INFECTIONS OF THE LIVER 0891-5520/00 $15.00 + .

OO

PYOGENIC LIVER ABSCESSES

Eric C . Johannsen, MD, Costi D. Sifri, MD,
and Lawrence C . Madoff, MD

Bacterial or pyogenic liver abscess does not represent a specific liver disease,
but rather a final common pathway of many pathologic processes. In the preanti-
biotic era, liver abscesses were typically the sequelae of unchecked appendicitis.
In such cases, prompt surgical drainage offered the only hope for cure. Many
advances, including the development of antibiotics, recognition of the role of
anaerobic bacteria, the advent of noninvasive imaging, and the use of nonsurgi-
cal drainage have improved this once bleak outlook. By improving treatment of
underlying diseases that once led to abscess formation, these advances also have
transformed the epidemiology and presentation of pyogenic liver abscess. The
classic triad of fever, right upper quadrant pain or fullness, and jaundice re-
sulting from advanced pylephlebitis seldom is seen now. Despite these changes,
pyogenic liver abscess remains an important clinical entity for which prompt
recognition and treatment are essential for a favorable outcome.

EPIDEMIOLOGY

In published reports, the incidence of pyogenic liver abscess ranges from 8

to 20 cases per 100,000 hospital admissions (Table 1).It is unclear whether the
slight increasing trend is due to changes in the true incidence, improved detec-
tion, or admission practices. A recent population-based study found 11 cases per
million persons per year.I7 With the availability of effective antimicrobials, pyo-
genic liver abscess shifted abruptly to a disease of middle-aged persons, and the
average patient age has remained consistently between 50 and 60 years, probably
because of the prevalence of biliary disease in the population, now the major
cause of pyogenic liver abscess. No significant sex, ethnic, or geographic differ-
ences seem to exist in disease frequency, in contrast to the epidemiology of

From the Channing Laboratory (ECJ, LCM), and Division of Infectious Disease (CDS,
L a ) , Department of Medicine, Brigham and Women’s Hospital, Boston, Massachu-
setts

INFECTIOUS DISEASE CLINICS OF NORTH AMERICA

VOLUME 14 * NUMBER 3 SEM‘EMBER 2000 547

INFECTIONS OF THE LIVER 0891-5520/00 $15.00 + .OO

PYOGENIC LIVER ABSCESSES

Eric C . Johannsen, MD, Costi D. Sifri, MD,
and Lawrence C . Madoff, MD

Bacterial or pyogenic liver abscess does not represent a specific liver disease,
but rather a final common pathway of many pathologic processes. In the preanti-
biotic era, liver abscesses were typically the sequelae of unchecked appendicitis.
In such cases, prompt surgical drainage offered the only hope for cure. Many
advances, including the development of antibiotics, recognition of the role of
anaerobic bacteria, the advent of noninvasive imaging, and the use of nonsurgi-
cal drainage have improved this once bleak outlook. By improving treatment of
underlying diseases that once led to abscess formation, these advances also have
transformed the epidemiology and presentation of pyogenic liver abscess. The
classic triad of fever, right upper quadrant pain or fullness, and jaundice re-
sulting from advanced pylephlebitis seldom is seen now. Despite these changes,
pyogenic liver abscess remains an important clinical entity for which prompt
recognition and treatment are essential for a favorable outcome.

EPIDEMIOLOGY

In published reports, the incidence of pyogenic liver abscess ranges from 8

to 20 cases per 100,000 hospital admissions (Table 1).It is unclear whether the
slight increasing trend is due to changes in the true incidence, improved detec-
tion, or admission practices. A recent population-based study found 11 cases per
million persons per year.I7 With the availability of effective antimicrobials, pyo-
genic liver abscess shifted abruptly to a disease of middle-aged persons, and the
average patient age has remained consistently between 50 and 60 years, probably
because of the prevalence of biliary disease in the population, now the major
cause of pyogenic liver abscess. No significant sex, ethnic, or geographic differ-
ences seem to exist in disease frequency, in contrast to the epidemiology of

From the Channing Laboratory (ECJ, LCM), and Division of Infectious Disease (CDS,
L a ) , Department of Medicine, Brigham and Women’s Hospital, Boston, Massachu-
setts

INFECTIOUS DISEASE CLINICS OF NORTH AMERICA

VOLUME 14 * NUMBER 3 SEM‘EMBER 2000 547

 PYOGENIC LIVER ABSCESSES 549

amebic liver abscess. About one half of patients have a solitary abscess. Ab-
scesses involve the right hepatic lobe in about three fourths of cases; the remain-
der are found mostly in left lobe (approximately 20%), with infrequent involve-
ment of the caudate lobe (approximately 5%). When multiple abscesses are
present this same general pattern of distribution is observed. The distribution
probably reflects the relative mass of each lobe, though more complicated expla-
nations such as patterns of hepatic blood flow may be invoked.

