Helmi Sulaiman Profile picture
Apr 17, 2023 17 tweets 7 min read Read on X
New drugs against GNB by Ursula Theuretzbacher #ECCMID2023

In Malaysia, we only have Cefta-avi for resistant GNB infections!
We hope @SHIONOGI_JP will include Malaysia in the list of countries for generic cefiderocol- a project by @gardp_amr

@KKMPutrajaya @DrZalihaMustafa Image
These are the drugs that are recently approved and we have none of these locally
We can only use Fe-troja(n)/Cefiderocol by @SHIONOGI_JP under the compassionate use program, and the drug is flown all the way from Europe

The cost is huge and our patients can rarely afford it Image
Again, the same table:
The red ones are called DBO/Diazabicyclooctanes. They have an added PBP activity in addition to BLI activity
Boronates have extended BLI activity (MBL)
The green one is the Tazobactam analogue

Here is an excellent podcast on these: asm.org/Podcasts/Edito… Image
This is the spectrum of activity of the new BLBLIs

And of these, only Sulbactam/durlobactam has activity against CRAB

Durlobactam is the next gen-DBO with an extended activity against the class D enzymes - which are the primary R mechanisms by Acinetobacter baumannii Image
And the coverage of NDM enzyme by some of the new agents is quite spotty, as shown here in the red bracket

Therefore, their performance against NDM-producing organisms in clinical practice needs further evaluation Image
The ability of these new BLBLI to inhibit the beta-lactamases depends on several factors, as shown below

And for Acinetobacter and Pseudomonas, their resistance is not only enzymes-based, making it difficult to develop agents that are active against them Image
Besides, different regions will have different prevalences of beta-lactamase enzymes

And in the Southeast Asia region, we have the highest burden of NDM, again highlighting the urgent need for agents that are active against it
Cefiderocol is one such agent Image
Again, in our region, the burden of NDM or MBL is very high, and Cefiderocol is the best agent currently against it

Susceptible rates by
CLSI: 88.1%
EUCAST: 66.3%
US FDA: 88.1% Image
What about Pseudomonas?
Are the new BLBLIs good against it?

The major issue with PA is that carbapenem resistance is driven not only by carbapenemases but by:
- PBP3 change
- Reduced uptake
- Change in outer membrane protein
- ampC overexpression Image
Again, the distribution of carbapenemases in Pseudomonas varies depending on the geographical location
How about CRAB?
There are 2 agents:
1) Sulbactam/Durlobactam
This is the new combo whereby Sulbactam, an old drug, can attack the Acinetobacter PBPs

However, it can be destroyed by the OXA enzymes, which is where the Durlobactam comes in - it protects it against the OXA enzymes Image
2) IV Rifabutin
It is an old drug
It has a very specific uptake mechanism into Acinetobacter

However, it cannot be taken alone for CRAB, as this will cause the emergence of resistance
And these are new oral BLBLIs that can be used to treat MDR GNB infections esp in UTI

For these agents, the accompanying agent plays a role in its (BLI) activity against the bug
Example: cumulative activity is the best for Ledaborbactam when it is combined with Ceftibuten Image
Image
What is in the pipeline now? Image
And why is it so difficult to find new candidates/novel agents against GNB? Image
And the last slide... Image

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More from @edenhelmi

Apr 28
SAB management updates by IDSA/ESCMID
#ESCMIDGlobal2024
The term “complicated” SAB varies and does not always suggest longer treatment
Solution: low vs. high-risk populations for SAB Image
How do we risk stratify SAB into the two levels? Image
How many sets of BC should be repeated?
1 or 2 sets
24 or 48 hours later Image
Read 13 tweets
Apr 10
A very enlightening talk by Angela Hutner on simple vs complicated UTI definitions
Simplicity wins
Anything that is beyond the bladder = complicated UTI (including prostatitis)

This will be updated in 2024 by both the IDSA and ESCMID

#IDTwitter #IDXposts
Image
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IDSA/ESCMID new guidelines: Image
Gupta has updated this on UpToDate too Image
Read 32 tweets
Apr 16, 2023
Fairytales or reality, checking some eminence paradigms for treatment of severe infections

#ECCMID2023 Image
Kill fast! These infections must be treated with a "bactericidal" antibiotic
Beatrice Grabein, Germany

Clindamycin is bad for invasive MRSA infection
journals.asm.org/doi/full/10.11… Image
Tolerance to oxacillin is bad
ncbi.nlm.nih.gov/pmc/articles/P… Image
Read 29 tweets
Apr 15, 2023
Polymyxins and carbapenems: their place in the treatment of MDR Gram-negative infection today
#ECCMID2023

This a very relevant talk for us in Southeast Asia (exc Singapore)

@alif82 @SyamhaninA @fikreeahmad @shaharudeen @GSRajahram @stevenlimcl @SazaliBasri @HanzHc
Image
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Read 19 tweets
Apr 15, 2023
Evolution of CM/ID Specialties by Dr. Rama
#ECCMID2023 Image
He talked about his evolution when he came back from the US and the UK
He needed to learn about the cultures in India

This includes antibiotics as a one-size-fits-all remedy

He captured the issues of empiric therapies - one empiric regimen after another. Image
Image
Read 9 tweets
Apr 15, 2023
Tricks and tips for the infectious diseases consultant by Esther CALBO, Spain at #ECCMID2023

Risk of death for ID physicians from "womb to tomb." Image
Our role is essential (ID consult can reduce the risk of death)

However, we must know how to sell our importance to the hospital suite ImageImageImage
Solicited interventions are more welcomed than the nonsolicited ones Image
Read 14 tweets

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