Infectious Complications of Cirrhosis
Oscar S. Brann, MD
Address
Gastroenterology Clinic, Naval Medical Center,
34800 Bob Wilson Drive, San Diego, CA 92134-3301, USA.
E-mail: osbrann@nmcsd.med.navy.mil
Current Gastroenterology Reports 2001, 3:285–292
Current Science Inc. ISSN 1522-8037
Copyright © 2001 by Current Science Inc.
Infectious complications in cirrhotic patients can cause
severe morbidity and mortality. Bacterial infections
are estimated to cause up to 25% of deaths in cirrhotic
patients. The most frequent are urinary tract infection,
spontaneous bacterial peritonitis, respiratory tract
infection, and bacteremia. It has been said that cirrhosis
is the most common form of acquired immunodeficiency,
exceeding even AIDS. The specific risk factors for infection
in cirrhotic patients are low serum albumin, gastrointestinal
bleeding, intensive care unit admission for any cause,
and therapeutic endoscopy. Certain infectious agents
are more virulent and more common in patients with
liver disease. These include Vibrio, Campylobacter, Yersinia,
Plesiomonas, Enterococcus, Aeromonas, Capnocytophaga,
and Listeria species, as well as organisms from other
species. Spontaneous bacterial peritonitis is a frequent,
severe, life-threatening complication of patients with
ascites. Current observations and recommendations
regarding treatment and prophylaxis are reviewed. A brief
synopsis of miscellaneous infections encountered
in cirrhotic patients is also included.
Introduction
Bacterial infections are estimated to cause up to 25% of
deaths in cirrhotic patients. Several studies have estab-
lished that 30% to 50% of cirrhotic patients either have an
infection at the time of hospital admission or acquire one
nosocomially. For any patient admitted to the hospital,
the risk for nosocomial infection is 5% to 7%; in cirrhotic
patients it is 15% to 35%. The most common are urinary
tract infection (12% to 29%), spontaneous bacterial
peritonitis (7% to 23%), respiratory tract infection (6% to
10%), and bacteremia (4% to 9%) [1]. Predisposing factors
for these types of infection include multiple mechanical
and immunologic defects central to the pathophysiology
of cirrhosis. It has been said that cirrhosis is the most
common form of acquired immunodeficiency, much more
so than AIDS [2•]. In the normal host, bacteria are
opsonized, ingested by motile or stationary phagocytes
(neutrophils, Kupffer cells), and then die an intracellular
death. The cirrhotic patient has low complement and
opsonin levels, a dysfunctional reticuloendothelial system,
neutrophil dysfunction, and gut mucosa that are unusually
permeable to bacteria. The more advanced the liver
disease, the higher is the propensity to infection and assoc-
iated increased mortality [3,4]. Approximately 75% of the
bacterial infections in cirrhotic patients are caused by
gram-negative bacteria (Escherichia coli, Klebsiella pneumo-
niae, Aeromonas hydrophila, and Pseudomonas and Vibrio spp,
among others), whereas gram-positive bacteria comprise
21.2% (Staphylococcus aureus, Streptococcus pneumoniae, and
Streptococcus viridans) and anaerobes only 3.2% (Bacteroides
and Peptostreptococcus spp) [5].
Enteric organisms can translocate across the gut wall
to then be captured by mesenteric lymph nodes. This has
been demonstrated in 40% of cirrhotic rats with ascites
and 80% of rats with experimentally induced spont-
aneous bacterial peritonitis. These findings support the
hypothesis that gut bacteria have ready access to the
systemic circulation in cirrhosis. One study from Spain
prospectively evaluated the evidence for bacterial trans-
location in humans. One hundred and one cirrhotic
patients undergoing either orthotopic liver transplanta-
tion or hepatic resection for hepatocellular carcinoma
were compared with 35 control patients without cirrhosis
undergoing laparotomy for nonhepatic reasons. At the
time of operation, mesenteric lymph nodes and scrapings
from the terminal ileum were obtained for culture. Simul-
taneous portal and peripheral blood samples were
obtained. Bacterial translocation was found to be five
times more frequent in advanced Child’s C liver disease,
whereas patients with Child’s A and B disease were no
different from controls. Preoperative intestinal bacterial
decontamination appeared to reduce this phenomenon
[6•]. The permeability of the intestinal mucosa may
actually be higher in alcoholic patients. In one study,
Rosa et al. [7] noted that both Child’s A and Child’s B
alcoholic patients were more susceptible to infection,
although mortality was higher only in Child’s C patients.
