Hepatol Int (2014) 8 (Suppl 2):S467–S474

DOI 10.1007/s12072-014-9522-z

SUPPLEMENT ISSUE: ALPD

Bacterial infections in cirrhosis

Gregory J. Botwin • Timothy R. Morgan

Received: 11 October 2013 / Accepted: 9 February 2014 / Published online: 18 April 2014
Ó Asian Pacific Association for the Study of the Liver 2014

Abstract Bacterial infections occur in 25–35 % of cir- antibiotic prophylaxis of cirrhotics with upper gastroin-
rhotics admitted to hospital. Health-care associated and testinal bleeding and long-term antibiotic prophylaxis of
hospital acquired (nosocomial) infections are the most selected cirrhotics with spontaneous bacterial peritonitis
common epidemiology, with community acquired infec- reduces infections and improves survival. Albumin
tions less common (15–30 %). Spontaneous bacterial administration to cirrhotics with SBP and evidence of
peritonitis and urinary infections are the most common advanced liver disease improves survival. The benefit of
sites, with spontaneous bacteremia, pneumonia, cellulitis albumin administration to cirrhotics with infections other
and other sites being less common. The risk of infection is than SBP is under investigation.
increased among subjects with more severe liver disease
and an infection in the past 6 months. Bacteria are isolated Keywords Infection
Cirrhosis
Antibiotics

from approximately half of patients with a clinical diag- Multidrug-resistant bacteria
Survival
Sepsis
nosis of infection. Gram-negative enterobacteriaceae are
the most common organisms among community acquired Abbreviations
infections; Gram-positive cocci are the most common ACLF Acute on chronic liver failure
organisms isolated among subjects with nosocomial CA Community acquired
infections. Up to 30 % of hospital associated infections are DF Discriminant function
with multidrug resistant bacteria. Consequently, empiric ESBL Extended-spectrum b-lactamase
antibiotic therapy that is recommended for community GNB Gram-negative bacteria
acquired infections is often inadequate for nosocomial GPC Gram-positive cocci
infections. Infections worsen liver function. In-hospital and HA Hospital acquired
1-year mortality of cirrhotics with infections is signifi- HCA Healthcare associated
cantly higher than among cirrhotics without infection. In- HR Hazard ratio
hospital complications of infections, such as severe sepsis MDR Multidrug-resistant
and septic shock, and mortality, are increased among OR Odds ratio
subjects with multidrug-resistant infections as compared SBP Spontaneous bacterial peritonitis
with cirrhotics with susceptible bacteria. Short-term UTI Urinary tract infection
VRE Vancomycin-resistant enterococci
WBC White blood cell count
G. J. Botwin
T. R. Morgan (&)
Gastroenterology Services, VA Long Beach Healthcare Group-
11 (GI), VA Long Beach Healthcare System, 5901 E. Seventh
Street, Long Beach, CA 90822, USA
e-mail: timothy.morgan@va.gov Introduction
G. J. Botwin
T. R. Morgan
Gastroenterology Section, Department of Medicine, University Bacterial infections occur in 25–35 % of hospitalized cir-
of California, Irvine, CA, USA rhotics, and infection worsens liver function and increases

