Printer Friendly

Lemierre's syndrome with septic shock caused by Fusobacterium necrophorum.

SUMMARY

Fusobacterium necrophorum infections are rare. We report a 15-year-old male who presented with tachycardia, nausea, vomiting; diarrhoea and ankle pain. He rapidly deteriorated requiring ventilation and vasopressors Imaging of his thorax showed airspace consolidation, pulmonary cavitations and empyema. The ankle required drainage of purulent material. A thrombus in his internal jugular vein (Lemierre's syndrome) and an abscess in his obturator internus were subsequently found. Fusobacterium necrophorum was identified in blood culture on day nine The patient recovered with antibiotics and surgical interventions for empyema and septic arthritis Fusobacterium necrophorum should be a suspected pathogen in septic shock complicated by metastatic abscess formation.

Key Words: shock, multi-organ dysfunction syndrome, pulmonary cavitation, empyema, septic joint, Lemierre's syndrome

**********

Anaerobic bacterial infections, although rare, can be potentially serious and life-threatening(1). Due to their slow growing nature in culture and their tendency to be found as part of the normal flora, it is difficult to identify anaerobic organisms as being the microbial pathogens responsible for infections. Fusobacterium necrophorum is a strictly anaerobic gram-negative rod that is found in the normal flora of humans in the oral cavity, alimentary canal and female genital tract(2, 3). There have been few reported paediatric cases of F. necrophorum infection and often the disease presentation is localised to a specific tissue. We present a case of disseminated F. necrophorum infection in a previously healthy juvenile male. All of the classic symptoms of disseminated F. necrophorum infection occurred in our patient including septic shock, multi-organ dysfunction syndrome (MODS), pulmonary infiltrate and cavitations, empyema, septic arthritis and Lemierre's syndrome (acute oropharyngeal infection with secondary septic thrombophlebitis of the internal jugular vein).

CASE HISTORY

The Institutional Ethics Board of the University of Western Ontario approved the reporting of this case. A 15-year-old male presented to the emergency room with a four-day history of vomiting, diarrhoea and a painful left ankle without previous trauma to the joint. The patient had been taking ibuprofen and aspirin. On inspection he appeared alert but looked unwell. His vital signs were heart rate 112/min, blood pressure 89/51 mmHg, respiratory rate 24/min and temperature 36.8[degrees]C. Pertinent physical examination abnormalities included dry mucous membranes, scleral icterus and hepatomegaly. Blood work showed a WBC of 41 x 1[0.sup.3]/m[m.sup.3] (neutrophils 39.4, lymphocytes 0.8 and monocytes 1.3), platelets 57 x 1[0.sup.3]/m[m.sup.3], creatinine 365 [micro]mol/1, blood urea nitrogen 40 mmol/1, albumin 22 g/1, bilirubin 220 mmol/1 and an INR 1.4, with his peripheral blood smear showing toxic changes. The initial diagnosis was sepsis with MODS consisting of haematological, renal and hepatic dysfunction.

He was admitted to the Critical Care Unit and started on a carbapenem, but given the suspicion of community-acquired methicillin-resistant Staphylococcus aureus infection, vancomycin was added to his antibiotic regimen. Despite intravenous antibiotics, his condition rapidly deteriorated, requiring intubation, ventilation and haemodynamic support with noradrenaline and vasopressin. Lymphocyte flow cytometry, quantitative immunoglobulins and complement levels were shown to be normal. Pulmonary infiltrates were evident on chest X-ray. His serum troponin-I was elevated at 0.66 [micro],g/1 (normal [less than or equal to]0.08 [micro]g/1), but a transthoracic echocardiogram showed normal function. On day four his liver dysfunction and acute renal failure worsened. His ankle became hot and swollen, prompting an MRI of the joint (Figure 1A) and subsequent incision and drainage of purulent material. The gram stain on the ankle joint fluid identified scant gram-negative rods, suggesting that anaerobic organisms may be present. A CT was performed six days after his admission and this showed significant airspace consolidation, as well as cavitary lung lesions and bilateral pleural effusions (Figure 1C). Chest tubes were placed bilaterally. The patient's P[a.sub.a][o.sub.2]/Fi[O.sub.2] ratio decreased below 200 indicating acute respiratory distress syndrome and thus, a protective ventilation strategy was initiated.