The specific risk factors for infection in cirrhotic
patients have been examined. Univariate analysis demon-
strates that patients with a low serum albumin level,
gastrointestinal bleeding, intensive care unit (ICU) admis-
sion for any cause, or therapeutic endoscopy have the high-
est risk. Logistic regression analysis reveals gastrointestinal
bleeding and low serum albumin as the two main inde-
pendent risk factors [8].
286 Gastrointestinal Infections
Specific Bacterial Infections in Cirrhosis
Certain infectious agents are more virulent and/or more
common in patients with liver disease. The following
sections represent the trends in recent literature.
Vibrio species
Vibrio species organisms are motile, gram-negative, lactose-
fermenting, virulent rods, which are halophilic (preferring
high salt concentrations). Many species are capable of
causing serious human illness, including V. parahaemolyti-
cus, V. alginolyticus, V. vulnificus, V. metschnikovii, and
“group F” [9]. The best-known Vibrio disease in humans is
Vibrio cholerae–induced secretory diarrhea, but noncholera
species can also cause disease, such as cellulitis, external
otitis, bacteremia, spontaneous bacterial peritonitis,
gastroenteritis, pneumonia, and meningitis. These organ-
isms concentrate in filter-feeding shellfish (oysters, crabs,
clams, and mussels) and other fish. V. vulnificans (vulnificus
is Latin for “wounding”) has become renowned for its
especially aggressive nature in immunocompromised
patients and has been called the “monster of the deep”
[10•]. It has been hypothesized that these infections date
back to the time of Hippocrates, who described the patient
Criton on the Greek island of Thasos in the fifth century
BC, who developed “violent pain in the foot” followed by
“small black blisters”[11].
V. vulnificus grows well in warm water (>20° F) and
low salinity (0.7% to 1.6%). Normally inhabiting
coastal waters, it is found worldwide; in the United States
it is found mainly in the waters of Hawaii, Utah,
Massachusetts, and states bordering the Gulf of Mexico
[12]. Because this disease has no relationship to fecal
contamination, there is no role for sanitation or public
health controls in routine prevention. Vibrio organisms are
truly “normal” marine flora. In peak summer months, up
to 50% of oysters and 11% of crabs are colonized. V. vulnif-
icans does not alter the taste, appearance, or odor of oys-
ters. Its pathogenesis is related to its ability to bind directly
to human intestinal cells and to enter the systemic vascu-
lature within hours of arrival in the duodenum. An acidic
antiphagocytic mucopolysaccharide capsule helps it elude
the immune system, and virulence is associated with
various toxins such as cytolysin and collagenase [13].
These toxins may be the mediators of necrosis, ischemia,
and edema of the legs, with resultant skin rash, blisters,
cellulitis, and fasciitis.
The first case of V. vulnificans infection reported in
modern literature appeared in 1970. The patient is
described as a previously healthy man who developed
acute hemorrhagic rash, vomiting, and diarrhea 2 days
after bathing and clamming. One of two clinical pictures
can occur: diarrhea from exposure to contaminated sea-
food or ingestion of sea water, or septicemia caused by
ingestion or open-wound contamination. Both instances
can be rapidly progressive and fatal, with 46% to 61%
mortality in primary septicemia and 7% to 22% in skin
infection. Primary septicemia occurs more frequently in
chronically ill patients, with 10% occurring in normal
hosts. Clinically, sepsis usually occurs 24 to 48 hours after
ingestion, but may occur up to 7 days after exposure. Signs
and symptoms include abdominal pain, watery diarrhea,
fever, and chills. Particularly serious is the onset of intense
lower extremity pain, with or without ecchymoses or
necrotic ulcers, which may lead to a compartment
syndrome requiring surgical debridement. Seventy-five
percent of septicemia patients develop skin manifestations.
