Selective reporting of of antibiotic susceptibility testing a Scandinavian experience and a EUCAST perspective Gunnar Kahlmeter Clinical microbiology Central Hospital 351 85 Växjö EUCAST Technical Data Coordinator EUCAST Development Laboratory ESCMID Past President
I have good news and bad news • The Bad news – my french is so bad I will not be able to give my presentation in your language. • The Good news – I will not give my presentation in my language
Selective reporting of antibiotic susceptibility test results in European countries: an ESCMID cross-sectional survey. Well implemented Partially implemented Not implemented Pulcini et al. International Journal of Antimicrobial Agents 2017 doi: 10.1016/j.ijantimicag.2016.11.014
Decrease over 10 years No change over 10 years Increase over 10 years The 10-year trend
Antimicrobial stewardship – to encourage appropriate and abolish unnecessary and poor use of antibiotics. …to ascertain best therapy for current and future patients through behavioural changes which in the end will slow, halt or revert antimicrobial resistance development. Success can be measured in 1. Behavioural changes 2. Resistance rates Hazards when measuring resistance rates:
We are often disappointed when trying to correlate changes in antimicrobial CONSUMPTION to changes in RESISTANCE. Also, we enthusistically embrace our positive results and immediately discard the failures.
(UK) (Sweden) The major difference in resistance between UK and Sweden is not explained by differences in consumption. Data from EARSS
Antimicrobial consumption UK SE Data: European Surveillance of Antimicrobial Consumption ( ESAC ) G Kahlmeter 2019
G Kahlmeter 2019
Streptococcus pyogenes Kronoberg county, Sweden Erythromycin resistance (%) 25 ERGAS 2002 - 19 20 25 20 15 15 10 5 0 10 2002 2004 2006 2008 2010 2012 2014 2016 2018 5 0 90 91 92 93 94 95 96 97 98 99 00 01 02 G Kahlmeter mfr22000:21 2002-06-02
Which antibiotics and how much we use is influenced by how dia iagnostics are used. 1. AST reports - relevant organisms only? • If we issue AST reports for 20 antibiotics on all Ps aeruginosa , colleagues will assume it is important. 2. AST - what we test and what we report? • If every E. coli is reported resistant to erythromycin, colleagues will assume that on another day erythromycin might be an alternative. 3. AST - quality (clinical trust)? It is often said that the Scandinavians are good at this – let us see.
Questionnaire to Scandinavian countries, Wales and Germany – October 2019 • Trusted colleagues and friends in these countries were asked to summarise their ”national practice ” in response to distributed questions. • When you see slides like this, these are questionnaire results. Denmark Germany Sweden Norway Finland Wales As standard practice? Y (Y)* Y Y Y N N/Y # For epidemiology and stewardship Y Y Y Y N
In your country, are colleagues recommended to test more agents than those released in the report …. Denmark Germany Sweden Norway Finland Wales As standard practice? Y Y Y Y Y N N/Y * For epidemiology and stewardship Y Y Y Y N * For stewardship only
Is the budget (income) of the laboratory related to…. Denmark Germany Norway Sweden Finland Wales N N Y N N Y Number of AST performed N N N N N Y Number of agents reported N N N N* N Y AST method used *Extended testing with brothmicrodilution in multiresistant bacteria may be invoiced separately
Would you say your country is restrictive … Would you say your country is Denmark Germany Norway Sweden Finland Wales restrictive … … when performing AST Y Y Y Y Y N … with the number of agents reported N N (N) Y Y N … with which agents are reported N Y Y Y Y N
Are there national guidelines for which agents to include in the AST report …. Denmark Finland Norway Sweden Wales Germany Lower uUTI N N* Y Y Y N Upper cUTI N N Y Y Y N Respir pathogens in nph N N Y Y Y N Blood stream infections N N Y Y Y N Other N N Y Y Y N *Work ongoing
E. coli in uUTI in primary care … how many antibiotics are normally Denmark Finland Norway Sweden Tested? 6 5 - 7 10 4-5 Reported? 6 5 - 7 5 5 …agents reported? ampicillin amox-clav amoxicillin cefadroxil mecillinam mecillinam mecillinam mecillinam trimethoprim trimethoprim trimethoprim trimethoprim sulfamethoxa trimsulfa trimsulfa - nitrofurantoin nitrofurantoin nitrofurantoin nitrofurantoin (ciprofloxacin) ciprofloxacin (ciprofloxacin)
