−31.6, 16.1)Lesion size 75–300 cm2, n/N (%)63/80 (78.8)58/77 (75.3)3.4% (−9.8, 16.7)50/55 (90.9)43/49 (87.8)3.2% (−9.3, 16.5)Success at PTE, n/N (%)135/148 (94)130/146 (90)4.1% (−2.4, 10.9)68/77 (87)58/69 (81)6.6% (−5.3, 18.9)WBC count ≥10,000 cells/mm3 or ≤4000 cells/mm3, n/N (%)57/60 (95.0)46/55 (83.6)11.4% (0.1, 24.1)24/29 (82.8)22/27 (81.5)1.3% (−19.6, 22.6)Fever >38.0°C, n/N (%)38/39 (97.4)40/43 (93.0)4.4% (−7.1, 16.5)19/20 (95.0)15/16 (93.8)1.3% (−18.9, 24.5)Lesion size 75–300 cm2, n/N (%)75/80 (93.8)69/77 (89.6)4.1% (−4.9, 13.8)50/55 (90.9)38/49 (77.6)13.4% (−0.6, 28.2)Micro-mITT, n64826756Success at PTE by S. aureus baseline pathogen*, n/N (%)48/51 (94)53/60 (88)44/52 (85)31/42 (74)*Success at PTE by MRSA baseline pathogen was achieved by 43/46 (93%) patients with cellulitis/erysipelas, and 42/56 (75%) patients with major abscesses; success at PTE by MSSA baseline pathogen was achieved by 59/66 (89%) patients with cellulitis/erysipelas, and 34/40 (85%) patients with major abscesses. Open table in a new tab