Oral dosing of omadacyline or linezolid was found equally efficacious to intravenous administration in treating acute bacterial skin and skin structure infections (ABSSSI) in a post hoc analysis of two trials that compared safety and efficacy of the 2 antibiotics.1
"Oral therapy can reduce the need for hospitalization or the length of stay for patients who are admitted, which are major drivers in the high costs associated with treating skin infections," observe George Rodriguez, PharmD, Division of Antimicrobial Stewardship, New York Presbyterian Queens, Flushing, NY, and colleagues.
To compare efficacy of oral to intravenous forms of the same antibiotic in treating ABSSSI, Rodriguez and colleagues conducted a post-hoc analysis of data from the OASIS-1 and Oasis-2 trials which had compared safety and efficacy of both dosage forms of omadacycline and linezolid.
Outcomes for a total of 645 inpatients with ABSSSI initially treated with intravenous antibiotic, were compared to those in 735 who had started with oral dosage. Most had solely gram-positive infections (97% in each group). The primary endpoint was early clinical response (ECR), defined as survival and ≥20% reduction in lesion size at 48 to 72 hours without rescue antibacterial therapy or unplanned surgical procedures.
Rodriquez and colleagues report ECR was attained in 85.2% of the IV-start group and 85.0% of the oral-start group.The incidence of treatment-emergent adverse events was similar between the groups; and discontinuation due to adverse event was infrequent in both groups.
Although the 2014 Infectious Disease Society of America (IDSA) guidelines for management of skin and soft tissue infections recommend intravenous antibiotics when there is concern about systemic infection and inflammatory response, the investigators were able to compare efficacy of oral and intravenous forms in multiple treatment settings because of the bioequivalence of both dosage forms of the two antibiotics.
Rodriguez and colleagues acknowledge limits on generalizing from this comparison, however, to other intravenous vs oral antibiotics that potentially cover the targeted pathogen at sufficiently high concentrations.
"Appropriate oral therapy is a challenge, as current guideline-recommended oral treatments do not fully cover the most common skin pathogens," Rodriguez and colleagues indicate. "Complex dosing based upon patient characteristics and comorbidities and lower bioavailability may also be contributing factors to the observed treatment failure."
Rodriguez elaborated on the complexities of finding oral therapy as efficacious as intravenous for ABSSSI, in discussing the study with Contagion.
"Beyond spectrum of activity, it would be appropriate to ensure that the local susceptibilities to the chosen antibiotic are above 85 to 90% for the likely pathogens, the pharmacokinetics of the oral agent are suitable, and the patient is likely to adhere to the prescribed medication regimen and any determined follow-up," Rodriguez said.
What You Need to Know
The post-hoc analysis of the OASIS-1 and OASIS-2 trials showed that oral administration of omadacycline or linezolid is equally efficacious as intravenous (IV) administration for treating acute bacterial skin and skin structure infections (ABSSSI), with early clinical response rates of 85.0% for oral therapy and 85.2% for IV therapy.
Oral antibiotics can minimize hospitalizations or shorten hospital stays, addressing major cost drivers in treating ABSSSI.
The study highlighted that not all oral antibiotics are suitable replacements for IV options due to factors like lower bioavailability, patient adherence, and variability in pathogen susceptibility.
Rodriguez suggested a particular patient population for whom an oral antibiotic regimen might be prioritized."Potentially one patient population to consider are the patients presenting to our emergency departments and are subsequently admitted with a skin and soft tissue infection.
"Admissions are largely multifactorial but regardless of the infection characteristics and antibiotic history, these patients commonly receive IV therapy," Rodriguez observed."We need to unlink the practice of giving IV antibiotic to patients hospitalized with an infection to the use of IV or oral antibiotic therapy is based solely on the clinical characteristics of the patient and infection."
The investigators concluded that the post-hoc analysis demonstrated that oral therapy is equally efficacious to IV therapy for ABSSSI when a potent and bioequivalent agent such as omadacycline or linezolid is the selected therapy.
Rodriguez pointed out that since the 2014 IDSA guidelines, multiple studies with new agents have provided evidence of efficacy, particularly for a subset of patients with moderate or severe cellulitis.
"As such, there is an opportunity to further increase utilization of appropriate oral antibiotics, which have been associated with reduced healthcare resource utilization and adverse effects associated with IV therapy and increased quality of life," Rodriguez said.
Reference
1.Rodriguez GD, Warren N, Yashayev R, et al. Intravenous versus oral omadacyline or linezolid for acute bacterial skin and skin infections: A post-hoc analysis of the OASIS Trials. Infect Dis Ther 2024; 12:2637-2648.
