Idea Transcript
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L e r D ho I t M u C a S y E Bacterial infections in specific patient populations: an update for the infectious diseases consultant
Liver cirrhosis
Pierluigi Viale
Infectious Disease Unit
Teaching Hospital S. Orsola–Malpighi Bologna Italy
The infectious risk in liver cirrhosis
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CONTENTS
L e r D ho I t M u C a S y E
• A CLINICAL-EPIDEMIOLOGICAL OVERVIEW
• THE PATHOGENESIS : ENDOGENOUS & EXOGENOUS RISK • ETIOLOGIES and ANTIMICROBIAL RESISTANCE TRENDS • MOVING TOWARD AN IMPROVED MANAGEMENT
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ED Visits Related to Cirrhosis: A Retrospective Study of the Nationwide Emergency Department Sample 2006 to 2011 Pant C et al, Medicine 2015; 94:e308 During the calendar years 2006 to 2011, there were an estimated total of 3,127,986 ED visits associated with an ICD-9-CM diagnosis code of cirrhosis in 951 US hospitals. The median age of patients was 56 years (interquartile range (IQR) 16)
L e r D ho I t M u C a S y E INFECTION
Rates of CirrhosisAssociated ED Visits
HE
15.5
EVB
HRS
6
4
20.1
The infectious risk in liver cirrhosis
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AN EPIDEMIOLOGICAL OVERVIEW
L e r D ho I t M u C a S y E
Approximately 30% of cirrhotic patients admitted to the hospital have an infection or develop an infection during the hospitalization (Fernandez J et al., Hepatology 2002)
Overall mortality of infected cirrhotic patients is 30.3% at 1 month and 63% at 12 months. (Arvaniti V et al., Gastroenterology 2010)
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Acute-on-chronic liver failure (ACLF) J Hepatol 2015;62: S131–S143
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L e r D ho I t M u C a S y E
Acute-on-chronic liver failure (ACLF) is a recently recognized syndrome characterized
encephalopathy,
by
acute
decompensation
gastrointestinal
of
hemorrhage
cirrhosis
and/or
(ascites, bacterial
infections) and organ/system failure(s) (liver, kidney, brain, coagulation, circulation and/or respiration) with
extremely poor survival (28-day
mortality rate 30–40%).
Acute-on-chronic liver failure is caused by bacterial infection in 32.8% of cases (Moreau R et al., Gastroenterology 2013)
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A short case report …
FC 52 year old, HCV related cirrhosis
Last ambulatory check March, 18
Hospital admission admission April April,3 3 Hospital
Body Weight
96 kg
Body Weight
110 kg
P.A.
130/80
P.A.
120/780
R.R.
16
R.R.
24
Mental status
0
Mental status
2
Bilirubin
4.9 mg/dl
Bilirubin
13 mg/dl
INR
1.45
INR
2.35
Creatinine
0,68 mg/dl
Creatinine
3,89 mg/dl
L e r D ho I t M u C a S y E ACLF-2
expected 90-day mortality: >50%
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PATHOGENESIS : the endogenous risk
The infectious risk in liver cirrhosis
SMALL INTESTINAL BACTERIAL OVERGROWTH and DYSBIOSIS
L e r D ho I t M u C a S y E
ABNORMAL BACTERIAL TRANSLOCATION
MESENTERIC LYMPHONODES
CIRRHOSIS ASSOCIATED IMMUNE DYSFUNCTION
BLOOD
BLOODSTREAM INFECTION
ASCITIC FLUID
SPONTANEOUS BACTERIAL PERITONITIS BLOOD
Jalan R et al J Hepatol. 2014;60:1310-24.
BLOODSTREAM INFECTION
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PATHOGENESIS : the exogenous risk
The infectious risk in liver cirrhosis
CAID
L e r D ho I t M u C a S y E HIGH COLONIZATION RATE
INVASIVE PROCEDURES
DRUGS
HIGH FREQUENCY
OF HOSPITAL ADMISSIONS
PNEUMONIA SSTI UTI
CR-BLOODSTREAM INFECTION ENDOTIPSITIS
POST- SURGICAL INFECTIONS
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The main involved microorganisms
The infectious risk in liver cirrhosis
Endogenous route
Exogenous route
L e r D ho I t M u C a S y E
PRIMARY BSI
SBP
PNEUMONIA
S. pneumoniae H. influentiae Non Fermentative Gram neg Enterobacteriaceae
Enterobacteriaceae Enterococcus spp Candida spp
CR-BSI
intense antibiotic exposure ESLD related dysbiosis CDAD
MDRO
ENDOTIPSITIS
SSTI
S. Aureus CoNS POST SURGICAL INFECTIONS
S. aureus , CoNS Enterobacteriaceae Candida spp
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Bacterial infection in compensated viral cirrhosis impairs 5-year survival (ANRS CO12 CirVir prospective cohort) Nahon P et al, Gut, November 6, 2015
L e r D ho I t M u C a S y E
Prospective study involving 35 French centers, enrolling Child–Pugh class A patients with HCV or HBV proven cirrhosis without previous cirrhosis related complications . Overall 1672 patients were enrolled (HCV 1323, HBV 318, HCV-HBV 31), between 2006-12.
