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Identification and Management of Fusobacterium Nucleatum Liver Abscess and Bacteremia in a Young Healthy Man

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Identification and Management of Fusobacterium Nucleatum Liver Abscess and Bacteremia in a Young Healthy Man

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A 21-year-old previously healthy young man was admitted with five days of fever, persistent cough, worsening shortness of breath, and vomiting. On presentation, laboratory evaluation revealed extremely elevated procalcitonin and leukopenia followed by leukocytosis. The patient was started on empiric antibiotics. Further diagnostic evaluation after initiation of antibiotics included a computed tomography scan, which revealed a large hepatic abscess.

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Pyogenic liver abscess caused by Fusobacterium in a 21-year-old immunocompetent male

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Pyogenic liver abscesses (PLA) are uncommon entities which require urgent diagnosis and treatment. If untreated they carry a high mortality. Hepatic abscess due to fusobacterium (gram negative anaerobic bacteria) is rare, but when reported they are associated with Lemierre's disease, an infectious thrombophlebitis of the internal jugular vein. Such infections are typically seen in the setting of instrumentation, dental work, and incidental oral flora translocation. Herein, we present the first case of de novo hepatic abscesses due to fusobacterium in an otherwise healthy 20-year-old Caucasian male with no identifiable source of infection. His course was further complicated by development of multiple intra-abdominal abscesses with subsequent direct seeding into the right pleural cavity causing empyema.

A 20-year-old Caucasian male was admitted with two weeks of progressive right upper quadrant abdominal pain, approximately 10 pound weight loss, fevers/chills, fatigue, and diarrhea. His social history was not significant for any IVDA, high risk sexual behavior, recent travel, exposure to contaminated water, or pet exposure. He was a college student and played baseball on the school team. On presentation his vital signs were stable and was afebrile. Examination revealed mild RUQ tenderness, but was otherwise unremarkable. His laboratory work revealed: leukocytosis with wbc count of 16.3 k/uL and anemia with Hgb of 7.6 gm/dL. Liver function tests revealed normal: AST (29 U/L)/ALT (44 U/L), total bilirubin (0.7 mg/dL); and mild elevation of alkaline phosphatase (158 U/L). Serologic workup was negative for human immunodeficiency virus, hepatitis B virus and hepatitis C virus. Computed tomography (CT) imaging of abdomen/pelvis revealed multiple hepatic abscesses, the largest in the right lobe measuring 8.9 cm × 9.4 cm × 9.5 cm (Figure 1A). Aerobic and anaerobic blood cultures were collected and empiric antibiotic treatment was initiated with Vancomycin and Piperacillin/Tazobactam. Two percutaneous drains were placed in the largest hepatic abscesses. The hepatic abscesses' anaerobic culture grew heavy Fusobacterium nucleatum ( F. nucleatum). The patient denied any neck pain or recent dental infection, but did report recent routine dental cleaning. Neck imaging revealed patent jugular veins without tenderness or palpable cords. An ERCP was done to rule out a biliary source, and revealed normal hepatic, biliary, and pancreatic ducts.

One week after initiating treatment the patient developed respiratory distress and was found to have a large right sided multiloculated pleural effusion for which a chest tube was placed and pleural fluid analysis revealed empyema, likely due to direct extension of the pyogenic liver abscesses. The chest tube did not resolve the pleural effusion and the patient subsequently developed a trapped lung. He underwent evacuation of the pleural fluid and partial decortication with a VATS procedure. He developed 2 more abdominal abscesses, and one pelvic abscess, all required percutaneous drain drainage with resolution. A 2D trans-thoracic echocardiogram was unremarkable, apart from a mild pericardial effusion. The patient was placed on IV Ertapenem for 8 wk and discharged home in stable condition. Repeat imaging during out-patient follow-up showed complete resolution of his abscesses after 9 wk of treatment (Figure 1B).

The two most common types of liver abscesses are: PLA and amebic abscess. PLA is defined as an encapsulated mass containing purulent material[ 1- 3]. Incidence varies with geographical location; PLA are more common in developed countries whereas amebic abscess are more common in developing countries. For PLA the reported incidence in the United States is 3.6 out of 100000 people[ 4, 5]. The right hepatic lobe is the most common site of involvement, due to its larger size and having greater blood supply when compared to the left and caudate hepatic lobes[ 6]. PLA are more commonly polymicrobial rather than monomicrobial. Meddings et al[ 5], evaluated close to 18000 patients with PLA in the United States; and found the most commonly recorded bacterial infections were: Streptococcus species (29.5%) and Escherichia coli (18.1%). Of note, Taiwan had the highest reported incidence at 17.6 out to 100000 people, with Klebsiella being the most prominent bacterial organism being found. Anaerobic species are also not uncommon in such patients, with Bacteroides being most commonly isolated. Anaerobes are probably under-reported because of difficulty associated with culturing them. There are only a few case reports, which report fusobacterium as the causative organism. Of the two large PLA studies done by Meddings et al[ 5] and Chuang et al[ 7], none of them were reported to have been caused by Fusobacterium.

Liver abscess can occur from three mechanisms: (1) dissemination via the portal venous system is most common cause of pyogenic liver abscess. Intra-abdominal infections in portal bed region organes, result in septic thrombophlebitis causing micro-abscess formation in the liver. These micro-abscesses later coalesce to form larger single or multiple abscesses; (2) biliary tract disease such as biliary duct stone, stricture or malignancy, results in direct extension of infection through biliary channels to liver; and (3) hematogenous spread from systemic bacteremia can result from endocarditis, septic thrombophlebitis (Lemierre's syndrome) or periodontal infections[ 8].

Notable risk factors for PLA include: diabetes mellitus, liver transplantation, intra-abdominal malignancy, biliary tract procedures, and immune system suppression[ 9]. Several recent studies from Taiwan mention an association between Klebsiella pneumoniae and colorectal cancer. Their studies show patients diagnosed with PLA had a fourfold increase in gastrointestinal malignancy, of which colorectal cancer was the most common[ 10- 15].

Treatment of PLA includes prompt initiation of intravenous antibiotics and drainage of purulent material. The preferred method is via percutaneous drainage, with needle aspiration being an inferior choice due to requirement of repeated aspirations. Surgical intervention is recommended for: abscesses > 5 cm, gas forming organism, or biliary fistulization. Empiric broad spectrum intravenous antibiotics should include one of the following: ampicillin/sulbactam, ceftriaxone plus metronidazole, or meropenem. Definitive therapy is based on speciation of isolated organism. Recommended duration of antibiotics varies, usually ranging from 2-6 wk; depending on clinical improvement and resolution of abscess seen on CT imaging[ 3].

The genus Fusobacterium currently includes 13 species and belongs to family bacteroidaceae[ 16, 17]. Most common species of Fusobacterium responsible for human infections are Fusobacterium necrophorum ( F. necrophorum) and F. nucleatum. Fusobacterium is a nonsporeforming, nonmotile, gram negative small spindle-shaped rod[ 17, 18]. F. nucleatum is part of normal oral flora[ 18, 19]. Fusobacterium species possesses outer membrane proteins like other gram-negative bacteria[ 17]. The Lipopolysaccharides in the outer membrane proteins can act as endotoxins and provide other antigenic properties such as adhesion and co-aggregation which helps in invasion of the tissue and contribute towards virulence[ 17].

In 1936, Dr. Lemierre was the first to describe a periodontal source leading to septicemia from Fusobacterium. F. necrophorum is associated with younger healthy population while nucleatum is mostly associated with older patients with chronic medical conditions[ 20]. F. nucleatum had been associated with infections such as tropical skin ulcers, peritonsillar abscesses, pyomyositis, septic arthritis, bacteremia, intrauterine infections, bacterial vaginosis, urinary tract infections, pericarditis, endocarditis, myocarditis, and pulmonary infections[ 17, 21]. F. Nucleatum has also recently been implicated as causative agent in chorioamnionitis and idiopathic preterm labor[ 16]. Association of F. Nucleatum infections with GI tract malignancies is attributed to the breach in mucosal lining resulting in invasive infections[ 18].

Annual incidence of Fusobacterium infections is between 0.6-3.5 cases per 1000000 people[ 20]. Su et al[ 22] pointed out that most Fusobacterium blood stream infections were from nucleatum species. Community acquired F. nucleatum infections tend to be more polymicrobial as compared to nosocomial which are almost always monomicrobial[ 23, 24]. Risk factors for poor prognosis were presence of comorbid conditions such as diabetes mellitus, renal failure, dialysis and malignancy[ 18, 20]. Nosocomial bacteremia was a significant mortality predictor with rates as high as 84% in one study[ 18]. F. nucleatum bacteremia without identifiable source is not uncommon. In such cases, a GI tract malignancy is often found[ 18].

