Ch Challe lenges for AST testin ting and AMR scr creening in in - - PowerPoint PPT Presentation

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The e nee eed for or a UAE Reference La Lab for or AMR Ch Challe lenges for AST testin ting and AMR scr creening in in UAE la labs Tibor Pl UAE In Inter ernational l Con Conference on on Antim timicrobial l Res esis istance

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SLIDE 1
  • T. Pál, Dept. Med. Microbiol. Immunol., CMHS

The e nee eed for

  • r a UAE Reference La

Lab for

  • r AMR

Ch Challe lenges for AST testin ting and AMR scr creening in in UAE la labs Tibor Pál UAE In Inter ernational l Con Conference on

  • n Antim

timicrobial l Res esis istance (IC (ICAMR)

Dub Dubai, 15-16 16 Mar arch 2018 2018

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SLIDE 2
  • T. Pál, Dept. Med. Microbiol. Immunol., CMHS

AN AMR REF LAB What it is NOT?

  • It is NOT a health care providing institution
  • NOT a diagnostic laboratory running diagnostic tests not run elsewhere
  • (This might be part of the tasks but definitely NOT one of the main ones)
  • NOT a commercial enterprise
  • It serves primarily public health purposes
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SLIDE 3
  • T. Pál, Dept. Med. Microbiol. Immunol., CMHS

AN AMR REF LAB What it is?

  • It is public health institution
  • Supporting clincial labs in their work
  • Addressing issues of public health concerns

Consequently, costs are not to be covered by patients or insurance companies but by the government

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SLIDE 4
  • T. Pál, Dept. Med. Microbiol. Immunol., CMHS

TASKS Hospital vs Ref Lab

Action Hospital laboratory Reference laboratory Clinically relevant susceptibility testing YES Seldom Detection of molecular background of selected resistance mechanisms Seldom YES Alertness and preparedness for new resistance mechanisms No YES Molecular typing No (seldom) YES QC of susceptibility testing At hospital level Coordinated over the coverage area Compiling and shareing susceptibility data At hospital level At the level of the coverage area Establishing a reference collection of strains At hospital level YES Targeted surveillance work Seldom YES Preparation (unification) of relevant guidelines No YES Education At hospital level At the level of the coverage area Coordination between hospitals No YES Connections with relevant international bodies No YES

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SLIDE 5
  • T. Pál, Dept. Med. Microbiol. Immunol., CMHS

TASKS Clinically relevant susceptibility testing

Clinically relevant – i.e. on time!!! Example – colsitin susceptibility testing 1 2 4 8 16 32 64 128 256 0,25 0,5 0,125 mg/L R > 2 mg/L S ≤ 2 mg/L

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SLIDE 6
  • T. Pál, Dept. Med. Microbiol. Immunol., CMHS

TASKS Clinically relevant susceptibility testing

Clinically relevant – i.e. on time!!! Example – colistin susceptibility testing 1 2 4 8 16 32 64 128 256 0,25 0,5 0,125 mg/L R > 2 mg/L S ≤ 2 mg/L

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SLIDE 7
  • T. Pál, Dept. Med. Microbiol. Immunol., CMHS

TASKS Detection of molecular background

Examples

  • mecA
  • vanA, vanB etc.
  • Various carbapenemases

Hospital lab Reference lab Methods Relying on kits May also use in-house tests Availability Seldom Yes Coverage of alleles etc. Varies Should be better Time Closer to be clinically relevant More time-consuming due to need to transfer samples Clinical relevance Yes Limited Surveillance relevance Limited Yes

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SLIDE 8
  • T. Pál, Dept. Med. Microbiol. Immunol., CMHS

TASKS Alertness and preparedness

Recent examples: new SCCmec types new carbapenemases (or their alleles) mcr-1, -2, -3, -4, -5

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SLIDE 9
  • T. Pál, Dept. Med. Microbiol. Immunol., CMHS

TASKS Molecular typing

A B C D E F G H I J K Tawam Al Ain Mafraq SKMC Rahba

AD1 (blaOXA69) AD2 (blaOXA64) AD3 (blaOXA66) Hospitals

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SLIDE 10
  • T. Pál, Dept. Med. Microbiol. Immunol., CMHS

EXAMPLE CRE in Abu Dhabi

Selected Annual Trends for Antimicrobial Resistance in Abu Dhabi Emirate Communicable Disease Bulletin 2017 8(1):7 (Data of Dr. Jens Thomsen)

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SLIDE 11
  • T. Pál, Dept. Med. Microbiol. Immunol., CMHS