PATHOGENESIS

Liver abscess formation occurs whenever the initial inflammatory response

fails to clear an infectious insult from the liver. Abscesses are classified by
presumed route of hepatic invasion: (1)biliary tree, (2) portal vein, (3) hepatic
artery, (4) direct extension from contiguous focus of infection, and (5)penetrating
trauma (Table 2).
Suppurative cholangitis is now the major identifiable cause of pyogenic
liver abscess. In such cases, multiple abscesses are generally present. Biliary
obstruction need not be from stone disease: patients with Caroli’s disease have
a particularly high rate of pyogenic liver abscess formation. In the third world,
infection of the biliary tree can result from invasion by Ascuris lumbricoides.
The portal venous system d r a almost all of the abdominal viscera. Py-
lephlebitis from diverticulitis, pancreatitis, omphalitis, inflammatory bowel dis-
ease, or postoperative infection can result in pyogenic liver abscess. Historically,
untreated appendicitis was a major cause in this category, but it was greatly
diminished in importance with the introduction of antibiotics.
Any systemic bacteremia (e.g., endocarditis or line sepsis) can spread to the
liver through the hepatic artery. Patients with overwhelming sepsis frequently
have extensive microabscess formation in their livers at autopsy. Most case series
of pyogenic liver abscess excluded such patients unless they also had evidence
of macroscopic liver abscess.
Direct extension from a contiguous focus of infection can occur with chole-
cystitis, subphrenic abscess, or perinephric abscess.
The mechanism by which penetrating trauma to the liver can result in
abscess formation poses no mystery, but can be as subtle as ingestion of a
toothpick.=,“ Blunt trauma, too, can predispose to pyogenic liver abscess forma-
tion, presumably because the resultant hepatic hematoma is susceptible to seed-
ing by bacteria. Similarly, hepatic destruction from sickle cell disease, tumor
necrosis (including iatrogenic embolization), or cirrhosis can predispose to ab-
scess formation.
Hepatic abscesses for which no direct cause can be found are common, and
these are classified in most series as cryptogenic. Indeed, cryptogenic abscesses
predominate in most series. Host factors that predispose to abscess formation
from routine hepatic bacterial insults can contribute to the formation of “crypto-
genic” abscesses. Systemic illness such as diabetes mellitus, cardiopulmonary
disease, malignancy, and cirrhosis are common in patients with liver abscesses
and may be predisposing factors. Moreover, neutrophil defects such as chronic
granulomatous disease or Job’s syndrome result in a marked predisposition to
abscesses of the liver and elsewhere. Finally, hemochromatosis conveys a particu-
lar susceptibility to abscesses caused by Yersinia enterocoliti~a.’~,
36,
 PYOGENIC LIVER ABSCESSES 549

amebic liver abscess. About one half of patients have a solitary abscess. Ab-
scesses involve the right hepatic lobe in about three fourths of cases; the remain-
der are found mostly in left lobe (approximately 20%), with infrequent involve-
ment of the caudate lobe (approximately 5%). When multiple abscesses are
present this same general pattern of distribution is observed. The distribution
probably reflects the relative mass of each lobe, though more complicated expla-
nations such as patterns of hepatic blood flow may be invoked.