[FIGURE 1 OMITTED]

All cultures were negative except a blood culture taken on admission that was flagged positive on day six with slow-growing gram-negative rods. On hospital day eight, an MRI of his abdomen and pelvis was suspicious of an abscess in the left obturator internus (Figure 1B), though this was not felt to warrant surgical intervention. An ultrasound of his pleural effusions showed septations consistent with ongoing bilateral empyema (Figure 1D), prompting administration of streptokinase via chest tubes bilaterally(4). Ultimately, he required bilateral video-assisted thoracoscopic surgery for decortication of the empyemas (5,6), at which time extensive left lower lobe necrosis was noted. Samples of his empyema were sterile and were notable only for fibropurulent debris. A tracheostomy tube was also placed at this time for predicted prolonged ventilatory needs.

A positive identification of F. necrophorum growth was obtained on day nine of his hospitalisation from the blood culture drawn on admission. This anaerobic bacterium was reported as being sensitive to meropenem, metronidazole and penicillin, and therefore intravenous metronidazole was added to his treatment. At this time, the patient was noted to maintain his head position rotated to the left and he grimaced with head straightening. Lemierre's syndrome was suspected and imaging of his neck later confirmed a clot measuring 0.74 cm in length in the left internal jugular vein (Figure 1E, 1F). Anticoagulation with heparin was ongoing and continued at prophylactic dosages, given the reported controversy with therapeutic heparin in the treatment of Lemierre's syndrome. This neck vein had not been cannulated.

A potential route of entry for F. necrophorum was revealed by a detailed dental assessment that showed significant decay of two teeth, eventually requiring extraction. On the 18th day of hospitalisation, his respiratory status improved and he was weaned from the ventilator to a tracheostomy mask with supplementary oxygen. His remaining chest tube was subsequently removed and his tracheostomy was decannulated. Still receiving prophylactic heparin therapy, a follow-up ultrasound prior to transfer showed his internal jugular vein thrombus had decreased in size to 0.33 cm.

The patient was discharged after 56 days in hospital on oral metronidazole for an additional month. At the time of this report, he had limited exercise tolerance secondary to pain with ambulation arising from his ankle, but was otherwise making a good recovery with aggressive physiotherapy and ongoing orthopaedic follow-up. His pulmonary function tests, completed six weeks post-discharge, were remarkably normal given the severity of the involvement of his lung parenchyma.

DISCUSSION

Before the advent of antibiotics, F. necrophorum infections were quite common, with >250 cases reported worldwide from the time of its initial description up to the 1940s'. Since then the number of cases has declined rapidly and this bacterium is now rarely isolated. The outcome of F. necrophorum infection has also improved significantly, from a mortality rate of 90% down to 4 to 18% with directed antibiotic treatment (8). Although the prevalence of infection with F. necrophorum is currently at about one in a million persons per year in the general population, the incidence has been rising in recent years'. For example, the number of F. necrophorum infections in one paediatric hospital has increased from a single isolate of the bacterium in culture between 1996 and 1999 to 15 isolates between 2000 and 2002'. Only one of these 15 isolates came from a disseminated case of the infection while the others consisted of either localised peritonsillar abscesses or Lemierre's syndrome (7). Despite increases in the total number of cases, the incidence of disseminated disease remains low and most physicians have not encountered F. necrophorumi nfectionl (10,11).

The pathogenesis of F. necrophorum infection is complex, explaining the bacterium's ability to generate a diverse array of symptoms. F. necrophorum has both a liposaccharide endotoxin and a heat stable extracellular leucocidin (2,9) these two molecules are responsible for the toxic and inflammatory effects of the bacterium,. F. necrophorum also has the ability to aggregate platelets leading to intravascular coagulation and thrombus formation (2,9,12). This latter characteristic is associated with only the most virulent strains of fusobacterium (9,12).

Tonsils and peritonsillar tissues are frequently the primary source of infections (10,11,13). Table 1 is a compilation of previously reported paediatric cases of disseminated F. necrophorum and shows that most of the infections originate in the pharynx. Less commonly, the bacterium can seed into the bloodstream because of parotitis, sinusitis, mastoiditis, otitis and dental infections (13). The presumed portal of bacterial entry in our patient was decayed teeth that were eventually extracted, however, this source of F. necrophorum infection was unclear until the identification of the bacterium. Delayed diagnosis of F. necrophorum infection can also be attributed to the oral infection having resolved or improved greatly before the onset of sepsis and other symptoms (9). Hence it is difficult to use the infection source to aid in empirical diagnosis with this bacterium.

