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Oral and Outpatient Therapy in ABSSSI
Optimizing Oral and Outpatient Therapy in ABSSSI—Balancing Efficacy, Safety, and Stewardship

Released: December 26, 2025

Thomas P. Lodise
Thomas P. Lodise, PharmD, PhD
Activity Information

Activity

Key Takeaways
  • Although more than one half of hospital admissions for ABSSSI occur among low-acuity patients, most of these cases can be safely managed as outpatients.
  • Oral antibiotic selection should balance coverage, safety, and patient-specific considerations.

Acute bacterial skin and skin structure infections (ABSSSIs) remain among the most common infectious diagnoses worldwide and a major contributor to healthcare utilization. Although many patients are hemodynamically stable and could be safely treated as outpatients, nearly 60% of hospital admissions for ABSSSI occur in low-acuity patients who are primarily admitted to receive intravenous antibiotics. The ongoing challenge is to align clinical efficacy, safety, and stewardship while delivering effective therapy and avoiding unnecessary hospitalization, cost, and complications such as Clostridioides difficile infection (CDI).  

Case Scenario
A 72-year-old woman with diabetes and mild renal dysfunction presents to the emergency department with an erythematous, tender 10-cm lesion on her lower leg. She is afebrile, stable, and without systemic inflammatory response. Cultures are pending, and there is no suspicion for necrotizing infection. The key decision: inpatient parenteral antibiotics or outpatient oral therapy?

Key Steps in Decision-making 

Step 1: Assess Risk and Severity
Guidelines from the Infectious Diseases Society of America and emergency department consensus statements emphasize that patients without altered mental status, systemic inflammatory response syndrome, hemodynamic instability, or deep infection often can be managed safely as outpatients. Early recognition of disease severity, comorbid stability, and adherence potential informs both the need for admission and the selection of an optimal oral regimen. 

Step 2: Choose the Right Oral Agent
Selecting therapy requires balancing spectrum, tolerability, and individual patient risk:

  • Sulfamethoxazole/trimethoprim remains a low-cost, high-bioavailability methicillin-resistant Staphylococcus aureus (MRSA) option but lacks reliable Streptococcus activity and can cause renal or electrolyte issues.
  • Doxycycline or minocycline are well-tolerated, once-daily or twice-daily MRSA-active agents with anti-inflammatory benefits but limited Streptococcus coverage.
  • Clindamycin covers MRSA and Streptococcus and is a single-agent option but carries a high CDI risk, which is particularly problematic in older patients or those who are immunocompromised.
  • Linezolid is highly effective for MRSA and Streptococcus and simplifies discharge with IV-to-oral equivalence but requires monitoring for hematologic toxicity and serotonin interactions.
  • Amoxicillin/clavulanate or cephalexin remains an excellent first-line option for nonpurulent, streptococcal-predominant infections.
  • Omadacycline, a once-daily oral aminomethylcycline, is a newer alternative. It has potent MRSA and Streptococcus coverage, activity against tetracycline-resistant strains, and a low risk of CDI, making it an option for patients at high CDI risk or those who have failed prior therapy. Its broad coverage, favorable safety profile, and minimal drug–drug interactions make it an attractive choice in patients with diabetes, renal dysfunction, or concomitant selective serotonin reuptake inhibitor use where linezolid may be contraindicated.

Step 3: Simplify Care When Possible
For patients unable to adhere to multiday regimens or requiring early discharge, long-acting parenteral options such as dalbavancin and oritavancin allow single-dose or weekly dosing without the need for a peripherally inserted central catheter. Studies have shown that these agents reduce hospital length of stay, readmissions, and overall costs while maintaining high satisfaction. 

Step 4: Stewardship at the Point of Care
Antimicrobial stewardship is most impactful when embedded in the emergency department and outpatient transitions. Pharmacist-led initiatives that integrate local antibiograms, monitor CDI and readmission rates, and encourage oral switch opportunities optimize both patient outcomes and resource utilization. 

Key Takeaways
Modern management of ABSSSI increasingly emphasizes outpatient care. By assessing risk, selecting appropriate oral or long-acting agents, and focusing on adherence and stewardship, healthcare professionals can safely minimize unnecessary hospitalizations while ensuring effective, patient-centered therapy and reducing antibiotic overuse. 

Your Thoughts
What antibiotic would you have chosen for the patient in this case scenario? What key factors most influenced your decision? Leave a comment to join the discussion!