Question: is switching to oral therapy for low risk SAB possible?
Low risk: negative follow-up BC, no mestatistic infection, intravascular catheters removed, no prosthetic vascular material, not immunosuppressed
Benefits and risks:
Design:
Study meds:
Reasonable choices, but noting that trimethoprim-sulfa inferior to vanc in Paul et al study for MRSA.
CONSORT diagram:
Ended up with smallish numbers still - 108 in oral and 105 in IV arms.
Baseline characteristics:
Only 5% MRSA. Line related infections about 60%.
Results:
No difference between treatment arms.
Certainly no difference in per protocol populations which the presentation focussed on.
Wasn't clear in presentation what the pre-defined non-inferiority margin was. If 5% then in the ITT may not have been NI.
Have looked at the trial protocol. The NI margin was intially 5% but then in the updated protocol increased to 10%. So looks like it meets the NI margin of 10% in the ITT for the primary outcome of SAB related complication in 90d: 0.007 (-0.078 to 0.091).
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Gianella CMI 2020. Lower mortality in those who had follow-up BC done -> 2 fold reduction.
Maskarinec CMI 2020. 1702 patients. FUBC in 68%. 20% FUBC persistently positive. Higher mortality if no FUBC. If done, FUBC+ higher mortality
I haven't read the studies, but do wonder about both immortal time bias and bias by indication in these studies. Is there something systematically different in those who do get FUBC?
Amipara EClinicalMedicine 2021
766 patients. Excluded if died within 72h. Propensity score adjustment
If FUBC not done, higher mortality. About 0.5 hazard ratio.
So the above 3 studies, consistently found 2 fold decline in mortality if FUBC done.
Infliximab - about 500 in active and placebo arms; no diff in time to recovery. 41% lower odds of day 28 mortality, 32% higher odds of clinical status at day 14.
No diff in adverse events
Abatacept - about 500 in active and placebo; no diff in time to recovery, Reduced odds of day 28 mortality. No diff in adverse events, with slightly higher bacterial infections (not stats sig).
Getting ready for Clinical Controversies in treatment of S. aureus bacteremia. #IDWeek2022
Increasing recognition that 'persistent' bacteremia should probably be earlier rather than later. Each day longer, associated with increased metastatic complications and mortality.
What is best treatment? ASP or cefazolin? Issues of increased toxicity vs cefazolin inoculum effect.
>>> we need to test in a clinical trial
If still BC+ at 5 days?
No routine role for combination antibiotics - no benefit with rifampin, daptomycin, aminoglycosides in trials
Debating role of vancomycin for MRSA at #IDWeek2022.
Dr Wagner argues that increasing duration of MRSA bacteraemia associated with poorer outcomes (mortality).
I accept this.
BUT, therapeutically reducing duration of bacteraemia has not been associated with improved mortality.
Duration of bacteremia is a SURROGATE. Although logical and biologically plausible that reducing duration of bacteremia with a particular antibiotic (vs another) should improve the outcome we care about (mortality), this has not yet been demonstrated.
Cites 43% of patients with trough-based dosing develop AKI.
We didn't find this in CAMERA2. Almost all on vanc and trough-based dosing. In control arm only 6% developed AKI. jamanetwork.com/journals/jama/…
Yes, that was in the context of a clinical trial. But 6% is far from 43%