The fusobacteria species are broadly susceptible to commonly used antibiotics, but reports of increasing resistance to: vancomycin, neomycin, erythromycin, amoxicillin, ampicillin, and phenoxymethylpenicillin; have emerged[ 17]. Recently some resistant patterns to quinolones had been identified with fusobacteria isolated from oral flora of dogs and cats[ 16]. An accurate identification of fusobacterium species is critical not only for taxonomic reasons but also for appropriate treatment of infection, since the susceptibility of different Fusobacterium species to antibiotics varies widely[ 17]. Only 13 cases have been reported of liver abscesses caused by F. nucleatum, 12 of which were in immunosuppressed individuals, and 1 mentioned by Kajiya et al[ 25] was an elderly immunocompetent individual[ 26- 29]. Apart from our case, no other case has been reported in an otherwise young and healthy immunocompetent patient.

Pyogenic liver abscess from fusobacterium is a rare diagnosis and behaves clinically like any other anaerobic body cavity infections. It presents with fever, chills and weight loss in most cases. Surprisingly, jaundice and RUQ pain are inconsistent findings[ 8]. Course is indolent which could be used as a clinical clue on initial presentation. Necrosis of the tissue with putrid discharge and abscess formation are seen in later stages of the disease. Anemia and weight loss are indicators of long standing chronic infection. The spectrum of infections that can occur with Fusobacterium species is broad and carry a high mortality if untreated. Suspicion for anaerobic infections such as Fusobacterium should be kept high when a host with risk factors presents with indolent disease course. Also it should be kept in mind that while often seen in immunocompromised individuals, it can present, as in our case, in otherwise healthy individuals. It is postulated the patient got this invasive strain from possible plaques and/or minor oral cavity manipulation during routine dental cleaning. Prompt drainage along with empiric anaerobic coverage is recommended initially. The sequelae of this condition are fatal, prompt diagnosis and treatment with source control being the focus are crucial in preventing mortality.

A 21-year-old immunocompetent male with pyogenic liver abscess from Fusobacterium.

Right upper quadrant pain, fevers/chills, and weight loss in an otherwise healthy patient.

Hepatitis, hepatic cancer, biliary obstruction.

WBC count of 16.3 k/uL; Hgb of 7.6 gm/dL; liver function tests relatively within normal limits; liver serology negative.

Computed tomography imaging of abdomen/pelvis revealed multiple hepatic abscesses, the largest in the right lobe measuring 8.9 cm x 9.4 cm x 9.5 cm.

Culture of aspirates showing: gram negative anaerobe- Fusobacterium nucleatum ( F. nucleatum), otherwise pathology negative.

Aspiration and drainage, along with IV antibiotics: Ertapenem.

Pyogenic liver abscesses' in otherwise healthy individuals is not very common, case reports describe: invasive oral cavity manipulation, biliary translocation, and gastrointestinal migration as causes; none of which were present in this case.

PLA is used to denote pyogenic liver abscess.

This case report illustrates importance of recognizing pyogenic liver abscess as a possible entity in otherwise healthy individuals with no predilection, and urgent treatment with: Drainage and antibiotics.

The author presented a young, immunocompetent patient had liver abscesses caused by F. nucleatum, a nonsporeforming, nonmotile, gram negative small spindle-shaped rod. F. nucleatum is a rare cause of pyogenic liver abscess and high morbidity and mortality will happen if delayed diagnosis and treatment. It is interesting to readers to keep in mind if same scenario happened.

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Pyogenic liver abscess caused by Fusobacterium in a 21-year-old immunocompetent male

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Pyogenic liver abscess caused by Fusobacterium in a 21-year-old immunocompetent male

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Fusobacterium nucleatum: a rare cause of pyogenic liver abscess

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Abstract

While pyogenic liver abscesses are uncommon, they are associated with significant mortality and morbidity. Most pyogenic liver abscesses are polymicrobial and are caused by enteric bacteria and anaerobes. Rarely, mono-microbial infections may occur, typically in immunocompromised individuals. We report the unusual case of a 69 year-old immunocompetent female who developed a pyogenic liver abscess due to Fusobacterium nucleatum infection, likely from a dental source. Poor oropharyngeal hygiene seems to have a major role in infection from this organism and therefore F. nucleatum should be considered as a differential for causes of pyogenic liver abscess in such patients. Drainage of the abscess and antibiotic therapy are the mainstays of therapy.

Keywords: Pyogenic liver abscess, Fusobacterium, Poor dental hygiene, Immunocompromised state

Introduction

Worldwide, amebic liver abscess remains the most common form of liver abscess, but in the United States pyogenic liver abscess (PLA) is the most common form (Wong et al. 2002). The incidence of pyogenic liver abscesses is estimated at about 2.3 per 100,000 patients (Huang et al. 1996; Kaplan et al. 2004) and mortality is estimated at 2-12% (Mohsen et al. 2002; Rahimian et al. 2004) despite advances in antibiotic therapy and investigation and management of these abscesses over the years.

Due to its rich blood supply from the portal and systemic circulations, the liver is a common site of metastatic disease and also the most common site of visceral abscesses. According to a large case series, an estimated 48% of intra-abdominal abscesses involve the liver (Altemeier et al. 1973). Intra-abdominal infections, particularly those involving the biliary tract are more likely to lead to the formation of a PLA (Huang et al. 1996; Rahimian et al. 2004). Bacteria may also spread through the portal vein or from hematogenous seeding from bacteremia from other sources (Huang et al. 1996), with periodontal disease being increasingly recognized as a potential source (Crippin and Wang 1992; Ohyama et al. 2009). Most PLA are polymicrobial and mixed enteric and anaerobic species are common pathogens, with one case series identifying anaerobes in up to 45% cases (Nozawa et al. 2011). However, monomicrobial infections are also possible.

Fusobacterium is an anaerobic bacterium that is found in the oropharyngeal cavity and is believed to be strongly associated with the formation of dental plaque (Bolstad et al. 1996). PLA secondary to F. nucleatum has rarely been reported previously, and mostly in immunodeficient hosts with the exception of a few (Tweedy and White 1987; Scoular et al. 1992; Etienne et al. 2001; Ala et al. 2001; Wells et al. 2005; Schattner and Gotler 2014; Dahya et al. 2015; Ahmed et al. 2015). We report the case of a 69 year-old immunocompetent female who was found to have a pyogenic liver abscess secondary to Fusobacterium nucleatum.

Case description

A 69 year-old female presented with a 2-month history of vague right upper quadrant (RUQ) pain, intermittent fevers and chills. Her pain was dull in nature and was slightly worse with deep inspiration. Her past medical and surgical histories were significant for emphysema, well controlled diabetes mellitus, known pancreatic and renal cysts and an infra-renal abdominal aortic aneurysm (AAA) endovascular repair a few years ago.

On presentation, her vitals showed a temperature of 38.1°C (100.6°F), heart rate 117 beats per minute, blood pressure 98/62 and an oxygen saturation of 96% on room air with a respiratory rate of 15 breaths per minute. Physical exam revealed poor dental hygiene and tenderness in the abdomen, which was worst in the RUQ. Murphy sign was negative and there were no signs of peritonitis. Labs revealed significant leucocytosis (22.82 × 10 ³/µl) with 94.2% neutrophils. Liver function tests revealed a normal AST and ALT (25 and 22 U/L, respectively) and a normal total bilirubin (1.3 mg/dL). Ultrasound imaging of the right upper quadrant (RUQ), done to investigate the pain, revealed a 9 × 7 × 7 cm hypoechoic density in the right hepatic lobe. Due to concern for possible infection, she was started on broad spectrum antibiotics, Vancomycin 1.5 g daily and Meropenem 500 mg bid. Abdominal computerized tomography (CT) showed a multiseptated thick walled mass in the right hepatic lobe (Figure 1 ). The CT did not show any other potential sources of infection or malignancy and the previously known pancreatic and renal cysts were stable in size and appearance. Vancomycin was stopped by Day 3 of admission due to low concern for MRSA infection. She underwent CT-guided pigtail drain placement which revealed thick, purulent material. Microscopic examination of the abscess fluid revealed polymorphonuclear leucocytes but gram stain was negative. However, cultures from the drain fluid as well as admission blood cultures (2 out of 2 each) revealed Fusobacterium nucleatum. X-rays of the teeth showed evidence of moderate to severe chronic periodontitis for which she underwent extraction of all remaining teeth. She also underwent a colonoscopy to rule out occult colonic malignancy as the incidence of PLA is disproportionately higher in patients with occult colonic malignancy (Qu et al. 2012; Kao et al. 2012; Huang et al. 2012; Lai et al. 2014). The colonoscopy only showed diverticulosis. She improved remarkably and was eventually discharged home on intravenous Ertapenem (chosen over penicillins/cephalosporins due to her allergies) to complete a total of 2 weeks of intravenous antibiotic therapy, followed by a 4 week suppressive regimen of oral Penicillin VK. A repeat CT at 4 months post discharge (Figure 2 ) showed complete resolution of the hepatic lesion.

