EUCAST breakpoint for B. pseudomallei, new meaning of "I" from EUCAST and its implication to melioidosis treatment

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Direk Limmathurotsakul

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Dec 5, 2020, 3:43:34 AM12/5/20
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Dear everyone,

 

 

I am certain that many of you have heard about new meaning of “I” from EUCAST. Nonetheless, I want to take this opportunity to update and kick off a discussion about its implication to melioidosis treatment  

 

1) new meaning of “I” from EUCAST

 

Please note that “I” is “Susceptible, increased exposure”. A microorganism is categorised as "Susceptible, Increased exposure*" when there is a high likelihood of therapeutic success because exposure to the agent is increased by adjusting the dosing regimen or by its concentration at the site of infection. *Exposure is a function of how the mode of administration, dose, dosing interval, infusion time, as well as distribution and excretion of the antimicrobial agent will influence the infecting organism at the site of infection. https://www.eucast.org/newsiandr/

EUCAST breakpoint table: https://www.eucast.org/clinical_breakpoints/  

 

 

2) The Burkholdera pseudomallei’s breakpoints and zone diameters are on page 101-102 (PDF attached – link below)  https://www.eucast.org/fileadmin/src/media/PDFs/EUCAST_files/Breakpoint_tables/v_10.0_Breakpoint_Tables.pdf     

 

 

3) Implication of “I” of B. pseudomallei to melioidosis treatment.

I assume that the common question would be

 

3.1) if B. pseudomallei is reported as “I” (Susceptible, increased exposure; and the lab is using EUCAST) to ceftazidime and the patient is already on ceftazidime and clinical status is stable, should the doctor continue ceftazidime, adjust dose of ceftazidime or switch to meropenem?

 

3.2) if B. pseudomallei is reported as “I” to ceftazidime (and the lab is using CLSI), what should we do? what should we recommend to the doctors about treatment?

 

I know that there is a case discussion about this scenario from UK – so, I will just kick off and allow many to come and share the updated recommendation on this situation.

 

 

Also, if any of you in this group email want to ask anything or comment anything; please just reply to or CC melio...@googlegroups.com. I am sure that every question and comment is valuable, and everyone could share the information together.  

 

Kind regards,

 

Direk

v_10.0_Breakpoint_Tables.pdf

Bart Currie

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Dec 5, 2020, 6:14:37 PM12/5/20
to Direk Limmathurotsakul, melio...@googlegroups.com
Thanks Direk
This is an important issue and the new EUCAST system and categories has been confusing for us all until the rationale was explained - that is I does not mean intermediate resistance but means sensitive BUT requires INCREASED dosing.
So for melioid it is fine to use the currently recommended high dose ceftazidime regimen.
Under this system all our B pseud get reported as I not S.
But this does not change our management which is ceftazidime initially for most - with meropenem reserved for those critically ill or with CNS melioid (where we use double dose merop of 1g 8 hourly adult dose). And switch from ceftazidime to meropenem for those who are seriously deteriorating on ceftazidime or still unwell AND blood culture positive after 7 days.
Bart