PATHOGENESIS

Liver abscess formation occurs whenever the initial inflammatory response

fails to clear an infectious insult from the liver. Abscesses are classified by
presumed route of hepatic invasion: (1)biliary tree, (2) portal vein, (3) hepatic
artery, (4) direct extension from contiguous focus of infection, and (5)penetrating
trauma (Table 2).
Suppurative cholangitis is now the major identifiable cause of pyogenic
liver abscess. In such cases, multiple abscesses are generally present. Biliary
obstruction need not be from stone disease: patients with Caroli’s disease have
a particularly high rate of pyogenic liver abscess formation. In the third world,
infection of the biliary tree can result from invasion by Ascuris lumbricoides.
The portal venous system d r a almost all of the abdominal viscera. Py-
lephlebitis from diverticulitis, pancreatitis, omphalitis, inflammatory bowel dis-
ease, or postoperative infection can result in pyogenic liver abscess. Historically,
untreated appendicitis was a major cause in this category, but it was greatly
diminished in importance with the introduction of antibiotics.
Any systemic bacteremia (e.g., endocarditis or line sepsis) can spread to the
liver through the hepatic artery. Patients with overwhelming sepsis frequently
have extensive microabscess formation in their livers at autopsy. Most case series
of pyogenic liver abscess excluded such patients unless they also had evidence
of macroscopic liver abscess.
Direct extension from a contiguous focus of infection can occur with chole-
cystitis, subphrenic abscess, or perinephric abscess.
The mechanism by which penetrating trauma to the liver can result in
abscess formation poses no mystery, but can be as subtle as ingestion of a
toothpick.=,“ Blunt trauma, too, can predispose to pyogenic liver abscess forma-
tion, presumably because the resultant hepatic hematoma is susceptible to seed-
ing by bacteria. Similarly, hepatic destruction from sickle cell disease, tumor
necrosis (including iatrogenic embolization), or cirrhosis can predispose to ab-
scess formation.
Hepatic abscesses for which no direct cause can be found are common, and
these are classified in most series as cryptogenic. Indeed, cryptogenic abscesses
predominate in most series. Host factors that predispose to abscess formation
from routine hepatic bacterial insults can contribute to the formation of “crypto-
genic” abscesses. Systemic illness such as diabetes mellitus, cardiopulmonary
disease, malignancy, and cirrhosis are common in patients with liver abscesses
and may be predisposing factors. Moreover, neutrophil defects such as chronic
granulomatous disease or Job’s syndrome result in a marked predisposition to
abscesses of the liver and elsewhere. Finally, hemochromatosis conveys a particu-
lar susceptibility to abscesses caused by Yersinia enterocoliti~a.’~,
36,
 PYOGENIC LIVER ABSCESSES 551

MICROBIOLOGY
With the diverse pathologic processes discussed above, sweeping general-
izations about the microbiology of pyogenic liver abscess are difficult. This
picture is further complicated because abscess material rarely is obtained prior
to the administration of antibiotics. Even in the preantibiotic era, the rates of
sterile cultures were high, and probably reflected inadequate culture techniques.
Despite these difficulties, progress has been made in the understanding of
the microbiology of pyogenic liver abscess. In particular, the demonstration of
anaerobic organisms in 45%of pyogenic liver abscess by Sabbaj et a1 in 1972 led
to an increased awareness of fastidious pathogens.35In practice, however, anaer-
obes seldom are recovered at this rate (Table 3). Because of the difficulty in
obtaining perfect culture data, these should be viewed as conservative estimates.
Moreover, it now is known that many liver abscesses are polymicrobial, but
estimates range widely (see Table 3). Some observers have noted that solitary
abscesses are more likely to be polymicrobial than are multiple ones?' 25 A
tendency of solitary abscesses to be more frequently cryptogenic in origin also
has been noted, but the association is weak?, 25 Although the small size of these
studies prevents conclusive statements, they suggest two alternative mechanisms
for abscess formation. In the first, a synergistic combination of organisms con-
verge by chance to form a single abscess; in the second, a highly pathogenic
organism forms abscesses wherever it is seeded.
In terms of specific pathogens, Escherichia coli and Klebsiella pneumoniae are
by far the most common isolates (Table 4). The latter frequently is associated
with gas-forming abscesses."I Enterococci and viridans streptococci are also
common, primarily in polymicrobial abscesses. Staphylococcus aureus by contrast
more commonly is associated with monomicrobial abscesses.

CLINICAL PRESENTATION
Only one in ten patients presents with the classic triad of fever, jaundice, and
right upper quadrant tenderness. Fever and constitutional symptoms including
malaise, fatigue, anorexia, and weight loss are common (Table 5). When present,
localizing symptoms such as vomiting or abdominal pain are not specific. The
duration of symptoms prior to presentation varied widely in most case series,
and there was seldom agreement on an average duration. Butler and McCarthy7
attempted to address this issue by stratifying according to acute and chronic
presentations. They found the former to be typically associated with acute,
identifiable abdominal pathology such as cholangitis or appendicitis, whereas
abscesses that presented chronically were often cryptogenic. Other series support
an association between cause and chronicity; for example, Seeto and Rockey
found that hematogenous liver abscesses presented most acutely (3 days),
whereas those secondary to pylephlebitis (42 days) had the longest duration of
symptoms.38Initial diagnostic impression often is wrong and can include cholan-
gitis, fever of unknown origin, intra-abdominal catastrophe, or pneumonia.%
Accordingly, a high index of suspicion is required to make a timely diagnosis of
pyogenic liver abscess.

