When S. aureus MIC to cefazolin increases in vitro when inoculum increased
Prevalence 3-15%
Retrospective studies find CzIE associated with poorer outcomes
Looking at dataset from pediatric OM
250 MSSA with 14.4% CzIE+. These were associated with progression from acute to chronic OM
Gold standard for detection is BMD. Cumbersome test. 3 days for test.
CzIE+ isolates release more BlaZ enzyme. Nitrocefin changes colour in the presence of B-lactamase
Novel 3 hr assay to detect CzIE
Aim: evaluate accuracy of nitrocefin test
Sensitivity ~80%, specificity ~90% compared to reference BMD. Overall accuracy of 89%
BlaZ type A most commonly associated with CzIE. Sens 96%, spec 80% for these
Looks like v useful test - probably needs further validation and validation in other labs
And of course the clinical Q remains: is the CzIE clinically relevant?
This is something @snap_trial can look at. Among MSSA cases randomised to flucloxacillin or cefazolin, determine CzIE. If relevant, hypothesis no diff in fluclox arm regardless of CzIE, but poorer outcomes in cefazolin arm if CzIE present (vs not)
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%