Bart Currie
Sent from my iPhone

> On 5 Dec 2020, at 6:14 pm, Direk Limmathurotsakul <di...@tropmedres.ac> wrote:
>
> Dear everyone,
>
>
> I am certain that many of you have heard about new meaning of “I” from EUCAST. Nonetheless, I want to take this opportunity to update and kick off a discussion about its implication to melioidosis treatment
>
> 1) new meaning of “I” from EUCAST
>
> Please note that “I” is “Susceptible, increased exposure”. A microorganism is categorised as "Susceptible, Increased exposure*" when there is a high likelihood of therapeutic success because exposure to the agent is increased by adjusting the dosing regimen or by its concentration at the site of infection. *Exposure is a function of how the mode of administration, dose, dosing interval, infusion time, as well as distribution and excretion of the antimicrobial agent will influence the infecting organism at the site of infection. https://www.eucast.org/newsiandr/<https://aus01.safelinks.protection.outlook.com/?url=https%3A%2F%2Fwww.eucast.org%2Fnewsiandr%2F&data=04%7C01%7CBart.Currie%40menzies.edu.au%7C36621fead99e41111dbe08d898f9dc83%7C9f2487678e1a42f3836fc092ab95ff70%7C0%7C0%7C637427546542326697%7CUnknown%7CTWFpbGZsb3d8eyJWIjoiMC4wLjAwMDAiLCJQIjoiV2luMzIiLCJBTiI6Ik1haWwiLCJXVCI6Mn0%3D%7C3000&sdata=m3gLakWkdY2TEFhxjziihePkLj5aes4v4gsoXH1NYqQ%3D&reserved=0>
> EUCAST breakpoint table: https://www.eucast.org/clinical_breakpoints/<https://aus01.safelinks.protection.outlook.com/?url=https%3A%2F%2Fwww.eucast.org%2Fclinical_breakpoints%2F&data=04%7C01%7CBart.Currie%40menzies.edu.au%7C36621fead99e41111dbe08d898f9dc83%7C9f2487678e1a42f3836fc092ab95ff70%7C0%7C0%7C637427546542326697%7CUnknown%7CTWFpbGZsb3d8eyJWIjoiMC4wLjAwMDAiLCJQIjoiV2luMzIiLCJBTiI6Ik1haWwiLCJXVCI6Mn0%3D%7C3000&sdata=aPK08Q9ZsmSS9igMaIoCoWg%2FTSzFp5QCuyokK3YDsio%3D&reserved=0>
>
>
> 2) The Burkholdera pseudomallei’s breakpoints and zone diameters are on page 101-102 (PDF attached – link below) https://www.eucast.org/fileadmin/src/media/PDFs/EUCAST_files/Breakpoint_tables/v_10.0_Breakpoint_Tables.pdf<https://aus01.safelinks.protection.outlook.com/?url=https%3A%2F%2Fwww.eucast.org%2Ffileadmin%2Fsrc%2Fmedia%2FPDFs%2FEUCAST_files%2FBreakpoint_tables%2Fv_10.0_Breakpoint_Tables.pdf&data=04%7C01%7CBart.Currie%40menzies.edu.au%7C36621fead99e41111dbe08d898f9dc83%7C9f2487678e1a42f3836fc092ab95ff70%7C0%7C1%7C637427546542336699%7CUnknown%7CTWFpbGZsb3d8eyJWIjoiMC4wLjAwMDAiLCJQIjoiV2luMzIiLCJBTiI6Ik1haWwiLCJXVCI6Mn0%3D%7C3000&sdata=UQqyG%2F7cmp85OK10b%2B1lItDlD3W%2BTHR9TzYa2ucMMYU%3D&reserved=0>
>
>
> 3) Implication of “I” of B. pseudomallei to melioidosis treatment.
> I assume that the common question would be
>
> 3.1) if B. pseudomallei is reported as “I” (Susceptible, increased exposure; and the lab is using EUCAST) to ceftazidime and the patient is already on ceftazidime and clinical status is stable, should the doctor continue ceftazidime, adjust dose of ceftazidime or switch to meropenem?
>
> 3.2) if B. pseudomallei is reported as “I” to ceftazidime (and the lab is using CLSI), what should we do? what should we recommend to the doctors about treatment?
>
> I know that there is a case discussion about this scenario from UK – so, I will just kick off and allow many to come and share the updated recommendation on this situation.
>
>
> Also, if any of you in this group email want to ask anything or comment anything; please just reply to or CC melio...@googlegroups.com<mailto:melio...@googlegroups.com>. I am sure that every question and comment is valuable, and everyone could share the information together.
>
> Kind regards,
>
> Direk
>
> --
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David Dance

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Dec 6, 2020, 7:41:14 AM12/6/20
to melio...@googlegroups.com, Direk Limmathurotsakul


Yes, it is important that everyone is aware of this consequence of adopting the recently published EUCAST criteria. I must accept some responsibility for this, as it was me who initiated the work with EUCAST on which this was based because I felt it was important to have internationally accepted guidelines for disc diffusion susceptibility testing of B. pseudomallei.  People should be aware that CLSI have only ever published MIC-based criteria for B. pseudomallei.