DIAGNOSIS
Clues to the diagnosis of pyogenic liver abscess on examination include
hepatomegaly and right upper quadrant tenderness, seen in about one half of
 PYOGENIC LIVER ABSCESSES 551

MICROBIOLOGY
With the diverse pathologic processes discussed above, sweeping general-
izations about the microbiology of pyogenic liver abscess are difficult. This
picture is further complicated because abscess material rarely is obtained prior
to the administration of antibiotics. Even in the preantibiotic era, the rates of
sterile cultures were high, and probably reflected inadequate culture techniques.
Despite these difficulties, progress has been made in the understanding of
the microbiology of pyogenic liver abscess. In particular, the demonstration of
anaerobic organisms in 45%of pyogenic liver abscess by Sabbaj et a1 in 1972 led
to an increased awareness of fastidious pathogens.35In practice, however, anaer-
obes seldom are recovered at this rate (Table 3). Because of the difficulty in
obtaining perfect culture data, these should be viewed as conservative estimates.
Moreover, it now is known that many liver abscesses are polymicrobial, but
estimates range widely (see Table 3). Some observers have noted that solitary
abscesses are more likely to be polymicrobial than are multiple ones?' 25 A
tendency of solitary abscesses to be more frequently cryptogenic in origin also
has been noted, but the association is weak?, 25 Although the small size of these
studies prevents conclusive statements, they suggest two alternative mechanisms
for abscess formation. In the first, a synergistic combination of organisms con-
verge by chance to form a single abscess; in the second, a highly pathogenic
organism forms abscesses wherever it is seeded.
In terms of specific pathogens, Escherichia coli and Klebsiella pneumoniae are
by far the most common isolates (Table 4). The latter frequently is associated
with gas-forming abscesses."I Enterococci and viridans streptococci are also
common, primarily in polymicrobial abscesses. Staphylococcus aureus by contrast
more commonly is associated with monomicrobial abscesses.

CLINICAL PRESENTATION
Only one in ten patients presents with the classic triad of fever, jaundice, and
right upper quadrant tenderness. Fever and constitutional symptoms including
malaise, fatigue, anorexia, and weight loss are common (Table 5). When present,
localizing symptoms such as vomiting or abdominal pain are not specific. The
duration of symptoms prior to presentation varied widely in most case series,
and there was seldom agreement on an average duration. Butler and McCarthy7
attempted to address this issue by stratifying according to acute and chronic
presentations. They found the former to be typically associated with acute,
identifiable abdominal pathology such as cholangitis or appendicitis, whereas
abscesses that presented chronically were often cryptogenic. Other series support
an association between cause and chronicity; for example, Seeto and Rockey
found that hematogenous liver abscesses presented most acutely (3 days),
whereas those secondary to pylephlebitis (42 days) had the longest duration of
symptoms.38Initial diagnostic impression often is wrong and can include cholan-
gitis, fever of unknown origin, intra-abdominal catastrophe, or pneumonia.%
Accordingly, a high index of suspicion is required to make a timely diagnosis of
pyogenic liver abscess.

DIAGNOSIS
Clues to the diagnosis of pyogenic liver abscess on examination include
hepatomegaly and right upper quadrant tenderness, seen in about one half of
 PYOGENIC LIVER ABSCESSES 553

Table 4. MICROBIOLOGYOF PYOGENIC LIVER ABSCESS

Study Common (210%) Uncommon (1%-10%)
Gram-negative aerobes E . coli Pseudomonas
Klebsiella spp. Proteus
En terobacter
Citrobacter
Morganella
Serratia
Gram-positive aerobes Staphylococcus aureus p-hemolytic streptococci
Enterococcus spp.
Viridans
streptococci
Anaerobes Bacteroides spp. Fusobacterium
Anaerobic streptococci
Clostridium
Lactobadli
Microaerophilic - Streptococcus milleri

