Increasing incidence and testing do not explain steep mortality rise associated to Clostridium...

Increasing incidence and testing do not explain steep mortality rise associated to Clostridium difficile infection Brussels and Flanders, 1998-2007.

Ignacio Gutiérrez, MD, MSc, Epiet FellowA. Kongs, D. Mazina, N. Marin-Baldo Vink, M.L. Lambert

Background : Clostridium difficile

• Most frequent cause of nosocomial diarrhoea and involved in many outbreaks

• Spore forming and toxine producing Gram + anaerobe bacterium

• Found in the environment (soil, water, surfaces)• Asymptomatic carriage in humans and animals• Mild diarrhoea to life threatening

pseudomembranous enterocolitis

Background: epidemiological notes

• Clostridium difficile infection (CDI) incidence and mortality increased in North America and Europe over the last decade• Emerging hypervirulent fluoroquinolones-resistant

strains (ribotype 027 and others)• Changing “environment” due to antibiotics• Outbreaks

• Belgium introduced moxifloxacine in 2002 and first ribotype 027 isolate dates from 2003

Objective

• To measure CDI-related mortality,

incidence and number of tests performed

for the period 1998-2007 in Brussels and Flanders

in order to provide evidence for public health action to reduce mortality

Methods: Data sources

• Mortality databases, Flanders and Brussels regions, (1998-2007) >7 million residents • Records with ICD-10 code for Clostridium difficile enterocolitis

• Hospital discharges database,(1999-2007), Belgium • Records with ICD-9-CM code for intestinal CDI

• Social security (INAMI) database (1998-2007), Belgium• Number of CDI-diagnostic tests billed by year of performance

• Population data from the National Institute for Statistics

Methods: Data validation

Mortality

Comparison among ICD 10 codes:

A04.7 (intestinal infection by Clostridium difficile)

A00-A09( intestinal infections)

K52.9 ("Noninfective gastroenteritis and colitis, unspecified")

In order to detect possible code “shifting”

Methods: Statistical analysis

• Total and age- and sex-specific mortality rates for 1998-2006• Hospital discharge rates for 1999-2006

• Direct standardization for mortality and hospital discharge rates by age, using Belgian 2000 midyear population

• Rate Ratios by year, using 2000 as a reference for • Age-standardized mortality rates*• Age-standardized hospital discharge rates*• Rate* of diagnostic tests performed

* Rates expressed in units per 100,000 general population

Clostridium difficile enterocolitis crudemortality rates in Brussels and Flanders, 1998-2007

0

0.5

1

1.5

2

2.5

3

3.5

1998 1999 2000 2001 2002 2003 2004 2005 2006 2007

Year

Dea

ths

per

100

,000

po

pu

lati

on

Underlying cause

Any cause

Clostridium difficile enterocolitis crudemortality rates in Brussels and Flanders, 1998-2007

0

0.5

1

1.5

2

2.5

3

3.5

1998 1999 2000 2001 2002 2003 2004 2005 2006 2007

Year

Dea

ths

per

100

,000

po

pu

lati

on

Underlying cause

Any cause

Moxifloxacine

Ribo 027

C.difficile enterocolitis as “underlying” cause of death, Brussels and Flanders 1998-2006 -Age- and sex-specific mortality rates

0

5

10

15

20

25

30

35

1998 1999 2000 2001 2002 2003 2004 2005 2006 2007

Year

Dea

ths

per

100

,000

po

pu

lati

on

males 65-79

males >=80

females 65-79

females >=80

Clostridium difficile enterocolitis and other ICD-10 codes used for data validation, Brussels and Flanders 1998-2007

0

20

40

60

80

100

120

140

160

180

1998 1999 2000 2001 2002 2003 2004 2005 2006 2007

Year

Nu

mb

er o

f d

iag

no

ses A04.7 "Enterocolitis due to

Clostridium difficile"

A00-A09(excludingA04.7)"Other intestinal infectious diseases"

K52.9:"Noninfectivegastroenteritis and colitis,unspecified"

Clostridium difficile-associated disease hospital discharge rates in Belgian population, 1999-2007

0

5

10

15

20

25

30

35

40

45

50

1999 2000 2001 2002 2003 2004 2005 2006 2007

Year

Nu

mb

er o

f C

.dif

f. d

isch

arg

es p

er 1

00,0

00

po

pu

lati

on

total diagnoses Crude

Main diagnose Crude

Tests billed to diagnose C.difficile by the social security by setting and year of performance, Belgium, 1998-2007

