Fusobacterium necrophorum sepsis after tonsillitis/pharyngitis

Abstract

Fusobacterium necrophorum is a rare infection most notable for causing Lemierre’s syndrome. This consists of a primary oropharyngeal infection and septic thrombophlebitis, and one or more metastatic focus. Prior to the widespread use of antibiotics, Lemierre’s syndrome commonly followed a rapidly progressing course, with a high mortality. We describe a case of a previously well 18-month-old boy who presented to the emergency department with a 3-week history of progressive, right-sided, painful neck swelling and systemic sepsis. He was initially treated conservatively with intravenous antibiotics, but ultimately required surgical drainage. Lemierre’s syndrome is a rare condition with increasing incidence which can have significant adverse outcomes including death. Early recognition and treatment are essential, but identifying Lemierre’s disease is challenging.

Background

Lemierre’s syndrome, a rare complication of Fusobacterium necrophorum pharyngitis, may follow a fulminant course, and can cause death. For this reason, it should be considered when previously well children with underlying oropharyngeal infection progressively deteriorate.

Case presentation

An 18-month-old boy, with no medical history, presented to the emergency department with a 3-week history of progressive right-sided, painful neck swelling associated with fever, coryzal symptoms, cough, irritability, lethargy, decreased oral intake, ‘pulling at’ right ear and, in the preceding 24 hours, rigors. He had attended his general practitioner on two occasions over the previous 2 weeks, initially diagnosed as suffering from a viral illness, and subsequently with mumps. The child’s vaccinations were up to date.

He was triaged as category 2 due to lethargy and irritability. Physical examination revealed tachycardia (179 beats/min), fever (39.7°C), oxygen saturations 99% and capillary refill time <2 s. The patient was noted to be listless and ‘off-form’. There was a firm mass in the right lateral neck, measuring 3 cm x 3 cm, with overlying erythema. Tonsils were enlarged and erythematous, with no visible exudate. Airway was patent.

No other source for infection was identified on history or examination.

Investigations

Laboratory tests performed included full blood count, urea and electrolytes, C-reactive protein (CRP), blood cultures, Epstein-Barr virus and cytomegalovirus serology (table 1).

Table 1.

Laboratory test results

WCC	26.1 (4.5–14.5×109/L)
Hb	10.5 (11.1–14.7 g/L)
MCV	75.7 (76–95 fL)
PLT	532 (170–450×109/L)
Neutrophil count	19.66 (1.5–8×109/L)
Sodium	135 (132–144 mmol/L)
Potassium	4.4 (3.5–5.1 mmol/L)
Urea	4.2 (2.8–8.4 mmol/L)
Creatinine	28 (14–31 μmol/L)
CRP	198 (0–5 mg/L)

CRP, C reactive protein; Hb, haemoglobin; MCV, mean corpuscular volume; PLT, platelet; WCC, white cell count.

An ultrasound study was undertaken, revealing two heterogeneous but predominantly hypoechoic soft-tissue masses, suggestive of necrotic lymphadenitis. No drainable collection was present.

Initial blood cultures were negative.

Differential diagnosis

Lymphadenitis.

Reactive lymphadenopathy.

Mumps.

Kawasaki disease.

Treatment

In consultation with ear nose throat (ENT) surgery, it was decided to trial conservative management. The patient was admitted under the care of the paediatric medical team for a course of intravenous flucloxacillin and clindamycin.

On day 4 of admission, vitals had normalised on intravenous antibiotics; however, there was clinical disimprovement in the neck swelling, with spread to the right mandibular and buccal area. In consultation with microbiology, gentamicin was added to the antibiotic regimen in order to achieve Gram-negative bacteria cover. ENT surgery advised further radiological evaluation of the mass and radiology-guided drainage.

On day 7 of admission, ultrasound showed a 7.4×4.5×5.1 cm solid-cystic phlegmonous abnormality with more pronounced internal fluid contents than on previous ultrasound, and with possible compression and/or thrombosis of the internal jugular vein. Proximal internal jugular and intracranial venous sinuses were visible and opacified. The distal internal jugular vein was patent. Computed tomography (CT)-guided aspiration of multiple separate fluid pockets was performed, with 5 mL of fluid aspirated and processed for microbiological culture and sensitivity. The patient’s leucocytosis remained at 26.8×10⁹/L, and CRP was 162.3 mg/L.