patients. Jaundice most commonly is seen in patients with underlying biliary

disease or those who are gravely ill. Leukocytosis is present in most patients
and can be high. Although liver function tests are abnormal in most patients,
these elevations are seldom marked; moreover, normal results do not exclude
the diagnosis. Alkaline phosphatase elevation is present in two thirds of patients
and tends to be farther out of the normal range than the other liver function
values. Abnormalities of alanine aminotransferase (ALT), aspartate aminotrans-
ferase (AST), and bilirubin are generally small, though they may be more
pronounced in some patients with biliary disease. Albumin and prothrombin
tend to be normal or nearly so. Prior to the advent of noninvasive imaging,
vitamin B,, levels were measured as a marker of hepatic destruction. In general,
laboratory studies can suggest liver abnormalities but are not specific for the
diagnosis of pyogenic liver abscess.
Radiographic imaging studies, however, are essential in making this diagno-
sis. Ultrasonography and computed tomography (CT) scanning have proven
particularly useful for abscess visualization and subsequent drainage (Fig. 1).
Both modalities have excellent sensitivity (Table 6). Ultrasonography is the study
of choice in patients with suspected biliary disease or in patients who must
avoid intravenous contrast or radiation exposure. Contrast-enhanced CT scan-
ning offers improved sensitivity over ultrasonography and is superior for guid-
ing complex drainage procedures. Intravenous contrast is required for optimal
imaging in two thirds of patients.32Because MRI studies are seldom required,
data regarding this technique are limited. Small retrospective series have demon-
strated specific findings to suggest the presence of an abscess, but do not
generally avert the need for diagnostic aspiration.' Furthermore, MRI is a cum-
bersome tool for guiding drainage procedures. Technetium sulfur colloid scan-
ning is of largely historic interest as the first reliable noninvasive modality, with
a sensitivity of 70% to 80%. Chest radiographs are abnormal about half of the
time, but of no real value in making the diagnosis.
Blood cultures are positive in about half of patients (Table 7). Multiple
samples of blood for anaerobic and aerobic cultures must be obtained, as they
often are the only cultures obtained prior to antibiotic administration and in
about 7% of cases provide the only positive culture data.=, 38 The diagnosis
 PYOGENIC LIVER ABSCESSES 553

Table 4. MICROBIOLOGYOF PYOGENIC LIVER ABSCESS

Study Common (210%) Uncommon (1%-10%)
Gram-negative aerobes E . coli Pseudomonas
Klebsiella spp. Proteus
En terobacter
Citrobacter
Morganella
Serratia
Gram-positive aerobes Staphylococcus aureus p-hemolytic streptococci
Enterococcus spp.
Viridans
streptococci
Anaerobes Bacteroides spp. Fusobacterium
Anaerobic streptococci
Clostridium
Lactobadli
Microaerophilic - Streptococcus milleri

patients. Jaundice most commonly is seen in patients with underlying biliary

disease or those who are gravely ill. Leukocytosis is present in most patients
and can be high. Although liver function tests are abnormal in most patients,
these elevations are seldom marked; moreover, normal results do not exclude
the diagnosis. Alkaline phosphatase elevation is present in two thirds of patients
and tends to be farther out of the normal range than the other liver function
values. Abnormalities of alanine aminotransferase (ALT), aspartate aminotrans-
ferase (AST), and bilirubin are generally small, though they may be more
pronounced in some patients with biliary disease. Albumin and prothrombin
tend to be normal or nearly so. Prior to the advent of noninvasive imaging,
vitamin B,, levels were measured as a marker of hepatic destruction. In general,
laboratory studies can suggest liver abnormalities but are not specific for the
diagnosis of pyogenic liver abscess.
Radiographic imaging studies, however, are essential in making this diagno-
sis. Ultrasonography and computed tomography (CT) scanning have proven
particularly useful for abscess visualization and subsequent drainage (Fig. 1).
Both modalities have excellent sensitivity (Table 6). Ultrasonography is the study
of choice in patients with suspected biliary disease or in patients who must
avoid intravenous contrast or radiation exposure. Contrast-enhanced CT scan-
ning offers improved sensitivity over ultrasonography and is superior for guid-
ing complex drainage procedures. Intravenous contrast is required for optimal
imaging in two thirds of patients.32Because MRI studies are seldom required,
data regarding this technique are limited. Small retrospective series have demon-
strated specific findings to suggest the presence of an abscess, but do not
generally avert the need for diagnostic aspiration.' Furthermore, MRI is a cum-
bersome tool for guiding drainage procedures. Technetium sulfur colloid scan-
ning is of largely historic interest as the first reliable noninvasive modality, with
a sensitivity of 70% to 80%. Chest radiographs are abnormal about half of the
time, but of no real value in making the diagnosis.
Blood cultures are positive in about half of patients (Table 7). Multiple
samples of blood for anaerobic and aerobic cultures must be obtained, as they
often are the only cultures obtained prior to antibiotic administration and in
about 7% of cases provide the only positive culture data.=, 38 The diagnosis
 PYOGENIC LIVER ABSCESSES 555

Figure 1. Diagnosis of liver abscesses by CT scan. A 36-year-old man without significant

past history presented with fevers, chills, rigors, abdominal pain, and hypotension. CT scan
with oral contrast showed multiple hypodense lesions in the right lobe of the liver. Antibiotic
therapy was administered and ultrasound-guided percutaneous catheter drainage removed
250 cm3of foul-smelling, blood-tinged pus. Gram’s stain of the aspirate revealed moderate
polymorphonuclear leukocytes with moderate gram negative rods and very rare gram-
variable rods. Cultures of the material grew abundant Bacferoides fragilis and Bacteroides
spp. Blood cultures obtained before the initiation of antibiotics also grew Escherichia
coli and B. fragilis. The patient was treated with ampicillin/sulbactam, levofloxacin, and
metronidazole, and indwelling catheter drainage. No source for the infection was identified.