0

20000

40000

60000

80000

100000

120000

140000

160000

1998 1999 2000 2001 2002 2003 2004 2005 2006 2007

Year

Nu

mb

er Ambulatory

Hospital

Total

Year N Test Rate

Test

RRN Disch

Rate

Disch RR

N

Mort Rate

Mort RR

1998 74711 732,76 0,92 N.A. N.A. N.A. 10 0,15 0,43

1999 80046 783,25 0,98 1730 17,10 0,93 18 0,27 0,77

2000 81864 798,57 Ref 1876 18,30 Ref 24 0,35 Ref

2001 83505 811,78 1,02 1886 18,10 0,99 19 0,27 0,77

2002 89647 867,59 1,09 2172 20,40 1,11 53 0,72 2,06

2003 101233 975,63 1,22 2928 27,10 1,48 105 1,40 4,00

2004 112741 1081,84 1,35 4060 36,70 2,01 232 3,01 8,60

2005 123420 1177,82 1,47 4487 39,80 2,17 212 2,64 7,54

2007 138378 1302,29 1,63 4751 41,70 2,28 162 2,00 5,71

Limitations

• Data:• Mortality data- Brussels and Flanders• Tests and hospital discharges- Belgium• No complete data for Wallonia

• Validation only for mortality data• ICD 10 code update in 2006

Conclusions

• Mortality due to Clostridium difficile enterocolitis increased in Brussels and Flanders during 1998-2007,especially in the eldest

• So did Hospital discharge and the number of tests performed in Belgium

• Mortality increased faster in Brussels and Flanders than CDI-associated hospital discharges and number of tests in Belgium

Conclusions

• Mortality probably influenced by other changes in:• virulence, • specific treatment , • exposure to ABs,• OUTBREAKS...

• GOOD NEWS :

DECREASING MORTALITY since 2004!!!

Recommendations

• A multidisciplinar aproach should lead to further research targeting hypervirulent strains and the role of antibiotic use in order to reduce C.diff. incidence and mortality

• It could be done from an international perspective if same trends are confirmed in other countries to optimize local resources by a coordinated aproach

Aknowledgements

E.KisslingEpiconcept, Paris, France

K. Bolaerts, S.Drieskens, E.Hendrickx, H.Van OyenScientific Institute of Public Health, Brussels, Belgium

M. DehnertRKI, Belin, Germany

M.A.LuquePEAC, Madrid, Spain

F.LuqueroEpiet, Paris, France

K.Alpers, A.Barrasa, M.A.Botrel, V.Bremer, B.Helynck, M.Muehlen, D.RadunEpiet coordination team

Project review group

Trends for CDI-associated tests, discharge rates and mortality rates, Belgium 1998-2007

0.1

1

10

100

1000

10000

100000

Year

log

Tests at Belgianhospitals

Discharges as"total"diagnoses/100,000population,Belgium

Deaths as "any"cause/100,000population,Brussels andFlanders

Belgium

Crude mortality rates due to Clostridium difficile enterocolitis in Belgium, by region 1998-2008

0

1

2

3

4

5

6

1998 1999 2000 2001 2002 2003 2004 2005 2006 2007 2008

Year

Nu

mb

er o

f d

eath

s p

er 1

00,0

00 p

op

ula

tio

n

Brussels

Flanders

Wallonia

Increase in C.diff.-related mortality rates, United States, 1999-2004

0

5

10

15

20

25

30

Year

Death

s/1

,000,0

00

U.S.

Belgium

Redelings MD, Sorvillo F, Mascola L. Increase in Clostridium difficile-related mortality rates, United States, 1999-2004. Emerg.Infect.Dis. 2007;13(9):1417-9.

Clostridium difficile-associated disease hospital discharge rates in Belgian population, 1999-2007

0

5

10

15

20

25

30

35

40

45

50

1999 2000 2001 2002 2003 2004 2005 2006 2007

Year

Nu

mb

er o

f C

.dif

f. d

isch

arg

es p

er

100,

000

po

pu

lati

on

total diagnoses Crude

total diagnoses Age-adjusted*

Main diagnose Crude

Main diagnose Age-adjusted*

Trends for Clostridium difficile associated hospital discharge and mortality standardized rates, Belgium 1998-2007

0,01

0,1

1

10

1998 1999 2000 2001 2002 2003 2004 2005 2006 2007

Year

log

Discharges as "main"diagnose/100,000population, Belgium

Deaths as "underlying"cause/100,000 population,Brussels and Flanders

Trends for Clostridium difficile associated hospital discharge and mortality standardized rates, Belgium 1998-2007

0,1

1

10

100

1998 1999 2000 2001 2002 2003 2004 2005 2006 2007

Years

log

Discharges as "total"diagnoses/100,000population, Belgium

Deaths as "any"cause/100,000 population,Brussels and Flanders

Increasing incidence and testing do not explain steep mortality rise associated to Clostridium...

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