Switching from intravenous to oral antibiotics for uncomplicated Staphylococcus aureus bacteremia

Early Intravenous to Oral Antibiotic Switch in Uncomplicated Staphylococcus Aureus Bacteraemia: The EVOS Randomized Controlled Trial

This study tests if switching from intravenous to oral antibiotics can safely help people with uncomplicated Staphylococcus aureus bacteremia after a few days of treatment.

Quick facts

• Phase: Phase 3
• Study type: Interventional
• Enrollment: 290 (estimated)
• Ages: 18 Years and up
• Sex: All
• Sponsor: Clinical Research Centre, Malaysia (Academic / other)
• Drugs / interventions: prednisone
• Locations: 12 sites (Johor Bahru, Johor and 11 other locations)
• Trial ID: NCT06336824 on ClinicalTrials.gov

What this trial studies

The Early Intravenous to Oral Antibiotic Switch in Uncomplicated Staphylococcus aureus Bacteraemia (EVOS) study is a multicenter, randomized, open-label, phase 3 trial that evaluates the safety and efficacy of switching from intravenous to oral antibiotics in patients with uncomplicated Staphylococcus aureus bacteremia. The study involves 290 patients who have received 3 to 7 days of intravenous therapy and are randomized into two groups: one receiving an early switch to oral antibiotics and the other continuing standard intravenous therapy. Participants will be monitored over a 90-day period to assess treatment outcomes and safety.

Who should consider this trial

Good fit: Ideal candidates are adults with uncomplicated Staphylococcus aureus bacteremia who have shown improvement after initial intravenous antibiotic therapy.

Not a fit: Patients with complicated infections or those requiring prolonged intravenous therapy may not benefit from this study.

Why it matters

Potential benefit: If successful, this approach could reduce hospital stays and improve patient comfort by allowing for oral antibiotic treatment sooner.

How similar studies have performed: Other studies have shown promising results with early oral antibiotic switch strategies, suggesting potential for success in this approach.

Eligibility criteria

Inclusion Criteria:

1. Blood culture positive for Staphylococcus aureus (S. aureus).
2. Received 3 to 7 days of definitive IV antimicrobial therapy, defined as:

   * Cloxacillin or cefazolin for methicillin-sensitive staphylococcus aureus (MSSA); Vancomycin or ceftaroline for methicillin-resistant staphylococcus aureus (MRSA).
   * Proven in-vitro susceptibility and adequate dosing given (as determined by the principal investigator).
3. Achieved clearance of bacteraemia, defined as at least one documented latest negative follow-up blood culture obtained within 72 hours after the initiation of definitive IV antimicrobial therapy.
4. Achieved defervescence, defined as sustained body temperature ≤37.5°C within 48 hours before randomization.
5. Able to provide written informed consent to participate trial.

Exclusion Criteria:

1. Evidence of metastatic infection of S. aureus: for example, infective endocarditis, intraabdominal abscess, lung empyema, and osteomyelitis. Radiological investigations such as chest X-ray, ultrasound, echocardiogram, and CT scan are not mandatory prior to enrolment, but should be done at the discretion of the treating physician if clinically indicated.
2. Septic shock, defined as hypotension requiring vasopressors to maintain MAP ≥65 mmHg despite adequate volume resuscitation.
3. Received more than 5 days of non-study antibiotics as empirical therapy prior to enrolment.
4. Polymicrobial bloodstream infection, defined as isolation of pathogens other than S. aureus from a blood culture obtained prior to randomization. Common skin contaminants such as coagulase-negative staphylococci, Bacillus spp., and diphtheroid will not be considered to represent polymicrobial infection.
5. Known history of S. aureus infection within the past 3 months.
6. Inability to tolerate oral therapy or poor absorption of oral medications, or not suitable for ongoing IV therapy (for example, difficult intravenous access)
7. No options of oral antibiotic available for patient due to:

   * In vitro resistance of S. aureus to all oral study drugs.
   * Known contraindications to receive the active oral study drugs. For example, hypersensitivity reaction to trimethoprim-sulfamethoxazole, thrombocytopenia secondary to linezolid etc.
   * Non-availability of oral study drugs at the study sites.
8. Patient is concomitantly receiving oral antibiotics which are active against S. aureus. For example, trimethoprim-sulfamethoxazole for Pneumocystis jirovecii pneumonia prophylaxis.
9. Presence of a non-removable foreign body such as prosthetic heart valve, vascular graft, pacemaker, automated implantable cardioverter-defibrillator, ventriculoperitoneal shunt, prosthetic joint, and fracture fixation implant
10. Failure or inability to remove intravascular catheter that is present when first positive blood culture was drawn.
11. Known comorbidity that increased the risk of complicated infections:

    * End-stage renal disease
    * Severe liver disease (Child-Pugh class C)
    * Severe immunodeficiency:

      * HIV-positive patients with CD4\<200 cells/uL or AIDS
      * primary immunodeficiency disorders
      * high-dose steroid therapy (\>1 mg/kg prednisone or equivalent doses given for \> 4 weeks or planned during intervention)
      * immunosuppressive therapy
      * neutropenia (\<500 neutrophils/μl) at randomization or neutropenia expected during intervention phase due to immunosuppressive treatment
      * solid organ or hematopoietic stem cell transplantation within the past 6 months or planned during treatment period

13.Short life expectancy \< 3 months

14.Pregnancy (for women of childbearing potential)

Where this trial is running

Johor Bahru, Johor and 11 other locations

• Hospital Sultanah Aminah — Johor Bahru, Johor, Malaysia (Recruiting)
• Hospital Sultanah Bahiyah — Alor Star, Kedah, Malaysia (Recruiting)
• Hospital Sultan Abdul Halim — Sungai Petani, Kedah, Malaysia (Recruiting)
• Hospital Tuanku Ja'afar — Seremban, Negeri Sembilan, Malaysia (Recruiting)
• Hospital Raja Permaisuri Bainun — Ipoh, Perak, Malaysia (Recruiting)
• Hospital Pulau Pinang — George Town, Pulau Pinang, Malaysia (Recruiting)
• Hospital Seberang Jaya — Seberang Jaya, Pulau Pinang, Malaysia (Recruiting)
• Hospital Ampang — Ampang, Selangor, Malaysia (Recruiting)
• Hospital Sultan Idris Shah Serdang — Kajang, Selangor, Malaysia (Recruiting)
• Hospital Tengku Ampuan Rahimah — Klang, Selangor, Malaysia (Recruiting)
• Hospital Selayang — Selayang Baru Utara, Selangor, Malaysia (Recruiting)
• Hospital Melaka — Malacca, Malaysia (Recruiting)

Study contacts

• Study coordinator: Steven Lim, MBBS, MRCP

Conditions Staphylococcus Aureus Bacteremia; bacteremia; oral antibiotics; Staphylococcus aureus