Concurrent fusobacterial pyogenic liver abscess and empyema

Abstract

We present a very rare case of concurrent empyema and liver abscess caused by Fusobacterium. Our patient presented with 3-month history of subtle abdominal discomfort and cough leading to eventually presenting with marked chest pain, dyspnoea and septic shock. CT revealed a liver abscess and large right-sided pleural effusion. Drainage of the pleural effusion yielded gross pus with the growth of Fusobacterium varium, while drainage of the liver abscess yielded Fusobacterium nucleatum. The patient responded to drainage and antibiotic therapy with resolution of symptoms and decrease in the size of empyema and abscess on follow-up imaging. We also include a review if literature of related fusobacterial infections.

Background

Fusobacterium is a Gram-negative bacillary anaerobic bacterium, many members of the Fusobacterium species are a part of the oral flora.¹ It has been associated with different infections including periodontal infections, tonsillitis, tonsillar abscess, Lemierre syndrome (thrombophlebitis of the jugular vein), aspiration pneumonia, soft tissue infections, empyema and liver abscess.^{1 2} Fusobacteria leading to monomicrobial pyogenic liver abscess (PLA) is uncommon specially in immunocompetent host.³ Fusobacterium was reported in cases of pneumonia, lung abscess but it is an uncommon aetiology of monomicrobial empyema. We hereby report a case of concurrent fusobacterial PLA and empyema in an immunocompetent host presenting with an indolent course eventually leading to septic shock. Fusobacterium nucleatum was the only isolated organism from the liver abscess and Fusobacterium varium was the only isolated organism from the empyema. We also include a review of literature with regard to F. nucleatum liver abscess, empyema, concurrent empyema and liver abscess in addition to F. varium empyema.

Case presentation

A 54-year-old male presented with 1-day history of severe sharp pleuritic, right-sided chest pain that woke him up from sleep. Three months prior, he presented to an outside hospital with a weeklong episode of dyspnoea, subjective fevers, right upper quadrant pain and intermittent night sweats. His evaluation revealed a soft abdomen, leukocytosis, unremarkable abdominal radiograph and changes suggestive of left lung base atelectasis on chest radiography. He was treated for left side pneumonia. Despite treatment, he had persistent cough for which he received two courses of doxycycline and a 5-day course of prednisone. He admitted to 35 pounds weight loss during those 3 months. He underwent a screening colonoscopy 10 days prior to presentation, showing two polyps consistent with tubular adenomas on pathology. Past medical history is significant for an all-terrain vehicle accident with disruption of pubic symphysis for which he underwent open reduction and internal fixation complicated by osteomyelitis requiring surgical intervention and antibiotic treatment 3 years prior to the current presentation. He otherwise had no other medical illness. He had no history of smoking, recreational drug use or excessive alcohol intake. No history of travel. He is a farmer with cattle exposure.

On examination, he was tachycardic with a heart rate of 148 beats per minute, febrile (102.8 F), had a blood pressure of 111/90 mm Hg and was hypoxic with oxygen saturation of 89% on room air. There were decreased breath sounds over the right side of the chest.

Investigations

ECG revealed sinus tachycardia with no ischaemic changes. Laboratory testing revealed the following: white cell count of 30.2×10⁹/L, haemoglobin of 10.3 gm/dL, platelet count >one million/dL, aspartate aminotransferase of 60 (10–40 IU/L), alanine aminotransferase of 87 (7–56 IU/L), alkaline phosphatase of 229 (44–147 IU/L) and total bilirubin of 0.6 (0.1–1.2 mg/dL). Lactic acid was at 6.3 (0.4–2 mg/dL). Chest X-ray revealed large right-sided pleural effusion (figure 1). CT of the chest showed large right-sided pleural effusion (figure 2) and CT of the abdomen and pelvis showed a 9.3×14.8×13.7 cm macrolobulated hypodense lesion in the liver suggestive of liver abscess (figure 3).

Figure 1.

Chest X-ray showing large right-sided pleural effusion.

Figure 2.

CT of the chest showing large right-sided pleural effusion.

Figure 3.

