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 preantibiotic 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 nonsurgical 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 resulting 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 detection, or admission practices. A recent population-based study found 11 cases per million persons per year.I7 With the availability of effective antimicrobials, pyogenic 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 differences 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 Womens Hospital, Boston, Massachusetts INFECTIOUS DISEASE CLINICS OF NORTH AMERICA
VOLUME 14 * NUMBER 3 SEMEMBER 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 preantibiotic 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 nonsurgical 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 resulting 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 detection, or admission practices. A recent population-based study found 11 cases per million persons per year.I7 With the availability of effective antimicrobials, pyogenic 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 differences 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 Womens Hospital, Boston, Massachusetts INFECTIOUS DISEASE CLINICS OF NORTH AMERICA
VOLUME 14 * NUMBER 3 SEMEMBER 2000

547

PYOGENIC LIVER ABSCESSES

549

amebic liver abscess. About one half of patients have a solitary abscess. Abscesses involve the right hepatic lobe in about three fourths of cases; the remainder are found mostly in left lobe (approximately 20%), with infrequent involvement 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 explanations 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 Carolis 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. Pylephlebitis from diverticulitis, pancreatitis, omphalitis, inflammatory bowel disease, 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 cholecystitis, 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 formation, presumably because the resultant hepatic hematoma is susceptible to seeding by bacteria. Similarly, hepatic destruction from sickle cell disease, tumor necrosis (including iatrogenic embolization), or cirrhosis can predispose to abscess 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 cryptogenic 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 Jobs syndrome result in a marked predisposition to abscesses of the liver and elsewhere. Finally, hemochromatosis conveys a particular 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. Abscesses involve the right hepatic lobe in about three fourths of cases; the remainder are found mostly in left lobe (approximately 20%), with infrequent involvement 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 explanations 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 Carolis 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. Pylephlebitis from diverticulitis, pancreatitis, omphalitis, inflammatory bowel disease, 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 cholecystitis, 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 formation, presumably because the resultant hepatic hematoma is susceptible to seeding by bacteria. Similarly, hepatic destruction from sickle cell disease, tumor necrosis (including iatrogenic embolization), or cirrhosis can predispose to abscess 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 cryptogenic 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 Jobs syndrome result in a marked predisposition to abscesses of the liver and elsewhere. Finally, hemochromatosis conveys a particular susceptibility to abscesses caused by Yersinia enterocoliti~a.~, 36,

PYOGENIC LIVER ABSCESSES

551

MICROBIOLOGY

With the diverse pathologic processes discussed above, sweeping generalizations 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.35 In practice, however, anaerobes 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 converge 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.38 Initial diagnostic impression often is wrong and can include cholangitis, 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

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551

MICROBIOLOGY

With the diverse pathologic processes discussed above, sweeping generalizations 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.35 In practice, however, anaerobes 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 converge 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.38 Initial diagnostic impression often is wrong and can include cholangitis, 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

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Table 4. MICROBIOLOGYOF PYOGENIC LIVER ABSCESS

Study

Common (210%)

Uncommon (1%-10%)

Gram-negative aerobes

E . coli Klebsiella spp.

Gram-positive aerobes

Anaerobes

Staphylococcus aureus Enterococcus spp. Viridans streptococci Bacteroides spp.

Pseudomonas Proteus En terobacter Citrobacter Morganella Serratia p-hemolytic streptococci

Microaerophilic

Fusobacterium Anaerobic streptococci Clostridium Lactobadli 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 aminotransferase (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 diagnosis. 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 scanning offers improved sensitivity over ultrasonography and is superior for guiding 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 demonstrated specific findings to suggest the presence of an abscess, but do not generally avert the need for diagnostic aspiration.' Furthermore, MRI is a cumbersome tool for guiding drainage procedures. Technetium sulfur colloid scanning 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 Klebsiella spp.

Gram-positive aerobes

Anaerobes

Staphylococcus aureus Enterococcus spp. Viridans streptococci Bacteroides spp.

Pseudomonas Proteus En terobacter Citrobacter Morganella Serratia p-hemolytic streptococci

Microaerophilic

Fusobacterium Anaerobic streptococci Clostridium Lactobadli 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 aminotransferase (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 diagnosis. 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 scanning offers improved sensitivity over ultrasonography and is superior for guiding 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 demonstrated specific findings to suggest the presence of an abscess, but do not generally avert the need for diagnostic aspiration.' Furthermore, MRI is a cumbersome tool for guiding drainage procedures. Technetium sulfur colloid scanning 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

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Figure 1. Diagnosis o f 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 o f the liver. Antibiotic therapy was administered and ultrasound-guided percutaneous catheter drainage removed 250 cm3o f foul-smelling, blood-tinged pus. Grams stain o f the aspirate revealed moderate polymorphonuclear leukocytes with moderate gram negative rods and very rare gramvariable 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 Traditionally, 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.

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Figure 1. Diagnosis o f 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 o f the liver. Antibiotic therapy was administered and ultrasound-guided percutaneous catheter drainage removed 250 cm3o f foul-smelling, blood-tinged pus. Grams stain o f the aspirate revealed moderate polymorphonuclear leukocytes with moderate gram negative rods and very rare gramvariable 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 Traditionally, 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 o f 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 o f the liver. Antibiotic therapy was administered and ultrasound-guided percutaneous catheter drainage removed 250 cm3o f foul-smelling, blood-tinged pus. Grams stain o f the aspirate revealed moderate polymorphonuclear leukocytes with moderate gram negative rods and very rare gramvariable 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 Traditionally, 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 3 8 , 39 Surgical intervention the initial management of pyogenic liver 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 Iocalization (achieved visually and with the occasional use of intraoperative ultrasound), 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, mycobacteria, 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 approach 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

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559

Figure 2. Drainage of liver abscesses by CT-guided percutaneous aspiration. A 67-yearold 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 Womens 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 laceration 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 respective 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 * ~ , ~o f 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 therapy 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 1 1 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-

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Table 8. EMPlRlC TREATMENT FOR PYOGENIC LIVER ABSCESS Suspected Source Primary Therapy Alternative Therapy

Biliary Colonic

Ampicillin + gentamicin - metronidazole

+/

Third-generationcephalosporin + metronidazole

Vancomycin + gentamicin + / metronidazole Imipenem or meropenem* Imipenem or meropenem* 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. W e 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 antibiotic 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 patients 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, antibiotics 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.
References
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