mnh chanoine bacterial infection in cirrhosis cairo 2008
TRANSCRIPT
8/8/2019 MNH Chanoine Bacterial Infection in Cirrhosis Cairo 2008
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Bacterial Infection in Liver Cirrhosis:the Microbiologist Point of View
Prof. Marie-Hélène NICOLAS-CHANOINE
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Bacterial infections
life-threatening complications in cirrhotic patientsand common
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30 to 5 0 % of hospitalized cirrhotic patients are concerned by bacterialinfections
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Spontaneous Bacterial Peritonitis (SBP)
(± bacteremia)
Urinary Tract Infection (UTI)(± bacteremia)
Pulmonaryinfection
Others(peritoneal
tuberculosis )
25 % of deathdirectly due to
bacterialinfection
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Host risk factors for SBP
Surviving to a previous SBP episodeLow ascitic fluid protein levels (<1 0 g/L)Gastrointestinal hemorrhage
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Physiopathology of SBP
SBP is caused by intestinal micro-organismsthat translocate through the mucosal barrier tothe mesenteric lymph nodes , enter the
bloodstream and reach the ascitic fluid.
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Parameter Number (%)
Community Nosocomial Total
Episode number 128 69 197
Isolate number 1 30 74 2 0 4
Plurimicrobial 2 5 7 (3.5) Enterobacteriacae 67 4 3 110
E.coli 61 (47) 27 (3 6 ) 88 (43) K lebsiella spp 2 6 8
Others 4 1 0 14
S treptococci 52 (40) 1 5 (20) 6 7 (32)Viridans group 27 11 3 8
S . bovis 9 2 11
Pneumococci 7 2 9
B group 8 0 8
S . aureus 2 5 7
Enterococcus spp 1 5 6 (3)Others 7 3 10
C andida 2 3 5 (2.5)
Bacterial species isolated from AF obtained from patients
with SBP and hospitalized in Beaujon hospital ( 199 8-2007)
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Are bacterial factors involved in morbidityor/and mortality in cirrhotic patients withSBP?
³Genetic background of Escherichia coli isolatesfrom patients with spontaneous bacterial peritonitis:relationship with host factors and prognosis´.
F. Bert et al, Clin. Microbiol. Infect. (in press)
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- 4 phylogenetic groups: A, B1, B2 and D
- extraintestinal pathogens: more often group B2isolates
- virulence factors (VF)-encoding genes
- group B2 isolates have more VF genes thannon B2 group isolates
Population structure of E. coli
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VF gene Prevalence of VF gene, No. (%) of isolates
Group A(n=2 0 )
Group B1(n= 3 )
Group B2(n= 3 5)
Group D(n=18)
Total(n=76)
Adhesins
pap C 7 ( 3 5) 0 26 (74) 6 ( 33 ) 3 9 (51)
pap G allele II 0 0 15 (4 3 ) 6 ( 33 ) 21 (28)
pap G allele III 0 0 11 ( 3 1) 0 11 (14)
sfa/foc 0 0 18 (51) 0 18 (24)
Toxins
hly 0 0 18 (51) 1 (5.6) 19 (25)
cnf 1 0 0 17 (49) 0 17 (22)
Siderophores
fyuA 8 (4 0 ) 1 ( 33 ) 3 5 (1 00 ) 11 (61) 55 (72)
aer 10 (50 ) 2 (66) 19 (54) 12 (67) 4 3 (56)
Prevalence of virulence factor (VF) genes according to phylogeneticgroups in 76 E. coli isolates from patients with SBP (1998-2 00 5)
Mean VF score of B2 versus non B2: 15.4 vs 7. 3 p<1 0 -4
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Value in the indicated group*
Variable Patients with B2isolates (n= 3 5)
Patients with non-B2isolates (n= 41)
PP
Age (year) 55 55 NS
Male gender 26 (75) 3 4 (8 3 ) NS
Alcoholism 22 (65) 25 (64) NS
Viral hepatitis 8 (24) 11 (28) NS
Hepatocellular carcinoma 7 (2 0 ) 4 (1 0 ) NS
Previous SBP episode 2 (6) 12 ( 30 ) 0 .0 15 3
Norfloxacin prophylaxis 1 ( 3 ) 9 (22) 0 .0 172
MELD score 26 29 0 .195 3
Blood neutrophils (cells/mm 3 ) 10 ,752 7,9 3 1 NS
Platelet (cells/m 3 ) 13 6,828 1 00 ,0 49 0 .0 82 3
Prothrombin ratio (%) 4 0 33 0 .0 558
Serum bilirubin ( mol/L) 2 00 178 NS
Serum creatinine ( mol/L) 142 182 NS
Serum sodium ( mol/L) 1 3 1 13 2 NS
AF neutrophils (cells/mm 3 ) 4,3 89 4,5 0 1 NS
AF protein (g/L) 11 1 0 0 .11 00
Hospital-acquired SBP 11 ( 3 1) 16 ( 3 9) NS
Positive blood cultures 9 (26) 15 ( 3 7) 0 .1487
Comparison of host factors in patients with B2 isolates and thosewith non-B2 isolates.
