Separation of Lanthanides/ Lanthanides and Actinides
Le infezioni nel cirrotico: aspetti clinici - Gastrolearning®
1. Infezioni batteriche nel cirrotico
Giovanni Battista Gaeta
Chair of Infectious Diseases
Viral Hepatitis Unit – Second University of Naples
2. Clinical case history
•69-year-old woman
•Liver transplantation in 1991 for HCV related cirrhosis
•HCV reinfection of the graft and cirrhosis
•First episode of decompensation (ascites) in January 2012
• Type II Diabetes Mellitus treated with Insulin
•Chronic Renal Insufficiency (Cr Clearance ~ 40 mL/m)
• Hypertension treated with calcium antagonists
3. On Admission (Dec, 9, 2012)
•Body temperature 37.5 °C
•Hypotension (100/60 mmHg)
•Tachycardia (90 b/min)
• Mild jaundice
•Moderate Ascites
•Edema of lower extremities
•Grade II Encephalopathy
4. December 2012
2 days prior to admission
•Mild elevation of body temperature
• Mild diarrhea
•Nausea
•Asthenia
• Oliguria
•Confusion and Sleepiness
5. Infections in cirrhotics: dimension
20-50% of cirrhotics admitted to hospital
have an infection
(Including patients who acquire hospital infection)
Fernandez, Hepatology 2002; Arvaniti, Gastroenterology 2010; Fernandez, Hepatology 2012
6. Diagnosi di infezione batterica
in cirrotici al ricovero
Pazienti con cirrosi:
N : 536 404 ricoveri in 361 pazienti
% %
Urinary tract 26.1 Urinary tract 41
SBP 23.9 Ascites 23
Bacteremia 18.5
Pneumonia 16.3 Bacteremia 21
Soft tissue 4.3 Pneumonia 17
Other 10.9 Soft tissue -
Multicenter Italian Database, unpublished Borzio et al, 2001
7. Risk of death in patients with and without infection
(in studies reporting complete information on mortality)
Arvaniti V. et al. Gastroenterology 2010 ; 139 : 1246-1256
8. Mortality of patients with cirrhosis after infection
Parameter N° of studies N° of pataients Median Mortality
Total mortality 178 11.987 38 %
- 1 mo 51 2449 30.3%
- 3 mo 27 1439 44 %
- 12 mo 40 2154 63 %
1978-1999 total mortality 89 4890 47.4 %
- 1 mo 21 737 37.3 %
- 3 mo 18 578 43 %
- 12 mo 25 758 69.7%
2000-2009 total mortality 89 7132 32.3%
- 1 mo 29 1621 26 %
- 3 mo 9 681 44%
- 12 mo 14 634 60%
Arvaniti V. et al. Gastroenterology 2010 ; 139 : 1246-1256
9. Three-month probability of survival of patients with
cirrhosis according to the cause of renal failure
Martin-Llahi. M. et al. Gastroenterology 2010
11. Urinalysis
Diuresis 600 ml/24h
Natriuria 38.7 mEq/24h
Cloruria 31.5 mEq/24h
Kaliuria 25.0 mEq /24h
Microalbuminuria (106 mg/24h)
>35 Leukocytes x field
10 RBC x field
12. Microbiological and Image
• Cultures of blood, urine, ascites
• Neutrophil count in ascites
• Chest Xray
•Abdominal US
13. The flow chart of antibiotic treatment
Infection considered
Microbiological investigations
Empirical treatment
POS (50%) NEG (50%)
Modify tx Response-based tx
14. Classification of bacterial infections
Community acquired
the diagnosis of infection is made within 48 hours of hospitalization and the patient did
not fulfill the criteria for HCA infection
Health Care Associated
the diagnosis is made within 48 hours of hospitalization in patients with any of the
following criteria: (1) had attended a hospital or a hemodialysis clinic, or had received
intravenous chemotherapy during the 30 days before infection; or (2) were hospitalized
for at least 2 days, or had undergone surgery during the 180 days before infection; or (3)
had resided in a nursing home or a long-term care
facility.
Hospital Acquired
the diagnosis of infection is made after more than 48 hours of hospital stay
15. Case discussion
Therapy
• Plasma expansion ( saline, albumin )
• Antibiotic therapy :
During the previous six months the patient had received :
• Quinolones
• 3rd generation cephalosporins
given by GP for UTI and upper respiratory infection
Therapy was started with Meropenem 500mg/12h
(according to creatinine clearance) and continued for 10
days
16. Systemic antibiotic exposure is a risk factor
for bacterial resistance in cirrhosis
169 infectious episodes in 115 patients
70 culture positive infections 33 (47%) antibiotic resistant strains
Independent risk factors for resistance
Systemic antibiotics in the previous 30 days
OR 13.5 (95% CI = 2.6 – 71.6)
Nosocomial infection
OR 4.2 (95% CI = 1.4 -12.5)
Non-adsorbable antibiotics
OR 0.4 (95% CI = 0.04 -2.8)
Tandon et al. Clin Gastroenterol Hepatol 2012; 10:1291-98
22. Prevalence of resistance to ESBL among E. coli isolates from
bacteremias (EARSS 2005)
No data
< 1%
1-5%
5-10%
10-25%
>25%
23. Case discussion
Microbiology, US and chest Xray
•Neutrophil count in ascites : 160/µl
•Ascites culture: sterile
• E.coli was isolated from blood and urine
•Chest Xray: no inflammatory images
•Abdominal US: mild ascites; no nodules
24.