These lesions typically occur on the lower extremities, and
they include simple erythema, necrotic ulcers, necrotizing
fasciitis, vasculitis, pustules, petechiae, generalized
papules, macules, gangrene, urticaria, and even erythema
multiforme. Gram stain and culture of the cutaneous
lesions reveal bacteria without inflammatory cells. Wide-
spread obliterative vasculitis and vascular necrosis make
antibiotic treatment an adjunct to primary surgical debri-
dement, with occasional need to amputate an extremity.
Open wounds may act as a portal of entry, with rapid
clinical deterioration via disseminated intravascular necro-
sis and hypotension. Blood cultures are positive in 97% of
patients. The prognosis in infected cirrhotic patients is
poor, with an overall mortality rate of 56% (24% for
wound infection) [14,15].
The pathophysiology for more severe infection in
chronic liver patients has been postulated to include
decreased complement levels, reduced phagocytic activity,
diminished chemotaxis, “bypass” of the reticuloendo-
thelial system, and free iron availability for growth of the
Vibrio organism. Patients with iron overload are much
more susceptible to V. vulnificus infection, supported by the
fact that this organism is rapidly destroyed by fresh blood
and plasma from a healthy host but grows well in the same
material from a patient with hereditary hemochromatosis.
The organism lacks the ability to acquire iron from unsat-
urated ferritin and “likes” the free iron available in patients
with liver disease [16].
Two cases of fulminant sepsis from Vibrio species infec-
tion occurred in solid organ transplants, one after the
patient suffered a “crab scratch” and another in a patient
with “severe” hand swelling after a minor fish knife wound
during saltwater fishing. Both patients recovered with
appropriate management, but one required leg amputa-
tion and the other fasciotomy and debridement [17].
The epidemiology of this organism underscores the
major risk in ingestion of poorly cooked, contaminated
seafood. In the summer months, more than 50% of oyster
lots in Florida and Texas Gulf Coast areas are contaminated
by Vibrio species organisms. The organism proliferates at
room temperature but is easily killed by either boiling or
freezing. Overall incidence for seriously ill patients is 0.4 to
1.9 cases/100,000. The case fatality ratio of V. vulnificus
infection from raw oyster ingestion in Florida has been
reported as 67% in patients with preexisting liver disease,
versus 38% without preexisting liver disease [18]. The rate

of illness for patients ingesting raw oysters in Florida is
72/million for liver patients but 0.9/million for those
without liver disease. A study in Florida revealed that less
than 15% of high-risk individuals were aware of the risks
from raw oyster consumption. Patients with liver disease
are at an 80-fold greater risk for illness and a 200-fold
greater risk for death [19]. From April 1993 to May 1996,
16 cases were seen in Los Angeles county, CA: 94% of the
patients were Spanish speaking, 75% had preexisting liver
disease, and all had eaten raw oysters 1 to 2 days before the
onset of symptoms. V. vulnificus infection is now accepted
as a leading cause of death related to foodborne illness in
parts of the United States. Despite aggressive ICU treat-
ment, the case fatality rate is still 50% to 60% [20].
The high case fatality rate makes education of liver
patients very important. Strong recommendations should
be made against the consumption of raw or poorly cooked
oysters or other shellfish, and avoidance of sea water
should be stressed during the warm summer months
(especially in patients with open wounds). Mandatory use
of protective gloves should be advocated for individuals
handling shellfish. Gulf Coast states now warn purchasers
about possible ill effects of shellfish because proper har-
vesting and handling do not diminish the risk. Even minor
wounds should be immediately treated with oral tetra-
cycline, trimethoprim/sulfamethoxazole, or a quinolone.