Discussion

Differential diagnoses for a liver hypodensity seen on imaging can be broad and can include an amebic or pyogenic liver abscess, primary or metastatic malignancy (especially colonic). Since the suspicion for PLA was high based on the ultrasound, the patient was started on broad spectrum antibiotic coverage with Vancomycin and Meropenem. The oral cavity was considered as a potential source of infection due to the patient's poor dental hygiene. However, hematogenous spread of infection leading to PLA, especially from an oropharyngeal source is extremely uncommon and F. nucleatum was not initially suspected as the causative organism.

Immunodeficient patients tend to develop opportunistic and superimposed infections, occasionally with rare organisms. Among the sixteen cases of PLA due to F. nucleatum that have been reported (including current case), only five patients (31.25%) had documented immunocompetence. Out of these five patients, four (80%) were found to have dental disease and the remaining one patient had evidence of a tonsil infection (Mémain et al. 2001). This probably implies that F. nucleatum leading to distant infection and abscess formation is very likely to have originated from the oropharyngeal region and likely secondary to poor dental hygiene leading to dental disease. Other rare organisms that have been known to cause PLA are Citrobacter koseri (Gupta et al. 2013), Gemella morbillorum (Borro et al. 2014) and S treptococcus milleri (Chen et al. 2012), which is especially known for its underlying association with colorectal neoplasia.

The liver is a major site of intraabdominal abscesses (Altemeier et al. 1973). However, it is not clear why the liver seems to be preferentially affected over other visceral organs by F. nucleatum. While this could just be due to the liver's dual blood supply which is derived from the portal as well as systemic circulations, it is also possible that the formation of liver abscesses in Fusobacterium bacteremia represents an early stage of infection and if left untreated, it might lead to involvement of other organs as well. Organism ( F. nucleatum) and organ (Liver) specific interaction and factors that are still unknown, might have a role to play as well.

Early identification and treatment of PLA is very essential, given the high likelihood of fatality in untreated cases (Stroup et al. 2007). Known risk factors for mortality are presence of anaerobic infection, abscess greater than 5 cm in size and the need for open surgical drainage (Yang et al. 2004; Lok et al. 2008; Chen et al. 2012). Treatment consists of abscess drainage as well as appropriate antibiotic therapy. Like other infections, collection of cultures should ideally be performed prior to initiation of antibiotic therapy.

Conclusions

We report an unusual case of a PLA due to F. nucleatum infection which seems to be an emerging causative organism for PLA. In this case the infection was likely from a dental source and the host was immunocompetent. Poor oropharyngeal hygiene seems to have a major role in infection from this organism and therefore F. nucleatum should be considered as a differential of PLA in patients with poor dental hygiene, especially with a known history of immunodeficiency. Radiology guided drainage of the abscess and antibiotic therapy (including anerobic coverage) are the mainstays of therapy and patients rarely require invasive surgery for PLA (Heneghan et al. 2011; Pang et al. 2011).

Authors' contributions

SJSN, DM and PP all acquired and interpreted the data and wrote the manuscript. PP also supervised the entire manuscript draft and SJSN made final revisions. All authors read and approved the final manuscript.

Acknowledgements

None.

Compliance with ethical guidelines

Competing interests The authors declare that they have no competing interests.

Ethics, consent and permissions Consent to publish was obtained from the participant to report individual patient data.

Abbreviations

PLA

Pyogenic liver abscess

RUQ

right upper quadrant

CT

computerized tomography

AAA

abdominal aortic aneurysm

Contributor Information

Sajan Jiv Singh Nagpal, Email: gro.fcc@slapgan.

Dhruvika Mukhija, Email: moc.liamg@4akivurhhdm.

Preethi Patel, Email: gro.fcc@3pletap.

References

Bolstad AI, Jensen HB, Bakken V. Taxonomy, biology, and periodontal aspects of [[Fusobacterium nucleatum. Clin Microbiol Rev. 1996;9:55-71. PMC free article] [PubMed] Google Scholar]

Borro P, Sumberaz A, Testino G. Pyogenic liver abscess caused by Gemella morbillorum. Colomb Médica Cali Colomb. 2014;45:81-84. [[PMC free article] [PubMed] Google Scholar]

Dahya V, Patel J, Wheeler M, Ketsela G. [Fusobacterium nucleatum endocarditis presenting as liver and brain abscesses in an immunocompetent patient. Am J Med Sci. 2015;349:284-285. doi: 10.1097/MAJ.0000000000000388. [PubMed] [CrossRef] Google Scholar]

Etienne M, Gueit I, Abboud P, Pons JL, Jacquot S, Caron F. [Fusobacterium nucleatum hepatic abscess with pylephlebitis associated with idiopathic CD4(+) T lymphocytopenia. Clin Infect Dis Off Publ Infect Dis Soc Am. 2001;32:326-328. doi: 10.1086/318468. [PubMed] [CrossRef] Google Scholar]

Mémain N, Arvaniti K, Bruneel F, Leport C, Wolff M, Regnier B. Septic shock with liver abscess in an immunocompetence patient. Presentation of an unusual [Fusobacterium nucleatum infection. Presse Médicale Paris Fr (1983) 2001;30:1777-1779. [PubMed] Google Scholar]

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Articles from SpringerPlus are provided here courtesy of Springer-Verlag

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Fusobacterium nucleatum: a rare cause of pyogenic liver abscess

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While pyogenic liver abscesses are uncommon, they are associated with significant mortality and morbidity. Most pyogenic liver abscesses are polymicrobial and are caused by enteric bacteria and anaerobes. Rarely, mono-microbial infections may occur, typically ...

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Hepatic Abscess | Johns Hopkins ABX Guide

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Type your tag names separated by a space and hit enter

Scott M. Smith, M.D., Christopher F. Carpenter, M.D.

Gram-positive cocci: Streptococcus species (especially S. intermedius group), enterococci, and Staphylococcus aureus.

Anaerobes: Bacteroides species, Fusobacterium sp, Actinomyces sp, Clostridium sp, etc.

Enterobacterales (, Klebsiella spp., etc) and other Gram-negative bacilli
Klebsiella pneumoniae, especially mucoid strains, are especially common in Asia.
K1 or K2 serotypes have hypercapsular and hypermucoid phenotypes.

Yersinia enterocolitica: a rare cause of liver abscess; if identified, consider underlying hemochromatosis.

Candida species

Notably, in neutropenic patients, may be multiple (hepatosplenic candidiasis).

Entamoeba histolytica: amebic liver abscesses may complicate up to 10% of the cases of amebic colitis

Echinococcus granulosus: most common cause of hydatid cysts

Risk factors for the development of hepatic abscess include:

Diabetes

Liver cirrhosis

Immunocompromised state, including neutropenia

Male sex

Advanced age

Proton-pump inhibitor use

Signs and symptoms: include fever +/- RUQ pain, tenderness w/ hepatomegaly

Some may only have nonspecific symptoms such as fever (60%) associated with weight loss, chills and malaise.

The presentation may be subacute or chronic, including weight loss and anorexia.

Occasionally, patients may be acutely ill with mental status changes.

Rarely, patients may present with sepsis and peritoneal signs from intraperitoneal rupture of the abscess.
Subdiaphramatic presentations may misdirect to initial concern for a pulmonary process.
Diaphragmatic irritation from an abscess might refer to pain in the right shoulder or result in a cough or pleural rub.

Approximately 50% of patients have a solitary hepatic abscess.
The majority of abscesses involve the right hepatic lobe (~75%), less commonly left (20%) or caudate (5%) lobes.

Classified by presumed etiology:

Bacterial:

Up to 50% develop from the biliary tract (cholangitis).

The remainder is from the hepatic artery (bacteremia), portal vein (abdominal source, e.g., diverticulitis), contiguous focus (local abscess or cholecystitis) or penetrating trauma.

Many are of cryptogenic origin.

Parasitic:

Entamoeba histolytica: abscess occurs via the portal system during amebic colitis.

Typically manifests as a right lobe solitary lesion.

Rare in most locales in the U.S., occurring almost exclusively among immigrants (especially from South and Central America) and travelers.
Identified more often in regions such as southern California, Texas, etc.

Men, especially MSM, are at higher risk for invasive disease from this parasite.

Echinococcal (hydatid) cysts: most commonly caused by Echinococcus granulosus and usually acquired from canines (sheepdogs).

Cystic echinococcosis can be seen worldwide, with the highest prevalence found in people with a history of shepherding sheep.

Rarely seen in the U.S.
Generally, infections are diagnosed in immigrants with late presentation or by incidental identification.

Usually asymptomatic; when symptoms develop, they are due to the size of enlarging cyst or leakage/rupture.

The underlying disease typically is the primary determinant of the outcome of hepatic abscess.
Increased mortality was reported in polymicrobial and fungal infections and immunocompromised patients.

Suspect in people with RUQ pain, fever, weight loss and other systemic symptoms.

