Antimicrobial resistance and strategies for Gram-negative bacteria - - PowerPoint PPT Presentation

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Antimicrobial resistance and strategies for Gram-negative bacteria - - PowerPoint PPT Presentation

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Antimicrobial resistance and strategies for Gram-negative bacteria Y Glupczynski UCL Mont-Godinne Belgium Epidemiology of antimicrobial resistance Several bias Selection of participating centres (bedsize,, activity, types of patients,

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Antimicrobial resistance and strategies for Gram-negative bacteria

Y Glupczynski UCL Mont-Godinne Belgium

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SLIDE 2

Epidemiology of antimicrobial resistance

Several bias

Selection of participating centres (bedsize,, activity, types of patients, pathologies, length of stay,…) Wide variations in study designs (many surveillance programs sponsored by industry) Variability/modification of definitions/criteria Differences/changes over time of susceptibiltiy testing methods and/or antibiotics tested (lack of standardisation)

Many « Snapshot » studies, few longitudinal, continous surveillance studies Studies more frequently focused on selected populations

(ICUs, Hematology,…) or on selected antibiotics

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Surveillance studies on resistance among Gram-negative organisms

  • Community-acquired and nosocomial pathogens
  • Enterobacteriaceae
  • Pseudomonas aeruginosa
  • Data gathered from local, Belgian multicentric studies (1995-2004)
  • NPRS program (1995-2001): ICU only (15-25 centres)
  • MYSTIC program (1998-2004); ICU, hematology, CF, general wards (8

centres)

  • EARSS (2001-2003); invasive E. coli infections, hospitalwide (27 centres)
  • Others
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SLIDE 4

Escherichia coli

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SLIDE 5

Organisms most frequently isolated in nosocomial bacteremia Oct 1992-Juin 2001

0% 10% 20% 30% 40% 50%

Proteus sp. Serratia sp. Acinetobacter sp. Klebsiella sp. Enterococcus sp. Pseudomonas sp. Streptococcus sp. Candida sp. Enterobacter sp.

  • S. aureus

Escherichia sp. Coag.-neg. Staph.

Secondary Primary Catheter Scientific Institute of Public Health

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SLIDE 6

Antimicrobial resistance of Escherichia coli invasive isolates from blood

EARSS report- 2003

C3 G-resistance FQ-resistance

http://www.earss.rivm.nl

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SLIDE 7

Antimicrobial susceptibility in invasive

  • E. coli isolates from bloodstream infections

(Belgium 2002 – EARSS Report)

55 46

10 20 30 40 50 60

Amox/Ampi Cipro Genta Cefotax Ceftaz

>48 h admitted <48 h admitted

48,5

% reduced susceptibility (NCCLS)

5,9 13,3 2,8 3,0 N= 1185 (27 hospitals)

1,9% ESBL-positive P < 0.005 Hendrickx & Pierard, ECCMID 2004

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SLIDE 8

Multidrug resistance in E. coli blood or CSF isolates according to EARSS protocol

(Belgium 2002)

43,9 48,4 49,5 46,2 6,6 5,4

5 10 15 20 25 30 35 40 45 50

Resistant to 0 antibiotic classes Resistant to 1-2 antibiotic classes Resistant to 3-4 antibiotic classes

>48 h admitted <48 h admitted

48% 6%

* % reduced susceptibility (NCCLS)

*aminopenicillins, C3G, aminoglycosides, quinolones

Hendrickx & Pierard, ECCMID 2004

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SLIDE 9

E.coli invasive isolates resistant to fluoroquinolones

(2001-2003)

http://www.earss.rivm.nl * * * * * * * Increase of resistance to FQ in 15/25 countries

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Escherichia coli invasive isolates resistant to 3rd gen. cephalosporins

(2001-2003)

* * * * *

Increase of resistance in 7/25 countries

↔ Spread of CTX-M ESBLs in E.coli * http://www.earss.rivm.nl

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SLIDE 11

30,7 2,9 1,5 0,7 14,6 6,6 2,9 0,7 0,7 0,7

5 10 15 20 25 30 35

A M P I A M C M E C C D R O X S X T N A L C I P R O N I T F O S G E N

Antimicrobial susceptibility of E. coli from

  • utpatients with uncomplicated UTI
  • The ECO-SENS Project (1999-2000)-

% resistance rate

Kahlmeter, JAC 2003; 51:69-76 N=275 pts (12 centres)

