Rapid Clinical Updates: Striving for Oral Stepdown: Novel Agents and Strategies for Avoiding OPAT-Slides

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The presentation "Striving for Oral Stepdown: Novel Agents and Strategies for Avoiding OPAT" by Drs. Jose Mercado and Reinaldo Perez focuses on evolving therapeutic approaches to reduce reliance on outpatient parenteral antibiotic therapy (OPAT) for severe infections. Historically, prolonged IV antibiotics were standard but carry risks such as line-associated complications, logistical challenges, high costs, and monitoring burdens.<br /><br />Key strategies highlighted include the use of antibiotics with high oral bioavailability and long half-lives, which simplify dosing, reduce the need for vascular access, and minimize antibiotic resistance through improved adherence and controlled drug levels. The importance of appropriate patient selection for oral stepdown is emphasized, particularly by considering gut absorption, presence of prosthetic material, immune status, and drug properties like bioavailability and tissue penetration.<br /><br />Long-acting infusions such as dalbavancin and oritavancin offer effective alternatives with evidence supporting their efficacy and safety. Dalbavancin demonstrated non-inferiority to standard care for complicated Staphylococcus aureus bloodstream infections and right-sided endocarditis in the DOTS trial, with similar or fewer adverse events. However, economic benefits over standard care are unclear. Oritavancin also showed comparable efficacy to vancomycin, reduced adverse events, and decreased 30-day readmissions and ER visits.<br /><br />New oral agents discussed include tedizolid, omadacycline, and sulopenem (recently FDA approved for uncomplicated cystitis). Tedizolid offers improved tolerability over linezolid but has poor CNS penetration. Omadacycline showed noninferiority to linezolid for skin infections and moxifloxacin for respiratory infections, with a reasonable safety profile even in long-term use. Sulopenem, an oral carbapenem, expands options for urinary tract infections but with some side effects due to probenecid co-formulation.<br /><br />In summary, combining long-acting infusions with early oral stepdown can effectively avoid many OPAT-related complications in carefully selected patients, supported by emerging evidence for novel agents. Optimal use requires assessing patient factors and drug characteristics to ensure therapeutic success and safety.

Keywords

Oral Stepdown Therapy

Outpatient Parenteral Antibiotic Therapy (OPAT)

Long-acting Antibiotic Infusions

Dalbavancin

Oritavancin

Tedizolid

Omadacycline

Sulopenem

Antibiotic Bioavailability

Patient Selection Criteria