ultimately rests on obtaining purulent material from the abscess cavity, generally
under radiographic guidance. Failure to find the expected pus should prompt a
reevaluation of the differential diagnosis, including liver cyst, malignancy, or
amebic liver abscess. Purulent material always should undergo Gram stain,
which can provide the only clue to a mixed infection in patients heavily treated
with antibiotics. Prompt delivery to the microbiology laboratory of anaerobic
specimens under proper conditions is essential.

THERAPY

Untreated pyogenic liver abscesses are almost uniformly fatal.3I Tradition-

ally, treatment consists of antibiotic administration and drainage of purulent
collections. Although this remains the standard approach to the patient with
hepatic abscess, some investigators have advocated the use of antibiotics alone
in selected patients.
 PYOGENIC LIVER ABSCESSES 555

Figure 1. Diagnosis of liver abscesses by CT scan. A 36-year-old man without significant

past history presented with fevers, chills, rigors, abdominal pain, and hypotension. CT scan
with oral contrast showed multiple hypodense lesions in the right lobe of the liver. Antibiotic
therapy was administered and ultrasound-guided percutaneous catheter drainage removed
250 cm3of foul-smelling, blood-tinged pus. Gram’s stain of the aspirate revealed moderate
polymorphonuclear leukocytes with moderate gram negative rods and very rare gram-
variable rods. Cultures of the material grew abundant Bacferoides fragilis and Bacteroides
spp. Blood cultures obtained before the initiation of antibiotics also grew Escherichia
coli and B. fragilis. The patient was treated with ampicillin/sulbactam, levofloxacin, and
metronidazole, and indwelling catheter drainage. No source for the infection was identified.

ultimately rests on obtaining purulent material from the abscess cavity, generally
under radiographic guidance. Failure to find the expected pus should prompt a
reevaluation of the differential diagnosis, including liver cyst, malignancy, or
amebic liver abscess. Purulent material always should undergo Gram stain,
which can provide the only clue to a mixed infection in patients heavily treated
with antibiotics. Prompt delivery to the microbiology laboratory of anaerobic
specimens under proper conditions is essential.

THERAPY

Untreated pyogenic liver abscesses are almost uniformly fatal.3I Tradition-

ally, treatment consists of antibiotic administration and drainage of purulent
collections. Although this remains the standard approach to the patient with
hepatic abscess, some investigators have advocated the use of antibiotics alone
in selected patients.
 PYOGENIC LIVER ABSCESSES 555

Figure 1. Diagnosis of liver abscesses by CT scan. A 36-year-old man without significant

past history presented with fevers, chills, rigors, abdominal pain, and hypotension. CT scan
with oral contrast showed multiple hypodense lesions in the right lobe of the liver. Antibiotic
therapy was administered and ultrasound-guided percutaneous catheter drainage removed
250 cm3of foul-smelling, blood-tinged pus. Gram’s stain of the aspirate revealed moderate
polymorphonuclear leukocytes with moderate gram negative rods and very rare gram-
variable rods. Cultures of the material grew abundant Bacferoides fragilis and Bacteroides
spp. Blood cultures obtained before the initiation of antibiotics also grew Escherichia
coli and B. fragilis. The patient was treated with ampicillin/sulbactam, levofloxacin, and
metronidazole, and indwelling catheter drainage. No source for the infection was identified.

ultimately rests on obtaining purulent material from the abscess cavity, generally
under radiographic guidance. Failure to find the expected pus should prompt a
reevaluation of the differential diagnosis, including liver cyst, malignancy, or
amebic liver abscess. Purulent material always should undergo Gram stain,
which can provide the only clue to a mixed infection in patients heavily treated
with antibiotics. Prompt delivery to the microbiology laboratory of anaerobic
specimens under proper conditions is essential.