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S468
mortality. The prevalence of infection with multidrug-
resistant bacteria is increasing among cirrhotics and is
associated with a greater likelihood of ineffective initial
antibiotic treatment, septic shock and death. In order to
understand bacterial infections in cirrhotics, it is important
to define infections, the systemic inflammatory response
syndrome (SIRS), degrees of sepsis, multidrug resistance,
and the likely source of bacteria.
Bacterial infections are defined by a constellation of
clinical signs and symptoms in conjunction with radiologic,
laboratory and/or microbiological findings. Importantly,
the clinical definitions for infections of specific organs
have been defined [1]. For example, spontaneous bacterial
peritonitis is defined as having C250 PMN/mm3 or having
a positive bacterial culture in ascites. Pneumonia is defined
as having presence of radiologic evidence of lung consol-
idation plus at least two of the following criteria: core
temperature [38 or \35 °C, dyspnea, cough and purulent
sputum, pleuretic chest pain, or signs of consolidation on
physical examination. Similarly, definitions exist for uri-
nary tract infections (UTI), spontaneous bacteremia, and
other infections.
The systemic inflammatory response is a clinical syn-
drome (SIRS) that develops in response to inflammation.
SIRS is defined as the presence of two or more of the
following four findings: (1) core temperature [38 or
\35 °C, (2) heart rate C90/min, (3) respiratory rate[20/min
or arterial partial pressure of carbon dioxide (PaCO2)
\32 mm Hg, or (4) a white blood cell (WBC) count
\4,000 or [12,000/mm3, or [10 % bands. The use of
SIRS in cirrhosis has less diagnostic accuracy than in
normal individuals because cirrhotics may have a hyper-
dynamic circulation in the absence of infection, be
receiving beta blockers which reduce heart rate, and have
hypersplenism which reduces white blood cell count.
Sepsis is a clinical syndrome that complicates an
infection and is marked by inflammation in tissues distant
from the infected organ. Sepsis is defined clinically as the
presence of infection (either documented or presumed)
along with systemic symptoms, usually defined as having
two or more of the SIRS criteria. Severe sepsis is defined as
sepsis-induced organ dysfunction (e.g., creatinine [2 mg/dL,
bilirubin [2 mg/dL, etc.) or tissue hypoperfusion (e.g.,
elevated lactate). Septic shock is defined as sepsis-induced
hypotension that persists despite the administration of
adequate intravenous fluids.
The patient’s relationship to hospitals at the time the
infection is acquired has important treatment and prog-
nostic implications. Hospital acquired (HA) infections
(also known as nosocomial infections) are diagnosed after
a patient has been in the hospital for more than 48 h.
Health-care associated (HCA) infections are those that
develop within the first 48 h of hospital admission in a
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Hepatol Int (2014) 8 (Suppl 2):S467–S474
patient who has one or more of the following: (1) has been
an inpatient for C2 days or received surgery in the prior
6 months (sometimes defined as the prior 3 months), (2)
has been seen in an outpatient clinic (e.g., clinic or he-
modialysis) or received chemotherapy in the prior 30 days,
or (3) has resided in nursing home or a long-term care
facility. Community acquired (CA) infections are those that
occur in a patient not meeting the definition for either
hospital acquired or HCA.
The current definition of multidrug resistant (MDR)
bacteria is acquired non-susceptibility to at least one agent
in three or more antimicrobial categories. However, pub-
lications cited in this review often use an older and broader
definition of MDR, including: (1) resistant to three or more
classes of antimicrobial agents, (2) methicillin-resistant
Staphlococcus aureus, (3) an Acinetobacter baumannii, or
(4) an extended-spectrum b-lactamase (ESBL) producing
Gram-negative strain.
Discussion
Prevalence and clinical characteristics of cirrhotics
with bacterial infections
The prevalence of bacterial infections is 25–35 % in pro-
spective studies of hospitalized cirrhotics (Table 1) [2–6].
For the past 15 years, Fernandez and colleagues from
Barcelona have prospectively studied bacterial infections
among hospitalized cirrhotics. Among 1,567 admissions
for decompensated cirrhosis between 1998 and 2000, 507
admissions (32 %) had infections on admission or during
hospitalization [3]. A follow-up study of 1,578 admissions
between 2005 and 2007 for complications of cirrhosis
reported that 390 admissions (25 %) had infections [2].
Merli et al. [4] from Rome found that 50 patients were
infected (54 infections) among 150 consecutive patients
admitted for decompensated cirrhosis in 2008–2009. The
etiology of cirrhosis in these studies was largely alcohol or
hepatitis C (approximately equal), with a small number of
patients with cirrhosis due to other causes. A similar
prevalence of infection is found in patients with alcoholic
hepatitis. Among 246 patients with biopsy-proved alco-
holic hepatitis and Maddrey discriminant function (DF)
score[32, 63 patients (25.6 %) were infected on admission
to hospital [7]. Of the 240 patients that received prednis-
olone as treatment for alcoholic hepatitis, 57 (23.7 %)
developed infections during corticosteroid treatment (24)
or after corticosteroids were stopped (33).
On admission to hospital, cirrhotics with infections
have worse liver function than cirrhotics without infec-
tions, as measured by laboratory variables such as lower
albumin, higher bilirubin, higher creatinine, and lower
Hepatol Int (2014) 8 (Suppl 2):S467–S474 S469

