Steven Tong Profile picture
Oct 21 4 tweets 1 min read
ACTIV-1 infliximab, abatacept and cenicriviroc (CVC) as immunomodulators in COVID-19. Emily Ko

#IDWeek22

COVID-19 with pneumonitis / hypoxia

Primary endpoint - time to recovery

Ages 55, 60% male, BMI 32, 50% obese

Receiving remdesivir and steroids, <10% IMV
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).
Increasingly apparent that immune modulation important. Consistent with tocilizumab and baricitinib.

Where is the sweet spot for immune modulation? Especially now with mainly vaccinated populations.

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More from @syctong

Oct 21
Follow-up BC in GN BSI
Majdi N. Al-Hasan

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.
Read 5 tweets
Oct 21
At #IDWeek2022

Role of follow-up blood cultures for Gram positives
Valeria Fabre

Detection of bacteria depends on:
Volume of blood and number of sets - should aim 40ml in 4 bottles (2 sets)
About 20% of GP bactermia are persistent. Mostly S. aureus. Strep not persistent. Wiggers BMC ID 2016

Persistance in SAB may occur in up to 40% of cases
Minejima CID 2020 mentioned again. @BradSpellberg
Risk factors for prolonged SAB - MRSA, endovascular source, ICU

Bacteremia of ≥3 days independent predictor of 30-day mortality
Read 9 tweets
Oct 21
Detecting the cefazolin inoculum effect with a rapid test. #IDWeek2022

Sara I. Gomez Villegas, MD; @SuperBugDoc

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
Read 6 tweets
Oct 21
Getting ready for Clinical Controversies in treatment of S. aureus bacteremia. #IDWeek2022 Image
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
Read 23 tweets
Oct 21
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%
Read 4 tweets
Oct 20
Oral abstract at #IDWeek2022 from Ryan Khodadadi, @MayoClinicINFD

Ceftriaxone as definitive therapy for MSSA (compared to ASP / cefazolin)

Multi-centre in Mayo Clinic campuses, and Florida, and Arizona. 2018-2019
Inclusion - receipt of ≥7 days outpatient therapy

Primary outcome - 90 day treatment failure (mortality or recurrence)

223 patients; 186 with ASP/cefazolin (mostly cefazolin) and 37 ceftriaxone

More uncomplicated patients for ceftriaxone
90 day treatment failure 27% in ceftriaxone group, 9% with ASP/cefazolin

On MV cox regression - ceftriaxone associated with failure with aHR 2.91 (95% CI1.3-6.5)
Read 4 tweets

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