EXAMPLE CRE in Abu Dhabi – 2009-2015

2 0 0 9 -1 0 (1 4 ) 2 0 1 1 (1 5 ) 2 0 1 2 (1 4 ) 2 0 1 3 (4 7 ) 2 0 1 4 (1 2 5 ) 2 0 1 5 (1 8 9 ) 5 0 1 0 0 1 5 0 2 0 0 2 0 4 0 6 0 8 0 1 0 0

Y e a rs (N ) N o . o f iso la te s in th e stu d y % c o ve ra g e

N o . o f is o la te s % c o v e ra g e

394 isolates 1st isolates from each patient with a unique carbapenem R mechanism

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SLIDE 12
  • T. Pál, Dept. Med. Microbiol. Immunol., CMHS

EXAMPLE CRE in Abu Dhabi – 2009-2015

M a fra q S K M C T a w a m A l A in Z a ye d M ilita ry R a h b a 1 0 2 0 3 0 4 0

%

H o s p ita ls

U r i n e R e s p i r a t

  • r

y W

  • u

n d B l

  • d

S c r e e n i n g U n k n

  • w

n 5 1 0 1 5 2 0 2 5

%

S a m p le ty p e K . p n e u m o n ia e E . co li E n te ro b a cte r sp . O th e r 2 0 4 0 6 0 8 0 1 0 0

%

3 2 4 4 5 1 5 1 0

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SLIDE 13
  • T. Pál, Dept. Med. Microbiol. Immunol., CMHS

CLINICAL USE Type of carbapenemases

N D M O X A V I M N D M

  • O

X A N D M

  • V

I M N

  • n

e M B L 1 0 2 0 3 0 4 0 5 0 C arb apen em ases % 9 8 1 7 3 3 5 6 1 6 3 1 5 8

In about 40% of the CRE cases the soon to be available beta-lactam/inhibitor combinations are not going to work Currently, most hospital laboratories do not detect MBL

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SLIDE 14
  • T. Pál, Dept. Med. Microbiol. Immunol., CMHS

CLINICAL USE Aminoglycoside resistance, 16S methylases

Carbapenemase produced (N) Frequency of 16S methylase within resistance group (%) Type of 16S methylase Frequency of types of 16S methylase (%) All (394) 43.4

  • NDM (98)

43.9 armA 92.9 rmtB 2.4 rmtC 4.8 rmtF 2.4 OXA-48-like (173) 46.8 armA 78.6 rmtB 1.2 rmtF 55.6 armA+rmtF 2.5 NDM+OXA (56) 78.6 armA 81.8 rmtF 2.3 armA+rmtF 9.1 armA+rmtB+rmtF 6.8 None (63) 4.8 rmtF 100

In over 40% of the CRE cases aminoglycoside therapy is useless

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SLIDE 15
  • T. Pál, Dept. Med. Microbiol. Immunol., CMHS

CLINICAL USE Colistin resistance

% Non-susceptible to CAZ CTX ETP IMI MER AZT TMP/ SMX CIP GM AK CHL COL TIG 93.1 95.9 100.0 89.1 84.5 89.8 85.0 88.1 74.6 52.3 75.4 16.2 57.6

As most hospital laboratories currently do not test for colistin susceptibility and, hence, colistin therapy is applied „blind”, every 6th-7th case is prone to fail to start with

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SLIDE 16
  • T. Pál, Dept. Med. Microbiol. Immunol., CMHS

PUBLIC HEALTH USE Molecular typing

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SLIDE 17
  • T. Pál, Dept. Med. Microbiol. Immunol., CMHS

PUBLIC HEALTH USE Prevalent clones

Clone N % among K. pneumoniae ST11 8 2.5 ST14 111 34.3 ST15 5 1.5 ST45 8 2.5 ST101 16 4.9 CC147 43 13.3 ST231 36 11.1 All clones 227 70.1 Sporadic isolates 97 29.9 The 4 major clones 206 63.6

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SLIDE 18
  • T. Pál, Dept. Med. Microbiol. Immunol., CMHS

PUBLIC HEALTH USE Clones are spreading

M a fra q (1 0 3 ) S K M C (8 5 ) T a w a m (6 9 ) A L A in (4 6 ) Z a ye d M ilita ry (1 2 ) R a h b a (9 ) 2 0 4 0 6 0 8 0 1 0 0 H ospitals (num ber of K . pneum oniae) % am o n g lo ca l K . p n eu m o n ia e

S T 1 4 (1 1 1 ) C C 1 4 7 (4 3 ) S T 2 3 1 (3 6 ) C C 1 0 1 (1 6 )

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SLIDE 19
  • T. Pál, Dept. Med. Microbiol. Immunol., CMHS