THERAPY

Untreated pyogenic liver abscesses are almost uniformly fatal.3I Tradition-

ally, treatment consists of antibiotic administration and drainage of purulent
collections. Although this remains the standard approach to the patient with
hepatic abscess, some investigators have advocated the use of antibiotics alone
in selected patients.
558 JOHANNSENet a1

Drainage

Until the early 1980s, drainage of pyogenic liver abscesses was usually
surgical. The development of ultrasonography and CT as tools in the diagnosis
of intra-abdominal pathology led to their increasing use in imaging-guided
drainage of pyogenic liver abscess6 Although some still advocate open surgical
drainage as primary therapy,17most authorities prefer percutaneous drainage in
the initial management of pyogenic liver 38, 39 Surgical intervention
usually is reserved for patients who have failed percutaneous drainage, for those
who require surgical management of concurrent intra-abdominal disease, and
for some patients with multiple large abscesses.11,38,39 Some authors suggest that
those patients with ascites or a severe bleeding diathesis also should be managed
surgicallyzo,25
Oschner and Debakey, in their classic 1938 paper, advocated an extraserous
approach to hepatic abscess drainage to avoid contaminating the peritoneal
In the following decades, antibiotics and improved surgical technique
allowed the transperitoneal approach to be used safely for surgical therapy of
pyogenic liver abscesses. Recently, successful laparoscopic drainage of pyogenic
liver abscesses was reported.40, Surgical drainage usually entails abscess Iocal-
ization (achieved visually and with the occasional use of intraoperative ultra-
sound), aspiration, core biopsy, irrigation, and catheter placement. Rare cases in
which a segment or lobe has been destroyed may necessitate surgical resection.”
All aspirated material should be Gram stained, and cultured for aerobic and
anaerobic bacteria. As discussed earlier, the diagnostic yield of anaerobic culture
depends on rapid and diligent specimen collection, transport, and processing.
Depending on the host, microbiologic evaluation for Entumoebu histolytica, myco-
bacteria, fungi, and fastidious organisms also can be considered. Histopathologic
examination of biopsy specimens should be performed.
Radiographically guided percutaneous drainage now is pursued in most
patients with pyogenic liver abscesses.18, 38 McFadzean et a1 first reported the
successful treatment of 14 patients with percutaneous aspiration and antibiotic
therapy in 1953.26 This report largely was ignored until improved imaging
techniques led to significant advances in the diagnosis of and therapeutic ap-
proach to intra-abdominal abscesses.14 Over the last 20 years, multiple studies
have shown that percutaneous catheter drainage with antimicrobial therapy has
a success rate of 69% to 90%.”9, lZ,zo, 38, 39 The procedure generally is tolerated
well, can be performed promptly (often at the time of radiographic diagnosis),
and avoids general anesthesia (Fig. 2). Aspirated material can be sent for full
microbiologic and pathologic studies. Catheters are left in place until drainage
has reduced to a minimum, usually 5 to 7 days after placement. Potential
complications include catheter dislodgment, bleeding, and sepsis. Some studies
have reported lower success rates for multiple abscesses than for solitary
abscess2 25 although other studies dispute
Over the past decade, percutaneous aspiration of pyogenic liver abscess
without catheter drainage has gained increased attention. In combination with
antibiotic therapy, percutaneous aspiration success rates between 58% and 88%
are reported, similar to rates for catheter drainage.’ 9, 1z 38*39 These reports come
from retrospective case series and may be subject to selection bias; a randomized
trial of percutaneous aspiration and catheter drainage has not been performed.
Two groups recently have reported high cure rates with percutaneous aspiration.
In both, needle aspiration was performed initially on all abscesses and then,
guided by clinical response and serial ultrasounds, repeated as necessary until
cure was achieved. Giorgio et a1 reported that needle aspiration was successful
 PYOGENIC LTVER ABSCESSES 559

Figure 2. Drainage of liver abscesses by CT-guided percutaneous aspiration. A 67-year-

old male with a history of diabetes mellitus, rheumatoid arthritis, a distant histoly, of a
Billroth II gastric resection, and recently diagnosed adenocarcinoma of the stomach, who
presented with fever, and a blood culture that grew E. coli. The liver was imaged by CT
(A) revealing multiple hypodense lesions in the right hepatic lobe. The lesion was aspirated
under radiolggic guidance and more than 500 cm3 of frank pus was drained. Cultures
produced$. coli and several anaerobic bacterial species. Cytology of the specimen was
consistent with metastatic adenocarcinoma. A radiodense percutaneous drainage catheter
(6)was left in place, and the patient was treated with intravenous antibiotics and continued
drainage. Note the position of the catheter and the decrease in size of the abscess. (Photos
courtesy of Lindsey Baden, MD, Brigham and Women’s Hospital, Boston, MA.)
560 JOHANNSENet a1

in 113 of 115 consecutive patients with a total of 147 hepatic abscesses.15 Each
abscess required, on average, 2.2 aspirations; a single aspiration was sufficient
in 57 patients. Two patients with large, viscous abscesses required surgical
intervention. No complications or deaths occurred in this series. Ch Yu et a1
found that needle aspiration was curative in 59 of 63 consecutive patients,
although 50% of the abscesses required more than one aspiration and 27%
required three or more aspirations.*In this series, two patients died from sepsis,
two patients required surgical drainage, and one patient sustained a liver lacera-
tion requiring laparotomy. Percutaneous aspiration is relatively contraindicated
in patients with multiloculated abscesses? Needle aspiration without catheter
placement is a promising therapeutic modality; a prospective randomized trial
comparing percutaneous aspiration and catheter drainage may clarify their re-
spective roles in the management of hepatic abscesses.