Table 1 Prevalence of infections among patients with cirrhosis 271 infections, being more frequent among patients
admitted to hospital receiving long-term norfloxacin prophylaxis for SBP (85
Admissions (patients) Infections vs. 47 %) [2].
A major concern with HA infections is inappropriate
Caly and Strauss [6] 170 47 %
empiric antibiotic treatment. Empiric antibiotic treatment
Borzio et al. [5] 405 34 % was effective in resolving infection in 83 % of CA infec-
Fernandez et al. [3] 1,567 32 % tions, 73 % of HCA infections, but only 40 % of HA
Merli et al. [4] 150 36 % infections (p \ 0.0001) [2]. The decreased efficacy of
Fernandez et al. [2] 1,578 25 % empiric treatment among HA infections was true for all
sites of infection.

serum sodium [4]. However, among subjects with alco-

Risk factors for development of infection
holic hepatitis, all of whom have severe liver dysfunction,
laboratory measures of liver function, including MELD
Several patient variables are associated with increased risk
and Maddrey DF, are similar between subjects with and
of being infected. On univariate analysis, worse liver
without infections [7].
function (higher MELD and/or Child–Pugh score), hospi-
The most common sites of infection are ascites (SBP)
talization in the past 6 months, infection in the past
and urinary tract, followed by spontaneous bacteremia,
12 months, having a transjugular intrahepatic portal-sys-
pneumonia, cellulitis, and other infections [2, 4, 7, 8].
temic shunt (TIPS), and protein malnutrition (mid-arm
Approximately 50 % of infections are proven microbio-
muscle circumference less than 5th percentile) were asso-
logically (26/54 = 48.15 % [4] and 271/507 = 53.45 %
ciated with increased risk of infection. On multivariate
[2]), with HCA and HA infections more likely to be
analysis, a history of infection in the past 6 months, MELD
microbiologically documented (50–70 %) than community
score C15, and protein malnutrition were independent
acquired (33–39 %). Culture-positivity is more likely for
predictors of infection [4].
UTI (91 %) than for cellulitis (47 %), SBP (41 %), or
Risk factors for acquisition of MDR have also been
pneumonia (37 %) [2].
evaluated. Fernandez found nosocomial acquisition of
Among CA and HCA infections, Gram-negative bacte-
infection [hazard ratio (HR), 4.43)], long-term norfloxacin
ria (GNB) were isolated approximately 60–65 % of the
prophylaxis (HR 2.69), use of b-lactams within the prior
time while Gram-positive cocci (GPC) were isolated in
3 months (HR 2.39), and infection by multiresistant bac-
43–46 % of infections [2, 4]. However, among hospital
teria in the last 6 months (HR 2.45) were independent
acquired infections, the frequency of GPC was either
predictors of MDR infection [2]. Variables associated with
similar to GNC (44 vs. 46 % [2]) or higher (64 % [4]).
increased risk of acquiring a HA infection include the
Enterobacteriaceae were the most commonly isolated
number of invasive procedures performed [3, 4] and
organisms, particularly Escherichia coli. S. aureus was the
placement in a room with another patient (i.e., not in an
second most frequently isolated organism [2, 4].
individual room) [4].
Multidrug-resistant bacteria are isolated in approxi-
mately 30 % of infections, with the likelihood dependent
on the epidemiology of the infection [2, 4]. Multidrug- Treatment of sepsis in cirrhosis
resistant bacteria are more frequently found in nosocomial
infections (20–35 % of infections) as compared with Selection of antibiotics for empiric treatment of sepsis
community acquired infections (approximately 4–16 %). depends on the site of acquisition (e.g., community, HCA,
The frequency of detecting MDR bacteria in HCA infec- or HA), the site of the infection, and the severity of the
tions is unsettled, and has been reported to be as high as infection (Table 2; Figs. 1, 2) [9, 10]. Community acquired
HA (40 % [4]) as well as closer to the rate for CA (14 % urinary tract infections that are not associated with sepsis
[2]). The prevalence of MDR is high in UTI (39 %), can be treated with b-lactams, quinolones, amoxicillin–
especially healthcare associated UTI (57 %). However, clavulanic acid, or trimethoprim–sulfamethoxazole intra-
the prevalence of MDR among nosocomial infections is venously or orally, depending on the severity. Community
higher than the prevalence in CA for all infections: SBP acquired SBP or spontaneous bacteremia can be treated
(22 vs. 5 %), cellulitis (27 vs. 7 %), and pneumonia (32 with a third-generation cephalosporin (e.g., Cefotaxime or
vs. 9 %) [2]. ESBL-enterobacteriaceae are the most fre- ceftriaxone) or amoxicillin–clavulanic acid. Hospital
quent multidrug resistant strains, followed by P. aeru- acquired infections should usually be treated with a carb-
ginosa, methicillin-resistant S. aureus (MRSA), and E. apenem. Final antibiotic selection depends on bacterial
faecium. Quinolone-resistant GNB were isolated in 97 of culture and sensitivity testing.