Differential diagnosis:

Before imaging: cholecystitis, cholangitis, biliary colic, viral hepatitis, gastritis, bacterial pneumonia, parapneumonic effusion, empyema, lung abscess, pyelonephritis.

After imaging: malignancy (including hepatocellular carcinoma), benign cysts

Labs:
For pyogenic liver abscess(es), positive blood cultures are seen in up to 50%.

Alkaline phosphatase and WBC counts are frequently elevated.

Hyperbilirubinemia with or without overt jaundice occurs in < 50% of patients.

Imaging:

Plain abdominal radiography: dx may be suggested on plain films (e.g., gas within the abscess)

Preferred: CT, US and MRI are the imaging modalities of choice in a suspected liver abscess or FUO

CT or US-guided percutaneous drainage or surgical drainage should be considered in all cases of hepatic abscess for diagnostic confirmation and culture.
Multiple, small abscesses may not be amendable to aspiration

Serology or therapeutic reponse:

Positive amebic or echinococcal serology helps differentiate parasitic liver abscess from pyogenic, especially in nonendemic areas; serology cannot distinguish between active and prior infection.
Response to metronidzole-containing regimens doesn't help distinguish amebic from bacterial explanations.

Uncomplicated or small abscesses may be due to Entamoeba histolytica in people living in endemic areas or hailing from them.

They may not require aspiration; consider empirical treatment.

Often responds dramatically within 72h of instituting metronidazole therapy which should alert to the potential diagnosis[15].

Abscess drainage is the optimal therapy for pyogenic liver abscesses

Aspirate should be sent for Gram stain and aerobic/anaerobic culture.

Evaluation for fungal and mycobacterial pathogens.

E. histolytica should be considered based on epidemiologic factors.

CT- or US-guided percutaneous needle aspiration +/- catheter drainage initial method of choice:

Success in up to 90% of cases.

If drainage is inadequate, surgical drainage may be required.

Percutaneous aspiration without catheter placement: recently found to have similar success rates as catheter placement

Repeat aspiration is required in approximately 50%.

Catheter placement should be considered in larger abscesses (>5 cm diameter).

Complications of percutaneous drainage include perforation of adjacent abdominal organs, pneumothorax, hemorrhage and leakage of abscess contents in peritoneum.

General recommendations are for at least one week of drainage with CT follow-up.

Surgical drainage: may consider as primary treatment in certain settings.

Complex or ruptured abscess

Multiple abscesses

Percutaneously unreachable abscess

Larger abscesses (> 5 cm)

If there are associated surgical problems also present (e.g., peritonitis)

Drainage may be done laparoscopically.

Hepatectomy: generally successful approach, but improvements in percutaneous techniques make it secondary management in most cases.

Medical management: consider patients at high risk for drainage procedures or with small/multiple abscesses (< 3-5 cm in diameter) not amenable to drainage.

Empiric coverage should include Enterobacterales, enterococci, anaerobes, and in certain situations, staphylococci and streptococci.

In a stable patient, antibiotics may be deferred until post-aspiration/drainage to increase culture yield.

Consider empiric antifungal treatment in immunosuppressed patients at risk for chronic disseminated candidiasis (CDC, a.k.a. hepatosplenic candidiasis, also see module).

Culture results may help narrow coverage, but for pyogenic abscesses, do not discontinue anaerobic coverage, given the difficulty of culturing these organisms.

Empiric regimens: may narrow based on culture results

Traditional: ampicillin 2.0g IV q6h plus gentamicin 1.7mg/kg IV q8h plus metronidazole 0.5g IV q8h

First line:

Alternatives:

Carbapenems: appropriate for monotherapy, especially if the patient is at high risk for resistant GNRs or has a documented multidrug-resistant organism.

Fluoroquinolones: often used as an oral regimen for prolonged therapy after completion of the initial parenteral therapy course

Duration: if adequate drainage achieved with a resolution of fever and leukocytosis

Usually 14-42 days total
Duration not well determined.

Longer courses (up to several months) may be required in the patient who is inadequately drained or treated without drainage.

Follow-up imaging studies: consider in patients with suboptimal clinical response.

Use CT or ultrasound

Note: imaging findings may lag behind other markers of clinical response.

See the Entamoeba histolytica module for additional details.

Requires treatment for both tissue infection and luminal clearance

Preferred Regimen:

Metronidazole 750mg PO three times a day x 7-10 days as a tissue agent, followed by a luminal agent to eliminate residual colonic colonization, usually paromomycin 500mg three times a day PO x 7d.

Tissue agents:

Luminal agents:

Combined Tissue and Luminal Agents:

Percutaneous aspiration has no apparent role in therapy but consider for diagnosis if uncertain (serology inconclusive or not available) or no response to appropriate antibacterial treatment.
Predictors of need for aspiration if initially targeting only amebic liver abscess include: age> 55 years, abscesses > 5 cm, involvement of both lobes of the liver, and failure of medical therapy after 7 days.

Most commonly, E. granulosus; see module for additional details.

Serology is helpful in most cases in non-endemic areas; sensitivity for liver cysts is 85-98%, and specificity is limited.

In patients with a rupture of the cyst into the biliary tree, transient but markedly elevated levels of alkaline phosphatase and bilirubin may occur.
Hyperamylasemia and eosinophilia occur in up to 60%.

Surgical resection standard intervention:

Uncomplicated cysts: PAIR (Percutaneous puncture with CT or US guidance, followed by Aspiration, Injection of a protoscolicidal agent such as hypertonic saline or ethanol, and finally, re-aspiration 15 minutes later) is becoming the more accepted treatment of choice at some centers due to high success rates with low morbidity.

Open or percutaneous (PAIR) procedures should be combined with albendazole treatment.

Preferred Antiparasitic Therapy:
Albendazole is 10-15mg/kg/day in two doses with a fat-rich meal

Alternative Antiparasitic Therapy:

Mebendazole 40-50mg/kg/day in three divided doses with a fat-rich meal

Praziquantel 40mg/kg once weekly used in combination with albendazole

Duration of Antiparasitic Therapy

Limited evidence for the duration of therapy

typically 1-3 months, occasionally up to 6 months in duration

Follow up:

Repeat the US examination every 3-6 months initially, then yearly after stability.

Serologic markers are difficult to interpret after treatment and may rise even in the setting of successful treatment.

Good coverage of Gram-positive, Gram-negative, and anaerobic pathogens; lacks Pseudomonas aeruginosa coverage but good Enterococcus species coverage. Rising rates of resistance in mean that this is no longer favored as an empiric choice but may be quite acceptable once culture results have returned.

Excellent coverage of Gram-negative w/ some Gram-positive pathogens; use in combination with an anaerobic agent for empiric therapy.

Excellent broad-spectrum (Gram-positive, Gram-negative, and anaerobe) coverage; would reserve for seriously ill patients. It has better coverage for than meropenem or doripenem; none of the carbapenems cover .

Excellent broad spectrum (Gram-positive, Gram-negative, and anaerobe) coverage; would reserve for seriously ill patients. Will cover E. faecalis; none of the carbapenems cover E. faecium.

Once-daily carbapenem with excellent broad-spectrum coverage except for organisms such as MRSA, P. aeruginosa, Acinetobacter spp., and enterococci.

Most recently approved carbapenem for complicated IAIs. Excellent Gram-positive (except E. faecium), Gram-negative and anaerobic coverage.

Excellent broad-spectrum coverage includes some anaerobic activity, many would still use metronidazole with liver abscess condition due to resistance among.

Piperacillin/tazobactam

Excellent broad spectrum coverage, including Gram-positive and Gram-negative coverage ( including Pseudomonas aeruginosa and β-lactamase producing pathogens) and anaerobic coverage.

Ticarcillin/clavulanic Acid

Broad spectrum coverage including Gram-positive coverage, Gram-negative coverage ( including Pseudomonas aeruginosa [but less active than piperacillin/tazobactam] and B-lactamase producing pathogens) and anaerobic coverage. No longer available in the U.S. marketplace.

It remains the premier anti-anaerobic drug and is preferred for pyogenic abscesses in combination therapy, it also treats amebic liver infections.

Broad spectrum agent related to minocycline, with excellent gram-positive (including MRSA and VRE), Gram-negative (except Pseudomonas aeruginosa and Proteus mirabilis) and anaerobic activity, approved for complicated intraabdominal infections.

If untreated, the mortality rate associated with pyogenic hepatic abscess approaches 100%.

With treatment, in some series, mortality is below 15%; the latter mortality depends on the underlying disease/comorbidities.

Recurrence is more frequent after simple percutaneous aspiration without placement of a temporary drain or in patients whose drains are removed too early.

Hepatic abscesses are frequently polymicrobial.

Single/multiple lesions occur in approximately a 1:1 ratio, with the majority in the right lobe (especially when solitary); cryptogenic abscesses are generally solitary.