Prevention includes boiling shellfish for 3 to 5 minutes
after they gape, or steaming for 4 to 9 minutes [21].
Empiric treatment recommendations include doxycycline,
100 mg every 12 hours, and ceftazidime, 2 mg every 8
hours. The differential diagnosis of the clinical presenta-
tion includes staphylococcal scalded skin syndrome,
anthrax, necrotizing fasciitis, and clostridial infection.
Other Vibrio species can cause disease in liver patients.
Infection with V. cholerae organisms (non-01) occurs in
endemic areas, such as the United States, Mexico, and
Southeast Asia. These organisms are found worldwide in
fresh and salt water, concentrating in fish or shellfish and
dividing rapidly in contaminated, undercooked food. In a
case report, V. cholerae organisms caused spontaneous
bacterial peritonitis in a patient with biopsy-proven cirrho-
sis who had eaten raw oysters 2 days prior to hospital
admission. The patient responded to treatment with cefo-
taxime. V. parahamolyticus has an incubation period of 4 to
96 hours, usually causing explosive, watery diarrhea,
abdominal cramps, nausea, vomiting, and occasionally
bloody dysentery. V. parahaemolyticus organisms have
caused fatal bacteremia in immunocompromised patients
with acute myelogenous leukemia or advanced cancer,
and this infection produces a rapid downhill course very
similar to that of infection with V. vulnificans. V. para-
haemolyticus infection caused fatal septicemia in a patient
with cirrhosis who presented with bloody diarrhea, severe
weakness, and numerous serosanguineous bullae on the
lower extremities. High-risk patients should avoid the
ingestion and handling of seafood products [22].
Infectious Complications of Cirrhosis • Brann 287
Yersinia enterocolitica
Patients with iron overload or chronic liver disease are at
increased risk for Yersinia species bacteremia or sepsis. In a
recent review of 11 patients, it was noted that 69% had
positive blood cultures and that mortality was 50%, on par
with mortality from spontaneous bacterial peritonitis. The
increased propensity for Yersinia infection in patients with
iron overload is based on the dependence of this organism
on iron and its inability to synthesize iron-binding com-
pounds. Desferoxamine may increase the risk because it can
serve as a growth factor for the organism. An additional risk
factor for invasive infection may be prior gastric resection.
The reduction of host acid-mediated defenses allows
increased delivery of the organism to the small bowel [23].
Plesiomonas shigelloides
Plesiomonas shigelloides is a gram-negative facultative
anaerobic, oxidase-positive, motile, rod-shaped organism of
the family Vibrionaceae. It is found in fresh and sea water
as well as in soil, but contaminated food or water is the
vehicle of transmission to humans. Clinical manifestations
range from mild gastroenteritis to fulminant, bloody disease
and occasional extraintestinal spread. About 70% of patients
have an underlying disease (eg, cancer), and sepsis has only
been documented in immunocompromised individuals
[24]. As a member of the Enterobacteriaceae family, it has
an inherent propensity for severe disease in iron overload
(eg, sickle-cell disease with secondary iron). Patients should
refrain from ingesting or handling shellfish and from swim-
ming in contaminated waters [25].
Enterococcus cecorum
Enterococcus cecorum was first isolated from chicken intes-
tines (initially called Streptococcus cecorum), but this organ-
ism is found in many animal hosts. The first infection in
humans was described in a malnourished patient in 1997. A
recently published report describes a fatal case of septicemia
in a cirrhotic patient with hepatocellular carcinoma [26].
Capnocytophagia canimorsus
Capnocytophagia canimorsus (formerly dysgonic fermenter-
DF-2) organisms have been increasingly associated with
sepsis. A fastidious gram-negative common to canine and
feline mouth flora, this organism is known to cause
life threatening sepsis in immunocompromised patients
after an animal bite. Strong consideration should be given
to prescribing prophylactic antibiotics (eg, amoxicillin
or amoxicillin-clavulanate) to immunocompromised
patients after a dog bite [27].