CT of the abdomen showing macrolobulated hypodense lesion in the liver suggestive of abscess.

Blood cultures were obtained before initiation of antibiotics, they eventually were reported to be negative.

Pleural fluid culture following thoracentesis (as follows under the treatment section) grew F. varium, whereas culture of samples from the liver abscess grew F. nucleatum. Mycobacterial, fungal and viral cultures of the liver abscess samples showed no growth. Serologic testing for Entamoeba histolytica, hepatitis A, B and C, in addition to HIV were negative.

Differential diagnosis

The differential diagnosis that we considered in our patient centred around either infectious or malignant aetiology. The fact that he was symptomatic for 3 months caused us to consider malignancy as a possibility. Malignancy could have led to this picture in one of two ways. Malignant liver lesions with intrathoracic extension and malignant effusion, or malignant hepatic disease leading to liver failure with resulting hydrothorax. These possibilities were considered, but drainage of both the pleural fluid and the liver lesion yielded purulent material making this less likely. Also, pathological examination of the liver was negative for malignancy.

Infectious aetiology includes multiple agents with bacteria being on the top of the differential while Mycobacterium tuberculosis (TB) and amoebic liver abscess with empyema being in the differential. The fact that the patient had no travel or recent exposure to either amoeba or TB made these less likely. Also, recent colonoscopy did not show any evidence of amoebic dysentery/colitis. Finally, culture of the empyema and the abscess drainage grew Fusobacteria with negative cultures for TB and negative serology for amoeba; hence, the diagnosis of fusobacterial PLA with concomitant empyema was made.

Treatment

He received normal saline boluses, blood cultures were collected and he was started on piperacillin/tazobactam. An attempt for thoracentesis resulted in 20cc of pus. The procedure was aborted and a chest tube was placed draining 3 L of grey/brown, foul smelling purulent fluid. The patient subsequently became hypotensive with systolic blood pressure in the 80 s, for which he received aggressive fluid resuscitation, started on norepinephrine drip, and the antibiotic therapy was broadened to meropenem and vancomycin. Patient subsequently underwent percutaneous drainage of the hepatic abscess with a 10 French pigtail drain. On the fourth day of hospitalisation, samples from the liver abscess grew F. nucleatum, while the empyema fluid grew F. varium. Meropenem and vancomycin were discontinued and the patient was started on oral metronidazole given culture results. Fever and leukocytosis resolved in response to treatment. The chest tube was removed on day 7 of hospitalisation and the patient was discharged to complete 6 weeks of metronidazole. The pigtail drain was removed 2 weeks after discharge.

Outcome and follow-up

The patient responded to treatment with resolution of fever, abdominal pain and respiratory complaints. He was also able to regain some of the lost weight, repeat CT of the chest 3 weeks post-discharge showed marked decrease in the size of the empyema and the liver abscess (figure 4).

Figure 4.

CT showing significant decrease in size of empyema and liver abscess post-treatment (bottom image) compared with pre-treatment (top image). To note the presence of the drain and gas in the liver abscess (red arrows).

Discussion

Liver abscess

Hepatic abscess is the most common intra-abdominal visceral abscess.⁴ Two main types of liver abscess exist: PLA is the most common type in the USA and amoebic liver abscess is the more prevalent type in developing countries. Pathogenesis is thought to involve spread through the portal circulation from related organs, direct spread from the biliary tract infections or hematogenous seeding from an extra-portal infectious source with dental infections being one of the recognised sources.⁵ A large retrospective study of PLA looking into 18 000 patients reported an incidence of 3.6 cases per 100 000 inhabitants in the USA.⁶ PLA is commonly polymicrobial in nature rather than monomicrobial.⁷ The leading organisms are Streptococcus species (29.5%) and Escherichia coli (18.1%).⁶ Antibiotic therapy and percutaneous drainage are the mainstay of treatment. Surgical drainage is limited to lack of response to percutaneous drainage or failure of drainage due to thick viscus purulent material frequently obstructing drainage catheter.