Abscesses are frequently associated with chronic medical conditions (e.g., diabetes), hematologic disease (e.g., leukemia), and chronic granulomatous disease (Staphylococcus aureus).

Chronic disseminated candidiasis (CDC, a.k.a. hepatosplenic candidiasis) occurs in immunosuppressed patients, e.g., bone marrow transplant recipients.

Pathogen-Specific Therapy Pathogen-Specific Therapy Basis for recommendation Basis for recommendation

Author opinion
Comment: Recommendations in this module are based on literature, given the lack of robust RCT data and guideline statements.

Siu LK, Yeh KM, Lin JC, et al. Klebsiella pneumoniae liver abscess: a new invasive syndrome. Lancet Infect Dis. 2012;12(11):881-7. [PMID:23099082]
Comment:
Provides an overview of clinical features and management of hepatic abscesses caused by Klebsiella. They may evolve to include metastatic foci from bacteremias such as as meningitis, endophthalmitis, and necrotizing fasciitis.

Citation

Smith, Scott M, and Christopher F Carpenter. "Hepatic Abscess." Johns Hopkins ABX Guide, The Johns Hopkins University, 2022. Johns Hopkins Guides, www.hopkinsguides.com/hopkins/view/Johns_Hopkins_ABX_Guide/540259/all/Hepatic_Abscess.

Smith SM, Carpenter CF. Hepatic Abscess. Johns Hopkins ABX Guide. The Johns Hopkins University; 2022. https://www.hopkinsguides.com/hopkins/view/Johns_Hopkins_ABX_Guide/540259/all/Hepatic_Abscess. Accessed October 28, 2023.

Smith, S. M., & Carpenter, C. F. (2022). Hepatic Abscess. In Johns Hopkins ABX Guide. The Johns Hopkins University. https://www.hopkinsguides.com/hopkins/view/Johns_Hopkins_ABX_Guide/540259/all/Hepatic_Abscess

Smith SM, Carpenter CF. Hepatic Abscess [Internet]. In: Johns Hopkins ABX Guide. The Johns Hopkins University; 2022. [cited 2023 October 28]. Available from: https://www.hopkinsguides.com/hopkins/view/Johns_Hopkins_ABX_Guide/540259/all/Hepatic_Abscess.

* Article titles in AMA citation format should be in sentence-case

TY - ELEC T1 - Hepatic Abscess ID - 540259 A1 - Smith,Scott,M.D. AU - Carpenter,Christopher,M.D. Y1 - 2022/11/09/ BT - Johns Hopkins ABX Guide UR - https://www.hopkinsguides.com/hopkins/view/Johns_Hopkins_ABX_Guide/540259/all/Hepatic_Abscess PB - The Johns Hopkins University DB - Johns Hopkins Guides DP - Unbound Medicine ER -

# data[].attributes.attachment_link.title
Hepatic Abscess | Johns Hopkins ABX Guide

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Hepatic Abscess answers are found in the Johns Hopkins ABX Guide powered by Unbound Medicine. Available for iPhone, iPad, Android, and Web.

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Fusobacterial liver abscess: a case report and review of the literature

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Abstract

Background

Fusobacteriae are facultative anaerobic gram-negative bacilli which cause a range of invasive infections, amongst which pyogenic liver abscesses are rare. We describe a case of Fusobacterium nucleatum liver abscess and review the relevant literature.

Case presentation

A 51-year-old lady presented with a 4-day history of abdominal pain, diarrhoea, fever, rigors, and lethargy. Imaging revealed an abscess which was drained. Cultures of the blood and abscess aspirate grew Fusobacterium nucleatum and Prevotella pleuritidis respectively. She achieved full recovery following treatment.

A MEDLINE search was undertaken using free-text and Medical Subject Headings (MeSH), keywords "Fusobacterium" and "Liver abscess". Non-English language reports and cases without confirmed growth of Fusobacterium species were excluded. Additional cases were identified by surveying the references of each report and by using the same keywords in a web-based search.

Forty-eight cases were identified, 41 in men. The median age was 42.5, with an interquartile range of 33. F. nucleatum and F. necrophorum were in involved in 22 cases each, and 4 cases were not further speciated. Among cases of F. nucleatum liver abscess, nine were attributed to periodontal disease, four to lower gastrointestinal tract disease, one to Lemierre's Syndrome, and eight were considered cryptogenic. All patients treated made a full recovery. Antimicrobial treatment duration ranged from 2 weeks to 6 months with a median of 6 weeks.

Conclusion

Fusobacterium nucleatum is an uncommon cause of liver abscess generally associated with good clinical outcomes with contemporary medical and surgical care.

Keywords: Fusobacterium, Liver abscess, Review, Case reports, Lemierre's syndrome, Periodontal diseases

Background

Fusobacteriae are arguably unique amongst non-spore forming anaerobes in their ability to cause severe, clinically distinct, mono-microbial infections in a range of organs, often with severe sequelae as originally described by Lemierre and others in the first half of the twentieth century [ 1]. Fusobacterial infections can affect the head and neck, the lung and pleura, the gastro-intestinal organs, and the female genital tract [ 2]. Despite their ability to cause severe infections, fusobacterium species are uncommonly identified as pathogens in clinical practice, accounting for less than 1% of anaerobic bacteremias. Regional population-based studies have described the incidence of Fusobacterial bacteraemia to be around 0.55 per 100,000 people per year [ 3, 4], and that of clinically significant infections to be 0.99 per 100,000 people per year [ 2]. Whilst the clinical presentations associated with fusobacterial infections are well defined, little is known about the clinical progress and outcomes of specific syndromes [ 1, 5, 6]. Fusobacteriae are a particularly uncommon cause of pyogenic liver abscesses. Therefore, our objective is to describe a case of this condition and to summarise the presentation and outcomes of Fusobacterial liver abscesses through a review of the relevant literature.

Case presentation

A 51-year-old previously fit and well woman who recently returned from Samoa presented with a four-day history of watery non-bloody diarrhoea, associated with generalised abdominal pain, fevers, chills, and lethargy. Family members reported similar symptoms of milder severity. On admission, she was febrile with a temperature of 38 °C, with otherwise unremarkable vital signs. Examination of the abdomen found a palpable mass in the right upper quadrant. There were no signs of periodontal disease on inspection of the oral cavity. Laboratory tests showed a white cell count of 26.7 × 10E9/L, deranged liver enzymes (alanine transaminase 263 U/L, aspartate transaminase 177 U/L, bilirubin 15 mg/L), and a C-reactive protein of 407 mg/L. A Computed Tomography (CT) scan of the abdomen with contrast revealed a 90 × 92 × 93 mm mixed density lesion in segment II and III of the liver The lesion was percutaneously drained under ultrasound guidance. Cultures of the aspirated abscess fluid and blood both grew anaerobic gram-negative bacilli. Following abscess drainage and treatment with ceftriaxone and metronidazole, the patient continued to experience fevers and diarrhoea and her inflammatory markers did not improve. A follow-up ultrasound scan of the liver revealed an emerging focal abscess in segment IV-b of the liver. The initial CT scan was then retrospectively reviewed to reveal subtle heterogeneous changes in this segment; however, no demarcated fluid collection was present at the time. The two abscesses were not contiguous with but in close proximity to each other. This abscess was also percutaneously drained. Samples from the blood culture were further identified as Fusobacterium nucleatum via Biomerieux Vitek (Knowledge database version 2.0) MALDI-TOF (Matrix assisted Laser Desorption/Ionisation - Time of Flight) mass spectrometry with a confidence of 99.9%. Cultures of the initial aspirate were not identifiable using MALDI-TOF and were referred to a quaternary level laboratory in Auckland and later identified as Prevotella pleuritidis through 16 s ribosomal Ribonucleic Acid identification. Both specimens underwent susceptibility testing using Clinical Laboratory Standards Institute (CLSI) - recommended media and breakpoint determination using MIC gradient strips. The Prevotella pleuritidis was tested on Brucella agar with sheep blood, haemin, and vitamin K, while the F. nucleatum required Brain Heart Infusion agar to achieve satisfactory growth.

Given the growth of a second organism common to the periodontal flora and in the absence of symptoms, signs, or imaging evidence of bowel pathology, a periodontal, rather than a gastrointestinal, source was considered more likely and no further evaluation of the large bowel was undertaken.

Treatment was changed on day nine to a two-week course of IV ertapenem, prior to susceptibilities being known, followed by four further weeks of oral amoxicillin-clavulanate. The patient recovered fully.

Although Fusobacterium was only grown in the blood culture and not in the aspirate culture, we were confident in treating this case as a Fusobacterial pyogenic liver abscess. The aspirate sample was collected afterhours and was not processed until 7 hours later. This delay could have significantly affected our ability to identify this anaerobic organism using standard culture methods, especially in the setting of antimicrobial therapy.

Review of literature

We conducted a literature review of cases of liver abscess associated with Fusobacterium species.