Antibiotics Without Drainage

Two decades ago, Reynolds et a1 reported the successful treatment of 13 of

15 patients with pyogenic liver abscesses treated only with antibiotics." 33 Shortly
thereafter, Herbert et a1 reported that 9 of 10 patients with hepatic abscess were
cured with conservative medical therapy.1g These reports have been criticized
because most of the patients, a combined total of 68%, underwent diagnostic
percutaneous aspiration. Thus, many of them had, in essence, at least partial
drainage of the abscess. Moreover, these reports stood in marked contrast to the
general experience of the time, in which conservative Ifiedical therapy carried
high mortality rates (59%to 1 0 0 ? ' 0 ) . ~ ~Most
* ~ , ~of these patients, however, were
managed conservatively because they were not surgical candidates; thus the
observation that nonsurgical therapy was ineffective may have been subject to a
substantial selection bias.
Recently, some investigators have returned to the question of medical ther-
apy alone in the management of patients with pyogenic liver abscesses. Seeto et
a1 reported that 15 of 20 patients in their case series were treated successfully
with antibiotics alone.%The other five patients died, all with the explicit decision
or directive not to pursue more aggressive therapy. Barakate et al reported that
11 of 13 patients treated with antibiotics alone were cured; the two patients not
treated successfullyhad advanced malignancies? Although conservative medical
therapy can be a reasonable option in selected patients, it has been employed
less frequently since the development of minimally invasive therapies for abscess
drainage.2O Until the indications are better defined, conservative medical therapy
should be considered only in those patients with small liver abscesses not
amenable to drainage or in those for whom drainage presents an unacceptable
risk.

Management of Antibiotics

Antibiotics should be started as soon as the diagnosis of pyogenic liver

abscess is suspected (Table 8). Blood specimens for culture should be obtained
before initiating empiric therapy, but delaying therapy until abscess material is
obtained is potentially dangerous and not advisable. The suspected origin of
infection should be considered when choosing initial antimicrobial therapy,
because it will predict the most likely pathogens. Pyogenic liver abscesses that
arise in a patient with biliary disease often include enterococci and enteric gram-
 PYOGENIC LIVER ABSCESSES 561

Table 8. EMPlRlC TREATMENT FOR PYOGENIC LIVER ABSCESS

Suspected
Source Primary Therapy Alternative Therapy
Biliary Ampicillin + gentamicin +/ Vancomycin + gentamicin + / -
- metronidazole metronidazole
Imipenem or meropenem*
Colonic Third-generationcephalosporin Imipenem or meropenem*
+ metronidazole Antipseudomonal penicillin with beta
lactamase inhibitor*
Fluoroquinolone + metronidazole + /
- aminoglycoside

‘Metronidazole should be included for presumptive therapy of amebic abscess if suspected.

negative bacilli. Pyogenic liver abscesses from a colonic or pelvic source are
more commonly due to coliforms and anaerobes. We include metronidazole in
the initial therapy for most cases of pyogenic liver abscess, to empirically
treat both anaerobes (especially Bacferoides fiugiZis) and E. histolyticu while these
possibilities are being evaluated. Once microbiologic data are obtained, antibiotic
therapy should be tailored to the organisms isolated and their respective antibi-
otic susceptibility profiles.
We usually treat pyogenic liver abscesses with parenteral antibiotic therapy
for 2 to 3 weeks and complete a 4 to 6-week course with oral antibiotics,’Z3O
although others have reported successful treatment with less than 2 weeks of
therapy? We use the patient‘s clinical response and follow-up imaging studies
to determine the duration of antibiotic therapy and the need, if any, for further
intervention. In general, abscesses completely resolve after a full course of
therapy. On occasion, a residual cavity persists despite prolonged therapy; if the
size is stable on serial imaging studies and the patient is asymptomatic, antibiot-
ics can be stopped and the patient observed closely for the development of
recurrent fevers or abdominal pain. In these situations, a follow-up CT scan is
advisable 1to 2 months after cessation of therapy.

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Lawrence C. Madoff, MD
Channing Laboratory and Division of Infectious Disease
Brigham and Women’s Hospital
181 Longwood Avenue
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lmadoff@channing.harvard.edu