TWENTY YEARS OF ANTIBIOTIC RESISTANCE IN NON

TWENTY YEARS OF ANTIBIOTIC RESISTANCE IN NON-INVASIVE STREPTOCOCCUS PNEUMONIAE ISOLATEDINVASIVE STREPTOCOCCUS PNEUMONIAE ISOLATED

IN BELGIUN (1995 – 2014).

Vanhoof , R. MD, PhDDep. Transmissible & Infectious Diseases

Unit of Antibiotic ResearchUnit of Antibiotic Research

21/05/2015

Rue Engelandstraat 642 | 1180 Brussels | BelgiumT +32 2 373.32.61 | F +32 2 373.32.68 | email: [email protected] | www.wiv-isp.be

Brussels, IPH Seminar

Collection of isolates from 1995 to 2014 (n = 5.442)

15 Participating centres:

Gent

Brugge Antwerpen

HasseltBonheiden

p g• Antwerpen, AZ Stuyvenberg - K. Camps & Vande Vyvere, M.• Arlon, Cl. St.Joseph - P. & J-B Goffinet.• Bonheiden, ImeldaZH - J. Frans & R. VanNoyen• Boussu, CHR Warquignies – I. Philippart• Brugge, AZ St.Jan – E. Nulens, B.Gordts &

Roeselare Leuven

Liège

Brussel

Yvoir

Marche-en-Famenne

Haine-St.PaulMons

Montignies-le-Tilleul

ggH. Van Landuyt

• Brussels, Cebiodi – B. Mulongo & O.Fagnart• Gent, AZ J.Palfijn – L.Ide & L. VanNimmen• Haine-St-Paul, Hôp Jolimont – Mukuku Sifa & F. Meunier• Hasselt, VirgaJesse ZH – R. Cartuyvels & K. Magerman• Liège Hôp Citadelle M Carpentier

Arlon

• Liège, Hôp Citadelle – M. Carpentier• Leuven, MCH – M. Lontie & B. Van Meensel• Marche-en-Famenne, Hôp Princesse Paola – P. Lefèvre• Montigny-le-Tilleul, CHR A.Vésale – D. Govaerts• Roeselare, H.Haert ZH – E. De Laere, S. Vervaeke & I. Surmont• Yvoir, CU Mont Godinne – Y. GlupczynskiYvoir, CU Mont Godinne Y. Glupczynski

MIC by Microdilution (EUCAST) :• Penicillin (PN)• Amoxicillin (AM)• Cefuroxime (CR)• Ciprofloxacin (CI) • Levofloxacin (LV)• Moxifloxacin (MX)• Erythromycin (ER)• Telithromycin (TL)

Data on age, origin, sample, type of patient (H/A), gender.

S. pneumoniae. Resistance Follow-up. 1995-2014

Telithromycin (TL)• Tetracycline (TC)

RESISTANCE RATES (%) FOR β-LACTAMS

19 8

25PEN AMX CRX

12 1

19.8

15.1

12.114.5

17.916.0

17.015

20

12.1 12.1

9.2

6 4

12.3

8.09.8

7.19.2

7 7

7.913.6

10.7

7.8

12.514.6 10.3

10

%

6.45.6

3.5

7.1 7.77.8

0

5

95 97 99 01 03 04 05 06 07 08 09 10 11 12 13 14

1995

1997

1999

2001

2003

2004

2005

2006

2007

2008

2009

2010

2011

2012

2013

2014


RESISTANCE RATES FOR β-LACTAMS

Evolution of Penicillin Non-susceptibility (I+R)

25

16.0

17.9

15.2

19.820

**** ****

14.5

10.1

10.4

12.8

10

15 ***

10.19.2

0

5

02001 2003 2004 2005 2006 2007 2008 2009 2010 2011 2012 2013 2014



Penicillin Non-susceptibility rates and type of treatment in pneumonia following EUCAST

