CASE SERIES

Tryna Tania
 Fusobacterium necrophorum
• anaerobic, non-spore forming pleomorphic Gram-
negative rod
• commensal of animal & human upper respiratory,
gastro-intestinal and female genital tract
• Cause a variety of human infections
– most commonly known main cause of postanginal
sepsis with suppurative thrombophlebitis of the
jugular vein (Lemièrre’s syndrome).
– Less well known : mastoiditis, intracranial
complication (meningitis, abcesses, and sinus
thrombosis)

Creemers-Schild D, Gronthoud F, Visser LG, et al. Fusobacterium necrophorum , an emerging pathogen of

otogenic and paranasal infections ? New Microbes New Infect. Epub ahead of print 2014. DOI:
10.1002/nmi2.39.
 Fusobacterium necrophorum
• A very virulent anaerobe  severe infection,
usually in children or young adults, originating
from pharyngotonsillitis, sometimes in
association with infectious mononucleosis.
• The most common anaerobe isolated from
peritonsillar abscesses in young adults and
may in fact be an etiological agent of
pharyngitis as often as Streptococcus
pyogenes.

Murray PR, Baron EJ, Forgensen JH, et al. Manual of Clinical Microbiology. 9th ed. Washington,
DC: ASM Press, 2007.
 Fusobacterium necrophorum
• Now encountered in serious infections less
often than in the pre-antimicrobial agent era,
because many clinicians may not be familiar.
• There are two subspecies:
– F. necrophorum subsp. necrophorum contains
lipase-positive, hemagglutinin- producing biovar A
– F. necrophorum subsp. funduliforme contains
lipase-negative, non-hemagglutinin-producing
biovar B.
Murray PR, Baron EJ, Forgensen JH, et al. Manual of Clinical Microbiology. 9th ed. Washington,
DC: ASM Press, 2007.
 Fusobacterium necrophorum

Umbonate colonies of Fusobacterium

necrophorum.