Methods

A MEDLINE Medical Subject Headings (MeSH®) and a free text search were conducted using the keywords "Fusobacterium" AND "liver abscess". The search was further limited to case reports in the English language and on human subjects. Cases in which a liver abscess was demonstrated by appropriate imaging techniques or direct visualization, and was associated with a positive culture (blood, abscess fluid, or tissue) for a Fusobacterium species were included. Additional studies were included through reviewing the references of the selected case reports. One additional case was identified when the same keywords were entered into a web-based search engine (Google TM, San Francisco, CA).

Results

Forty-eight cases were identified using the above search strategy. Table ​Table1 1 summarises them. Forty-one cases involved males, and seven involved females. The age of the patients ranged from 17 to 78 years with a median of 42.5 years and an interquartile range of 33 years. Twenty-two cases identifie d F. nucleatum and 22 cases identified F. necrophorum as the aetiological pathogen. In another five cases, the microbe was not identified past Fusobacterium spp. 29 of 48 cases involved multiple abscesses as opposed to a single abscess. The most common presumed sources were the periodontal flora (12 cases) and Lemierre's Syndrome (10 cases), followed by the lower GI tract (six cases), the upper GI tract (four cases), and the cervix (one case). Fifteen cases were considered cryptogenic.

Table 1

Age

Sex

Organism (specimen cultured)

Treatment

Single or multiple abscess(es)

Presumed source

1 [ 35]

21

M

F. nucleatum
(abscess aspirate)

- Drainage of the two largest abscesses (R).
- Piperacillin/tazobactam (UTP)
- Ertapenem (8 weeks)

Multiple

Oropharynx (PF)

2 [ 36]

48

M

F. nucleatum
(abscess aspirate)

- Drainage of abscess (R)
- Ceftriaxone and metronidazole (3 days)
- IV penicillin and metronidazole (10 weeks)

Multiple

Oropharynx (PF)

7 [ 41]

59

F

F. nucleatum, Treponema denticola, Prevotella intermedia, Porphyromonas gingivalis, Bacteroides vulgatus (tissue culture and abscess apsirate culture)

- None

Multiple

Oropharynx (PF)

14 [ 47]

54

F

F. nucleatum (abscess aspirate)
S. viridans (abscess aspirate)
Actinomyces odontolyticus (abscess aspirate)

- Drainage of hepatic abscess (R)
- Extraction of 11 teeth
- IV antibiotics (agent and period of treatment unsepciified)

Multiple

Oropharynx (PF)

18 [ 50]

24

M

Actinomyces israeli (abscess aspirate)
F. nucleatum (Abscess aspirate)

- Open drainage of abscess (S)
- Penicillin G 20 million units (4 weeks)
- Oral penicillin (6 months)

Single

Unidentified

20 [ 52]

47

M

F. nucleatum (tissue culture)
Peptostreptococcus (tissue culture)

Multiple

Unidentified

21 [ 53]

44

F

F. nucleatum
(blood culture)

Single

Unidentified

23 [ 55]

28

M

F. necrophorum
(blood culture)

- Ceftriaxone (6 days)
- Meropenem (14 days)

Single

Oropharynx (PLS)

27 [ 58]

25

M

F. necrophorum
(blood culture)

- Piperacillin/tazobactam (UTP)
- IV penicillin (6 weeks)

Single

Oropharynx (PLS)

31 [ 62]

21

M

F. necrophorum (abscess drainage)
F. nucleatum (peritonsillar abscess)

- Drainage of the largest hepatic abscess (R)
- Piperacillin/tazobactam and metronidazole (6 weeks)

Multiple

Oropharynx (PLS)

32 [ 10]

25

M

F. necrophorum (abscess aspirate)
Prevotella spp. (blood culture and abscess aspirate)

- Drainage of abscess
- Removal of diseased teeth
- Oral amoxicillin/clavulanate (3 weeks)

SIngle

Oropharynx (PF)

37 [ 66]

44

M

F. necrophorum (abscess aspirate)
H. Parainfluenzae (abscess aspirate)

- Drainage of hepatic abscess (R)
- IV tetracycline (3 days)
- Co-trimoxazole (8 days)
- IV cefazolin + IV gentamicin (UTP)
- IV ceftriaxone (3 weeks)

Single

Unidentified

38 [ 67]

18

M

F. necrophorum (blood culture)

- Cefotaxime, vancomycin, and azithromycin. Then cefepime and metronidazole (unspecified chronology or time period)

Single

Oropharynx (PLS)

48 [ 76]

22

M

Fusobacterium Spp (blood cultures)

- Penicillin (31 days)

Multiple

Unidentified

Among the cases that identified F. nucleatum, the most common presumed source was the periodontal flora (nine out of 22 cases). Eight cases were cryptogenic. The presumed source was considered to be the lower GI tract in four cases, and Lemierre's syndrome in one case.

Treatment mostly consisted of abscess drainage and prolonged antimicrobial therapy. The duration of treatment was specified in 39 cases. Among them, the minimum duration was 2 weeks, and the maximum was 6 months, with a median of 6 weeks, and an interquartile range of 2 weeks. The duration was less than 4 weeks in five cases, between four to 8 weeks in 26 cases, and more than 8 weeks in eight case. Commonly used antibiotics include beta-lactams (in combination with metronidazole in some cases), carbapenems, metronidazole monotherapy, and less frequently fluoroquinolones.

Treatment outcomes were favourable with 47 of 48 cases reporting complete recovery.

Discussion

Whilst the essential features of disease caused by Fusobacteriae have been recognised for over a century, presentations remain uncommon and widely distributed across medical specialties [ 1]. Thus the historical background, aetiopathogenesis, and likely clinical outcomes of fusobacterial disease are poorly understood by most clinicians. This report demonstrates the common features of fusobacterial liver abscess and by combining individual reports and case series provides insights into the associated spectrum of underlying illness.

Loeffler identified a thin, gram-negative rod present in necrotic tissue in calf diptheriae in 1884 [ 7]. The term 'necrobacillosis' was coined by Bang, who isolated the organism from diseased cattle and pigs [ 8]. Koch's postulates were satisfied accidentally when Schmorl and an assistant suffered pyogenic infection of their fingers whilst working with diseased rabbits, samples from both of which yielded Fusobacteriae [ 5]. Cases of de novo necrobacillosis were described in humans by the turn of the twentieth century. Lemierre gave his classic dissertation on anaerobic bacteremia in 1936, earning the right to an eponymous syndrome of tonsillar abscess progressing to internal jugular vein thrombosis, distant abscess formation, and overwhelming sepsis [ 9].

In the twentieth century it was axiomatic, based on very little evidence, that Fusobacteriae were part of the normal human oropharyngeal, gastro-intestinal (GI) tract and female genital tract flora. The apparent rarity of illness caused by these organisms reinforced the notion that they were opportunists, causing illness only when natural barriers to infection were compromised [ 1, 10, 11]. Contemporary studies have shed light on the true environmental niche and pathogenic potential of Fusobacteriae in general and Fusobacterium nucleatum specifically. Fusobacterium nucleatum is a major constituent of the gingival, oropharyngeal and together with F. necrophorum, the appendiceal flora. Neither organism is a component of the healthy colonic flora nor do they form a major component of the healthy vaginal micro-biome [ 1, 12, 13]. F. necrophorum was found to exist in the healthy oropharyngeal flora in only one polymerase chain reaction (PCR) based study reported and in none of the culture-based studies [ 1]. Gingivo-periodontitis, endodontic infection and suppurative appendicitis occur in the setting of clonal expansion and invasion of Fusobacteriae, and it has been postulated that adverse obstetric outcomes arise from haematogenous spread of F. nucleatum to placental tissue [ 14, 15]. Prevotella pleuritidis was identified in the case we described and the gingival/oropharyngeal flora were identified as co-pathogens in 18% of liver abscess caused by F. nucleatum in our review of the literature.

Indeed, our review of fusobacterial pyogenic liver abscesses showed a low prevalence of general risk factors for liver abscess including malignancy, dialysis treatment, and older age [ 4]. Most cases occurred in young or middle-aged, immunocompetent individuals with risk factors for haematogenous spread of Fusobacteriae such as periodontal disease and recent pharyngitis.

Attribution of the lower GI tract as a source of liver abscess was relatively uncommon and the grounds for doing so were often unclear. The utility of investigating for a presumed source is unknown at this point due to the lack of research assessing this particular question. Our findings support the contention that the majority of disseminated fusobacterial infections originate from the oral cavity even without symptoms of a dental disease. Dental X-Rays to identify possible dental abscesses and cavities or more sophisticated imaging modalities of the oral cavity and the sinuses may be of the most benefit, should clinicians choose to investigate the underlying sources of bacteremia in patients without localising symptoms [ 16].

