Otogenic Fusobacterium meningitis, sepsis, and mastoiditis in an adolescent.

Abstract: Fusobacterium necrophorum is a strict anaerobic organism responsible for a number of clinical syndromes known as necrobacillosis. Although meningeal infections with anaerobes are rare, delayed diagnosis and treatment can be potentially fatal. We report a unique case of Fusobacterium meningitis, mastoiditis, and sepsis in a previously healthy adolescent. Diagnosis and management of this condition are discussed in the context of a literature review.

Key Words: Fusobacterium, meningitis, necrobacillosis

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Fusobacterium necrophorum is a Gram-negative, strictly anaerobic, nonmotile rod that belongs to the family of Bacteroidaceae and is the cause of a constellation of clinical syndromes known collectively as necrobacillosis. Although it is an uncommon cause of meningitis in children and adolescents, delayed diagnosis because of difficulties isolating the organism and inappropriate antimicrobial management have contributed to the disease's debilitating and potentially fatal outcome. (1) We report an uncommon case of anaerobic meningitis, mastoiditis, and sepsis in a previously healthy adolescent in which the causative agent was F necrophorum.

Case Report

A 15-year-old healthy white female presented to the emergency department with a 2-week history of left ear pain and otorrhea. She had no other medical history except depression, for which she took bupropion and trazodone. Other medications included oral ciprofloxacin and benzocaine/antipyrine otic solution, which were initiated on Day 2 of her illness; however, during the following 2 weeks, she developed headache, neck stiffness, photophobia, vomiting, and fever.

On presentation to the emergency department, the patient was awake and oriented but ill appearing. The patient's temperature was 38.3[degrees]C, her pulse was 114 beats/min, her respiratory rate was 20 breaths/min, and her blood pressure was 88/51 mm Hg. Initial physical examination revealed purulent discharge from the left ear canal, left mastoid tenderness with edema, and left postauricular erythema. There was no sinus tenderness and the pharynx was clear. Left anterior and posterior cervical lymph nodes were enlarged. Cardiac examination revealed normal S1 and S2 without murmurs and the lungs were clear. The patient's abdomen was non-tender without hepatosplenomegaly. Neurologic examination revealed positive Kernig and Brudzinski signs.

A lumbar puncture was performed and the cerebrospinal fluid revealed grossly cloudy fluid, a white blood cell count of 2,389/[mm.sup.3], 100% polymorphonuclear cells, a red blood cell count of 1/[mm.sup.3], a glucose level of <20 mg/dL, and a protein level of 197 mg/dL; Gram stain showed no organisms and many white blood cells. The peripheral white blood cell count was 18,200/[mm.sup.3] with a differential of 86% polymorphonuclear cells, 5% bands, 6% lymphocytes, and 3% monocytes. Her hemoglobin was 11.5 g/dL, and her hematocrit was 34.1%. Platelets were reported as "adequate." Serum chemistry was normal except for a potassium level of 3.3 mmol/L. Chest radiography was negative for infiltrates. Highresolution computed tomography of the head revealed complete left middle ear and mastoid opacification with coalescence and minimal medial demineralization of the mastoid air cells.

Treatment for bacterial meningitis and mastoiditis was initiated with intravenous (IV) vancomycin, ceftazidime, and metronidazole. The left ear canal was suctioned, revealing a posterosuperior tympanic membrane perforation and a left mastoidectomy was performed. Subsequently, cultures of blood, cerebrospinal fluid, and left ear canal aspirate grew F necrophorum.

During her 2-week hospitalization, IV antibiotics were administered, and at hospital discharge, the otorrhea had resolved; however, she still experienced intermittent headache and nausea. Subsequently, IV penicillin and metronidazole were continued for an additional 4 weeks on an outpatient basis. During this time, she had no fever, rash, or abdominal discomfort and her headaches resolved. After 6 weeks of therapy, audiologic evaluation revealed high-frequency sensorineural hearing loss from 2,000 to 8,000 kHz that was unchanged from her preoperative audiogram, and a computed tomographic scan of the head showed no evidence of osteomyelitis or intracranial involvement.