E. coli in uUTI in primary care … how many antibiotics are Wales Germany Tested? 6-11 12-16 Reported? 4-6 12-16 …agents always reported mecillinam AMP, ASU, PTZ, (MEC) CXM, CTX, CPD, trimethoprim CAZ, MER, IPM nitrofurantoin NIT, FOS, CIP fosfomycin
E. coli in cUTI in a hospitalised patient… how many antibiotics are normally Denmark Finland Norway Sweden Tested? 12 12 11 5+ Reported? 8-10 12 8-9 5 …agents reported variation amox-clav ampicillin cefadroxil ++ Mecillinam/piptaz mecillinam mecillinam ceftriax/ceftazidime cefotaxime trimethoprim trimsulfa trimsulfa - nitrofurantoin nitrofurantoin nitrofurantoin ciprofloxacin ciprofloxacin ciprofloxacin meropenem meropenem fosfomycin gentamicin
E. coli in cUTI in a hospitalised patient… how many antibiotics are normally Wales Germany Tested? 6 - 12 12-16 Reported? 4 - 6 12-16 …agents reported MEC, TRI, NIT, FOS AMP, ASU, PTZ, (MEC) CXM, CTX, CPD, CAZ, MER, CIP, CPD, AMO-CLA IPM NIT, FOS, CIP
What will make laboratories ext xtend/increase the number of of agents tested? Denmark Germany Sweden Norway Finland Wales Clinical request for a specific agent? Y Y Y Y Y Y Clinical general request for broader panels? Y Y Y Y Y Y Resistance to agents in the standard panel? Y Y Y Y Y Y National guidelines? - - Y Y Y (Y) Reimbursement? N N N N - -* *Reimbursement not applicable – the maximum number is already tested.
Effects of of issuing guidelines, , recommendations and/or short AST reports?
Sweden Outpatient sales This group of people is increasing Swedish Public Health Agency
Swedish official guidance for treatment of UTI since almost 10 years. • STOP using • Ciprofloxacin/levofloxacin • Trimethoprim • START using • Pivmecillinam • Nitrofurantoin
Sales in UTI in women Sales in UTI in men Mecillinam Fluoroquinolone Nitrofurantoin Fluoroquinolone Trimethoprim Nitrofurantoin Trimethoprim Swedish Public Health Agency
.. ..the proof is in the pudding…… x x behaviour! resistance?
Resistance in E. coli in UTI Swedish national data 2009 - 2018 Ampicillin/Amoxicillin Trimethoprim Fluoroquinolones # Cefadroxil # Mecillinam Nitrofurantoin # Influx of ESBLs increase cephalosporin and fluroquinolone resistance Swedish Public Health Agency
National data may be ” average ”. How about lo local data? Over a lo longer tim ime frame?
Is resistance to E. coli - Kronoberg county, Sweden % resistance trimethoprim and Primary care, age 2 - 65 years ciprofloxacin levelling off? Is resistance to mecillinam 25 Resistance over 30 years increasing? 20 15 Trimethoprim 10 Ciprofloxacin 5 Mecillinam Nitrofurantoin 0 1990 1991 1992 1993 1994 1995 1996 1997 1998 1999 2000 2001 2002 2003 2004 2005 2006 2007 2008 2009 2010 2011 2012 2013 2014 2015 2016 2017 2018 2019 Trimethoprim Ciprofloxacin Mecillinam Nitrofurantoin
.. ..the proof is in the pudding…… x x behaviour! ? resistance?
Sele lective testing or selective reporting • Selective testing – testing and reporting few antibiotics • to encourage the use of some and discourage the use of other antibiotics • to save time and money • always combined with ” cascade testing ” • Selective reporting – test many but release results only as needed. • to encourage the use of some and discourage the use of other antibiotics • to contribute to AMR surveillance • to avoid the negative epidemiological effects of ” cascade testing ”
”Cascade testing ” alg lgorithms corrupt AMR data: • Any isolate, resistant to one agent (even if not chemically related) is much more likely to be resistant to any other agent! • Cross resistance • Associated resistance • So if some agents are tested because of resistance to others, even when unrelated, resistance rates in these agents will be erroneously high. By much?
Cascade testing and associated resistance
International and national diagnostic stewardship guidelines • International guidelines need to be very general • National or regional guideline • Resistance patterns • Tradition • Availability of agents • Goals should be clear and tiered • Do not be too prescriptive – define minimum criteria (one 3rd gen cephalosporine, one fluoroquinolone, one aminoglycoside) • Start with primary care recommendations, start with uUTI • Seek consensus and joint ownership during development
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