The burden of extended-spectrum β-lactamase-producing Enterobacteriaceae in patients with cirrhosis
Richard Moreau
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R. Moreau Service d'Hepatologie, Departement Hospitalo-Universitaire (DHU) UNITY
, Hopital Beaujon, AP-HP, Clichy,
France
1
R. Moreau Faculte de Medecine,
Universite Paris Diderot
,
Paris, France
2
R. Moreau (&) Inserm UMR_S 1149,
Centre de Recherche sur l'Inflammation (CRI), Inserm et Universite Paris-Diderot
, Paris 7 - Site Bichat, 16 Rue Henri Huchard, 75890 Paris Cedex 18,
France
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R. Moreau Laboratoire d'Excellence (Labex) Inflamex
, PRES Sorbonne Paris Cite,
Paris, France
Patients with cirrhosis have high susceptibility to bacterial infections [1]; 24 % of patients admitted to the hospital for an acute decompensation of cirrhosis have bacterial infection [2]. The most common infection is spontaneous bacterial peritonitis (SBP) [1, 2]. It is well known that SBP is caused by Gram-negative bacteria such as Escherichia coli or Klebsiella pneumoniae originating from the intestinal lumen [3]. The translocation of intestinal bacteria is a crucial step in the process leading to SBP [1, 4]. Little is known about underlying mechanisms that explain bacterial translocation [4]. During the last 30 years the mortality of SBP has decreased from 70 to 30 % [3]. This was the result of large use of a strategy which includes high index of suspicion leading to diagnosis paracentesis, diagnosis of SBP based on neutrophil count C250/mL in the ascitic fluid and subsequent rapid initiation (before results of culture) of wide spectrum, non-nephrotoxic antibiotics (e.g., third generation cephalosporins) against Enterobacteriaceae (E. coli, K. pneumonia) which are the most common causes
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of SBP [3]. In the late 1990s mortality of SBP was further
decreased to 10 % with the combined use of empiric
antibiotics and the intravenous administration of human
albumin [5]. This beneficial effect was related to a
significant decrease in the development of kidney failure (known
as hepatorenal syndrome, HRS) [5]. Today, SBP remains
the most common trigger of infection-induced
acute-onchronic liver failure (ACLF) [2]. ACLF whichever its
trigger, is characterized by the failure(s) of organs
(including kidney, cerebral, liver, coagulation, circulation
and lungs) and high risk of death depending on the number
of failing organs [2].
Due to the severity of SBP, efforts have been made to
prevent this complication. In patients who survive an
episode of SBP long-term prophylaxis with the
fluoroquinolone norfloxacin significantly decreases the risk of
recurrent SBP [3]. The impact on survival is unknown. In
patients with low ascitic fluid protein levels (\1.5 g/dL)
but without a prior episode of SBP the efficacy of primary
prophylaxis using a fuoroquinolone is still unclear. One
trial has shown that norfloxacin significantly decreased the
risk for developing a first episode of SBP [6], a finding that
was not confirmed in another trial with ciprofloxacin [7].
Recently, an increasing number of cases of SBP due to
extended spectrum b-lactamase (ESBL)-producing E. coli,
K. pneumonia have been reported in Asia [811] and
Europe [1216]. Some risk factors for SBP caused by
ESBL-producing bacteria Enterobacteriaceae have been
identified including the in-hospital acquisition of infection
[1015], long-term norfloxacin prophylaxis [13], use of
blactams within the last 3 months [13], and infection by
multiresistant bacteria in the last 6 months [13].
ESBLproducing strains are resistant not only to third-generation
cephalosporins, amoxicillin-clavulanic acid but also to
quinolones and trimethoprim-sulfamethoxazole [13].
ESBL-producing strains are usually sensitive to
carbapenems although some cases have reported of
carbapenemaseproducing Enterobacteriacea [16]. In any case, these
findings indicate that international recommendations
stating that third-generation cephalosporins or
amoxicillinclavulanic acid are the empiric antibiotics of choice for
SBP [3] and are inappropriate for SBP episodes caused by
ESBL-producing bacteria. Finally, studies have shown that
SBP episodes due to ESBL-producing bacteria are more
severe than episodes caused by strains sensitive to
recommended empiric antibiotics [1014]. The reasons for the
severity of infections due to ESBL-producing bacteria are
unknown; theoretically, poor prognosis may be related to a
greater severity of the underlying liver disease, higher
prevalence of septic shock, or delayed initiation of
appropriate antibiotics.
In this issue of Hepatology International Kim et al. [17]
report results of a retrospective analysis conducted in 231
patients with SBP due to E. coli or K. pneumonia of which
52 were caused by ESBL-producing strains. This study
confirms that SBP caused by ESBL-producing strains are
more severe than those due to other bacteria, whereby
morality at day-7 and day-30 was 21.2 vs. 10.1 %
(p = 0.03) and 34.6 vs. 18.4 % (p = 0.01), respectively.
As expected [13], infections due to ESBL-producing
bacteria were more frequently hospital-acquired. Interestingly,
the severity o (...truncated)