INCIDENCE OF BACTERIAL INFECTIONS IN CIRRHOSIS

Transcription

1 INCIDENCE OF BACTERIAL INFECTIONS IN CIRRHOSIS Yoshida H et al (1993)* Deschenes M et al (1999)** Strauss E et al (1993) Borzio M et al (2002) PATIENTS INFECTIONS 15.4% 20% 47% 34% * Many Child Pugh A patients ** Only hospital acquired infections

2 TYPES OF BACTERIAL INFECTIONS IN CIRRHOSIS. 572 INFECTIONS DURING 507 ADMISSIONS IN 405 PATIENTS INFECTIONS COMMUNITY ACQUIRED NOSOCOMIAL TOTAL SBP UTI Pneumonia Scondary Bacteremia Spontaneous Bacteremia Other Infections

3 PATHOGENESIS OF SBP Gut flora Bacteria in: -Mesenteric lymph nodes - Abdomninal lymphatics - Thoracic duct TRANSLOCATION IMPAIRED RES ACTIVITY Bacteremia SBP IMPAIRED ASCITIC FLUID OPSONIC ACTIVITY

4 MECHANISM OF BACTERIAL TRANSLOCATION IN CIRRHOSIS Portal hypertension Splanchnic arterial vasodilation Disruption of intestinal barrier Increased sympathetic nervous activity Increased permeability Intestinal hypomotility and bacterial overgrowth BACTERIAL TRANSLOCATION

5 SCHEMATIC DRAWING OF NORADRENERGIC INNERVATION ON GUT-ASSOCIATED LYMPHOID TISSUE. Felten DL, et. Al. J.Immunology 1985

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7 ACUTE BACTERIAL INFECTIONS IN CIRRHOTICS ACCORDING TO THE RES PHAGOCYTIC ACTIVITY (RES-PA)* Normal RES-PA (n=16) Reduced RES-PA (n=25) Urinary tract infection SBP and/or bacteremia Other infections p< * follow-up period: 28±3 months Rimola, 1984

8 ASCITIC FLUID OPSONIC ACTIVITY A B C A: Cirrhotic with SBP, B: Cirrhotics without SBP, C: Non cirrhotic ascites Runyon, 1988

9 Probability PROBABILITY OF DEVELOPMENT OF FIRST SBP ACCORDING TO THE ASCITES PROTEIN CONCENTRATION <1 g/dl (n=73) g/dl (n=51) Months Llach et al, Hepatology 1992

10 Probability EFFECT OF LONG-TERM NORFLOXACIN ADMINISTRATION IN SBP RECURRENCE IN CIRRHOSIS 1.0 TOTAL SBP CAUSED BY AEROBIC GRAM-NEGATIVE BACTERIA Placebo p= Placebo p= Norfloxacin Months 0 Norfloxacin Months Ginès, 1990

11 Recommended empirical therapy Type of infection Type of empirical antibiotic therapy SBP Ceftriaxone UTI Ceftriaxone Cellulitis Community-acquired pneumonia Nosocomial Pneumonia Ceftriaxone + Cloxacillin or Amoxicillin- Clavulanic Acid Ceftriaxone + Macrolide or Clindamycin or Levofloxacin Ceftazidime + Ciprofloxacin SBP: Spontaneous bacterial peritonitis, UTI: Urinary tract infection

12 Prevalence of MR bacteria Type of infection All infections Communityacquired Nosocomial SBP 10 (8%) 3 (3%) 7 (22%) UTI 38 (40%) 13 (24%) 25 (60%) Cellulitis 7 (11%) 4 (7%) 3 (27%) Pneumonia 11 (25%) 2 (11%) 9 (35%) Others 25 (15%) 6 (6%) 19 (31%) TOTAL 91 (18%) 28 (9%) P< (36%) SBP: Spontaneous bacterial peritonitis, UTI: Urinary tract infection

13 Efficacy of empirical therapy Infections treated with recommended empirical therapy All infections Response to empirical therapy Communityacquired Nosocomial SBP (n=107) 72 (67%) 67 (76%) 5 (26%) UTI (n=89) 48 (54%) 36 (71%) 12 (32%) Pneumonia (n=28) 10 (36%) 7 (64%) 3 (18%) Cellulitis (n=54) 43 (80%) 40 (83%) 3 (50%) Others (n=136) 97 (71%) 74 (84%) 23 (48%) TOTAL (n=414) 271 (65%) 224 (78%) P< (36%) SBP: Spontaneous bacterial peritonitis, UTI: Urinary tract infection