In our review of literature, we identified only 12 cases of F. nucleatum monomicrobial PLA in immunocompetent cancer-free hosts in the English literature (table 1).3 5 8–17 Only one of those patients was diabetic. Four patients (33.3%) had a single abscess with the remainder of cases having multiple hepatic abscess. Dental disease or instrumentation was the suspected source in six patients (50%), peritonsillar abscess was the source in a single case, diverticular disease in two patients and no clear source identified in three patients (25%). Only one patient had concurrent empyema but there was no mention of pleural fluid culture results.⁸

Table 1.

Cases of Fusobacterium nucleatum pyogenic liver abscess

	Age/ sex*	No.†	DM	Other concurrent infection	Imaging	Treatment	Empyema?
Hammami et al 5 2018	63/M	M	No	Periapical dental abscess‡	US, CT and MRI	Percutaneous drainage Tooth extraction Unspecified antibiotic treatment	No
Karantanos et al 9 2017	43/M	M	No	None identified	US, CT and MRI	Percutaneous drainage Intravenous antibiotics × 6 weeks then Oral antibiotics × 3 months	No
Wijarnpreecha et al 10 2016	60/M	S	No	Diverticulitis‡	US and CT	Percutaneous drainage Intravenous antibiotics × 5 days then Oral antibiotics × 4 weeks	No
Nagpal et al 11 2015	69/F	S	Yes	Periodontitis‡ Bacteraemia	US and CT	Percutaneous drainage Teeth extractions Intravenous antibiotics × 2 weeks then Oral antibiotics × 4 weeks	No
Ahmed et al 8 2015	21/M	M	No	Empyema Two abdominal abscesses One pelvic abscess. Dental cleaning‡	CT	Percutaneous drainage Tube thoracostomy Pleural decortication Intravenous antibiotics × 9 weeks	Yes
Dahya et al 12 2014	48/M	S	No	Periodontitis‡ Endocarditis Brain abscesses	CT	Percutaneous drainage Intravenous antibiotics × 10 weeks	No
Kearney et al 13 2015	23/M	M	No	Myopericarditis Bacteraemia	CT	Percutaneous drainage Intravenous antibiotics × 6 weeks	No
Schattner et al 14 2014	58/M	M	No	Diverticular abscess‡ Pylephlebitis	CT	Percutaneous drainage of liver abscess Surgical drainage of diverticular abscess with colostomy creation Intravenous antibiotics × 6 weeks Low molecular weight heparin	No
Rashidi et al 15 2012	48/M	M	No	None identified	US, CT and MRI	Percutaneous drainage Intravenous antibiotics × 2 weeks then Oral antibiotics × 4 weeks	No
David et al 16 2009	21/M	M	No	Peritonsillar abscess‡	CT	Percutaneous drainage Intravenous antibiotics then oral antibiotics for total of 6 weeks	No
Kajiya et al 3 2008	59/M	S	No	Dental carries‡ Bacteraemia	US and CT	Percutaneous drainage Intravenous antibiotics × 4 days then Oral antibiotics × 4 weeks	No
Crippin et al 17 1992	69/M	M	No	Periapical dental abscess‡	CT	Percutaneous drainage and unspecified antibiotic treatment	No

*Age in years.

†Number of hepatic abscess. M indicates multiple while S indicates single.

‡Suspected primary source of the infection.

DM, diabetes mellitus; F, female; M, male; US, ultrasonography.