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S470 Hepatol Int (2014) 8 (Suppl 2):S467–S474

Table 2 Empiric antibiotics for community acquired, HCA, and hospital acquired infections, in areas with high prevalence of ESBL-E and VSE
(adapted from Fernandez and Gustot [10])
Infection Community acquired HCA or HA

SBP, spontaneous First line: Carbapenum IV (e.g., meropenum 1 g/8 h IV)

bacteremia, not severe Cefotaxime 2 g/12 h IV or Ceftriaxone 1 g/12–24 h IV
(no sepsis or shock) or Amoxicillin–clavulanic acid 1/0.2 g/6–8 h IV
Acceptable:
Ciprofloxacin 200 mg/12 H IV or Ofloxacin 400 mg/
12 h PO
SBP, spontaneous Meropenum 1 g/8 h IV plus glycopeptide Meropenum 1 g/8 h IV plus glycopeptide
bacteremia, with sepsis
or septic shock
Uncomplicated UTI Cefotaxime 2 g/12 h IV or Ceftriaxone 1 g/12–24 h IV Nitrofurantoin 500 mg/6 h PO
or Amoxicillin–clavulanic acid 1/0.2 g/6–8 h IV or
PO or Trimethoprim–sulfamethoxazole 160/800 mg/
12 h PO
UTI with sepsis (SIRS) Carbapenum IV (e.g., meropenum 1 g/8 h IV) Carbapenum IV (e.g., meropenum 1 g/8 h IV)
UTI with severe sepsis or Carbapenum IV (e.g., meropenum 1 g/8 h IV) Carbapenum IV (e.g., meropenum 1 g/8 h IV)
shock
Pneumonia Ceftriaxone 1 g/12–24 h IV or Amoxicillin–clavulanic Carbapenum IV (e.g., meropenum 1 g/8 h IV) or
acid 1/0.2 g/6–8 h IV plus macrolide, or Ceftazidime 2 g/8 h IV plus ciprofloxacin 400 mg/8 h
Levofloxacin 500 mg/24 h IV or PO IVIV Vancomycin or linezolid should be added for
patients with risk factors for MRSA
Cellulitis Amoxicillin–clavulanic acid 1/0.2 g/6–8 h IV or Carbapenum IV (e.g., meropenum 1 g/8 h IV) or
Ceftriaxone 1 g/12–24 h IV plus cloxacillin 2 g/6 h Ceftazidime 2 g/8 h IV plus a glycopeptide
IV

Fig. 1 Algorithm for empirical

Spontaneous Bacterial Infection
treatment of spontaneous
infections in patients with (SBP or SB)
cirrhosis according to site of
acquisition and presence of risk
factors for multidrug-resistant
bacteria. *Risk factors for Community Acquired Health-care Nosocomial
multidrug-resistant bacteria: Infection Associated Infection Infection
infection by MDR in the prior
6 months, use of b-lactams in
the prior 3 months, and long- Presence of 2 risk factors for
term use of norfloxacin
multidrug resistant bacteria* or
prophylaxis. **Linezolid or
daptomycin should replace severe sepsis or shock?
glycopeptides in areas with high
prevalence of VRE (adapted
from Acevedo [7]) No Yes