* data are no (%) of patients or mean value ; NS, non significant (p 0 .2) ; SBP, spontaneous bacterial peritonitisAF, ascitic fluid, red indicates host factors independently associated with non-B2 isolates
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Overall, we found that the prevalence
of non B2 isolates (fewer VF andmore often resistant) increased withthe severity of liver disease
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Variable OR CI 95 % P
MELD score 1.8 3 2 1.29 2.59 0 .000 7
Hospital-acquiredSBP
4.1 3 1.2 0 14.21 0 .0 247
Prothrombin ratio 1.51 3 1.0 2 14. 0 5 0 .0 412
Serum creatininelevel
1.77 4 1.1 3 2.78 0 .0 127
Hospital-acquiredSBP
4.0 4 1.16 14. 0 5 0 .0 281
Multiple logistic regression of risk factors for in-hospitalmortality 1
1: the first multivariate analysis tested the MELD score and the second multivariateanalysis tested the components of the score, 2: value for an increase of 5, 3 : value for adecrease of 1 0 %, 4: value for an increase of 5 0 mol/L
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Host factors, namely the severity of renal and hepatic dysfunctionsoutweigh bacterial factors in
predicting SBP in-hospital mortality
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Viridans S treptococci
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Viridans group streptococci (VGS) in 56 episodes*of SBP and/or bacteremia in 51 patients** (1998-2 00 6)
Species SBP(n = 3 9)***
Bacteremia withoutSBP (n = 17)
S . oralis 14 6S . mitis 10 1S . salivarius 4 6S . gordonii 3 3
S . sanguis 3 0
S . vestibularis
3 0
S . mutans 0 1
others 2 0
* 60 ,7 % acquired in the community,** 5 patients with 2 consecutive episodes*** 4 episodes with bacteremia
Liver Transplantation (in press)
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Antibiotic susceptibility
of the 56 VGS
Ten patients had a prior episode of SBP andwere receivingnorflaxacin prophylaxis.
No VGS resistant tofluoroquinolones .
penicillin: 71 %amoxicillin: 87.5 %cefotaxime: 89. 3 %erythromycin: 59 %levofloxacin: 1 00 %moxifloxacin: 1 00 %
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Demographic and biological data in 115 episodes of SBPcaused by viridans group streptococci or E. coli
VariableSBP caused by
pVGS (n = 3 9) E. coli (n = 76)
Age (year) 59. 3 54.7 NS
Male gender 30 (76.9 %) 6 0 (78.9 %) NS
Alcoholism 18 (46.2 %) 46 (6 3 %) NS
Viral hepatitis 17 (4 3 .6 %) 19 ( 3 6 %) NS
Carcinoma 7 (17.8 %) 11 (14.5 %) NS
MELD score 19.5 27.9 < 0 .0 1
Norfloxacin prophylaxis 9 (2 3 .1 %) 1 0 (13 .2 %) NS
Blood PMN (cells/mm 3 ) 7,672 8,85 0 NS
AF PMN (cells/mm3
) 1,426 4,451 < 0 .00 1AF protein (g/L) 9.2 1 0 .4 NS
Nosocomial origin 1 3 (33 .3 %) 24 ( 3 1.6 %) NS
Positive blood cultures 4 (1 0 .5 %) 29 ( 3 5.5 %) < 0 .0 1
15-day mortality 9 (2 3 .1 %) 27 ( 3 8 %)* NS NS, non significant; PMN, polymorphonuclear leucocytes; AF, ascitic fluid.* Data available for 71 patients.