Empyema

Empyema is defined as the presence of frank pus or documented presence of bacteria in pleural effusion. This can be unveiled using gram stain, culture or nucleic acid detection techniques.¹⁸ Around 85 000 cases of empyema are diagnosed in the USA every year.¹⁹ Empyema is associated with high mortality, estimated to be around 15%–20%.^{18 20} Classically, it is thought of bacterial empyema to be an extension of parenchymal lung infection with the bacteria gaining access to the visceral pleura, recent studies showing difference in bacterial causative agents between pneumonia and empyema led to challenging this concept.^{18 20–22} In addition to parapneumonic, empyema can be a stand-alone condition, as in trauma with infected hemothorax, postsurgical with introduction of bacteria into the pleural space, hematogenous spread or even direct spread from contagious infections like PLA.^{20 23} Data from the MIST1 trial which enrolled 454 patients showed that the leading causative organism of community acquired empyema is the Streptococcus milleri group while it is Staphylococcus aureus in hospital-acquired empyema with pure anaerobes making up to 20% and 8% of the isolates, respectively. The most commonly isolated anaerobe is the fusobacterium group.²² Tube thoracostomy and antibiotics are the mainstay of treatment with video-assisted thoracoscopy (VATS) and open thoracotomy used in cases of extensive fibrin deposition and loculation.^{24 25} VATS is preferred over open thoracotomy unless evidence of organised fibrinous peel and trapped lung exists.²⁵ Penicillin-beta lactamase combinations or third-generation cephalosporin in addition to metronidazole is usually sufficient to treat community-acquired cases; however, coverage for S. aureus and Pseudomonas is recommended in hospital-acquired cases. Antibiotic coverage should be narrowed based on culture results, with considerations for continuous anaerobic coverage even with negative cultures.²⁵ A minimum duration of 2–4 weeks is usually sufficient. Switching from parenteral to oral antibiotics depends on clinical response.

In our review of literature, we identified only two cases of F. nucleatum monomicrobial empyema in immunocompetent hosts and only one case of monomicrobial F. varium which was in the context of a missed foreign body inhalation. These are listed in table 2.^26–28 None of these cases had concurrent liver abscess.

Table 2.

Cases of Fusobacterium nucleatum and Fusobacterium varium empyema

	Age/ sex*	Organism	Other concurrent infection	Imaging	Treatment	Liver abscess?
Waqas et al 26 2008	51/M	Fusobacterium nucleatum	Dental caries† Right side thigh abscess and femoral osteomyelitis	X-ray nd CT	Tube thoracostomy Incision and drainage of thigh abscess and osteomyelitis Intravenous antibiotics × 8 weeks then Oral antibiotics × 6 weeks	No
Hockensmith et al 27 1999	57/M	Fusobacterium nucleatum	None identified	X-ray and CT	Tube thoracostomy followed by pleural decortication. Antibiotics of unspecified route and duration	No
Boots et al 28 2007	62/M	Fusobacterium varium	Possible aspiration pneumonia Foreign body aspiration†	X-ray and CT	Catheter drainage. Thoracotomy. Rigid bronchoscopy for foreign body removal. Intravenous antibiotics × 4 weeks then Oral antibiotics × 2 weeks	No

*Age in years.

†Suspected primary source of the infection.

‡Number of hepatic abscess. M indicates multiple while S indicates single.

DM, diabetes mellitus; F, female; M, male.

Our patient represents an interesting case being the only reported case with concurrent F. nucleatum liver abscess and F. varium empyema. The fact that our patient initially presented with right upper quadrant abdominal pain and an indolent course of fevers, in addition to chest imaging showing clear right lung at the onset of his symptoms may suggest that he developed the liver abscess first. Unrecognition and undertreatment of the liver abscess with antibiotics tailored to a suspected pneumonia on the left side, have caused the infection to spread trans-diaphragmatic into the right plural space leading to empyema (figure 5). However, the growth of two different species of Fusobacteria would argue against direct spread. Colonoscopy 10 days prior to presentation showed no evidence of diverticulitis or diverticular abscess, abdominal imaging did not show any other visceral abscess or evidence of biliary disease. The history of periodontal infection 3 years prior to presentation makes dental disease a possible source for the infection.

Figure 5.

Both sagittal (left) and coronal (right) views of the abdominal CT showing possible communication between the hepatic abscess and the empyema (red arrows).

Learning points.

• While parapneumonic empyema commonly caused by aerobic bacteria tend to present acutely, it is important to remember that empyema caused by anaerobic organisms can present subacutely and insidiously with non-specific features such as anorexia, weight loss and fatigue.

• Anaerobic coverage is encouraged even in abscess of positive cultures in case of empyema.

• Liver abscess treatment is centred around drainage, needle aspiration is not sufficient and drain placement is necessary.

• Patients with liver abscess can develop empyema due to transdiaphragmatic extension, so one should have a low threshold for chest imaging in those patients.