20

25

10

15

0

5

1995 1997 1999 2001 2003 2004 2005 2006 2007 2008 2009 2010 2011 2012 2013 2014

Infection/θ Regimen Breakpoint

Infections≠meningitis 1.2g x 42.4g x 4 or 1.2g x 6 2.4g x 6

S NS

Infections ≠ meningitis ≤0.06 ≥0.12

Pneumonia: 1.2g X 4 ≤0.5 ≥1

2.4g X 4 or 1.2g X 6 ≤1 ≥2


2.4g X 4 or 1.2g X 6 ≤1 ≥2

2.4g X 6 ≤2 ≥4


Evolution of Amoxicillin Non-susceptibility (IR)

12 314

12.3

9.8 9.210

12

**** ***

8.0

6.54 6

7.1

7.7

6

8

**

4.63.5

4.6

2

4

01999 2001 2003 2004 2005 2006 2007 2008 2009 2010 2011 2012 2013 2014



Evolution of Cefuroxime Non-susceptibility (CRX)

17.014 616

18

13.69 7

12.5

14.6

10.312

14

16*******

11.9

9.2

9.7

7.88.7

6

8

10

2

4

6

02001 2003 2004 2005 2006 2007 2008 2009 2010 2011 2012 2013 2014



Evolution of non-susceptibility of CRX and CRX-ax (EUCAST)

20.825

17.014.614.8

19.0

15.2

18.2

13.115

20

7.99.4 9.7

7.8

10.38.6 12.7

13.2 15.4

5

10

01995 1997 1999 2001 2003 2004 2005 2006 2007 2008 2009 2010 2011 2012 2013 2014

CRX CRX-ax



S. pneumoniae: Serotypes

35.356.9 %2012 9.85.9 2.0 3.9

PCV13 1 3 4 5 6A 6B 7F 9V 14 18C 19A 19F 23F

53.0 %2013 16.710.6 15.21.5 3.01.5 1.53.0

% PEN NS in PCV13 isolates from Adults

40.0 %2014 30.0 10.0

2012 79.3 %

% PEN-NS in PCV13 isolates from Adults

2013 91.4 %

2014 95.0 %


RESISTANCE RATES (%) FOR FLUOROQUINOLONES

4

3.12.8

3.3

2.43

1.41.1

0 81.0

1.20 9

2%

0.60.8

0.5

0.3

0.8

0.3

0.50.20.70.2

0.9

0

1

01995 1997 1999 2001 2003 2004 2005 2006 2007 2008 2009 2010 2011 2012 2013 2014

LEV MOX


RESISTANCE RATES (%) FOR

MLS & TETRACYCLINEMLS & TETRACYCLINE

43 74

50

32.9

37.7

29.7

40.9

32.736.9

27.927 1

43.7

26.930

35

40

45

20.0

24.8

27.1

25.8

26.931.2

25.9

32.429.3

32.0

26.3

15

20

25

30

%

4.12.6 0.9 0.7

2.4 1.1 1.6 2.9

0

5

10

15

1995 1997 1999 2001 2003 2004 2005 2006 2007 2008 2009 2010 2011 2012 2013 2014ERY TEL TET


RESISTANCE and AGE

60Age Distribution (SP2014)

40

50

102030

0

10

0-5

6-10

11-1

516

-20

21-2

526

-30

31-3

536

-40

41-4

546

-50

51-5

556

-60

61-6

566

-70

71-7

576

-80

81-8

586

-90

91-9

596

-100


RESISTANCE and AGE

62.0 (S****)

46 151.9

60

70

Mean age by region (SP2014)

39.2 (N***)46.1

30

40

50

60

01020

BRUSS NORTH SOUTH NAT

Evolution of mean age and % of children (≤ 5y)

60

1016.712.5

20.718.415.314.718.218.417.915.426.4

11.416.918.322.5

0

20

40

1995 1997 1999 2001 2003 2004 2005 2006 2007 2008 2009 2010 2011 2012 2013 2014

%


%Ch ≤5y mean age

RESISTANCE and AGE

38 6

Resistance rates: Childrens versus Adults (SP2014)

