The Early Intravenous to Oral Antibiotic Switch in Uncomplicated Staphylococcus aureus Bacteraemia (EVOS) study is a multicentre, randomized, open-label, parallel group, phase 3, non-inferiority trial of early intravenous to oral antibiotic switch in comparison with standard intravenous antibiotic regime among patients with uncomplicated Staphylococcus aureus bacteraemia (SAB). The study is based on the hypothesis that an early switch from IV to oral antimicrobial therapy is non-inferior and safe compared to conventional minimum 14-day course of IV therapy in patients with low-risk uncomplicated SAB.
Blood culture positive for Staphylococcus aureus (S. aureus).
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).
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.
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.
Septic shock, defined as hypotension requiring vasopressors to maintain MAP ≥65 mmHg despite adequate volume resuscitation.
Received more than 5 days of non-study antibiotics as empirical therapy prior to enrolment.
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.
Parallel
Tab. Trimethoprim-sulfamethoxazole, Tab. Clindamycin, Tab. Cephalexin, or Tab. Linezolid
DrugThe choice of study drug will depend on the susceptibility of the respective isolate, expected drug interactions, contraindications, and expected side effects. Investigators will assess whether the "first-choice" regimen can be given and then consider the alternative regimen. The antibiotics can be switched from first choice to the respective alternative medications during the intervention period if clinically necessary. The route of administration must be maintained according to the randomized group.
IV Cloxacillin, IV Cefazolin, IV Vancomycin, or IV Ceftaroline
DrugThe choice of study drug will depend on the susceptibility of the respective isolate, expected drug interactions, contraindications, and expected side effects. Investigators will assess whether the "first-choice" regimen can be given and then consider the alternative regimen. The antibiotics can be switched from first choice to the respective alternative medications during the intervention period if clinically necessary. The route of administration must be maintained according to the randomized group.
Rate of SAB-relapse
defined as any new positive blood culture with S. aureus, and/or newly diagnosed metastatic S. aureus infection resulting from hematogenous dissemination
Number of days of hospitalization
Number of calendar days of hospitalisation after the first positive blood culture for S. aureus.
Rate of all-cause mortality
Any death occurred within 90 days of randomization.
Rate of complications related to IV therapy
Any complications related to insertion or usage of peripheral branula or central catheter, and administration of IV drugs
Rate of Clostridium difficile diarrhoea
A diagnosis of diarrhoea with ≥1 stool sample tested positive for C. difficile toxin or toxin gene.
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Clinical Research Centre, Malaysia
Lead sponsor
Ministry of Health, Malaysia
Sponsor institution