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SLIDE 12

Enterobacteriaceae

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SLIDE 13

Gram- Negative pathogens isolated from Belgian (8) ICUs from 1997-2000

Pseudomonas aeruginosa 383 (21,6%) Escherichia coli 343 (19,4%) Enterobacter cloacae 165 ( 9,3%) Enterobacter aerogenes 137 ( 7,7%) Proteus mirabilis 132 ( 7,5%) Klebsiella pneumoniae 123 ( 6,9%) Serratia marcescens 103 ( 5,8%) Klebsiella oxytoca 88 ( 5,0%) Acinetobacter baumanii 32 ( 1,8%) Other 265 (15,0%) MYSTIC Program, Belgium data Goossens, JAC 2001

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Activity vs Enterobacteriaceae

Enterobacteriaceae - MYSTIC Belgium - 1998/2004

50 60 70 80 90 100 MER IMI CAZ CPM PTZ CIP AMU % susceptible strains

1998 1999 2000 2001 2002 2003 2004

n=512 n=602 n=746 n=581 n=512 n=650 n=803

MYSTIC Program Belgium data

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Trends in Antimicrobial Spectrum and Potency for Enterobacteriaceae

MIC90 (% susceptibility) Agent Year n MEM IMP CAZ CEP 1998 512 0.064 (99.8) 1 (98.8) 32 (84.4) 1 (97.7) 1999 602 0.125 (99.8) 2 (96.5) 32 (84.6) 2 (97.5) 2000 746 0.064 (100) 1 (99.1) 32 (85.1) 1 (99.8) 2001 581 0.064 (99.8) 1 (98.6) 16 (88.5) 0.5 (99.5) 2002 512 0.032 (100) 1 (98.1) 32 (87.7) 0.5 (98.8) 2003 650 0.064 (100) 1 (98.8) 16 (88.3) 1 (98.4) 2004 803 0.125 (99.8) 2 (96.8) 128 (81.3) 2 (98.3) MYSTIC Program, Belgium data

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SLIDE 16

Trends in Antimicrobial Spectrum and Potency for Enterobacteriaceae

MIC90 (% susceptibility) Agent Year n TAZ AMI CIP 1998 512 32 (89.1) 8 (97.7) 8 (85.6) 1999 602 16 (91.2) 4 (98.7) 4 (86.1) 2000 746 16 (90.8) 4 (99.0) 8 (85.9) 2001 581 16 (93.6) 4 (99.3) 2 (88.6) 2002 512 16 (92.4) 4 (98.1) 8 (86.1) 2003 650 32 (85.9) 8 (95.9) 8 (85.2) 2004 803 128 (77.1) 16 (92.8) 32 (79.6) MYSTIC Program, Belgium data

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Trends over Time in Susceptibility of Enterobacter aerogenes to several antimicrobial agents

Enterobacter aerogenes - MYSTIC BELGIUM 1998/2004

20 40 60 80 100 MER IMI CAZ CPM TAZ CIP AMU % susceptible strains

1998 1999 2000 2001 2002 2003 2004

N=59 N=68 N=88 N=65 N=50 N=72 N=107

MYSTIC Program, Belgium data

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SLIDE 18

Distribution of nosocomial Gram-negative bacteria isolated from ICU patients

> 50% < repiratory tract

10 20 30

%

Pyo

  • E. coli
  • E. aerog.
  • K. pneu.
  • P. mirab.

1996-97 1998-99 2000-01

Glupczynski, Acta Clin Belgica 2001

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SLIDE 19

Trends in Antimicrobial Spectrum and Potency for E. aerogenes (up to 2003)

1 0 1 0 2 0 2 0 3 0 3 0 4 0 4 0 5 0 5 0 6 0 6 0 7 0 7 0 8 0 8 0 9 0 9 0 1 0 1 0 0 M E M ER I M I CAZ CPM PT PT Z CI P % s % suscept ceptible s strains

Be lg lgiu ium N orthe r he rn Eur n Europe pe Sout Southe r he rn Eur Europe

  • pe

U SA U SA

NE : Germany, UK,Finland,Sweden SE : Italy, Spain, Portugal, Greece, Malta

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Extended-Spectrum ß-Lactamases (ESBL)

  • TEM and SHV mutants (+ other emerging ESBLs; eg. CTX-M)
  • Initially reported in K. pneumoniae, than spread to other

Enterobacteriaceae species

  • Plasmid-mediated
  • Worldwide prevalent, especially in the ICU
  • Risk factor for selection: ceftazidime
  • Resistant to cephalosporins, aztreonam, piperacillin
  • Therapeutic options :
  • carbapenems
  • others ? (cefepime, inhibitor combinations)
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SLIDE 21