Following aspiration, the patient was changed from triple antibiotic therapy (flucloxacillin, clindamycin and gentamicin), to co-amoxiclav only, as per microbiology advice.

The patient underwent incision and drainage of the neck abscess under general anaesthesia on day 12 of admission due to an unresolved fluctuant right neck mass (figure 1). A sample of thick pus was collected and sent for culture and sensitivity, and the abscess was thoroughly washed out, and a drain inserted for 4 days.

Figure 1.

A CT coronal image at C4 vertebra with neck abscess.

Outcome and follow-up

Culture and susceptibility processed from samples collected during incision and drainage in theatre isolated F. necrophorum. On day 15, the patient was discharged on 1 week of oral co-amoxiclav. On subsequent outpatient follow-up, the patient has made an excellent recovery.

Discussion

F. necrophorum is a rare infection most notable for causing Lemierre’s syndrome. This consists of a primary oropharyngeal infection and evidence of septic thrombophlebitis, bacteraemia, clinical and/or radiological evidence of internal jugular vein thrombosis, associated with septic metastases. In the preantibiotic era, Lemierre’s syndrome often resulted in death.¹ A Medline search revealed 249 case reports of Lemierre’s syndrome; however, there are relatively few reported cases in paediatrics. It is estimated that the incidence of Lemierre’s syndrome is one per million people per year.² It is more common during the winter,³ and it typically occurs in previously healthy young adults.⁴ In one case series, the three most common sites for isolation of F. necrophorum and other Fusobacterium sp. were acute tonsillitis, peritonsillar abscess and acute otitis.⁵

Fusobacteriae are anaerobic Gram-negative rods, found in normal flora of the upper respiratory tract, the gut and the female genital tract. Fusobacteriae produce a lipopolysaccharide endotoxin which has a strong biological activity, in addition to a leucocidin and haemolysin, assisting in the breakdown of white blood cells and red blood cells.⁶ Leucocidin production has been correlated with the virulence of Fusobacteriae strains in animal studies.^{7 8} Haemagglutinin creation causes platelet aggregation which contributes to septic thrombus formation.⁹ Lemierre’s syndrome is most commonly caused by F. necrophorum and F. nucleatum, but other species of Fusobacterium can also be pathogenic.¹⁰

When pharyngitis due to Fusobacterium species occurs, infection may spread from the oropharynx to the internal jugular vein. This commonly occurs within a week of developing pharyngitis. Bacteraemia triggers platelet aggregation and thrombus formation once this invasion of the internal jugular vein has occurred.¹¹ Formation of thrombi and rapid bacterial spread facilitate metastatic septic embolisation. Metastatic infection most commonly affects the lungs. Pleural effusion, empyema, pulmonary infiltrates and lung abscess or numerous cavitating lung lesions may result.¹² Metastatic infection can also result in osteomyelitis, septic arthritis, pericarditis, liver abscesses and central nervous system infection.¹³

Lemierre’s syndrome consists of primary oropharyngeal infection, bacteraemia, internal jugular vein thrombosis and septic metastatic foci. Our patient had not yet progressed to include septic metastatic foci, and so did not meet full criteria for Lemierre’s syndrome.

Lemierre’s syndrome should be included in the differential diagnosis of healthy children who deteriorate in the context of a pharyngeal infection. Lateral neck swelling and tenderness (due to internal jugular thrombophlebitis) can resemble cervical lymphadenopathy. Some patients may have the ‘cord sign’, induration of internal jugular vein underneath the sternocleidomastoid muscle.¹⁴ However, it is a difficult diagnosis to make, and it usually is not diagnosed until Fusobacteriae are identified.¹⁵

Treatment of Fusobacterium species in Lemierre’s syndrome is intravenous high-dose penicillin and metronidazole. Clindamycin may be used alternatively in penicillin-allergic patients.¹⁶

Learning points.

• Lemierre’s syndrome should be included in the differential diagnosis of young, previously healthy patients who clinically deteriorate in the context of a pharyngeal infection.

• This patient attended his general practitioner 3 weeks prior to presentation to the emergency department (ED). This is a rare but severe and potentially fatal infection. Thus, early recognition is important to ensure similar cases have similar good outcomes.

• This case illustrates the importance of anaerobic blood cultures in the routine workup of a paediatric ED patients.