Tortora GJ, Funke BR, Case CL. Survey of the Microbial World. In: Funke BR, Case CL (eds) Microbiology an
introduction. Boston: Pearson, 2006, p. 324.
Murray PR, Baron EJ, Forgensen JH, et al. Manual of Clinical Microbiology. 9th ed. Washington,
DC: ASM Press, 2007.
Clinical and Laboratory Standards Institute. Performance Standards for Antimicrobial. 28th ed.
Philadelphia, 2018.
Clinical and Laboratory Standards Institute. Performance Standards for Antimicrobial. 28th ed.
Philadelphia, 2018.
CASE SERIES
 Case 1
• 9-year-old healthy girl
• presented to the emergency department:
– fever, headache and vomiting.
• Before admission:
– 2 weeks :
• the general practitioner  acute otitis media  co-
amoxiclav 7 days.
• fever persisted intermittently with otalgia
– 1 day :
• otorrhoea and vomiting
 On admission
• acutely ill, T = 39.6°C
• purulent discharge of the right ear, postauricular
tenderness and nuchal rigidity
• CSF: neutrophilic pleocytosis (2399/µL)
• Empiric antibiotic  ceftazidime.
• CT-scan brain :
– total obliteration of right mastoid, thrombosis of
sigmoid sinus and epidural empyema of 8 mm in the
posterior surface of the temporal bone.
– Urgent mastoidectomy was performed.
 Microbiology
• Gram staining:
– middle ear fluid : pleomorphic Gram-negative rods
 Haemophilus influenzae ?
– CSF : negative for bacteria
• Culture after 1 day : negative
• Antibiotic switched: meropenem
• Repeated CT-scan brain: massive cerebral
oedema with brainstem herniation
• Post-operatively:
– patient did not regain consciousness
– no pupillary light reflexes.
– patient died after 24 h after admission
 Post-mortem
• Autopsy of brain:
– cerebral oedema with herniation
– thrombosis of the sigmoid sinus and transverse
sinus
– purulent discharge mainly in the posterior cranial
fossa
• Cultures taken during life (middle ear and
mastoid) and autopsy:
– F. necrophorum identified by MALDI-TOF MS
 Case 2
• 9-year-old girl
• presented to the emergency department:
– suspicion of meningitis
• before admission:
– 9 days : otitis and otorrhea  topical treatment
(dexamethasone–framycetin–gramicidin eardrops)
– 5 days : high fever, headache, vomiting
– 2 days : neck pain and stiffness
 On admission
• acutely ill, but fully conscious.
• CSF: neutrophilic pleocytosis (1.280.000/µL).
• Empiric antibiotic: ceftazidime
• Gram stain CSF: pleomorphic Gram-negative
rods  switched to meropenem.
• CT-scan brain:
– mastoiditis with thrombosis of the sigmoid sinus
and a small empyema.
– urgent mastoidectomy was performed  ICU
 Follow up
• Fusobacterium necrophorum was cultured after
24 h from CSF, identified by MALDI-TOF MS 
Antibiotic was changed to penicillin.
• MRI : right-sided pontine infarct
• Recovered slowly and after 4 days  paediatric
ward
– penicillin was continued for 18 days
– switched to clindamycin for another 3 weeks
– tinzaparin was started for the sinus thrombosis and
continued for 3 months.
 Follow up
• 20 days of hospitalization  discharged
– at that moment she experienced urinary and
faecal incontinence and a hemiparesis of the left
leg.
• 6 months later:
• urinary and faecal incontinence had recovered
• still a very mild hemiparesis of the left leg.
 Case 3
• 2-year-old boy
• presented at the ENT:
– fever, otorrhoea and mastoiditis
• 6 weeks prior to admission:
– adenoidectomy and received tympanostomy
tubes in another hospital.
– Post-operatively: re-admitted with fever and otitis
 amoxicillin, co-amoxiclav and ceftazidime.
– 1 week after discharge his symptoms returned.
 On admission
• T = 39°C
• Since 2 days otorrhoea  mastoiditis was
suspected
• Co-amoxiclav and ceftazidime were given.
• CT-scan of mastoid:
– Bezold’s abscess with partial thrombosis of the
sigmoid sinus and the right vena jugularis.
– A cortical mastoidectomy was performed with
drainage of the abscess.
 Microbiology
• Gram stains of fluid from right ear and right
mastoid :
– slender, small Gram-negative rods.
• Cultures :
– Anaerobic cultures revealed F. necrophorum (shown
by using MALDI-TOF MS)
– No aerobic growth
– F. necrophorum was also cultured from the Bezold’s
abscess.
– Blood culture remained negative.
• Antibiotic treatment was changed to penicillin.
 Follow up
• The patient showed good clinical
improvement.
• After 2 weeks  discharged with clindamycin
for 1 month.
 Case 4
• 42-year-old man
• Suspicion:
– mastoiditis and meningitis was transferred from
another hospital to the intensive care unit
• History:
– Right ear pain and a sore throat, started a few days
before his first admission.
• 1 day before admission:
– an altered mental status
– Lateralization
– lowered level of consciousness.
 On admission
• febrile with tachycardia
• a lowered level of consciousness
• left muscle weakness
• right ear discharge, possibly liquorrhoea
• CT-scan of brain:
– otitis and mastoiditis with total obliteration of the right mastoid
– subdural empyema
– two intraparenchymal abscesses in the right frontal and
temporal lobe
– a midline shift to the left
• amoxicillin, ceftriaxone and metronidazole were
administered
 Microbiology
• Cultures of right middle ear:
– F. necrophorum (identified by Vitek 2)
• Amoxicillin was discontinued.
• Blood cultures remained negative.
 Follow up
• A hemicraniectomy was performed to drain the
subdural empyema.
– a loss of sensitivity of his right ear and temporal skin
– conductive hearing loss.
• 14 days post-operation
– MRI scan of brain:
• fronto-temporal abscess on the right side
• increase in subdural effusion on the left side and midline
shift to the right.
• Underwent surgery  antibiotic therapy was
changed to meropenem and vancomycin.
 Follow up
• The patient improved.
• After 10 days:
– vancomycin was stopped
– transferred back to the other hospital in good
clinical condition with meropenem.
– After 8 days the patient was discharged.
• Antibiotic therapy was continued for 3 months
according to the decision of the clinician.
• He experienced permanent hearing loss of the right ear.
 Case 5
• 14-year-old boy
• admitted to neurosurgical ward:
– ethmoiditis and meningeal irritation
• History:
– several days headache
– fever 38.5°C