Prevalence of ESBL Producing Enterobacteriaceae in Europe

% ESBL Country 1997 1998 1999 2000 2001 2002 Russia 24 34 42 47 22 30 Poland 37 23 21 40 33 37 Turkey

  • 23

40 21 26 Czech Republic 5 8 8 6 14 10 Italy 40 10 15 9 11 7 UK 5 7 22 7 6 11 Germany 2 3 1 5 2 3 Belgium

  • 6

5 8 5 8

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SLIDE 22

Trends in the Occurrence of ESBL Phenotype Strains of E.coli

2 4 6 8 1 0 1 0 1 2 1 2 1 9 9 8 1 9 9 8 1 9 9 9 1 9 9 9 2 0 0 0 2 0 0 0 2 0 0 1 2 0 0 1 2 0 0 2 2 0 0 2 2 0 0 3 2 0 0 3 2 0 0 4 2 0 0 4

% E % ESBL

Be Be lgium Eu Europe U S U SA

2%

N=156 N=147 N=166 N=153 N=157 N=195 N=176

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SLIDE 23

Trends in the Occurrence of ESBL Phenotype Strains of K.pneumoniae

5 1 0 1 0 1 5 1 5 2 0 2 0 2 5 2 5 3 0 3 0 1 9 9 8 1 9 9 8 1 9 9 9 1 9 9 9 2 0 0 0 2 0 0 0 2 0 0 1 2 0 0 1 2 0 0 2 2 0 0 2 2 0 0 3 2 0 0 3 2 0 0 4 2 0 0 4

% ESB ESBL

Be lgium lgium Eu Europe U S U SA

9%

N=46 N=64 N=81 N=63 N=51 N=88 N=85

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SLIDE 24

Activity of Meropenem and Comparator Agents against ESBL-and AmpC-producing Strains in Europe

Organism

  • No. ESBL-or AmpC-

MEM IMP TAZ CIP GM producing strains/ MIC90 MIC90 MIC90 MIC90 MIC90

  • no. isolates tested (%)

(%S)a (%S) (%S) (%S) (%S) ESBL producers:

  • E. coli

338/5487 (6.2) 0.125 (100) 0.5 (99.4) 128 (69.5) 64 (37.6) >128 (53.4)

  • K. pneumoniae

382/3004 (12.7) 0.125 (99.7) 0.5 (99.5) >128 (48.8) 32 (63.7) >128 (33.9) AmpC-producers:

  • C. freundii

107/414 (25.8) 0.25 (100) 2 (100) >128 (27.4) 16 (74.8) 32 (84.3)

  • E. cloacae

557/2056 (27.1) 0.5 (98.7) 2 (98.7) >128 (14.6) 16 (79.4) 128 (75.1)

  • S. marcescens

107/1011 (10.6) 1 (99.1) 4 (94.3) >128 (33.0) 32 (54.2) >128 (53.0) MEM=meropenem; IMP=imipenem; CAZ=ceftazidime; TAZ=piperacillin+tazobactam; CIP=ciprofloxacin; GM=gentamicin

aSusceptibility criteria of the NCCLS 2002

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SLIDE 25

Pseudomonas aeruginosa

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SLIDE 26

Most frequently isolated micro-organisms in early and late nosocomial pneumonia 1997-2002 (n=5119)

P s e u d

  • m
  • n

a s s p p . 0% 5% 10% 15% 20% 25% S t a p h y l

  • c
  • c

c u s a u r e u s E n t e r

  • b

a c t e r s p p . E s c h e r i c i a s p p . C a n d i d a s p p . K l e b s i e l l a s p p . H a e m

  • p

h i l u s s p p . S e r r a t i a s p p . S t r e p t

  • c
  • c

c u s s p p . P r

  • t

e u s s p p . S t e n

  • t

r

  • p

h

  • m
  • n

a s s p p . A c i n e t

  • b

a c t e r s p p . M

  • r

g a n e l l a s p p . E n t e r

  • c
  • c

c u s s p p . A s p e r g i l l u s s p p .