During a median follow-up of 43 months, 234 Bacterial Infections occurred in 171 patients (5 year Cumulative Incidence: 12.9%). Among infected patients 14.6% had septic shock.
BIs represented the third cause of death (14.1%) after liver failure and liver cancer Most BIs occurred as a first event prior to liver decompensation (n=140, 81.8%) and were community acquired (84.2%).
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Bacterial infection in compensated viral cirrhosis impairs 5-year survival (ANRS CO12 CirVir prospective cohort) Nahon P et al, Gut, November 6, 2015
L e r D ho I t M u C a S y E OVERALL SURVIVAL
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Bacterial infection in compensated viral cirrhosis impairs 5-year survival (ANRS CO12 CirVir prospective cohort) Nahon P et al, Gut, November 6, 2015
L e r D ho I t M u C a S y E
Features associated with occurrence of BI according to Cox proportional hazards model
Variable
OR
95% CI
p
Age >50
1.72
1.10 to 2.68
Albumin 90 beats/minute
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L e r D ho I t M u C a S y E
respiratory rate > 20 breaths/min WBC > 12.000 / < 4.000/mmc
SEPSIS
glycemia > 120 mg/dL lactemia > 2 mmol/L
plasma C-reactive protein >2 SD above the normal value (0.5 mg/L) plasma procalcitonin > 2 SD above the normal value (0.1 pg/ml) refilling > 2 seconds
altered mental status
hypotension (systolic < 90 mmHg) lactemia > 4 mmol/L organ disfunction/s
hypotension despite 20-40 ml/kg 1^h
SEVERE SEPSIS SEPTIC SHOCK
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How to stratify the risk of mortality in patients with cirrhosis and bacterial infections?
L e r D ho I t M u C a S y E
LIMITATIONS of SEPSIS CRITERIA
• Low WBC and PLTs count may be due to portal hypertension and hypersplenism • Acute Phase protein are less accurate (reduction liver synthesis)
• Hyperventilation may be present in patients with large volume of ascites or in case of hepatic encephalopathy • Liver disease slows lactate removal
• Normal hearth rate may be the consequence of prophylaxis with beta-blockers or tachyardia can be due to hyperdynamic circulation
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Are SIRS criteria useful for diagnosis of bacterial infections in cirrhotic patients?
L e r D ho I t M u C a S y E
In a signle-center study patients with ESLD consecutively admitted to hospital were enrolled
Multicenter prospective study with the aim to determine the prognostic factors in a population of patients with cirrhosis and functional renal failure enrolling 83 pts
Only 57% patients with infection met SIRS criteria
56% of patients with SIRS had an infection
Cazzaniga M et al Journal of Hepatology 2009 Thabut D et al Hepatology 2007
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Acute-on-Chronic Liver Failure Is a Distinct Syndrome That Develops in patients With Acute Decompensation of Cirrhosis Moreau R et al, Gastroenterology 2013 ;144:1426-37
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L e r D ho I t M u C a S y E
CLIF SOFA define 4 groups of patients with ACLF based on number of organ failures NO ACLF ACLF 1 ACLF 2 ACLF 3
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Epidemiology and Outcomes of Bloodstream Infection In Patients with Cirrhosis
Bartoletti M et al, J Hepatol 2014;61:51-8
A retrospective analysis of all consecutive BSIs in patients with liver cirrhosis at our 1350-bed teaching hospital (Jan 2008 to Jun 2012): 162 cases detected (11.7 per 10,000 patient-days)
L e r D ho I t M u C a S y E
MELD score as prognostic index for 30-day survival
Non-survivors Day 30; n=47 (29%)
Median MELD +/- 95% CI
35
30
25
20
15
Survivors Day 30; n=115 (71%)
10
Baseline diagnosis
24h
48h
Time of Assessment
72h
96h
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Epidemiology and Outcomes of Bloodstream Infection In Patients with Cirrhosis
Bartoletti M et al, J Hepatol 2014;61:51-8
100
Comparison of aROC for MELD score variables as a predictor of 30-day survival status
L e r D ho I t M u C a S y E ∆ MELD BSI
Sensitivity
80
60
MELD at BSI
∆ MELD 72h
Δ MELD was evaluable in 150 patients, 9±6 in NS vs. 2±3 in S, P