Aeromonas veronii biotype sobria
Aeromonads are gram-negative, facultative nonsporulated
anaerobic rods that are ubiquitous in fresh and brackish
water but do not belong to normal fecal flora. They are an
important pathogen in fish and amphybia and can cause
disease in both immunocompetent and immunodeficient
288 Gastrointestinal Infections
patients. Choleriform diarrhea or a form of chronic colitis
can occur after ingestion of contaminated food or water. In
cirrhotic patients, this organism is a rare cause of spontane-
ous bacterial peritonitis or empyema [28]. One case report
described severe soft-tissue damage with an elevated creati-
nine phosphokinase (CPK) level suggestive of rhabdomy-
olysis. The patient had scattered hemorrhagic bullae,
massively bloody stools, and eventual multiorgan system
failure [29]. This organism is normally resistant to amox-
icillin-clavulanate; thus, third-generation cephalosporins,
trimethoprim/sulfamethoxazole, and quinolones are the
drugs of choice [30]. Cirrhotic patients are instructed to
avoid exposing themselves or their food to untreated water.
Listeria monocytogenes
Listeria monocytogenes is a gram-positive facultative ana-
erobic rod found in numerous sources including water,
sewage, live animals, and dairy products. It can be isolated
from about 5% of normal human feces. It is more invasive
at the extremes of age and in immunocompromised
patients. Eating habits and antibiotic resistance patterns
may explain the differences in incidence with respect to
worldwide geographic location. The majority of severe
infections are meningitis and bacteremia, but 12 cases of L.
monocytogenes spontaneous bacterial peritonitis have been
reported [31]. A factor in pathogenesis may be iron-
enhanced growth of the organism. In one reported study,
the ascites fluid almost always grew the organism, and 50%
of blood cultures were positive. Some patients (3/8) had
an ascitic protein level higher than 2 g/mL, indicating that
complement and immunoglobulins are not major host
defenses against this organism. Treatment is complicated.
Third-generation cephalosporins are insufficient; peni-
cillin and ampicillin are effective (gentamicin may be
synergistic). Trimethoprim/sulfamethoxazole is the usual
alternative treatment. In a 52-year-old female patient with
end-stage liver disease and Listeria-induced spontaneous
bacterial peritonitis, the absence of response to cefotaxime
required a change to ampicillin/sulbactam and gentamicin
for a 3-week course, which cleared the infection and led to
eventual successful liver transplantation. Clinical suspicion
for Listeria species infection should be elevated in patients
with any or all of the following symptoms or signs: diph-
theria-like (gram-positive bacillus) organism on culture,
iron overload state such as hereditary hemochromatosis,
exposure to farm animals, or an inadequate response to
standard therapy after 48 to 72 hours [32].
Streptococcus bovis
Our group has reported a case of Streptococcus bovis causing
spontaneous bacterial peritonitis [33].
Campylobacter fetus and C. jejuni
Campylobacter fetus and jejuni organisms are micro-
aerophilic gram-negative rods. Many domestic animals
harbor this organism, which is easily transmitted to
humans by food and water products. These organisms
cause either intestinal or extraintestinal clinical syndromes.
The majority of cases are from poorly cooked chicken.
Twenty-five percent of sepsis caused by this organism
occurs in cirrhotic patients. The first case of spontaneous
bacterial peritonitis caused by C. fetus was published in
1976, describing a patient with cirrhosis. These organisms
have also caused spontaneous bacterial peritonitis in the
Budd-Chiari syndrome [34]. Third-generation cepha-
losporins are the antibiotics of choice, although this
organism appears to need a longer duration of therapy,
ie, 2 to 4 weeks [35,36].
Arcobacter species
Arcobacter species organisms are Campylobacter-like, as first
described in 1981, and isolated from cattle and pigs. A.
butzleri organisms cause the most frequent human
infections—primarily diarrhea but occasionally an invasive
infection. Studies have raised the question of cephalosporin
resistance, but the organism is sensitive to quinolones [37].