Third-generation Carbipenem +
cephalosporin Glycopeptide **

Clinical course
Patients developing infection or sepsis have a worsening in
their liver function when measured by CTP (additional 1.9
and 2.5 points for infection and sepsis, respectively) or
MELD (increase of 3.8 and 4.9 points, respectively) [4].
Individual laboratory tests also worsened among infected
cirrhotics: bilirubin (?4.4 ± 12 mg/dL), albumin
(-0.34 ± 0.9 g/dL), creatinine (?0.6 ± 1.8 mg/dL), and
serum sodium (-3.3 ± 6.1 mEq/L).
In-hospital and 30-day post-hospital mortality is
increased among infected cirrhotics. In a prospective study
of 100 uninfected and 50 infected cirrhotics, Merli et al. [4]
reported a 28 % in-hospital mortality for infected cirrhotics
versus 4 % for uninfected cirrhotics (p \ 0.00007). In-
hospital mortality was also higher for patients with sepsis

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Hepatol Int (2014) 8 (Suppl 2):S467–S474
Fig. 2 Algorithm for treatment
of urinary tract infections
according to the severity of the
infection and its site of
acquisition. *Linezolid or
daptomycin should replace Community Acquired
glycopeptides in areas with high
prevalence of VRE (adapted Infection
from Acevedo [7])
or trimethoprim-
sulfamethoxazole
(12/31, 38 %) than among infected cirrhotics without
sepsis (2/19, 10 %, p \ 0.00001).
Retrospective studies also report increased mortality
among infected cirrhotics. An analysis of 178 studies (225
cohorts, 11,987 patients) reporting mortality data among
cirrhotics found the median mortality for infected patients
was 30.3 % at 30 days and 63 % at 1 year [11]. The pooled
odds ratio for death of infected versus non-infected cirrhotics
was 3.75 (95 % confidence interval 2.12–4.23). Mortality in
publications prior to 2000 was 47.7 % as compared with
32.3 % among publications after 2000. However, mortality
rates in publications after 2000 improved solely because of
reduced 30-day mortality among patients with SBP (49 %
prior to 2000 vs. 31.5 % after 2000, p = 0.005), presumably
due to the use of antibiotic prophylaxis and/or albumin
infusion with the initial infection. Unfortunately, 1-year
mortality was not reduced after 2000 for SBP, and neither
short-term nor long-term mortality was reduced after 2000
for infection at any other site. Overall, there has been limited
progress in improving post-hospital survival among infected
cirrhotics during the past 20 years.
In-hospital mortality is related to the epidemiology of
infection, with higher mortality among patients with HA
infections (37 %) and HCA infections (36 %) than among
CA infections. On multivariate analysis, independent pre-
dictors of mortality were Child–Pugh Class C (odd ratio
[OR], 6.3), sepsis (OR 6.01), and protein malnutrition (OR
10.44) [4]. Two additional investigations of in-hospital
mortality among infected cirrhotics found that MELD
score and the presence of SIRS were independent predic-
tors of mortality [12, 13].
A prospective, multicenter study from the United States
evaluated the predictors of 30-day mortality among 207
S471
Urinary Tract Infection
Health-care Nosocomial
Associated Infection Infection
Sepsis, severe sepsis or shock?
No Yes
Oral nitrofurantoin IV carbapenem +
Glycopeptide*
infected cirrhotic patients [8]. Average age was 55 years,
60 % were male and average MELD score was 20. Second
infections occurred in 50 (24 %) of patients, including
aspiration (14), urinary (13), fungal (7), and Clostridium
difficile (6). Case fatality rate was highest for C. difficile
(40 %), respiratory (37.5 %), and spontaneous bacteremia
(37 %), and lower for SBP (17 %) and urinary infections
(15 %). Second infections were more frequent among
patients in whom the first infection was nosocomial as
compared to HCA or CA. Multivariate analysis found the
independent predictors of mortality were MELD score
(OR, 1.12), heart rate (OR, 1.03), albumin (OR, 0.5), and
second infection (OR, 4.42).
Acute on chronic liver failure (ACLF)
Acute on chronic liver failure is defined as the presence of
additional organ failures in a patient with liver failure [14].
The 28-day mortality is significantly increased among
patients with ACLF (33.9 %) as compared with patients