22.2

29.3

20 627.7 27.0

38.6

303540

14.316.5

22.2 20.6

10152025

0 0.805

10

Pen Lev Ery Tet IR

Children Adults


RESISTANCE and AGE

0-5y Adults 0-5y Adults 0-5y Adults 0-5y Adults 0-5y AdultsPENICILLIN LEVOFLOXACIN ERYTHROMYCIN TETRACYCLINE NS-ISOLATES2

Non susceptibility rates (%)1 for 4 indicator antibiotics in children (≤ 5 y) and adults

0 5y Adults 0 5y Adults 0 5y Adults 0 5y Adults 0 5y Adults1995 25.8** 7.5 0 0 25.8 18.7 29.0 26.2 41.9 32.71997 13.3 11.6 0 1.6 46.7** 24.8 33.3 28.7 53.3 34.91999 23.1 13.8 0.8 2.4 53.9** 29.3 34.6 24.4 61.5 43.92001 25.0 19.4 3.6 3.2 35.7 27.3 50.0 42.6 60.7 50.02003 11.7 15.6 1.9 3.7 29.1 24.3 46.6 38.3 55.3 47.62003 11.7 15.6 1.9 3.7 29.1 24.3 46.6 38.3 55.3 47.62004 15.4 14.8 3.1 2.9 47.7**** 20.0 40.0*** 24.3 58.5*** 35.12005 20.0 13.8 1.3 0.6 40.0* 28.5 35.0 28.5 50.0 40.62006 12.7 12.5 0 0.6 55.7**** 33.9 44.3*** 27.9 58.2**** 37.62007 14.7 11.8 0 1.2 40.0 29.4 35.7 27.2 45.3 35.92008 15.2 11.4 0 0.8 43.9*** 27.3 31.8 23.8 47.0* 32.42009 19.0** 8.7 0 0.9 46.0 40.1 36.5 30.2 49.2 43.12010 11.8 8.7 0 1.0 42.6* 30.2 33.8 29.9 47.1 36.82011 19.7*** 7.8 0 1.4 43.4* 30.0 42.1 30.7 47.4 36.02012 25.7* 13.3 0 3.6 37.1 29.5 37.1 27.3 42.9 38.02013 15.2 18.3 0 1.6 37.0 36.6 30.4 32.2 39.1 43.22014 13.5 16.5 0 0.8 23.1 29.3 21.2 27.7 26.9 38.6

2Isolates showing resistance to whichever of the indicator antibiotics

1Significant difference are indicated by an asterisk. *0.05>P>0.02; **0.02>P>0.01; ***0.01>P>0.001; ***P<0.001


RESISTANCE and AGE

NS-rates mostly CHILD > ADULT; except FQ

Erythromycin Resistance following age53 8 55.760

46.7

53.8

35 7

47.7

40.040 0

43.946.0

42.6 43.4

37.1 37.040

50

25.8

35.7

30.3

40.0

23.124.829.3 28.7

24.028.5

33.929.4

27.3

40.1

30.2 30.0 29.5

36.629.3

20

30%

18.7 20.0

0

10

0

1995

1997

**19

99**

2001

2003

2004

****

2005

*20

06***

*20

0720

08*** 2009

2010

*20

11*

2012

2013

2014

0-5y Adults


RESISTANCE and REGION

39.8

51.9

50

60

Distribution of isolates following Region (SP2014)

8.3

10

20

30

40

%

Resistance rates by region (SP2014)0

Brussels North South

Brussels North South34.6 34.0 34.7

42.0

30

35

40

45

y g ( )