Spontaneous Bacterial Peritonitis
Spontaneous bacterial peritonitis (SBP) is a frequent,
severe, life-threatening complication of patients with
ascites, predominantly those with advanced cirrhosis. The
prevalence among all patients with ascites is 10% to 30%.
Approximately half of the cases are diagnosed at hospital
admission, and the rest develop in the hospital [38•].
Multivariate analysis of the risk factors for spontaneous
bacterial peritonitis has revealed that low ascitic fluid total
protein (<1 g/L) and higher total bilirubin (>2.5 mg/dL)
are the major risks for both primary and subsequent
episodes [39]. Most SBP patients are symptomatic, with
specific symptoms including abdominal pain, fever, ileus,
hepatic encephalopathy, and renal failure. Occasionally,
patients may have minor symptoms or no symptoms [40].
The pathogenesis of SBP involves several factors: intra-
hepatic shunting, bypass of the reticuloendothelial system,
and impaired host defenses, such as impaired neutrophil
function, decreased complement, and fibronectin. Also,
leaky bowel epithelia allow transmural migration of bact-
eria from the gastrointestinal tract into the bloodstream
[41]. Diagnosis is made by evidence of “peritoneal inflam-
matory reaction” manifested as an elevated ascites poly-
morphonuclear leukocyte count. Sensitivity is greatest
with a cut-off of 250 leukocytes/mm3, whereas specificity
is greatest at 500 leukocytes/mm3. If the ascites fluid is
bloody, the correction factor of 1 leukocyte/250 erythro-
cytes may be used. Paracentesis should be performed in all
patients with new-onset ascites and in any patient admit-
ted to the hospital with ascites. Immediate repeat
paracentesis should be performed if the patient develops
unexplained symptoms of peritoneal irritation (ie, abdom-
inal pain, nausea, vomiting, ileus, fever, increased
leukocyte count, septic shock, worsening or new-onset

encephalopathy, or deterioration in renal function). In
patients admitted for a gastrointestinal bleed, with the
inherent high risk of spontaneous bacterial peritonitis,
paracentesis prior to initiation of antibiotic treatment is
optimal. Ascites fluid culture performed by conventional
methods is negative in 40% of patients, but studies have
shown that direct injection of a minimum of 10 cm3 of
ascitic fluid into both aerobic and anaerobic blood culture
bottles may increase the yield to greater than 90% [42,43].
Nevertheless, subsequent studies have demonstrated that,
even with direct injection, ascites fluid cultures are still
routinely negative in 30% to 50% of patients (ie, “culture
negative neutrocytic ascites”) [44]. A variant of this is
“bacterascites,” which refers to an instance when the ascitic
fluid is culture-positive but the classic inflammatory reac-
tion is not evident (leukocyte count <250/mm 3 ). This
appears to occur in only 2.5% of patients undergoing ther-
apeutic paracentesis [45]. Patients with bacterascites either
progress to frank spontaneous bacterial peritonitis or
resolve spontaneously. If this condition is diagnosed, a
repeat paracentesis after 2 or 3 days is recommended [46].
If the ascitic leukoycyte count is greater than 250/mm3,
or if the patient has symptoms, antibiotic therapy should
be started [47]. In patients with suspected or proven
spontaneous bacterial peritonitis, blood cultures should
also be obtained.
A small group of patients may actually have bacterial
peritonitis that is caused by acute inflammation of intra-
abdominal organs, a perforated viscus, or an intra-abdom-
inal procedure, so called “secondary” bacterial peritonitis.
Suspicion for secondary causes arises when 1) there is an
insufficient decrease (or an actual increase) of ascitic fluid
polymorphonuclear leukoycytes on repeat paracentesis
after 48 to 72 hours of appropriate antibiotic therapy;
2) there is growth of more than one organism on ascitic
fluid culture; 3) anaerobes are isolated; and 4) ascitic fluid
glucose is less than 50 mg/dL, total protein is greater than
1 g/L, or ascitic fluid lactate dehydrogenase is greater than
serum [48]. This is a life-threatening condition with a
nearly 100% mortality rate without prompt surgery.