25. Quale terapia per le infezioni sostenute da
ESBL+?
Antibiotici ESBLs
Cefalosporine di terza generazione –
Cefepime –
Fluorochinoloni +/–
Piperacillina/tazobactam +/–
Carbapenemici +++
Tigeciclina ++
Colistin (for carbapenem resistance)
26. Risk Factors of Infections by Multiresistant Bacteria in
Cirrhosis
*
*
*
*
Fernandez, Hepatology 2012
27. ANTIBIOTIC THERAPY STOPPED ON DAY 10
Time course of bilirubin, creatinine, wbc, neutrophil and temperature
n/µL
TC°
Days Days
mg/dL
Days
Diuresis (ml/d) 600 1200 1650
28. Caratteristiche cliniche delle
Caratteristiche cliniche delle
infezioni batteriche nel cirrotico
infezioni batteriche nel cirrotico
Deterioramento Segni e sintomi tipici di
della funzione infezione
epatica
Febbre
Ittero (assente nel 30-50%)
Creat. clearance Leucocitosi neutrofila
Encefalopatia (relativa!)
Possibile esordio grave: febbre, coagulopatia, coma
Cazzaniga, J Hepatol 2009; 51:475-482; Wong, Gut 2005; 54:718-25; Fasolato, Hepatology 2007; 45:223-2
29. SIRS criteria: less diagnostic accuracy in cirrhosis ?
SIRS criteria
In cirrhosis
• Hyperdynamic circulation
leads to tachycardia
• Beta-blockers cause a
reduced heart rate
• Hypersplenism decreases
white blood cell count
Cazzaniga M,. J Hepatol 2009;51:475–482. Thabut D, Hepatology 2007;46:1872–1882.
30. Il paziente con cirrosi è immunocompromesso
Bonnel, Clinical Gastroenterol Hepatol 2011
31. Mechanisms of bacterial (and their products)
translocation
Portal hypertension
Splancnic vasodilation
Disruption of Increased sympathetic
intestinal barrier nerve activity
Intestinal hypomobility and
permeability
germ overgrow
Translocation
Transolacation is associated to increased plasma levels of cytokines
(TNFα, IL-6,), MAP-K,
33. Plasma levels of TNFα in patients with cirrhosis
with and without SBP
(pg/ml)
* = P < 0.001 vs cirrhosis without SBP
*
M. Navasa et al. Hepatology 1998 ; 27 : 1227-1232.
34. Bacterial translocation becomes clinically significant
when it produces SBP, bacteremia, post-surgical
infections
Bacterial peptides (Porins; HSP60;) are present in the
ascites of afebrile patients with increased TNFα and IFN-
gamma concentrations
Cano et al. J Mol Med, 2010, e-Pub
35. SBP – A chronic inflammatory disease with flares?
bacterial translocation
bacterial products which cause:
cytokine production
inflammatory response
nitric oxide production
SBP SBP
time
36. Acute-on-chronic Liver Failure
Patients’ features at enrollement
R. Moreau et al. (Canonic study) Gastroenterology 2013 (in press)
37. Renal failure in cirrhosis
Leucocyte count in patients with and without ACLF
________ Patients with no prior decompensation of cirrhosis
___ _ ___ Patients with prior decompensation of cirrhosis
ACLF
NO ACLF
R. Moreau et al. (Canonic study) Gastroenterology 2013 (in press)
38. C reactive protein values in patients with and without ACLF
* = p < 0.01 versus No ACLF *
# = p < 0.05 versus No ACLF
* * * *
# *
R. Moreau et al. (Canonic study) Gastroenterology 2013 (in press)
39. Mechanisms for sepsis-induced organ failure
microorganism-associated
molecular patterns (MAMPs)
PRRs, pattern recognition receptors
PAI-1, plasminogen activator inhibitor
APC, activated protein C
TF, tissue factor. From: Gustot et al, HEPATOLOGY 2009;50:2022-2033
40. Summary & Conclusions
Bacterial infection is one of the most frequent cause of
decompensation and death in cirrhosis
Immune defects, mainly acquired but also genetic,
and bacterial translocation are the main mechanisms
involved in its pathogenesis
The prevalence of infections is likelely to be
underestimated in clinical practice due to the reduced
diagnostic capacity of the standard diagnostic criteria
Gram positive and MDR bacteria are increasing
etiologic agents