Among cases where F. necrophorum were cultured, only three of the 23 liver abscesses were associated with a co-pathogen. None of these cases had clinical findings consistent with classic Lemierre syndrome. Whilst the environmental niche of F. necrophorum is less understood than that of F. nucleatum, it is among the most commonly identified cause of tonsillar abscess after Lancefield Group A beta-hemolytic streptococci [ 17, 18]. This potentially points to a more evolved role for F. necrophorum as a human pathogen.

We observed good outcomes with appropriate source control and antimicrobial therapy. The only case involving a fatality was a post-mortem diagnosis and treatment had not been initiated. There was significant variation between studies with regards to the choice and duration of antimicrobial therapy. Current evidence suggests the need for prolonged antimicrobial therapy for patients with liver abscess and risk factors for treatment failure. These include malignancy, older age, presence of septic shock at presentation, certain biochemical derangements (e.g. anaemia, azotaemia, and hyperbilirubinaemia), and an Acute Physiology and Chronic Health Evaluation (APACHE) II score of more than 15 [ 19- 21].

Routine prolonged broad-spectrum antimicrobial therapy may not be warranted in cases of fusobacterial liver abscess with a presumed oral or periodontal origin, especially in the setting of abscess drainage. Fusobacteriae remain highly susceptible to beta-lactams. Studies on susceptibility patterns have shown no increase in amoxicillin-resistant Fusobacteriae over the past decade [ 22- 24]. They are unlikely to be accompanied by highly resistant co-pathogens in polymicrobial infection of oral or periodontal origin. Metronidazole has been associated with good clinical responses in the treatment of fusobacterial and mixed anaerobic infections [ 25]. Where source control is achieved, and with the aid of reliable clinical biomarkers such as C-reactive protein, antimicrobial therapy may be shortened [ 26, 27]. Further research into shorter course therapy for highly sensitive organisms such as Fusobacteriae could better delineate optimal antimicrobial treatment duration for patients with liver abscesses.

The strengths of this review are that it employed an extensive search strategy to identify a greater number of cases than previous reviews on the same topic. Previous literature reviews of case reports have focused mainly on only one Fusobacteriae species ( F. necrophorum or F. nucleatum) [ 28, 29]. To our knowledge, this is the first review to include all Fusobacteriae spp., to demonstrate their homogeneity in clinical presentation, clinical findings, co-pathogens and outcomes.

Our study has several weaknesses. The main weakness is that in the case presented, Fusobacterium nucleatum was identified in the blood culture but not in the abscess aspirate. We remain confident in attributing F.nucleatum as a causative co-pathogen for a number of reasons. Firstly, delays in sample processing have been known to increase the difficulty in identifying anaerobes through conventional culture methods [ 30], especially in the setting of antimicrobial therapy, which was commenced in advance of abscess drainage. Studies using pyrosequencing of direct samples have shown that pyogenic abscesses are frequently polymicrobial, with the number of aetiologic agents identified significantly exceeding what is achieved using standard culture-based methods [ 30, 31]. Secondly, many population-based studies accept blood cultures as an appropriate standard in diagnosing causative organisms and in guiding antimicrobial treatment in pyogenic liver abscess [ 32]. Some cases included in our review identified Fusobacteriae by blood culture alone [ 33, 34]. Therefore, we have grounds to believe that F. nucleatum was indeed a causative agent.

In terms of other weaknesses, we reported only published observations; publications may have been biased towards those of specific interest to a journal's readership or those that were associated with good clinical outcomes. Cases in languages other than English were excluded. Attribution of underlying source was presumptive rather than definitive in a significant number of case series. Furthermore, there was minimal information on microbiologic methods. This may have led to an over-reporting of mono-microbial infection, for example, where culture-based methods lacked sensitivity or where growth of the anaerobic flora at low quantities was under-reported.

Conclusion

In this case report and review of the literature, we found that fusobacterial liver abscesses resulted in good outcomes with contemporary medical and surgical care.

Acknowledgments

We acknowledge the help of Chris Mansell and Sean Edward Munroe of Waikato Hospital Laboratory who provided us with details of the logistics and methods of microbiological sample processing, Marion Smith, at LabPlus Auckland, who performed the susceptibility testing and provided us with the information on the methods used to identify Prevotella pleuritidis, as well as Graham Mills and Rennie Qin for their feedback on the final manuscript.

Availability of data materials

Available from corresponding author on reasonable request.

Authors' contributions

DJ and PH conceived the study and developed the search strategy. DJ conducted the review of relevant articles, and produced the first draft of manuscript. LW was the primary clinician involved in the case and provided input into the case. PH provided significant input into editing the overall manuscript and developing the discussion. All authors read and approved the final manuscript.

Competing interests

The authors declare that they have no competing interests.

Consent for publication

Written consent for potentially identifying information being published as a case report obtained from patient during admission. Consent was also reconfirmed verbally prior to submission of written article for publication.

Ethics approval and consent to participate

Not applicable

Publisher's Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Abbreviations

BD

Twice daily

CLSI

Clinical Laboratory Standards Institute

CT

Computed tomography

DNA

Deoxyribonucleic acid

GI

Gastrointestinal

IV

Intravenous

L

Litre

LS

Lemierre's syndrome

mg

Milligrams

mm

Millimetre

PCR

Polymerase chain reaction

PF

Periodontal flora

R

Radiological drainage

S

Surgical drainage

U

Units

UTP

Unspecified time period

References

43. Cheung WY, Bellas J. Fusobacterium: elusive cause of life-threatening septic thromboembolism. Can Fam Physician. 2007;53:1451-1453. [[ PMC free article] [ PubMed] Google Scholar]

51. Ralph ED. Successful antimicrobial therapy of hepatic, intra-abdominal and intrapelvic abscesses. Can Med Assoc J. 1984;131:605-607. [[ PMC free article] [ PubMed] Google Scholar]

53. Wilson R, LeBlanc R, Hamour AA. Cryptogenic pyogenic liver abscess due to Fusobacterium nucleatum: A case report. BCMJ. 2016;56:130-134. [ Google Scholar]

56. Fatakhov E, Patel MK, Santha S, Koch CF. Fusobacterium necrophorum: a rare cause of hepatic abscess in an immunocompetent individual. BMJ Case Rep. 2013;2013. doi:10.1136/bcr-2013-200748. [ PMC free article] [ PubMed]

59. Shahani L, Khardori N. Fusobacterium necrophorum--beyond Lemierres syndrome. BMJ Case Rep. 2011;2011. doi:10.1136/bcr.07.2011.4527. [ PMC free article] [ PubMed]

73. Bytyci F, Khromenko E. Hepatic abscess caused by Fusobacterium necrophorum after a trip to the dentist. BMJ Case Rep. 2016;2016. doi:10.1136/bcr-2015-210235. [ PMC free article] [ PubMed]

Articles from BMC Infectious Diseases are provided here courtesy of BMC

# data[].attributes.attachment_link.title
Fusobacterial liver abscess: a case report and review of the literature

# data[].attributes.attachment_link.description
Fusobacteriae are facultative anaerobic gram-negative bacilli which cause a range of invasive infections, amongst which pyogenic liver abscesses are rare. We describe a case of Fusobacterium nucleatum liver abscess and review the relevant literature.A ...

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Recurrent pyogenic liver abscess as a presenting manifestation of colorectal cancer

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Recurrent pyogenic liver abscess as a presenting manifestation of colorectal cancer

# data[].attributes.attachment_link.description
Although an association between pyogenic liver abscess and colon cancer has been suggested, liver abscess as a presenting sign of occult colorectal cancer has rarely been reported [ 1, 2]. Destruction of the mucosal barrier by a colorectal neoplasm, followed by bacterial translocation into the portal venous system, might contribute to the formation of liver abscess [ 2].

# data[].attributes.attachment_caption
Pyogenic Liver Abscess Secondary to Sigmoid Diverticulitis: An Unusual Presentation

# data[].attributes.attachment_link.title
Pyogenic Liver Abscess Secondary to Sigmoid Diverticulitis: An Unusual Presentation

# data[].attributes.attachment_link.description
Abstract. Pyogenic liver abscesses, despite being a rare complication of diverticulitis and inflammatory bowel disease, are potentially serious life-threatening pathologies. Diverticular diseases can lead to disruption of the colonic mucosal barrier and can serve as a route for bacterial infection via the portal venous system.

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Sigmoid Colon Cancer Masked by Refractory Diverticulitis With Abscess

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Monitoring Editor: Alexander Muacevic and John R Adler

Abstract

Colorectal cancer (CRC) can occasionally coexist with diverticulitis, thereby complicating diagnosis and treatment. In cases of refractory diverticulitis, it is important to consider the possibility of malignancy and determine appropriate treatment strategies. An 85-year-old male presented with lower left abdominal pain; he was admitted for further examination and the treatment of suspected sigmoid diverticulitis. On examination, a firm mass was palpated in the lower left quadrant. Imaging revealed sigmoid diverticulitis, partial abscess formation, and the involvement of the small bowel and abdominal wall. Although malignancy was suspected, a definitive diagnosis was not made. Because of the refractory nature of the disease, early surgical intervention, sigmoid colectomy, partial small bowel resection, abdominal wall resection, and lymph node dissection, was performed in accordance with the malignancy protocol. Pathologic diagnosis revealed adenocarcinoma within the diverticulitis with negative resection margins, indicating curative surgery. The low preoperative diagnostic rate of CRC associated with diverticulitis highlights the need for vigilance. Refractory diverticulitis may indicate the presence of concealed malignancy requiring surgical intervention. In the management of refractory diverticulitis, it is important to consider the potential coexistence of cancer. Even if extensive investigations are performed and a definitive diagnosis remains elusive, surgery must be considered.