Treatment of spontaneous bacterial peritonitis should
be immediate if the ascitic polymorphonuclear leukocyte
count is greater than 250 cells/mm3. Empiric antibiotic
coverage should be predominantly against Enterobacteria-
iceae and non-enterococcal Streptococcus organisms and
should penetrate the peritoneal space. The “top” choice
remains cefotaxime, primarily because of its efficacy, lack
of superinfection, and lack of renal toxicity. The standard
dose should be a minimum of 2 g every 12 hours for a
minimum of 5 days. Other third-generation cephalo-
sporins (eg, ceftriaxone, ceftizoxime, or ceftazidime) have
similar efficacy. Aminoglycosides should be avoided
because of the increased risk of renal toxicity. Symptoms
resolve with appropriate treatment in at least 90% of
patients. An excellent marker for treatment response is at
least 25% decrement in the ascitic fluid leukoycte count on
Infectious Complications of Cirrhosis • Brann 289
repeat paracentesis at 48 hours [49]. Survival is markedly
lower in patients not responding by this time; careful eval-
uation for secondary peritonitis or antibiotic-resistant
organisms is necessary. Some studies have shown that oral
antibiotics have equal efficacy to intravenous dosing in
uncomplicated SBP [50]. If a patient already on prophylac-
tic antibiotics develops SBP, the organisms causing infec-
tion are usually gram-positive cocci or quinolone-resistant
gram-negatives. Cefotaxime would be the first choice of
drug in these patients.
A recent meta-analysis reveals a survival benefit for
patients receiving prophylactic antibiotics in certain clinical
situations [51•]. Norfloxacin, a poorly absorbed quinolone,
has been used since 1987, but trimethoprim/sulfamethox-
azole is just as safe, more cost effective, and efficacious [52]
The following are indications for prophylaxis:
1. Prophylaxis is indicated for cirrhotic patients with
gastrointestinal bleeding, with or without ascites.
In bleeding patients with ascites, 20% are already
infected on admission, and 50% develop SBP after
admission. Significant reduction of spontaneous
bacteremia and SBP has been accomplished
with empiric “intestinal decontamination.”
A recent meta-analysis demonstrated improved
survival with this treatment [53]. Norfloxacin,
400 mg twice daily for a minimum of 7 days,
has been recommended.
2. It is also indicated for cirrhotic patients with a
prior episode of SBP. The risk of developing
repeat infection is increased, with a 1-year
recurrence rate of 40% to 70%. Prophylactic
antibiotics reduce the risk by over half. Any patient
with a history of documented spontaneous
bacterial peritonitis should remain on prophylaxis
indefinitely, or until liver transplant.
3. The risk of SBP (outside of gastrointestinal bleeds)
is 0% to 1%/year. In patients with higher
Child-Pugh scores (associated with lower
total ascitic fluid protein), the risk is greater.
A current recommendation for hospitalized
patients with a total ascitic fluid protein
count of less than 1 g/L is that they receive oral
antibiotics “during their hospitalization” [54•].
An increasing concern regarding the use of quinolones for
prophylaxis is the development of bacterial resistance. The
source of infection in patients on quinolone prophylaxis is
usually gram-positive organisms. Trimethoprin/sul-
famethoxazole is often a better treatment alternative. Older
literature indicated that therapeutic paracentesis removed
complement and opsonins, increasing risk of SBP [55].
Recent literature appears to support a prophylactic benefit
to repeated therapeutic paracentesis, ostensibly by keeping
the ascitic fluid volume low [56].
The prognosis for survival after one episode of spon-
taneous bacterial peritonitis is poor: 30% to 50% of
290 Gastrointestinal Infections
patients are alive at 1 year, and 25% to 30% are alive at
2 years. One of the causes of death, hepatorenal syndrome,
occurs in 30% to 40% of patients within weeks of the
episode. Recent literature has examined the utility of intra-
venous albumin to prevent this life-threatening compli-
cation. In one study, the risk of hepatorenal syndrome
diminished from 33% in the control group to 10% in the
treatment group. This translated into a diminished mortal-
ity rate from 41% in the untreated group to 21% in the
treated group [57•].