14 Recommended empirical antibiotic in patients at risk of nosocomial multiresitant infections* Type of infection Type of empirical antibiotic therapy Spontaneous bacterial peritonitis Meropenem + teicoplanin Urinary infections Meropenem + teicoplanin Cellulitis Meropenem + teicoplanin Nosocomial pneumonia Spontaneous bacteremia *Risk factors: recent exposition to quinolones or β-lactams or current/recent hospitalization Meropenem + ciprofloxacin** Meropenem + teicoplanin **: Add linezolid if recent mechanical ventilation

15 Creatinine (mg/dl) ACUTE ON CHRONIC LIVER FAILURE (A-CLIF) 6 Type-2 HRS Type-1 HRS 5 Cefotaxime Therapeutic paracentesis Encephalopathy Jaundice Months Weeks

16 EVOLUTION OF TNFα AND IL-6 PLASMA LEVELS SBP Non Liver patients with sepsis Non infected cirrhotics Baudouin et al 1993

17 CARDIOVASCULAR HEMODYNAMICS IN 12 PATIENTS DEVELOPING TYPE-1 HRS* Baseline Type-1 HRS p MAP (mmhg) 84±2.6 70±2.3 <0.001 PRA (ng/ml.h) 12.9± ±3.4 <0.01 NE (pg/ml) 735± ±99 <0.001 SVR (dyn.s/cm -5 ) 1099± ±97 NS CO (L/min) 5.8± ±0.3 <0.01 RAP (mmhg) 7±0.8 5±0.5 <0.01 PCP (mmhg) 8.7±1 6.5±1 <0.01 HR (bpm) 86±5 84±4 NS * baseline measurements: 9±1 months prior HRS Ruiz del Arbol et al., Hepatology 2005

18 MECHANISM OF ACUTE ON CHRONIC LIVER FAILURE IN SBP Severe Circulatory Dysfunction Intense Inflammatory Response Acute Impairment of Cardiovascular Function Extrahepatic organ failure (ACLF)

19 PRIMARY PROPHYLAXIS WITH NORFLOXACIN IN PATIENTS AT HIGH RISK OF SBP AND TYPE-1 HRS Inclusion criteria: Risk factors of SBP - ascitic fluid protein <1.5 g/dl, Child-Pugh score >9 and bilirubin >3 mg/dl Risk factors of type-1 HRS - serum creatinine >1.2 mg/dl or serum sodium <130 meq/l 70 patients* Norfloxacin (n=37) Placebo (n=33) Patients developing SBP received i.v. albumin to prevent type-1 HRS Fernandez et al. (Gastroenterology, 2007)

20 Probability of spontaneous bacterial peritonitis PRIMARY PROPHYLAXIS OF SBP Placebo (n=33) 0.4 p= Norfloxacin (n=35) Days SBP: 12 patients; Type-1 HRS associated to SBP: no patient Fernandez et al. (Gastroenterology, 2007)

21 PRIMARY PROPHYLAXIS OF SBP: PROBABILITY OF HRS AND SURVIVAL 0.6 Probability of type-1 HRS 1.0 Probability of survival 0.4 p=0.02 Placebo (n=33) 0.8 Norfloxacin (n=35) 0.2 Norfloxacin (n=35) 0.6 Placebo (n=33) p= Days Days Fernandez et al. (Gastroenterology, 2007)

22 CEFOTAXIME vs CEFOTAXIME + ALBUMIN IN SBP DESIGN OF THE TRIAL 126 patients with SBP Cefotaxime 2 g/8 h (n=63) Cefotaxime 2 g/8 h + I.V. Albumin 1st day: 1.5 g/kg b.wt. 3rd day: 1 g /Kg b.wt. (n=63) Sort et al., N Engl J Med 1999

23 PRA (ng/ml.h) EFFECT OF TREATMENT ON CIRCULATORY FUNCTION *p<0.05 * * * Days Cefotaxime + Albumin Cefotaxime

24 CIRCULATORY SUPPORT WITH I.V. ALBUMIN IN PATIENTS WITH SBP. EFFECT ON HRS DEVELOPMENT AND HOSPITAL MORTALITY Cefotaxime (n=63) Cefotaxime + Albumin (n=63) Resolution of infection 57 (93%) 59 (98%) HRS Hospital mortality 20 (32%) 17 (27%) 6 (10%)* 6 (10%)* *p<0.001 Sort, N.Engl.J.Med.1999

25 CONCLUSIONS 1. Infections are frequent in cirrhosis. Epidemiology has changed markedly in the last few years 2. The traditional recommended empirical antibiotic therapy is not effective in a high proportion of patients. 3. Acute on chronic liver failure (ACLF), a multiorgan failure or circulatory origin, is the most frequent cause of death in patients with cirrhosis and SBP. 4.Primary selective intestinal decontamination with norfloxacin in patients with advanced liver failure and circulatory support with albumin at the time SBP diagnosis are effective in preventing ACLF.