with decompensated liver disease but without ACLF
(1.9 %). Patients with ACLF are more likely to have a
history of alcohol use, and more likely to have a bacterial
infection (32.6 %) than patients without ACLF (21.8 %;
p \ 0.01 for bacterial infections). The most common sites
of bacterial infection are ascites (SBP) and lungs. Infec-
tions were the second most common cause of death at
28 days among patients with ACLF (27.8 %), behind
multiple organ failure without septic or hypovolemic shock
(43.8 %). However, among patients with ACLF, the mor-
tality rate at 28 days did not differ between those with
bacterial infection (36.7 %) or without bacterial infection
(33 %).
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Clinical course of infection with MDR bacteria
Infection with MDR bacteria is associated with worse
outcome than is infection with a susceptible bacteria or
infection in which bacteria is not isolated [2]. Final reso-
lution of infection occurred in 92 % of cirrhotics without
bacteria isolated or with susceptible bacteria as compared
with 70 % of cirrhotics with MDR (p \ 0.0001). Similarly,
septic shock occurred in 10 % of cirrhotics with suscepti-
ble or without bacteria isolated versus 26 % of cirrhotics
with MDR (p \ 0.0001). In-hospital mortality was 12 %
for cirrhotics without isolated bacteria or susceptible bac-
teria as compared with 25 % for MDR (p = 0.001).
Prophylaxis of infections and complications
of infections in cirrhosis
Upper gastrointestinal bleeding
Approximately 20 % of cirrhotics with upper gastrointes-
tinal bleeding are infected on admission and up to 50 %
develop infection in the first week if prophylactic antibi-
otics are not administered [15, 16]. Multiple antibiotics
have been tested to prevent bacterial infections, including
amoxicillin (with/without clavulanic acid), cephalosporins,
quinolones, and non-absorbable antibiotics. In general, the
incidence of infection decreased with antibiotic prophy-
laxis (10–20 %) as compared with no antibiotic (45–65 %),
with meta-analyses demonstrating a statistically significant
decrease in mortality with short-term antibiotic adminis-
tration [17, 18]. Antibiotics may also decrease rebleeding,
although the evidence for this is less convincing [19, 20].
AASLD and EASL guidelines recommend administration
of antibiotics for 7 days after an upper gastrointestinal
bleed in cirrhotics, with initial administration of antibiotics
given as soon as possible after admission and, at the latest,
shortly after endoscopy. Norfloxin, 400 mg orally twice a
day, is a recommended regimen. However, ceftriaxone, 1 g
IV daily for 7 days, may be more effective among patients
with severe liver disease (defined as two or more of the
following: ascites, encephalopathy, jaundice, or severe
malnutrition) [21].
Ascites
Prophylaxis of spontaneous bacterial peritonitis is recom-
mended for selected patients with advanced liver disease
who have never had an episode of SBP, and for all patients
surviving an episode of SBP. Patients with ascites protein
level \1.5 mg/dL and advanced liver disease (defined as
Child–Pugh score B9 and serum bilirubin C3 mg/dL) or
impaired renal function (i.e., serum creatinine C1.2 mg/dL,
blood urea nitrogen C25 mg/dL, or serum sodium
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Hepatol Int (2014) 8 (Suppl 2):S467–S474
B130 mEq/L) benefit from primary prophylaxis with
norfloxin 400 mg/day for 1 year [22]. Among cirrhotics
receiving norfloxin, the 1-year probability of developing
SBP (7 vs. 61 %) and hepatorenal syndrome (28 vs. 41 %)
were significantly reduced, and survival increased (94 vs.
62 %). Oral ciprofloxin 500 mg/day is an acceptable
alternative to norfloxin [23].
Patients who survive an episode of SBP have a 60–70 %
probability of developing SBP in the next 12 months [24].
Among these subjects, daily norfloxin 400 mg decreases
the probability of SBP during the subsequent year to
20–25 %. Daily norfloxin appears to be more effective than
weekly quinolone for the prevention of SBP [25].
Albumin administration
In addition to serving as the primary protein contributing to
intravascular oncotic pressure, albumin also binds endo-
