Omadacycline a potential treatment for bacterial skin infections
The aminomethylcycline antibiotic omadacycline is as efficacious as linezolid in treating bacterial skin and skin structure infections, according to the phase III OASIS-1* trial.
Adults with acute bacterial skin or skin-structure infections were randomized to receive intravenous omadacycline (100 mg administered every 12 hours for two doses, followed by 100 mg every 24 hours; n=316, median lesion size 299.5 cm2) or linezolid (600 mg every 12 hours; n=311, median lesion size 315.0 cm2). After 3 days, patients could opt for oral versions of omadacycline (300 mg every 24 hours) or linezolid (600 mg every 12 hours). The total treatment time was 7–14 days.
Patients with a sole gram-negative causative pathogen were excluded from the modified intention-to-treat population. Most patients (71.9 percent) had a monomicrobial gram-positive infection and 11 and nine patients assigned to omadacycline and linezolid, respectively, had bacteraemia.
Patients on omadacycline and linezolid had comparable outcomes in terms of early clinical response (survival with ≥20 percent reduction in lesion size without rescue antibacterial therapy at 48–72 hours after first dose of drug; rate of response, 84.8 percent vs 85.5 percent, difference, -0.7 percentage points, 95 percent confidence interval [CI], -6.3 to 4.9). [N Engl J Med 2019;380:528-538]
Median lesion size reduced by about 50 percent in both groups at day 3, and by 99 percent at treatment end.
Clinical response at the post-treatment evaluation conducted 7–14 days after the last dose, was also similar between omadacycline and linezolid recipients with 86.1 and 83.6 percent of patients, respectively, demonstrating survival with resolution or improvement in infection signs and symptoms with no need for further antibacterial therapy (difference, 2.5 percentage points, 95 percent CI, -3.2 to 8.2).
“The growing proportion of resistant bacterial pathogens presents a challenge to treatment selection,” said the researchers. In this trial, omadacycline and linezolid were efficacious against methicillin-resistant and methicillin-susceptible Staphylococcus aureus infections.
Adverse event (AE) incidence occurred at a similar rate between omadacycline and linezolid recipients (48.3 percent vs 45.7 percent), the most common of which was gastrointestinal AEs (18.0 percent vs 15.8 percent), namely nausea (12.4 percent vs 9.9 percent) and vomiting (5.3 percent vs 5.0 percent). One patient each on omadacycline and linezolid discontinued treatment due to gastrointestinal events. Twenty patients experienced serious AEs, among whom 10 had worsening of their skin or skin-structure infections or developed another infection (eight and two of omadacycline and linezolid recipients, respectively); however, none were deemed treatment-related.
“[T]he efficacy of once-daily omadacycline, administered intravenously with the option to transition to oral administration, was noninferior to that of twice-daily linezolid for the treatment of acute bacterial skin and skin-structure infections,” said the researchers.
However, Professor Henry F. Chambers from the Zuckerberg San Francisco General Hospital and University of California San Francisco, California, US, pointed out that omadacycline may not be superior to other available agents in this setting.
“The oral formulation of omadacycline may offer an advantage in certain circumstances – for example, it could be given instead of linezolid as treatment for the occasional patient receiving monoamine oxidase inhibitor or antiserotonergic antidepressant therapy,” he said in an editorial. [N Engl J Med 2019;380:588-589]
The efficacy of omadacycline against gram-negative pathogens was not ascertained in this trial and should be assessed in future research, he added.
The precise timing of switching from intravenous to oral therapy that would occur at hospital discharge also needs further investigation, noted the researchers.