In summary, prophylaxis of SBP is definitely indicated in
patients with gastrointestinal bleed or prior history, but the
use of prophylactic antibiotics in patients with low ascitic
fluid protein is still controversial. Importantly, SBP is one of
the main indications for liver transplantation referral.
Miscellaneous Infections
The following are other instances in which infectious
complications may be observed.
Urinary tract infection
Urinary tract infection (UTI) is the most frequently diag-
nosed infection in cirrhotic patients. Whereas most UTIs are
minimally symptomatic, they can still lead to bacteremia.
The risk appears to be proportional to known hazards such
as urinary catheters. Treatment includes quinolones or trime-
thoprim/sulfamethoxazole. Less commonly used alternatives
are amoxicillin-clavulanate or oral cephalosporins.
Pneumonia
Community-acquired pneumonia is also frequent in
cirrhotic patients. Causes include infection from Strepto-
coccus pneumoniae, Hemophilus influenzae, and Klebsiella,
Mycoplasma, and Legionella species. A macrolide or a
quinolone (levofloxacin), along with cephalosporin, are
recommended for antibiotic treatment. Hospital-acquired
pneumonia is predominantly caused by gram-negative
organisms and staphylococci. Risk factors include those
complications unique to cirrhosis (ie, encephalopathy,
Sengstaken-Blakemore tube) or to any sick patient (intuba-
tion). Empiric treatment with cefipime is a reasonable first
choice, with the addition of clindamycin if aspiration
pneumonia is possible.
Tuberculous peritonitis
In patients with low-grade fever, high protein ascites, and
lymphocyte elevation, the possibility of tuberculosis peri-
tonitis should be considered. Diagnosis usually requires
laparoscopy. Antituberculous therapy is usually successful.
Soft-tissue infections
Cellulitis of the lower extremities or abdominal wall is
common in cirrhotic patients. The usual organisms include
staphylococci and streptococci, but Enterobacteriaceae and
Vibrio anaerobes can also be involved. Infectious disease
consultation should be considered in serious soft-tissue
infections in cirrhotic patients [58].
Influenza A
Influenza is an RNA virus that is usually an acute, self-lim-
iting illness and can be severe in the immunocompro-
mised setting. During the 1997 and 1998 influenza A
(H3N2) epidemic, it was observed that influenza virus
could cause significant hepatic decompensation in patients
with end-stage liver disease who were awaiting transplant.
This has now been reported in patients after liver trans-
plant. The ferret and mouse models have shown a critical
step in hepatic damage, that of deranged lipid metabolism
(similar to Reye’s syndrome). Additionally, multiple cyto-
kines are liberated during the invasion of the lower respira-
tory tract, which adversely affects the liver. The risk for
direct damage or allograft rejection is substantial. Vaccina-
tion is the main preventive tool, with between 92% and
95% of pre–liver transplant patients developing an
apposite reaction to immunization. Vaccination should be
performed in October or November. Amantadine, rimanta-
dine, oseltamivir, and zanamivir are drugs approved for
treatment and are effective within 30 hours of onset of
symptoms in immunocompetent patients. The efficacy of
these drugs in the liver transplant population is unknown.
Prevention is key, with vaccination and isolation from
infected contacts the best means to minimize risk [59,60].
Conclusions
In general, physicians should have a high degree of suspi-
cion that cirrhotic patients may already be infected, or that
they will become infected when admitted to the hospital.
These circumstances increase the risk of possible further
deterioration in liver function or other life-threatening
complications. Health-care workers managing cirrhotic
patients should have a low threshold for culturing blood,
sputum, ascites, and urine, as indicated, if infection is
suspected. Immediate initiation of empiric antibiotic treat-
ment while culture results are awaited is appropriate.
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• Of importance
•• Of major importance
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292 Gastrointestinal Infections
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