ESCMID 2025: Antimicrobial Prescribing: Myths or Pearls?

Why Treat IV when PO is Possible?

Speakers: Dr Brad Spellberg, Dr Flaminia Olearo

Introduction:

The session discussed antimicrobial stewardship and myths around IV antibiotic use and the rationale for using oral antibiotics in infections traditionally treated with IV therapy.

Oral Antibiotics Over IV Therapy:

Oral (PO) antibiotics have been shown to be as effective as intravenous (IV) therapy for serious infections like osteomyelitis, bacteremia, and endocarditis, challenging long-standing clinical practice. Modern oral antibiotics were noted to reach therapeutic concentrations in both bone and blood, with outcomes comparable to IV therapy. Prolonged IV treatment (typically 4-6 weeks) was associated with significant risks, including deep vein thrombosis (DVT), catheter-related infections, and line fractures, with adverse events occurring in 10-30% of patients. Across 23 randomized controlled trials, oral therapy was consistently found to be non-inferior to IV therapy, with none demonstrating IV superiority.

Condition-Specific Evidence:

• Osteomyelitis: Over 40 observational studies and 10 randomized trials indicated that oral therapy produced outcomes equivalent to IV therapy. Several modern oral agents—including fluoroquinolones, metronidazole, linezolid, and rifampicin—were found to achieve effective bone concentrations.
• Bacteremia: 11 randomized trials (seven for gram-positive and four for gram-negative) showed oral therapy to be as effective as IV, with linezolid demonstrating superior efficacy in select cases.
• Endocarditis: Evidence from 20 observational studies, including those involving left-sided disease, prosthetic valves and staphylococcal infection (including MRSA), exhibited comparable cure rates between oral and IV therapy. In large case-control cohort studies, oral therapy was associated with higher survival rates. Three randomized controlled trials involving streptococcal and staphylococcal endocarditis reported that oral or step-down therapy was non-inferior to IV therapy.

Criteria for Transition from IV to Oral Therapy:

• Clinical judgment for switching to oral therapy was supported by five criteria: (1) hemodynamic stability, (2) effective source control, (3) clearance of bacteremia, (4) availability of an appropriate oral regimen, and (5) intact functioning of the GI tract with no major adherence barriers.

Antimicrobial De-escalation:

• Antimicrobial de-escalation was presented as a key strategy to minimize antibiotic exposure by narrowing antibiotic spectrum, discontinuing redundant drugs, avoiding unnecessary coverage, and shortening treatment duration. Confidence in de-escalation was strengthened by pathogen identification, susceptibility profiles, and serial cultures data.
• ICUs were emphasized as high-risk zones for antimicrobial resistance, with over 80% of patients receiving antibiotics. However, for community-acquired infections without risk factors for multidrug-resistant (MDR) organisms, narrow-spectrum agents were deemed sufficient.

Evidence Supporting De-escalation:

• DIANA Study: Conducted across 28 countries, it demonstrated similar clinical cure rates between de-escalated and non-de-escalated groups. De-escalation was implemented in 60% of eligible patients.
• US Sepsis Study (2024): Among patients initially treated with anti-MRSA + anti-Pseudomonal therapy, de-escalation by day 4 led to improved outcomes—lower acute kidney injury, fewer late ICU admissions, and reduced Clostridioides difficile
• US Pneumonia Study: Only 30% underwent de-escalation done by day 4, and it was linked to lower ICU transfer rates, reduced hospital stays, and cost reductions.
• Lopez-Cortes Trial (Bacteremia, 2023): In bloodstream infections caused by Enterobacteriaceae, de-escalation from anti-pseudomonal to non-anti-pseudomonal was found non-inferior in clinical cure with no significant difference in secondary outcomes.
• Febrile Neutropenia (France): A safe reduction in carbapenem and vancomycin use was achieved without compromising clinical outcomes.  

Clinical Significance:

Strong evidence supports the safety and efficacy of oral antibiotics and de-escalation strategies for serious infections, offering opportunities to reduce IV-associated complications and antimicrobial resistance. Broader adoption of these practices may optimize patient care, particularly when supported by microbiological data and stewardship protocols.

ESCMID Global, April 11-15, 2025, Vienna