14.821.0 23.4

7.7

21.8

771015202530

%North

South

Bruss

1.2

7.7 7.7

0

5

10

Pen* Lev Ery Tet IR


RESISTANCE and REGION

PEN

2014

N

2013

S

2012

S

2007 20082003 2004 2005 2006 2009 2010 2011

S S S*** S** S S S S S****

LEV

ERY S***

SS

S***S***

N*S* S N N S N N N S

S* S*** S*** S S S S** S**** S****

TET

IR

S****

S***

S

S*

S

S*S S S**

S S S S S S

S* S*** S**** S S**** S***

S*** S*** S*


RESISTANCE RATES (%) in CAP and AECB isolates*

45

25303540 CAP (%) AECB (%)

10152025

05

PEN AMX CRX CRX-ax LEV MOX ERY TEL TET IR


*Period 2006-2014; compiled data

MIC Distributions of PEN G

60

70 199519971999

R-EUCAST

40

50

%

2001200320042005

20

30

% 2006200720082009

0

10

0 0 01 02 03 06 12 25 0,5 1 2 4 8

2010201120122013

Bimodal Distribution

0,0

0,0

0,0

0,0

0,1

0,2 0,

2014

S. pneumoniae. Resistance Follow-up. MIC Distribution 1995-2014

MIC Distributions of PEN G

Evolution of the MIC50 in PEN-S and PEN-NS isolates

0.004 0.008 0.015 0.03 0.06 0.12 0.25 0.5 1 2 41995199719992001200120032004200520062007200720082009201020112012201220132014

PEN-S PEN-I PEN-R

S. pneumoniae. Resistance Follow-up. MIC Distribution. 1995-2014

MIC Distributions of FQ

70 19951997S

60

40

50

60

%

1997199920012003200420052006

NS

30

40

50

%

NS

10

20

30

% 200620072008200920102011

10

20

30%LEV MOX

0

0,03

0,06

0,12

0,25 0,5 1 2 4 8 16

201220132014

0

0,01

0,02

0,03

0,06

0,12

0,25 0,

5 1 2 4

S. pneumoniae. Resistance Follow-up. MIC Distribution 1995-2014

MIC Distributions of FQ

0.03 0.06 0.12 0.25 0.5 1 2 4 8 161995

Evolution of the MIC50 in LEV-S and LEV-NS isolates

1997 21999 42001 8 12003 7 62004 11 12005 2 12006 22007 1 32007 1 32008 1 22009 1 22010 2 12011 2 22012 10 12013 3 1 12014 1 1

0.015 0.03 0.06 0.12 0.25 0.5 1 2 4 819951997

Evolution of the MIC50 in MOX-S and MOX-R isolates

LEV-S LEV-NS 19971999 22001 2 12003 1 12004 12005 12006 12007 2 12008 1 12009 12010 12011 22012 12013 32014 1

MOX-S MOX-NS

S. pneumoniae. Resistance Follow-up. MIC Distribution. 1995-2014

MOX S MOX NS

Cross-Resistance

%Susceptible PEN-NS AMX-NS CRX-NS LEV-NS MOX-NS ERY-NS TEL-NS TET-NSPEN - 0 0.3 65.8 58.3 69.1 45.8 71.2AMX 46 7 36 5 79 7 62 5 82 2 64 9 84 0

Degree of activity (%) of the indicated antimicrobials on S. pneumoniae isolates non-susceptible (NS) to the various compounds (1995-2014)

AMX 46.7 - 36.5 79.7 62.5 82.2 64.9 84.0CRX 17.7 0.5 - 68.4 58.3 72.7 49.4 74.9LEV 96.5 95.9 95.9 - 0 98.0 92.8 98.0MOX 98.6 97.7 98.2 69.6 - 99.5 96.4 99.4ERY 32 7 22 7 23 2 55 7 62 5 - 0 19 8ERY 32.7 22.7 23.2 55.7 62.5 - 0 19.8TEL 93.0 90.4 92.1 90.8 84.2 94.6 - 94.7TET 34.2 30.9 30.5 57.0 58.3 21.1 8.4 -

Degree exceeding 95%Degree exceeding 90%


Conclusions

Decreasing Rates of Non Susceptibility (NS) in period 2001-2010

Significant increase of PEN-, AMX-, CRX-NS since 2011. PEN-NS isolates: 40 - 57% of isolates comprised in PCV13 Especially in adults (≥ 80%)p y (≥ ) Decrease RR in 2014

In general Rate of NS: Children > Adults (not always significant)

Regional Differences can be found

Rate of NS AECB > CAP (not significant)

Cross-Resistance: important %S to MOX, LEV, TEL


Documents

TWENTY YEARS OF ANTIBIOTIC RESISTANCE IN NON