Post on 11-Dec-2015
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
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
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
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
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
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
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