 

The work on which this was based was meticulously co-ordinated by EUCAST.  The reason why we have ended up with almost all wild-type B. pseudomallei being classified as ‘I’ to drugs like ceftazidime is that this initiative coincided with a fundamental change in the EUCAST approach, which has also affected some other Gram negative bacteria like Pseudomonas aeruginosa and essentially reflects the fact that they are not as susceptible as some other organisms and thus require higher doses of the agents concerned.  

 

As Gunnar Kahlmeter from EUCAST explains it “We now have two levels of sensitive rather than two levels of resistant (which was the practical consequence of the old definition).”  He suggests that it will be important to educate our clinical colleagues  that “(a)  an ‘I’ is as good as an ‘S’, and you need not go hunt for an S, and (b) meropenem should be avoided for as long as possible” (for stewardship reasons). “ 

 

I suggest that laboratory people who adopt the EUCAST approach need to educate their local clinicians to explain the consequences of the changes and should consider adding a comment along the lines of  “Susceptible but  requires high doses” to their reports in such circumstances. 

 

Gunnar has undertaken a series of online seminars to help explain all this. They are available on the EUCAST website: 

https://www.eucast.org/videos_from_eucast/online_seminars/

 

BW

 

David

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Andrew Simpson

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Dec 7, 2020, 5:09:19 AM12/7/20
to melio...@googlegroups.com, Direk Limmathurotsakul

Thanks all. This is an important issue and it’s good to see it being discussed.

In Mahosot Hospital, Vientiane, we spoke at a clinical meeting with hospital staff to explain the changes and field questions in advance of the EUCAST breakpoints being introduced. We now add a comment to reports for B. pseudomallei (this is deliberately kept short), as follows:

Where ‘Intermediate’ is reported, this organism is still considered susceptible. This patient should be treated according to the standard Melioidosis Treatment Guidelines.

 

Many thanks

Andy

Direk Limmathurotsakul

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Mar 20, 2021, 5:55:28 AM3/20/21
to melio...@googlegroups.com

Dear everyone,

 

There is a new publication from a few of us talking about “Interpreting Burkholderia pseudomallei disc diffusion susceptibility test results by the EUCAST method” published at CMI https://pubmed.ncbi.nlm.nih.gov/33636339/ The paper is directly related to what we discussed in this group email.

 

Although we did request for open-access, the process with CMI is slow. CMI gave us a link to share for anyone to be able to download this paper freely by May 8, 2021 first. On behalf of David, I would like to share the link with you all.

Your personalized Share Link:
https://authors.elsevier.com/a/1cmJG,RGPgKYeR

David is working with CMI, and we hope that the paper will be fully open-access very soon.

 

Kind regards,


Direk

 

 

 

From: Elsevier - Article Status <Article...@elsevier.com>
Date: Friday, 19 March 2021 at 22:12
To: David Dance <Dav...@tropmedres.ac>
Subject: Share your article [CMI_2432] published in Clinical Microbiology and Infection

 

Elsevier

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Dear Dr. Dance,

We are pleased to let you know that your article Interpreting Burkholderia pseudomallei disc diffusion susceptibility test results by the EUCAST method is now available online with author corrections incorporated. Full citation details, e.g. volume and/or issue number, publication year and page numbers, will be added when the final version becomes available.

To help you access and share this work, we have created a Share Link – a personalized URL providing 50 days' free access to your article. Anyone clicking on this link before May 08, 2021 will be taken directly to the latest version of your article on ScienceDirect, which they are welcome to read or download. No sign up, registration or fees are required.

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