< D7 > = D7

Scientific Institute of Public Health

  • C. Suetens, IPH Seminar, 22/11/2002
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SLIDE 27

Antimicrobial susceptibility of P. aeruginosa isolates in Belgian hospitals

Van Eldere, JAC 2003; 51: 347-52

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SLIDE 28

Activity vs Pseudomonas aeruginosa

Pseudomonas aeruginosa - MYSTIC Belgium - 1998/2004

10 20 30 40 50 60 70 80 90 100 MER IMI CAZ CPM PTZ CIP AMU % susceptible strains

1998 1999 2000 2001 2002 2003 2004

n=263 n=211 n=233 n=264 n=214 n=204 n=242

MYSTIC Program, Belgium data

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SLIDE 29

Trends in Antimicrobial Spectrum and Potency for Pseudomonas aeruginosa

MIC90 (% susceptibility) Agent Year n MEM IMP CAZ CEP 1998 263 32 (85.2) 64 (75.3) 128 (65.8) 128 (53.6) 1999 211 8 (86.7) 32 (72.5) 64 (70.1) 64 (64.5) 2000 233 32 (81.1) 64 (77.3) 64 (73.4) 64 (67.8) 2001 264 16 (80.3) 64 (71.5) 128 (71.2) 64 (62.9) 2002 214 8 (83.6) 32 (80.4) 64 (79.9) 32 (73.4) 2003 217 32 (76.5) 64 (71.0) 128 (65.9) 64 (64.2) 2004 242 64 (79.3) 64 (66.9) 64 (76.4) 64 (76.4) MYSTIC Program, Belgium data

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SLIDE 30

Trends in Antimicrobial Spectrum and Potency for Pseudomonas aeruginosa

MIC90 (% susceptibility) Agent Year n TAZ AMI CIP 1998 263 >128 (73.0) 128 (66.2) 64 (56.3) 1999 211 >128 (78.2) 64 (79.2) 16 (61.9) 2000 233 >128 (80.3) 128 (69.2) 64 (67.0) 2001 264 >128 (78.8) 128 (71.6) 64 (57.2) 2002 214 128 (87.9) 64 (75.2) 16 (76.6) 2003 217 >128 (76.5) 64 (76.8) 64 (55.8) 2004 242 >128 (78.9) >128 (71.2) 32 (70.2)

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Multi Drug Resistant Isolates of Pseudomonas aeruginosa 1997 - 2004

Country N° Centers N° of isolates (%) Ps.aeruginosa MDR Belgium 8 1613 157 (9.8) Czech Republic 1 164 39 (2.4) Germany 7 1799 172 (9.6) Italy 3 1111 252 (22.7) Poland 1 178 3 (1.7) Russia 1 160 41 (25.6) Sweden 4 267 5 (1.9) Turkey 9 1280 383 (29.9) UK 5 1056 82 (7.8) Total MDR : 12.2% (2000) → 14.8% (2004) P = 0.002

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SLIDE 32

Prevalence of MDR Isolates of

  • Ps. aeruginosa by Country

10 20 30 40

B e l g i u m C z e c h R e p u b l i c a G e r m a n y I t a l y P

  • l

a n d R u s s i a S w e d e n S w i t z e r l a n d T u r k e y U K

1997-2000 1997-2004

% of MDR isolates % of MDR isolates MYSTIC Programme Europe

Total MDR : 12.2% (2000) → 14.8% (2004) P = 0.002

R to cefta (MIC > 32 µg/ml); R to genta (MIC > 16 µg/ml); R to cipro (MIC > 4 µg/ml)

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SLIDE 33

Percentage Resistance of MDR Pseudomonas aeruginosa

*MEM / IPM = 16 mg/L TAZ = 128 mg/L AMK = 64 mg/L CPE = 32 mg/L

MYSTIC Programme Europe

23,4 33,7 41,3 33,5 50,6 10 20 30 40 50 60 MEM IMP TAZ AMIK CPE 1997 - 2004

% resistant at % resistant at NCCLs NCCLs breakpoints* breakpoints*

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SLIDE 34

Conclusions by Organism and Antibiotic Class in Belgium

  • Possible increase in resistance of E. coli to fluoroquinolones, and co-

resistance to several classes of antimicrobials

  • The occurence of ESBL-producing E. coli and K. pneumoniae seems

stable and is significantly lower in Belgium comparing to the rest of Europe

  • Higher incidence resistance in E. aerogenes in Belgium compared to
  • ther European countries and USA isolates (spread of ESBL-producing

clones)

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SLIDE 35

Conclusions by Organisms and Antibiotic Class in Belgium

  • Carbapenems retain activity against most ESBL-and AmpC-producing

pathogens

  • In general, carbapenems exhibit higher potency than other antibiotic

agents against all Gram-negative organisms tested

  • There is a clear tendency towards decreased susceptibility of P.

aeruginosa for different antibiotics

  • Pip/tazo and meropenem remain the most active agents against P.

aeruginosa → Global trends towards higher rates of resistance and multi-resistant strains both in community-acquired and nosocomial pathogens