Bacterial infection in liver cirrhosis the microbiologist point of view
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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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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 infection in liver cirrhosis the microbiologist point of view

Bacterial infections

life-threatening complications in cirrhotic patients and common


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

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


Bacterial infection in liver cirrhosis the microbiologist point of view

25 % of death directly due to bacterial infection

Spontaneous Bacterial Peritonitis (SBP) (± bacteremia)

Urinary Tract Infection (UTI) (± bacteremia)

Pulmonary infection

Others

(peritoneal tuberculosis)


Host risk factors for sbp

Host risk factors for SBP

  • Surviving to a previous SBP episode

  • Low ascitic fluid protein levels (<10g/L)

  • Gastrointestinal hemorrhage


Physiopathology of sbp

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.


Bacterial infection in liver cirrhosis the microbiologist point of view

Bacterial species isolated from AF obtained from patients

with SBP and hospitalized in Beaujon hospital (1998-2007)


Bacterial infection in liver cirrhosis the microbiologist point of view

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)


Bacterial infection in liver cirrhosis the microbiologist point of view

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


Bacterial infection in liver cirrhosis the microbiologist point of view

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


Bacterial infection in liver cirrhosis the microbiologist point of view

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


Bacterial infection in liver cirrhosis the microbiologist point of view

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


Bacterial infection in liver cirrhosis the microbiologist point of view

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


Bacterial infection in liver cirrhosis the microbiologist point of view

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


Bacterial infection in liver cirrhosis the microbiologist point of view

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


Bacterial infection in liver cirrhosis the microbiologist point of view

Viridans Streptococci


Bacterial infection in liver cirrhosis the microbiologist point of view

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)


Bacterial infection in liver cirrhosis the microbiologist point of view

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 %


Bacterial infection in liver cirrhosis the microbiologist point of view

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.


Bacterial infection in liver cirrhosis the microbiologist point of view

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


Bacterial infection in liver cirrhosis the microbiologist point of view

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)


Bacterial infection in liver cirrhosis the microbiologist point of view

Groupe B2

Resistance to fluoroquinolones

Lower number of VF-encoding genes than expected in B2 isolates


Bacterial infection in liver cirrhosis the microbiologist point of view

Canada

France

Spain

England

Turkey

India

Portugal

Switzerland

Korea


Bacterial infection in liver cirrhosis the microbiologist point of view

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)


Bacterial infection in liver cirrhosis the microbiologist point of view

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


Bacterial infection in liver cirrhosis the microbiologist point of view

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


Bacterial infection in liver cirrhosis the microbiologist point of view

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


Bacterial infection in liver cirrhosis the microbiologist point of view

Characteristics of cirrhotic patients in 76

episodes of spontaneous bacterialperitonitis

(SBP)

* Data are means ± SD or numbers (%) of patients


Bacterial infection in liver cirrhosis the microbiologist point of view

Distribution of phylogenetic groups and virulence factor (VF)

genes in relation to susceptibility to ciprofloxacin


Bacterial infection in liver cirrhosis the microbiologist point of view

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


Bacterial infection in liver cirrhosis the microbiologist point of view

Bacteremia without SBP (n = 17)*

* one patient with endocardites

 primary bacteremia = 16


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