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Bacterial Infection in Liver Cirrhosis: the Microbiologist Point of View

Bacterial Infection in Liver Cirrhosis: the Microbiologist Point of View. Prof. Marie-Hélène NICOLAS-CHANOINE. Bacterial infections. life-threatening complications in cirrhotic patients and common. 30 to 50 % of hospitalized cirrhotic patients are concerned by bacterial infections.

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Bacterial Infection in Liver Cirrhosis: the Microbiologist Point of View

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  1. Bacterial Infection in Liver Cirrhosis: the Microbiologist Point of View Prof. Marie-Hélène NICOLAS-CHANOINE

  2. Bacterial infections life-threatening complications in cirrhotic patients and common

  3. 30 to 50 % of hospitalized cirrhotic patients are concerned by bacterial infections

  4. 25 % of death directly due to bacterial infection Spontaneous Bacterial Peritonitis (SBP) (± bacteremia) Urinary Tract Infection (UTI) (± bacteremia) Pulmonary infection Others (peritoneal tuberculosis)

  5. Host risk factors for SBP • Surviving to a previous SBP episode • Low ascitic fluid protein levels (<10g/L) • Gastrointestinal hemorrhage

  6. Physiopathology of SBP SBP is caused by intestinal micro-organisms that translocate through the mucosal barrier to the mesenteric lymph nodes , enter the bloodstream and reach the ascitic fluid.

  7. Bacterial species isolated from AF obtained from patients with SBP and hospitalized in Beaujon hospital (1998-2007)

  8. Are bacterial factors involved in morbidity or/and mortality in cirrhotic patients with SBP? “Genetic background of Escherichia coli isolates from patients with spontaneous bacterial peritonitis: relationship with host factors and prognosis”. F. Bert et al, Clin. Microbiol. Infect. (in press)

  9. Population structure of E. coli • - 4 phylogenetic groups: A, B1, B2 and D • - extraintestinal pathogens: more often group B2 • isolates • - virulence factors (VF)-encodinggenes • - group B2 isolates have more VF genes than • non B2 group isolates

  10. Prevalence of virulence factor (VF) genes according to phylogenetic groups in 76 E. coli isolates from patients with SBP (1998-2005) Mean VF score of B2 versus non B2: 15.4 vs 7.3 p<10-4

  11. Comparison of host factors in patients with B2 isolates and those with non-B2 isolates. * data are no (%) of patients or mean value ; NS, non significant (p ≥ 0.2) ; SBP, spontaneous bacterial peritonitis AF, ascitic fluid,red indicates host factors independently associated with non-B2 isolates

  12. 10/76 (13%) patients with fluoroquinolone prophylaxis Prevalence of fluoroquinolone resistance in the 76 SBP E. coli = 16% Fluorouinolone resistance significantly higher in patients with norfloxacin prophylaxis than in those without :70% vs 7.6%, p <10-4 Fluoroquinolone resistance significantly higher in non B2 isolates than in B2 isolates: 30% vs 0% , p <0.001

  13. Overall, we found that the prevalence of non B2 isolates (fewer VF and more often resistant) increased with the severity of liver disease

  14. Multiple logistic regression of risk factors for in-hospital mortality1 1: the first multivariate analysis tested the MELD score and the second multivariate analysis tested the componentsof the score, 2: value for an increase of 5, 3: value for a decrease of 10 %,4: value for an increase of 50 μmol/L

  15. Host factors, namely the severity of renal and hepatic dysfunctions outweigh bacterial factors in predicting SBP in-hospital mortality

  16. Viridans Streptococci

  17. Viridans group streptococci (VGS) in 56 episodes*of SBP and/or bacteremia in 51 patients** (1998-2006) * 60,7 % acquired in the community,** 5 patients with 2 consecutive episodes *** 4 episodes with bacteremia Liver Transplantation (in press)

  18. Antibiotic susceptibility of the 56 VGS Ten patients had a prior episode of SBP and were receiving norflaxacin prophylaxis. No VGS resistant to fluoroquinolones. penicillin: 71 % amoxicillin: 87.5 % cefotaxime: 89.3 % erythromycin: 59 % levofloxacin: 100 % moxifloxacin: 100 %

  19. Demographic and biological data in 115 episodes of SBP caused by viridans group streptococci or E. coli NS, non significant; PMN, polymorphonuclear leucocytes; AF, ascitic fluid.* Data available for 71 patients.

  20. Multi drug-resistance in E. colirelated to extended-spectrum ß-lactamase (ESBL) production, notably CTX-M enzymes

  21. TOHO-like CTX-M-1, 3, 15 CTX-M-2 CTX-M-2, -5 CTX-M-3, 15 CTX-M-9, -14, 18, 19, 20, 21 CTX-M-14 CTX-M-, 3, 15 CTX-M-9, -13, -14 CTX-M-3 CTX-M-4, -6 CTX-M-3 CTX-M-3, 15 CTX-M-16, -17 CTX-M-9,-14 CTX-M-1,10,15,32 CTX-M-1 CTX-M-9, -16 CTX-M-2 CTX-M-8 CTX-M-8 CTX-M-9 CTX-M-2 Endémic Sporadic CTX-M-2, -5 CTX-M-9,-14 CTX-M-15 CTX-M-1,10,15 CTX-M-3 2005 Canton R. Curr. Opin. Microbial. 2006 Lewis J, AAC 2007, « CTX-M-type as the predominant ESBL isolated in a US health care system » (dominance of CTX-M-15)

  22. Groupe B2 Resistance to fluoroquinolones Lower number of VF-encoding genes than expected in B2 isolates

  23. Canada France Spain England Turkey India Portugal Switzerland Korea

  24. ESBL-producing E.coli and cirrhotic patients ? • Still rare as agent responsible for SBP / bacteremia • - 2 patients, June and Sept 2007 at Beaujon hospital • Korean J Hepatol sept 2007: survey on 12 years, emergence of ESBL-producing E. coli but carried in the digestive tract (rectal swabs)

  25. BeaujonHospital (2006): incidence of fecal ESBL-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 ST131

  26. In 2008 Good and bad news about clinical and microbiological data with regard to SBP Good news: norfloxacin prophylaxis not only decreases the risk of second SBP but also delays hepato-renal syndrome and improves survival in cirrhosis. Fernandez J et al, Gastroenterology. 2007 Sep;133(3):818-24. Bad news. E. coli is become the enterobacterial species the most concerned by ESBL and fluoroquinolone resistance is extremely frequent in those E. coli producing CTX-M enzyme

  27. Frederic Bert: infection in cirrhotic patients and patients with liver transplant Véronique Leflon Guibout: molecular mechanisms of resistance and molecular epidemiology Latifa Noussair: Mycobacterium tuberculosis infection diagnosis including tuberculosis peritonitis in cirrhotic patients

  28. Characteristics of cirrhotic patients in 76 episodes of spontaneous bacterialperitonitis (SBP) * Data are means ± SD or numbers (%) of patients

  29. Distribution of phylogenetic groups and virulence factor (VF) genes in relation to susceptibility to ciprofloxacin

  30. 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

  31. Bacteremia without SBP (n = 17)* * one patient with endocardites  primary bacteremia = 16

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