PUBLIC HEALTH USE Clones are highly resistant

Clones N % with MIC values MIC of IMI MIC of MER ≤4 ≤8 ≤4 ≤8 All clones 227 13.2 38.3 11.9 16.3 Sporadic 97 39.2 56.7 52.6 58.8 ST14 111 2.7 26.1 2.7 10.8 ST101 16 12.5 62.5 10.2 12.5 ST147 43 16.2 18.6 14.0 14.0 ST231 36 13.9 72.2 8.3 8.3 Strains with MIC ≤ 8 mg/L meropenem or imipenem can still be considered for carbapenem TX

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SLIDE 20
  • T. Pál, Dept. Med. Microbiol. Immunol., CMHS

PUBLIC HEALTH USE Clones are highly resistant

20 40 60 80 100

All clones ST14 Sporadic %

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SLIDE 21
  • T. Pál, Dept. Med. Microbiol. Immunol., CMHS

PUBLIC HEALTH USE Connecting the dots

The spread

  • f resistant bacteria

Clinical microbiology identifies “dots”, i.e. strains suspected to relate to each other (e.g. carba resistant same-species isolates) Molecular typing, “fingerprinting” Identifies those “dots” which are to be connected (i.e. strains which are similar enough likely to be related) Epidemiology connects the “dots”, i.e. reveals possible connections, modes of transmission

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SLIDE 22
  • T. Pál, Dept. Med. Microbiol. Immunol., CMHS

PUBLIC HEALTH USE How does it work?

Clinical microbiology identifies “dots”, i.e. strains suspected to relate to each other (e.g. carba resistant same-species isolates) Molecular typing, “fingerprinting” Identifies those “dots” which are to be connected (i.e. strains which are similar enough likely to be related) Epidemiology connects the “dots”, i.e. reveals possible connections, modes of transmission

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SLIDE 23
  • T. Pál, Dept. Med. Microbiol. Immunol., CMHS

PUBLIC HEALTH USE What do we have?

Clinical microbiology identifies “dots”, i.e. strains suspected to relate to each other (e.g. carba resistant same-species isolates) Molecular typing, “fingerprinting” Identifies those “dots” which are to be connected (i.e. strains which are similar enough likely to be related) Epidemiology connects the “dots”, i.e. reveals possible connections, modes of transmission

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SLIDE 24
  • T. Pál, Dept. Med. Microbiol. Immunol., CMHS

PUBLIC HEALTH USE What do we have?

Clinical microbiology identifies “dots”, i.e. strains suspected to relate to each other (e.g. carba resistant same-species isolates) Epidemiology connects the “dots”, i.e. reveals possible connections, modes of transmission

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SLIDE 25
  • T. Pál, Dept. Med. Microbiol. Immunol., CMHS

CHALLENGES

  • A considerable misunderstanding about what a reference lab is and what it

is good for

  • A lack of INTERNAL intent to have it, and hence, a lack of commitment to

have one (beyond verbal)

  • Fragmentation MOH, DHA, HAAD, …………
  • Lack of communication
  • Very different background of microbiologists and staff
  • Lack of uniformity
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SLIDE 26
  • T. Pál, Dept. Med. Microbiol. Immunol., CMHS

CHALLENGES Local challenges

  • It costs money
  • What can be promised in return?
  • It will not make money
  • It will not cure anybody
  • It will not make the problem go away
  • It may save (a lot of) money (and lifes) but that is indirect benefit

Will the decision makers take it and act upon it? Are those, who are professionally qualified, and are in positions to do so, willing and capable to take the case to those who are the real decision makers?

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SLIDE 27
  • T. Pál, Dept. Med. Microbiol. Immunol., CMHS

Action Hospital laboratory Reference laboratory Clinically relevant susceptibility testing YES Seldom Detection of molecular background of selected resistance mechanisms Seldom YES Alertness and preparedness for new resistance mechanisms No YES Molecular typing No (seldom) YES QC of susceptibility testing At hospital level Coordinated over the coverage area Compiling and shareing susceptibility data At hospital level At the level of the coverage area Establishing a reference collection of strains At hospital level YES Targeted surveillance work Seldom YES Preparation (unification) of relevant guidelines No YES Education At hospital level At the level of the coverage area Coordination between hospitals No YES Connections with relevant international bodies No YES

TASKS Why a reference lab is needed?

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SLIDE 28
  • T. Pál, Dept. Med. Microbiol. Immunol., CMHS

It is easy to foul an outsider

What is behind the door?

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SLIDE 29
  • T. Pál, Dept. Med. Microbiol. Immunol., CMHS

Thank you

Do not „Slowly, slowly” Do not „gradually” Do not „step by step”… We are already, dangerously way behind……