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Multi drug-resistance in E. coli
related to extended-spectrumß-lactamase (ESBL) production,notably CTX-M enzymes
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Endémic CTX-M-1 CTX-M-8 CTX-M-9Sporadic CTX-M-2
2005
CTX-M-2, -5
CTX-M-16, -17
CTX-M-8
CTX-M-9, -16
CTX-M-1, 3, 15
CTX-M-9, -14, 18, 19, 20, 21
CTX-M-2, -5
CTX-M-, 3, 15
CTX-M-2
TOHO-like
CTX-M-2
CTX-M-3, 15
CTX-M-14
CTX-M-3, 15
CTX-M-9, -13, -14
CTX-M-3
CTX-M-3
CTX-M-9,-14
CTX-M-1,10,15
CTX-M-4, -6
CTX-M-3
CTX-M-15
CTX-M-9,-14
CTX-M-1,10,15,32
L ewis J, AAC 2007, « CTX-M-type as the predominant ESB L isolated in a US health
care system » (dominance of CTX-M- 1 5)
Canton R. Curr. Opin. Microbial. 2 00 6
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Groupe B2Resistance to fluoroquinolonesLower number of VF-encoding genes than expected in B2 isolates
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Canada
France
Spain
England
Turkey
India
Portugal
Switzerland
Korea
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ESBL-producing E.coli and cirrhotic patients ?
Still rare as agent responsible for SBP / bacteremia
- 2 patients, June and Sept 2 00 7 at Beaujon hospital- Korean J Hepatol sept 2 00 7: survey on 12 years,
emergence of ESBL-producing E. coli
but carried in the digestive tract (rectal swabs)
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Period Incidence / 1 00 screened patients
Hepatology* ICU** Hospital
7/2 6/ 3 3 .75 4.7
15/6 15/12 4 2
Beaujon Hospital (2 00 6): incidence of fecalESBL-positive enterobacteriaceae
* patients screened at admission,** patients screened at admission, then once a week
8 patients with ESBL-producing E. coli, 5 CTX-M-15 and 2 isolates belonging to clone ST1 3 1
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In 2 00 8Good and bad news about clinical andmicrobiological data with regard to SBP
Good news: norfloxacin prophylaxis not only
decreases the risk of second SBP but also delayshepato-renal syndrome and improves survival incirrhosis. Fernandez J et al, Gastroenterology. 2 00 7 Sep;1 33 (3 ):818-24.