Keywords: case report, colon cancer, colorectal cancer, refractory, diverticulitis

Introduction

Colorectal cancer (CRC) is sporadically encountered along with diverticulitis. In Western countries, there is an increased risk of CRC in patients with diverticulitis [ 1]. Additionally, an increased risk of CRC has been demonstrated during short-term follow-up after diverticulitis treatment [ 2]. Therefore, colonoscopy is recommended at 6-8 weeks after diverticulitis treatment [ 3, 4].

However, the diagnosis of coexisting CRC at the onset of diverticulitis is challenging. Imaging studies often yield analogous findings for malignancy and diverticulitis, hindering their differentiation [ 5]. Thus, when diagnosing diverticulitis, there is a need to consider the potential coexistence of cancer and tailor treatment strategies accordingly.

We report the case of a patient in whom diverticulitis management was problematic and who had suspected concomitant CRC. The condition was completely resolved after prompt surgical intervention.

Case presentation

An 85-year-old male presented to a local clinic with lower left abdominal pain. Based on the suspicion of diverticulitis, oral antibiotic treatment was initiated. However, the patient's symptoms did not improve, and he was admitted to our hospital for further evaluation and treatment. The patient had a history of diabetes mellitus. On admission, a physical examination revealed a body temperature of 38.3℃ and a palpable, firm mass in the lower left abdomen. Laboratory tests revealed an elevated white blood cell count (13,500/μL) and C-reactive protein level (10.4 mg/dL). Tumor marker levels were within normal limits. Abdominal computed tomography showed multiple diverticula in the sigmoid colon with circumferential wall thickening, as well as contrast enhancement and increased density in the surrounding adipose tissue. The wall structure was intact, but an abscess with air was present adjacent to the small bowel and abdominal wall (Figure , ). A colonoscopy revealed a circumferential stricture in the sigmoid colon that could not be passed by the endoscope. No protruding lesion was observed on the mucosal surface. Biopsy results were not suggestive of malignancy. Barium enema examination revealed a 10 cm stricture without fistulae in the sigmoid colon.

Figure 1

Based on the above findings, the patient was diagnosed with sigmoid diverticulitis with abscess. Despite fasting and conservative treatment involving antibiotics, the inflammation recurred. Abdominal computed tomography showed no improvement in the diverticulitis, and conservative treatment was considered ineffective. A surgical approach was used, based on the possibility of CRC indicated by the palpable mass. During surgery, the sigmoid colon displayed adherence to a portion of the small bowel and abdominal wall. Sigmoid colectomy, partial small bowel resection, combined abdominal wall resection, and standard local lymph node dissection were performed in accordance with recommendations for the surgical treatment of CRC. The gross examination of the resected specimen revealed 10 cm circumferential wall thickening and sclerosis. The most constricted portion of the bowel exhibited significant bowing, which hindered the visualization of the mucosa, but no palpable tumor was apparent.

Histopathologic examination revealed that the most constricted portion of the sigmoid colon had overlapping and folded intestinal loops that had fused because of inflammation (Figure , ). Within this area, a 33 mm adenocarcinoma was identified. The predominant histologic type was moderately differentiated tubular adenocarcinoma. Invasion reached the resected abdominal wall, but the resection margins were negative. Cancer cells exhibited slight exposure to the mucosa; tumor cells were observed in a portion of the invaginated intestine and from the muscular layer to the submucosa of the folded and overlapping separate intestinal loops (Figure , ). Detached regenerated epithelium was present on the surface of the invaginated mucosa. Diverticula were observed in the vicinity of the tumor, suggesting that the invaginated mucosal structure had been formed by diverticulitis and the cancer had developed at this site. No lymph node metastasis or small bowel invasion was observed. The final diagnosis was sigmoid colon cancer with concomitant diverticulitis, stage IIC (T4bN0M0), according to the eighth Union for International Cancer Control (UICC) classification. The postoperative course was uneventful. Because of the patient's advanced age, no adjuvant chemotherapy was administered after surgery. No recurrence was observed at one year postoperatively.

Figure 2

Figure 3

Discussion

The one-year incidence of CRC in patients with diverticulitis is 1.9% [ 6], and diverticulitis is associated with an increased risk of CRC [ 1, 7- 9]. Diverticulitis and CRC occur predominantly in older adults; population aging is leading to an increasing frequency of cases involving both conditions [ 2, 6, 10]. The characteristics of CRC associated with diverticulitis include an increased rate of development in the sigmoid colon, diagnosis related to manifestations such as perforation or significant stricture, and a significant proportion of cases classified as T3 or higher according to the eighth UICC classification [ 11]. Therefore, it is important to consider the potential coexistence of CRC when diagnosing sigmoid diverticulitis in an older patient.

Reports of CRC arising from diverticular mucosa are scarce, presumably because of the difficulty in confirming colonic diverticular mucosa-related carcinogenesis based on pathologic findings. CRC arising within diverticula tends to be more advanced because the lack of a muscular layer facilitates serosal penetration [ 12]. Mechanistic analysis suggests that chronic inflammation from diverticulitis contributes to cancer development [ 12, 13]. In the present case, multiple diverticula surrounded the malignant lesion, which formed at a site covered by a stricture and diverticulitis-related abscess. Diffuse infiltrative-type CRC was also present, which is atypical. Similar to inflammatory bowel disease-associated cancer, diverticulitis as a chronic inflammatory condition may have influenced cancer development and progression in the present case. The pathologic findings revealed cancer originating from the invaginated mucosa, with cancer cells present in the submucosa of a distinct bowel loop. Based on this evidence, we suspected that CRC had originated from the diverticular mucosa in this patient.

The preoperative diagnostic rate of CRC associated with diverticulitis is strikingly low, at 37% [ 11]. This low rate is because tumor cells predominantly infiltrate the submucosal layer, proliferate diffusely, and have limited exposure to the mucosal surface. Additionally, diverticulitis causes luminal narrowing related to medial muscular layer thickening, fibrosis, and mucosal overgrowth, hindering satisfactory assessment by endoscopy. On imaging, the intestinal wall structure appears to be preserved in diverticulitis, whereas it typically deteriorates in cancer [ 14, 15]. However, in the present case, the presence of luminal stenosis, the absence of tumor cells on the mucosal surface (determined by pathologic examination), and the observation of circumferential wall thickening with preserved layer structure (determined by computed tomography) made preoperative diagnosis challenging, despite the suspicion of concurrent cancer.

In cases where diverticulitis does not improve with conservative treatment, concealed cancer is a possibility. Several predictive factors for diverticulitis have been reported [ 16]; however, the presence or absence of concomitant cancer is a critical consideration. When diverticulitis and CRC coexist, the resulting protracted diverticulitis may cause the cancer to be missed. This presumably occurs because inflammation persists in areas containing cancer cells, where mucosal regeneration is impeded. In the present case, the pathologic findings supported the hypothesis that inflammation was prolonged by the cancer-mediated inhibition of mucosal regeneration, as demonstrated by the presence of detached regenerative mucosa in the region containing cancer cells.

Interval surgery is considered beneficial in the management of diverticulitis [ 17]. However, in cases of refractory diverticulitis, it is important to consider the possibility of concurrent cancer. In the present case, curative resection was achieved in accordance with the recommendations for CRC surgery. If extensive investigations are performed but no definitive diagnosis is made, surgical intervention must be considered.

Conclusions

The diagnosis and treatment of colorectal cancer associated with diverticulitis are complex and challenging. In refractory diverticulitis with abscess, it is important to consider the possibility of concealed malignancy. However, preoperative diagnosis is typically difficult; thus, it is important to suspect cancer in older patients with diverticulitis and select treatment strategies accordingly.

Acknowledgments

The authors would like to thank Textcheck (www.textcheck.com) for English language editing.

Notes

The authors have declared that no competing interests exist.

Human Ethics

Consent was obtained or waived by all participants in this study

Articles from Cureus are provided here courtesy of Cureus Inc.

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Sigmoid Colon Cancer Masked by Refractory Diverticulitis With Abscess

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Colorectal cancer (CRC) can occasionally coexist with diverticulitis, thereby complicating diagnosis and treatment. In cases of refractory diverticulitis, it is important to consider the possibility of malignancy and determine appropriate treatment strategies. ...