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 Pál UAE In Inter ernational l Con Conference on on Antim timicrobial l Res esis istance (IC (ICAMR) Dub Dubai, 15-16 16 Mar arch 2018 2018 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 o (This might be part of the tasks but definitely NOT one of the main ones) • NOT a commercial enterprise o It serves primarily public health purposes T. Pál, Dept. Med. Microbiol. Immunol., CMHS
AN AMR REF LAB What it is? • It is public health institution o Supporting clincial labs in their work o Addressing issues of public health concerns Consequently, costs are not to be covered by patients or insurance companies but by the government 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 Seldom YES selected resistance mechanisms Alertness and preparedness for new No YES resistance mechanisms Molecular typing No (seldom) YES QC of susceptibility testing At hospital level Coordinated over the coverage area Compiling and shareing susceptibility At hospital level At the level of the coverage area data Establishing a reference collection of At hospital level YES strains Targeted surveillance work Seldom YES Preparation (unification) of relevant No YES guidelines Education At hospital level At the level of the coverage area Coordination between hospitals No YES Connections with relevant international No YES bodies T. Pál, Dept. Med. Microbiol. Immunol., CMHS
TASKS Clinically relevant susceptibility testing Clinically relevant – i.e. on time!!! Example – colsitin susceptibility testing S ≤ 2 mg/L R > 2 mg/L 0,125 0,25 0,5 1 2 4 8 16 32 64 128 256 mg/L T. Pál, Dept. Med. Microbiol. Immunol., CMHS
TASKS Clinically relevant susceptibility testing Clinically relevant – i.e. on time!!! Example – colistin susceptibility testing S ≤ 2 mg/L R > 2 mg/L 0,125 0,25 0,5 1 2 4 8 16 32 64 128 256 mg/L 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 Closer to be clinically More time-consuming due Time relevant to need to transfer samples Clinical relevance Yes Limited Surveillance relevance Limited Yes T. Pál, Dept. Med. Microbiol. Immunol., CMHS
TASKS Alertness and preparedness Recent examples: new SCC mec types new carbapenemases (or their alleles) mcr-1, -2, -3, -4, -5 T. Pál, Dept. Med. Microbiol. Immunol., CMHS
TASKS Molecular typing Tawam Al Ain Mafraq SKMC A B C D E F G H I J K Rahba Hospitals AD3 ( bla OXA66 ) AD1 ( bla OXA69 ) AD2 ( bla OXA64 ) 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 ) T. Pál, Dept. Med. Microbiol. Immunol., CMHS
EXAMPLE CRE in Abu Dhabi – 2009-2015 394 isolates 1st isolates from each patient with a unique carbapenem R mechanism 2 0 0 1 0 0 N o . o f iso la te s in th e stu d y 8 0 % c o v e ra g e 1 5 0 N o . o f is o la te s % c o ve ra g e 6 0 1 0 0 4 0 5 0 2 0 0 0 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 ) Y e a rs (N ) T. Pál, Dept. Med. Microbiol. Immunol., CMHS
EXAMPLE CRE in Abu Dhabi – 2009-2015 4 0 2 5 2 0 3 0 1 5 2 0 % % 1 0 1 0 5 0 0 A l A in M a fra q S K M C Z a ye d M ilita ry R a h b a e y d d n T a w a m g n r n o n w o i u o i r t n o o l U a B n e r W i k e p n r s c U e S R H o s p ita ls S a m p le ty p e 1 0 0 3 2 4 8 0 6 0 % 4 0 2 0 4 5 1 5 1 0 0 E n te ro b a cte r sp . K . p n e u m o n ia e E . co li O th e r T. Pál, Dept. Med. Microbiol. Immunol., CMHS
CLINICAL USE Type of carbapenemases 5 0 1 7 3 1 5 8 4 0 3 0 9 8 % 2 0 6 3 5 6 1 0 3 1 0 A M A e L M M B X n I X D I V o V M O O N N - - M M D D N N C arb apen em ases 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 T. Pál, Dept. Med. Microbiol. Immunol., CMHS
CLINICAL USE Aminoglycoside resistance, 16S methylases Frequency of 16S Frequency of Carbapenemase Type of 16S methylase within types of 16S produced (N) methylase resistance group (%) methylase (%) All (394) 43.4 - - armA 92.9 rmtB 2.4 NDM (98) 43.9 rmtC 4.8 rmtF 2.4 armA 78.6 rmtB 1.2 OXA-48-like (173) 46.8 rmtF 55.6 armA+rmtF 2.5 armA 81.8 rmtF 2.3 NDM+OXA (56) 78.6 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 T. Pál, Dept. Med. Microbiol. Immunol., CMHS
CLINICAL USE Colistin resistance % Non-susceptible to TMP/ CAZ CTX ETP IMI MER AZT CIP GM AK CHL COL TIG SMX 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 6 th -7 th case is prone to fail to start with T. Pál, Dept. Med. Microbiol. Immunol., CMHS
PUBLIC HEALTH USE Molecular typing 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 T. Pál, Dept. Med. Microbiol. Immunol., CMHS
PUBLIC HEALTH USE Clones are spreading 1 0 0 S T 1 4 (1 1 1 ) % am o n g lo ca l K . p n eu m o n ia e C C 1 4 7 (4 3 ) 8 0 S T 2 3 1 (3 6 ) C C 1 0 1 (1 6 ) 6 0 4 0 2 0 0 A L A in (4 6 ) Z a ye d M ilita ry (1 2 ) M a fra q (1 0 3 ) S K M C (8 5 ) R a h b a (9 ) T a w a m (6 9 ) H ospitals (num ber of K . pneum oniae ) T. Pál, Dept. Med. Microbiol. Immunol., CMHS
PUBLIC HEALTH USE Clones are highly resistant Strains with MIC ≤ 8 mg/L meropenem or imipenem can still be considered for carbapenem TX % with MIC values Clones N MIC of IMI MIC of MER ≤4 ≤8 ≤4 ≤8 13.2 38.3 11.9 16.3 All clones 227 39.2 56.7 52.6 58.8 Sporadic 97 2.7 26.1 2.7 10.8 ST14 111 12.5 62.5 10.2 12.5 ST101 16 16.2 18.6 14.0 14.0 ST147 43 13.9 72.2 8.3 8.3 ST231 36 T. Pál, Dept. Med. Microbiol. Immunol., CMHS
PUBLIC HEALTH USE Clones are highly resistant All clones % 100 ST14 Sporadic 80 60 40 20 T. Pál, Dept. Med. Microbiol. Immunol., CMHS
PUBLIC HEALTH USE Connecting the dots Clinical microbiology identifies “dots”, i.e. strains suspected to The spread relate to each other of resistant bacteria (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 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 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 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 T. Pál, Dept. Med. Microbiol. Immunol., CMHS
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