Bad news. E. coli is become the enterobacterialspecies the most concerned by ESBL andfluoroquinolone resistance is extremely frequent in
those E. coli producing CTX-M enzyme
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Frederic Bert: infection in cirrhotic patients and patientswith liver transplant
Véronique Leflon Guibout: molecular mechanisms of resistance
and molecular epidemiology
Latifa Noussair: M ycobacterium tuberculosis infection diagnosisincluding tuberculosis peritonitis in cirrhotic patients
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Characteristic Value*
Epidemiological featuresAge (yr) 54.7 ± 1 0 .6
Male gender 6 0 (78.9)
Alcoholism 46 (6 3 )
Viral Hepatitis 19 ( 3 6)
Carcinoma 11 (14.5)
Previous SBP episode 14 (18.4) Norfloxacin prophylaxis 1 0 (13 .2)
Meld score 27.9 ± 9.7
Blood variables
PMN (cells/mm 3 ) 8,85 0 ± 5,989
Platelet (cells/mm 3 ) 117, 000 ± 85,618
Prothrombin ratio (%)3
5.9 ± 15.6Bilirubin (µmol/L) 188 ± 1 3 8
Creatinine (µmol/L) 16 3 ± 14 0
Sodium (mmol/L) 1 3 1 ± 5.6
Ascitic fluid variables
PMN (cells/mm 3 ) 4,451 ± 4,72 0
Total protein (g/L) 1 0 .4 ± 5.1
Characteristics of cirrhotic patients in 7 6
episodes of spontaneous bacterial peritonitis(SBP)
* Data are means ± SD or numbers (%) of patients
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Prevalence of group or VF gene, no. (%)
TraitCiprofloxacin-susceptible
(n= 64)Ciprofloxacin-resistant
(n=12)
Phylogenetic group
A 1 3 (20 .3 ) 7 (58. 3 )
B1 2 ( 3 .1) 1 (8. 3 )
B23
5 (54.7)0
D 14 (21.9) 4 ( 33 .3 )
VF genes
pap C 3 4 (5 3 .1) 5 (41.7)
pap GII 21 ( 3 2.8) 0
pap GIII 11 (17.2) 0
sfa/foc 18 (28.1) 0
hly 19 ( 29.7) 0
cnf 1 17 (26.6) 0
fyuA 49 (76.6) 6 (5 0 )
aer 3 6 (56.2) 7 (58. 3 )
Distribution of phylogenetic groups and virulence factor (VF)genes in relation to susceptibility to ciprofloxacin
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Value in the indicated group*
Variable Patients who died (n= 3 8) Patients who survived (n= 33 ) P
Age (year) 51.7 5 3 NS
Male gender 3 1 (81.6) 25 (75.7) NS
Alcoholism 21 (58. 3 ) 22 (68.7) NS
Viral hepatitis 1 0 (27.8) 8 (25) NS
Hepatocellular carcinoma 6 (15.8) 5 (15.1) NS
Previous SBP episode 5 (1 3 .2) 8 (24.2) NS
Norfloxacin prophylaxis 3 (7.9) 6 (18.2) NS
MELD score 3 1.6 2 3 .1 0 .00 12
Blood neutrophils (cells/mm 3) 10 ,29 3 7,85 0 0 .116 3
Platelet (cells/m 3) 117,552 114,18 0 NS
Prothrombin ratio (%)3
1.1 42.20
.00
48Serum bilirubin ( mol/L) 227.2 15 3 .3 0 .03 57
Serum creatinine ( mol/L) 2 0 1.7 112.6 0 .0 93
Serum sodium ( mol/L) 1 30 .9 1 3 1.9 NS
AF neutrophils (cells/mm 3) 4,992 4,181 NS
AF protein (g/L) 1 0 .4 9.7 NS
B2 group 16 (48.1) 17 (51.5) NS
VF score 2.9 2.9 NS
Amoxicillin resistance 21 (55. 3 ) 14 (42.4) NS
Amoxi-clavulanate resistance 5 (1 3 .2) 5 (15.1) NS
Cefatoxime resistance 1 (2.6) 1 ( 3 ) NS
Ciprofloxacin resistance 5 (1 3 .2) 6 (18.2) NS
Cotrimoxazole resistance 14 ( 3 6.8) 7 (21.2) 0 .1542
Hospital-acquired SBP 16 (42.1) 7 (21.2) 0 .00 65
Positive blood cultures 16 (42.1) 8 (24.2) 0 .1161
Appropriate empiric antibiotics 33 (94. 3 ) 30 (96.7) NS
Albumin therapy 9 (2 3 .7) 11 ( 33 .3 ) NS
Unvariate analysis of host and bacterial factors associated with in-hospital mortality
* data are no (%) of patients or mean value ; NS, non significant (p 0 .2) ; SBP, spontaneous bacterial peritonitis ; AF, ascite fluid ; VF, virulence factor
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Bacteremia without SBP (n = 17)*Ascite Number
without 3
Sterile ascite 9
Bacterascites (PNM < 25 0 mm 3 ) 5* one patient with endocardites
@ primary bacteremia = 16