Staphylococcus Aureus Network Adaptive Platform Trial

Exclusion Criteria

• •Potentially eligible participants meeting any of the following criteria at the time of eligibility assessment for platform entry will be excluded from the randomised platform (but may still participate in the registry):
• •1. Time of anticipated platform entry is greater than 72 hours post collection of the index blood culture (Where the time of culture collection is not recorded, the time of laboratory registration of the sample will be used as an alternative)
• •2. Polymicrobial bacteraemia, defined as more than one organism (at species level) in the index blood cultures OR in any subsequent blood culture reported between the collection of the index blood culture and platform eligibility assessment, excluding those organisms judged to be contaminants by either the microbiology laboratory or treating clinician.
• •3. Known previous participation in the randomised SNAP platform
• •4. Known positive blood culture for S. aureus (of the same silo: PSSA, MSSA or MRSA) between 72 hours and 180 days prior to the time of eligibility assessment
• •5. Treating team deems enrolment in the study is not in the best interest of the patient
• •6. Treating team believes that death is imminent and inevitable
• •7. Patient is for end-of-life care and antibiotic treatment is considered not appropriate
• •8. Patient \<18 years of age and paediatric recruitment not approved at recruiting site
• •9. Patient has died since the collection of the index blood culture
• •To be included in any of the following DOMAINS the participant must met eligible for the PLATFORM (as listed above)
• •ADJUNCTIVE TREATMENT DOMAIN
• •1\. Previous type 1 hypersensitivity reaction to lincosamides 2. Currently receiving clindamycin (lincomycin) or linezolid which cannot be ceased or substituted 3. Necrotising fasciitis 4. Current C. difficile associated diarrhoea (any severity) 5. Current severe diarrhoea from any cause (defined as Grade 3 or higher) 5. Known CDAD (C.Difficile Associated Diarrhoea) in the past 3 months, or CDAD relapse in the past 12 months 6. At the time of domain eligibility assessment, more than 4 hours has elapsed since platform entry 7. Treating clinician deems enrolment in this domain is not in the best interest of the patient
• •PSSA, MSSA TREATMENT DOMAIN (backbone)
• •1. \>72 hours have elapsed since the collection of the index blood culture (i.e. the time of collection of the first positive blood culture from the patient during this episode)
• •2. History of type I hypersensitivity reaction (i.e. anaphylaxis or angioedema) to any penicillin or cephalosporin
• •3. History of severe delayed reaction (e.g. allergic interstitial nephritis, cutaneous vasculitis, Stevens-Johnson, DRESS, etc.) to any penicillin or cephalosporin
• •5. Treating team deems enrolment in this domain is not in the best interest of the patient
• •6. Currently receiving maintenance dialysis (haemodialysis or peritoneal dialysis); (Acute renal replacement therapy (including CRRT, haemodialysis or peritoneal dialysis) are not exclusions. Such patients are eligible as long as appropriate vascular access is available or can be arranged.)
• •7. Polymicrobial bacteraemia (defined as more than one organism \[at species level\] in blood cultures, excluding those organisms judged to be contaminants by either the microbiology laboratory or treating clinician) reported between collection of the index blood culture and backbone domain eligibility assessment
• •8. Patient currently being treated with a systemic antibacterial agent that cannot be ceased or substituted for interventions allocated within the platform (unless antibiotic is listed in Table 1 of the DSA, which specifies allowed antibiotics with limited absorption from the gastrointestinal tract or negligible antimicrobial activity against S. aureus)
• •MRSA TREATMENT DOMAIN (backbone)
• •1. Time to allocation reveal is \>72 hours from time of index blood culture collection
• •2. Severe allergy to any beta-lactam (including cefazolin) Immediate severe allergy: Anaphylaxis/angioedema Severe delayed allergy: Severe cutaneous adverse reaction (SCAR; including Steven Johnson Syndrome, Toxic Epidermal Necrolysis, Drug Rash with Eosinophilia and Systemic Symptoms (DRESS) and acute generalised exanthematous pustulosis (AGEP)), severe drug induced liver injury, proven allergic interstitial nephritis, immune-mediated haemolytic anaemia and other severe cytopenia.
• •3\. Severe allergy or non-severe rash to both vancomycin AND daptomycin Vancomycin infusion reaction (formerly known as "red man syndrome") is due to direct histamine release and is not generally an allergy, and therefore is not considered an exclusion.
• •5\. Treating team deems enrolment in the domain is not in the best interest of the patient 6. Polymicrobial bacteraemia (defined as more than one organism \[at species level\] in blood cultures, excluding those organisms judged to be contaminants by either the microbiology laboratory or treating clinician) reported between collection of the index blood culture and backbone domain eligibility assessment.
• •7\. Patient currently being treated with a systemic antibacterial agent that cannot be ceased or substituted for interventions allocated within the platform (unless antibiotic is listed in Table 1 of the DSA, which specifies allowed antibiotics with limited absorption from the gastrointestinal tract or negligible antimicrobial activity against S. aureus)
• •EARLY ORAL SWITCH DOMAIN
• •1. Adherence to oral agents unlikely (as judged by site PI in consultation with the treating team)
• •2. Unreliable gastrointestinal absorption (e.g. vomiting, diarrhoea, nil by mouth, anatomical reasons)
• •3. There are no appropriate oral antibiotics due to contraindications, drug availability, or antibiotic resistance
• •4. Ongoing IV therapy unsuitable e.g. no IV access
• •5. Clinician deems not appropriate for early oral switch
• •6. Patient no longer willing to participate in domain In the lead-up to judging eligibility, it may be helpful to discuss with the patient the potential for continued IV treatment versus oral switch, to allow hospital discharge planning
• •7. Clinical team deems that sufficient duration of antibiotic therapy has already been provided
• •Exclusions when judging eligibility for early oral switch at trial Day 7 (+/- 2 days):
• •1. Presence of prosthetic cardiac valve, pacemaker or other intracardiac implant
• •2. Presence of intravascular clot, graft, or other intravascular prosthetic material Intravascular clot excludes superficial peripheral IV line-related thrombophlebitis. Intravascular prosthetic material excludes coronary artery stents)
• •3. Intravascular/intracardiac infections (e.g. endocarditis, mycotic aneurysm)
• •4. Presence of other intracardiac abnormalities felt to put patient at increased risk of endocarditis (e.g., bicuspid aortic valve)
• •PET/CT DOMAIN
• •1. Pregnant - patients of childbearing potential should be assessed for pregnancy status and a pregnancy test performed (if not performed within the past 10 days)
• •2. Currently breastfeeding
• •3. \< 18 years of age
• •4. Patient has had PET/CT in the past 7 days
• •5. Patient needs PET/CT in the next 7 days (in the opinion of the clinical team, at the time of eligibility assessment)
• •6. Clinically unstable for PET/CT (as judged by the treating clinical team, taking into account need for organ support (including inotropes) and capacity to lie flat for the PET/CT)
• •7. Contraindication to PET/CT (e.g., claustrophobia, persistently elevated blood sugar levels \[\>12.5mmol/L\] that cannot be corrected).
• •8. Patient no longer willing to participate in the domain - in the days leading up to judging eligibility, it may be helpful to discuss with the patient the potential for PET/CT vs no PET/CT to allow imaging planning
• •9. Clinician deems participation in this domain is not in the patient's best interests