Antimicrobial Resistance Surveillance Systems and Bias!

Antimicrobial Resistance Surveillance Systems and bias!

Gunnar Kahlmeter ESCMID Online Lecture Library AMR Surveillance

• International official programmes – none • European official programmes – EARSS / EARS-NET • National official programmes – Many initiatives • Many commercial intiatives – Alexander project – SENTRY © by author – MYSTIC – ECO-SENS Links to national and international programmes: http://www.ecdc.europa.eu/en/activities/surveillance – … ESCMID Online/EARS-Net/external_sites/Pages/external_sites.aspx Lecture Library

Systems

• Commercial systems – often pointed toward a specific microorganism and/or class of drugs (Alexander project (URTI), ECO-SENS (E.coli)) – Isolates sent to central laboratory (cash per isolate) • Voluntary manual reporting of certain microorganisms, drugs and infections (EARS-NET) • Voluntary computer-supported or fully automatic reporting of some/all microrganisms (NL, SE) • Mandatory reporting systems© by for author – defined bacteria (M.tb) – defined resistance geno/phenotypes (MRSA, VRE, NDM1, etc) ESCMID Online Lecture Library AMR surveillance is biased because it is based on routine ”consecutive” isolates

• Bias – The Sick – ”we do not culture the healthy” – The Failures – ”we only culture when therapy fails” © by author

ESCMID Online Lecture Library How and where we collect our data will affect resistance levels 1. Breakpoints 2. Associated resistance 3. ”Repeat isolates from a single patient” – rare resistance 4. ”Repeat isolates from several patients” – clonal outbreak 5. Frequency of sampling 6. Origin of patients i. International influence/local strains ii. suburban/countryside© ,by author iii. ICU/hospital/primary care 7. Age 8. Gender ESCMID Online Lecture Library Examples of bias:

ESCMID Online Lecture Library Associerad resistens

ESCMID Online Lecture Library Associated resistance: Resistance rates resulting from independant susceptibility tests are lower than those obtained through an algorithm (see cefotaxime; all tests 8.8%, independant tests 5.3%).

ESCMID Online Lecture Library Västra Götaland county, Sweden Skåne county, Sweden 80% 80% 0-12 years > 12 years 70% 0-12 years 70% > 12 years 60% 60% 50% 50% 40% 40% 30% 30% 20% 20% 10% 10% 0% 0% 1990 1992 1994 1996 1998 2000 2001 2003 1990 1992 1994 1996 1998 2000 2001 2003 Fusidic acid resistance in S.aureus in children (0 – 12 yrs) and in adults (>12 yrs)

Blekinge county, Sweden Kronoberg county, Sweden

80% 80% 0-12 years 70% > 12 years 70% 0-12 years 60% 60% > 12 years 50% © by 50%author 40% 40% 30% 30% 20% 20% 10% 10% 0% ESCMID Online Lecture0% Library 1990 1991 1992 1993 1994 1995 1996 1997 1998 1999 2000 2001 2001 2002 2003 1990 1992 1994 1996 1998 2000 2001 2003 Penicillin non-susceptibility over time in a county in Sweden Streptococcus pneumoniae Penicillin MIC >0.125 mg/L Kronoberg county (%) Lagan (No of isolates) 50 25

40 20 Two contingents of refugees August 1992, May 1993. 30 15

20 10

10 © by author 5

0 0 92ESCMID 93 94 95Online96 Lecture97 Library 98 99 00 01 Streptococcus pyogenes Quarterly and yearly (red) rates Kronoberg county, Sweden Events (unrelated to the use of the drug) may affect resistance Erythromycin resistance (%) 25

10 © by author 5

0 90 91ESCMID 92 93 94 Online 95 96 Lecture 97 98 99 Library 00 01 02 03 04 05 G Kahlmeter mfr22000:22 2006-02-01 Breakpoints obviously afect resistance levels

E.coli vs. Ciprofloxacin in EARSS 2002 EARSS dataGermany from Germanyand Sweden and Sweden Per cent resistance with the various R-breakpoints >0.125 mg/L = 8.3 % 500 >1 mg/L = 4.3 % 450 >2 mg/L = 3.9 % 400 WT <0.064 mg/L = 12.7 % 350 300 250 200 150 100 50 © by author 0 0,002 0,004 0,008 0,016 0,032 0,064 0,125 0,250 0,500 1,000 2,000 4,000 8,000 ESCMID Online Lecture Library 16,000 32,000 S.pneumoniae vs. penicillin 1995 - 2006 Resistance rates based on 100, 200 and 500 consecutive clinical isolates.

20 100 200 15 500

5 © by author

0 0 ESCMID1000 2000 Online3000 Lecture4000 5000Library6000 7000 E. coli vs ampicillin 22,0%

20,0%

18,0%

16,0%

14,0%

12,0%

10,0% resistance rate resistance 8,0%

6,0%

4,0%

2,0%

0,0% 1990 1991 1992 1993 1994 1995© by1996 author1997 1998 1999 2000 2001 2002 2003

Effect on ampicillin resistance rate in community isolates of E. coli of different time cut-offs for the exclusion of duplicate isolates. Bars in the following order: No exclusion,ESCMID Exclusion algorithm Online 7, 14, 30, Lecture 45, 90, 180, 270 Library and 365 days. ResNet 2009; E.coli, Nalidixinsyra (090504) 13,6% R

ESCMID Online Lecture Library ResNet 2009: E.coli från urin Sweden

35 30,5 2002 30 2003

25 2004 20,7 20 2005 % R 15 13,6 2006 2007 10 2008 3,6 5 1,8 1,8 © by author 2009 0 Ampicillin Mecillinam Cefadroxil Nitrofurantoin Quinolones (=Nal) Trimethoprim

ESCMID Online Lecture Library

ESCMID Online Lecture Library Highlights of EARS-Net Annual Report 2009

Courtesy of Ole Heuer and the EARS-NET team ECDC

ESCMID Online Lecture Library

Pathogens in EARS-NET • S. aureus • E. coli • K. pneumoniae • P. aeruginosa • E. faecalis and E. fecium • S. pneumoniae

ESCMID Online Lecture Library Countries participating in EARS-Net in 2010

As of January 1st, 2010, five non-EU Member States previously participating in EARSS (Bosnia-Herzegovina, Croatia, Israel, Switzerland and Turkey)ESCMID had to be detached from theOnline network. Lecture Library EARS-Net Annual Report 2009

The EARS-Net Annual report 2009 (pdf) is available at the ECDC homepage: http://ecdc.europa.eu/en/Pages/home.aspx The report can be found under “recent publications”.

Escherichia coli: Proportion of invasive isolates with resistance to fluoroquinolones in 2009 (data: EARS-Net) ESCMID Online Lecture Library

Escherichia coli: Proportion of third generation cephalosporin resistance in 2009 (Data: EARS-Net) ESCMID Online Lecture Library ESBL in E. coli and K. pneumoniae

ESCMID Online Lecture Library

Staphylococcus aureus: proportionESCMID of invasive isolates Online resistant to meticillin Lecture (MRSA) in 2009Library (Data: EARS -Net)