Discussion

Fusobacterium organisms are long, thin, non-spore-forming, Gram-negative rods with pointed ends, often arranged end to end in pairs. There has been uncertainty in the past surrounding the nomenclature of this group of bacteria, for which there are currently 52 synonyms. (1) These organisms can be found in the gastrointestinal, respiratory, and female genital tracts and are more virulent than most of the normal anaerobic flora. They have been reported to cause bacteremia and a variety of rapidly progressive infections, known collectively as necrobacillosis. (1)

All strains of Fusobacterium are able to produce a toxin and some strains may produce [beta]-lactamase, causing penicillin resistance. Culture of Fusobacterium must be carried out in strict anaerobic conditions, and identification is supported by the following observations: 1) obligate anaerobic nature with characteristic fusiform rods, 2) Gram-negativity, 3) absence of spores, and 4) production of n-butyric acid. F necrophorum is further separated from others in the species by its characteristic production of lipase and by propionic acid production from lactate. (1,2)

The most common manifestations of necrobacillosis include postanginal sepsis, bone and joint infections, and abdominal and genital tract infections. Although most meningeal infections are caused by aerobic pathogens, there have been an increasing number of reports of anaerobic meningitis in the literature. Most of these cases are caused by Fusobacterium, Bacteroides fragilis species, and anaerobic streptococci, which are commonly associated with focal pyogenic infections such as brain abscesses and subdural empyemas. (3) Anaerobes are less commonly seen in epidural abscess and are seldom involved in meningitis. Because anaerobic cerebrospinal fluid cultures are not routinely performed at most institutions, the delay in diagnosis and subsequent treatment may lead to an increased incidence of death and morbidity.

A review of the English-language literature revealed only 23 cases of Fusobacterium meningitis. (1,2,4-20) Of note was the ability of Fusobacterium meningitis to cause severe fulminating disease despite appropriate antibiotic coverage. Overall, the fatality rate was 17% (4 of 23), and the morbidity was 53% (10 of 19). Cranial nerve palsies, hemiplegia, Horner syndrome, and educational difficulties were among the most common forms of morbidity. Concurrent sepsis was noted in 85%, whereas mastoid involvement was seen in only 20% of cases reviewed. (1,2,4-20)

Interestingly, although F necrophorum is sensitive to most antibiotics in vitro, including penicillin, clinical improvement is slower to develop than sensitivities would imply. (21-23) Furthermore, some authors have noted that definitive clinical improvement coincided with the addition of metronidazole to the treatment regimen. (21-23) Of the 24 cases of Fusobacterium meningitis reviewed, 13 cases included metronidazole in the treatment regimen. (1,2,4,9,10,13,17,18) In this group, there was only one fatality. In contrast, three of the four cases in which metronidazole was not used resulted in death. (12,15,16,20) In the remaining seven cases, the antibiotic coverage was unknown. (5-8,11,14,19) Overall, these reported experiences support the role of metronidazole in the treatment of Fusobacterium meningitis.

Conclusion

An adolescent patient developed Fusobacterium meningitis, mastoiditis, and sepsis that were preceded by a purulent otitis and tympanic membrane perforation. Treatment modalities including surgical intervention and administration of broad-spectrum IV antibiotics followed by organism-directed therapy, including metronidazole, was successful in treating the disease process. A literature review revealed Fusobacterium meningitis in neonates, children, and adolescents and young adults aged 6 weeks to 23 years. However, this occurrence in a healthy adolescent is quite unique because mastoiditis is rare in this patient population.

The dramatic nature of this disease moves us to endorse the recommendations by Heerema et al. (3) that include obtaining anaerobic cultures in any case of meningitis associated with chronic otitis and/or mastoiditis, chronic sinusitis, and pharyngeal suppuration. Finally, given the favorable clinical outcome in this case and others when metronidazole was used, we are further moved to suggest that metronidazole be added to the antibiotic regimen in any case of suspected meningitis that satisfies the criteria set forth by Heerema et al. (3)

Sometimes give your services for nothing....
--Hippocrates

Accepted July 23, 2002.