– a swollen left eye
– vomiting
– malaise
– dizziness
 On admission
• T = 39°C
• meningeal irritation
• a red pharynx
• a swollen left eyelid which he was unable to
open and a red left conjunctiva.
• MRI scan:
– abscess in paranasal sinus with obliteration of the
left orbita and intracerebral frontal involvement
with dural enhancement.
 Microbiology
• Culture:
– A blood culture
– a nasal swab
• Empiric antibiotic  ceftriaxone and metronidazole.
• Next day:
• anaerobic blood culture bottle  positive  slender
pleomorphic Gram-negative rods which were also seen in
the Gram stain of the nasal swab.
• Fusobacterium necrophorum (MALDI-TOF MS) was
cultured from the blood and nasal swab.
 Follow up
• After 5 days:
– somnolent
– MRI scan of brain: progression of the abscess
subcutaneously, left intraorbital and intracranial along
with progression of subdural empyema and a
suspected thrombosis of the superior sagittal sinus
and right sigmoid sinus.
– A craniotomy was performed.
– Gram stain of pus from temporal pocket  Gram-
negative rods, but cultures remained negative.
– Ceftriaxone was changed to meropenem.
 Follow up
• Clinical improvement.
• 4 days later:
– increasing headache and a left hemiparesis.
– Evacuation of right frontal subdural abscess was performed.
– Meropenem was changed to penicillin.
– A low protein S level was found for which further analysis was
initiated.
• 6 days later:
– intraorbital abscess was evacuated. His left hemiparesis
disappeared completely.
• 3 weeks later:
– discharged in good condition with penicillin for 1 month
DISCUSSION
• Five patients with a diagnosis of complicated
infection with F. necrophorum originating from
otitis or sinusitis within a time period of 9
months.
– two patients recovered completely
– one patient died due to complications of the
infection
– one patient retained a slight hemiparesis
– one patient had permanent hearing loss.
 Lemièrre’s syndrome
• (Veillon & Zuber, 1898) : first description of human systemic
infection with F. necrophorum:
– a young child with chronic purulent otitis media with septic
arthritis of the knee, cerebral abscess and signs of
overwhelming systemic infection.
• (Courmont & Cade, 1900) : first description of human
postanginal septicaemic infection with F. necrophorum.
• Clearly characterized by Lemièrre in 1936, but it was not
until 1983  Lemièrre’s syndrome
– Most common presentation:
• postanginal septicaemia with septic thrombophlebitis of the internal
jugular vein
• distant septic metastases secondary to an acute oropharyngeal
infection.
 Fusobacterium necrophorum
• unusual cause of mastoiditis, sinusitis and meningitis
with a limited number of published reports.
• can cause invasive disease with severe complications in
previously healthy children and adults.
• Pathogenesis of abnormal coagulation and
inflammation :
Thrombotic complications
– binding and activation of plasminogen observed in four of five
– platelet aggregation patients!
– production of haemagglutinin
• Some strains appear to be more virulent due to binding
of factor H, a complement controlling glycoprotein.
 Fusobacterium necrophorum
• Uncommon presentation and the difficulties in isolating 
delay of adequate treatment  high morbidity and mortality.
• Case 1 : appropriate antibiotics were delayed for 12 h due to
the initial suspicion of infection with encapsulated H.
influenzae.
• In cases of a severe course of an acute otitis media or
sinusitis, especially with thromboembolic complications,
abscess formation and pleomorphic Gram-negative rods in
the Gram stain, the empiric antibiotic treatment must include
agents to treat F. necrophorum.
• No uniform guidelines exist, though most authors recommend
the combination of penicillin and metronidazole or
carbapenems.
Conflicting reports in literature on susceptibility
of Fusobacterium isolates to penicillin
• Older studies report on beta-lactamase-
producing strains of Fusobacterium isolates.
• In a recent study, all F. necrophorum isolates
were susceptible to penicillin (MIC <0.5 mg/L).
• In the Netherlands, resistance of
Fusobacterium isolates to penicillin is very rare
and was not found in two previously
published cases of F. necrophorum infections
in the Netherlands, nor in our case series.
• F. necrophorum is considered to be a
commensal of human upper respiratory tract,
its role as a pathogen of throat infection is
also considered.
• Using real-time PCR :
– Jensen : F. necrophorum in 48% of 61 throat swabs
from patients with non-streptococcal tonsillitis
and in 21% of 92 throat swabs from healthy
controls.
• Within a short time period (9 months), we encountered five
patients with a complicated infection with F. necrophorum
originating from otitis or sinusitis.
• 2 recent studies from Israel : emergence of F. necrophorum
infections associated with complicated mastoiditis.
• Yarden-Bilavsky et al. describe seven children with acute F.
necrophorum mastoiditis diagnosed during a 3.5 year period of
whom five presented in the last 6 months of the study.
• A study: 17 of 27 F. necrophorum infections in children were
diagnosed during the last 4 years of a 10 year study period.
• The most common source of infection was otogenic (70%).
• Most authors speculates :
– the more restricted use of antibiotics and the shift
in prescribed antibiotics from traditional
antibiotics such as penicillin to macrolides and
cephalosporines, which lack activity against F.
necrophorum, as well as improved identification
methods by the use of broad-spectrum 16S rRNA
PCR have contributed to this increase in incidence.
 Conclusion
• 5 patients diagnosed recently with complicated
infection with F. necrophorum originating from an
otitis or sinusitis.
• Imaging should be considered in all infections
with Fusobacterium arising from the upper
respiratory tract or head region due to the high
incidence of thrombotic complications and
abscess formation.
• Appropriate antibiotics should not be delayed.
• The reason for the recent emergence of F.
necrophorum infections is not clearly established.
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