toxin (bacterial lipopolysaccharide) and has antioxidant
properties. Albumin administration to selected patients
with SBP, in combination with appropriate antibiotics,
decreases the development of hepatorenal syndrome and
improves survival. Sort and coworkers randomized patients
with SBP to receive cefotaxime alone or cefotaxime with
intravenous albumin 1.5 g/kg body weight on day 1 and
1.0 g/kg body weight again on day 3 [26]. Renal impair-
ment developed in 33 % of patients receiving cefotaxime
alone as compared with 10 % among subjects receiving
cefotaxime and albumin. Mortality decreased from 29 %
among subjects receiving cefotaxime to 10 % among
subjects receiving cefotaxime and albumin. A subsequent
analysis suggests that albumin should be given to patients
with SBP who have creatinine [1.0 mg/dL, blood urea
nitrogen [30 mg/dL, or total bilirubin [4 mg/dL [27]. A
retrospective study found improved survival among cir-
rhotics with SBP who had advanced liver disease, defined
as blood urea nitrogen [11 mmoles/L ([31 mg/dL) or
bilirubin[68 umol/L (4 mg/dL), who received intravenous
albumin [28]. Patients with SBP without one of these
markers of advanced liver disease had a high survival
without intravenous albumin.
The benefit of albumin infusion among selected subjects
with SBP led to investigations of albumin infusion among
cirrhotics with infections other than SBP. Guevara and
colleagues randomized 110 patients with cirrhosis and
infections to antibiotics alone or antibiotics with intrave-
nous albumin (1.5 g/kg body weight on day 1 and 1.0 g/kg
body weight on day 3) [29]. Renal function improved
among subjects receiving albumin but survival was similar
at 3 months in both groups. Multivariate analysis of
patients receiving treatment per-protocol suggested that use
of albumin improved survival. A subsequent randomized
trial of albumin administration has been undertaken among
Hepatol Int (2014) 8 (Suppl 2):S467–S474
subjects with cirrhosis and infection who have poor prog-
nostic signs (e.g., two or more of the following laboratory
abnormalities: (1) creatinine C1.2 mg/dL, (2) bilirubin
C4 mg/dL, or (3) serum sodium B130 mEq/L, or who have
pneumonia and one or more laboratory abnormality). Pre-
liminary results suggest that albumin improves 28-day
mortality although publication of the results of the study is
awaited.
Conclusion and perspective
Bacterial infections occur in 25–35 % of hospitalized
cirrhotics, with the majority of infections being hospital
acquired or health-care associated. The most common
sites of infection include ascites (SBP) and urinary tract.
The risk of infection is greater among cirrhotics with
more severe liver disease or with a history of infection in
the prior 6 months. Bacteria are isolated from approxi-
mately half of patients with a clinical diagnosis of
infection, with Gram-negative enterobacteriaceae the most
commonly isolated organism among community acquired
infections and Gram-positive bacteria the most commonly
isolated organism in HA and HCA infections. Up to 30 %
of hospital acquired infections are with multidrug-resis-
tant bacteria. Consequently, empiric antibiotic treatment
appropriate for community-acquired infections is often
inadequate for hospital and HCA infections. Infections
worsen liver function, and increase in-hospital and 1-year
mortality. Severe sepsis, septic shock, and mortality are
more common among cirrhotics infected with MDR than
among cirrhotics infected with susceptible bacteria. Short-
term antibiotic prophylaxis after upper gastrointestinal
bleeding and long-term antibiotic prophylaxis in selected
patients with spontaneous bacterial peritonitis reduce
infections and improve survival. Albumin administration
to selected patients with spontaneous bacterial peritonitis
also improves survival. The benefit of albumin adminis-
tration to cirrhotics with other infections is not yet
known.
Compliance with ethical requirements and Conflict of inter-
est This article does not contain studies with human or animal
subjects performed by any of the authors. Gregory J. Botwin and
Timothy R. Morgan declare that they have no conflict of interest.
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