Copyright [c] 2004 by The Southern Medical Association

0038-4348/04/9704-0416

References

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3. Heerema MS, Ein ME, Musher DM, et al. Anaerobic bacterial meningitis. Am J Med 1979;67:219-226.

4. Figueras G, Garcia O, Vall O, et al. Otogenic Fusobacterium necrophorum meningitis in children. Pediatr Infect Dis J 1995;14:627-628.

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8. Jacobs JA, Hendriks JJ, Verschure PD, et al. Meningitis due to Fusobacterium necrophorum subspecies necrophorum: case report and review of the literature. Infection 1993;21:57-60.

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12. Cron RQ, Webb KH. Necrobacillosis: an unusual cause of purulent otitis media and sepsis. Pediatr Emerg Care 1995;11:379-380.

13. Larsen PD. Fusobacterium necrophorum meningitis associated with cerebral vessel thrombosis. Pediatr Infect Dis J 1997;16:330-331.

14. MacDonald AA, Harar RPS, Prior AJ. Necrobacillosis: are we missing the early stages of this life-threatening infection? Lancet 1995;346:1705.

15. Islam AKMS, Shineerson JM. Primary meningitis caused by Bacteroides fragilis and Fusobacterium necrophorum. Postgrad Med J 1980;56:351-353.

16. Maller R, Fryden A, Nordstrom K, et al. Septicemia and meningitis caused by Fusobacterium aquatile. Scand J Infect Dis 1978;10:146-148.

17. Reynolds MA, Hart CA, Harris F, et al. Anaerobes in acute otitis media. J Infect 1985;10:262-264.

18. Bader-Meunier B, Pinto G, Tardieu M, et al. Mastoiditis, meningitis and venous sinus thrombosis caused by Fusobacterium necrophorum. Eur J Pediatr 1994;153:339-341.

19. Kasik JW, Bolam DL, Nelson RM. Sepsis and meningitis associated with an anal dilation in a newborn infant. Clin Pediatr 1984;23:509-510.

20. Moloy PJ. Anaerobic mastoiditis: a report of two cases with complications. Laryngoscope 1982;92:1311-1315.

21. Moore-Gillon, Lee TH, Eykyn SJ, et al. Necrobacillosis: a forgotten disease. BMJ 1994;288:1526-1528.

22. Seidenfeld SM, Sutker WL, Luby JP. Fusobacterium necrophorum septicemia following oropharyngeal infection. JAMA 1982;248:1348-1350.

23. Vogel LC, Boyer KM. Metastatic complications of Fusobacterium necrophorum sepsis: two cases of Lemierre's postanginal septicemia. Am J Dis Child 1980;134:356-358.

RELATED ARTICLE: Key Points

* Fusobacterium necrophorum is a Gram-negative, strictly anaerobic, nonmotile rod that is the cause of a constellation of clinical syndromes known collectively as necrobacillosis.

* The most common manifestations of necrobacillosis include postanginal sepsis, bone and joint infections, and abdominal and genital tract infections.

* F necrophorum is an uncommon cause of meningitis, mastoiditis, and sepsis in children and adolescents.

* Anaerobic cultures should be obtained in cases of meningitis associated with chronic otitis and/or mastoiditis, chronic sinusitis, and pharyngeal suppuration.

* The role of metronidazole in cases of suspected meningitis that satisfy the above criteria is supported by the favorable outcome in this case and other reports.

Alan Morrison, DO, Ian Weir, DO, and Tomas Silber, MD, MASS

From the Department of Internal Medicine, Nova Southeastern University, College of Osteopathic Medicine, Fort Lauderdale, FL, and the Department of Pediatrics, George Washington University School of Medicine, Washington, DC.

Reprint requests to Alan Morrison, DO, Department of Internal Medicine, College of Osteopathic Medicine, Nova Southeastern University, 3200 S. University Drive, Fort Lauderdale, FL 33328. Email: [e-mail]