Once the bacterium has disseminated from the primary site of infection, it is capable of causing severe sepsis and metastatic complications (10). Due to anatomical proximity, the infection often spreads to the lateral pharyngeal space in which the carotid sheath and its contents are located. By using proteolytic enzymes, the bacteria can then invade the internal jugular vein leading to thrombosis and sepsis (2,3). Direct extension of the thrombus from the peritonsillar veins into the internal jugular vein can also occur (2,3,9). Septic emboli originate from the internal jugular vein thrombi and can easily disseminate, with lungs being the most common site of metastases'. Nodular infiltrates and cavitations are usually detected early and tend to progress rapidly despite antibiotic therapy; empyemas and lung abscesses are frequently observed (2,7,9). Metastases to joints such as the hip, knee, shoulder, ankle, elbow and sacroiliac lead to septic arthritis (13 to 27% of cases) and soft tissue sepsis (0 to 16% of cases) (7,9). Liver failure with hepatomegaly and jaundice is commonly recorded in F. necrophorum infections and is probably due to circulating endotoxins (2). Acute renal failure is much less common (9,10).

Table 1 illustrates the considerable variation in the presenting complaints of systemic F. necrophorum infections. The severity of the disease ranges from septic arthritis of a single joint 14 to the full spectrum of symptoms seen in our patient. Other sites of metastases include the heart and CNS (15,16). Due to the diversity of symptoms exhibited by those infected with the bacteria, initial presentation of the disease can involve a variety of health care specialties, including primary care, emergency medicine, orthopaedics and otolaryngology.

Diagnosis of F. necrophorum infection is also hindered by the slow-growing nature of the anaerobe. In this patient, the bacterium was present in blood after six days of growth and positively identified as F. necrophorum on culture day nine. This lengthy culture period is also reflected in most of the cases described in Table 1. The patient's condition deteriorated considerably during growth of F. necrophorum in culture, despite anaerobic antibiotic coverage, indicating an ongoing systemic inflammatory cascade. Although the culture report for this patient indicated bacterial sensitivity to meropenem, the most effective antibiotic against F. necrophorum appears to be metronidazole (2,9), which was added to the treatment regimen after identification of the bacteria. Penicillin, clindamycin and tetracyclines seem to be effective in vitro, although they are considered relatively ineffective in practice due possibly to poor tissue penetration (2,9). Other cases of disseminated F. necrophorum have detailed the necessity for changes in antibiotic usage once the bacterium has been identified, (8,14,17,18).

The case presented here required surgical interventions, which is common for disseminated F. necrophorum infections (Table 1). Anticoagulant use with Lemierre's Syndrome is controversial since the thrombus often resolves with antibiotic treatment alone (2). Anticoagulant use might only be necessary when there is either a lack of thrombus regression with antibiotic usage or spreading of the thrombus towards the cavernous sinus (2,9). In extreme cases where the thrombus is unresponsive to treatment, ligation or resection of the internal jugular vein is utilised (9).

This case is an example of a rare but serious infection caused by anaerobic flora in a previously healthy paediatric patient with normal immunological studies. The delayed diagnosis secondary to slow bacterial growth in culture is common with F. necrophorum infection, as is the diversity and severity of symptoms. Thus, when septic shock and MOD S occurs in conjunction with multiple metastatic abscesses, F. necrophorum should be considered on the list of possible pathogens and early anaerobic coverage be instituted.

ACKNOWLEDGEMENTS

DW is supported by a Summer Research Training Program award from the Schulich School of Medicine at the University of Western Ontario. DDF is supported by the Children's Health Research Institute and the Centre for Critical Illness Research. DDF is a strategic training fellow of the Canadian Institutes of Health Research in the Canadian Child Health Clinician Scientist Program.

Accepted for publication on May 18, 2007.

REFERENCES

(1.) Brook I. Clinical review: bacteremia caused by anaerobic bacteria in children. Crit Care 2002; 6:205-211.

(2.) Golpe R, Marin B, Alonso M. Lemierre's syndrome (necrobacillosis). Postgrad Med J 1999; 75:141-144.

(3.) Brook I. Fusobacterial infections in children. J Infect 1994; 28:155-165.

(4.) Diacon AH, Theron J, Schummans MM, Van de Wal BW, Bolliger CT. Intrapleural streptokinase for empyema and complicated parapneumonic effusions. Am J Respir Crit Care Med 2004; 170:49-53.

(5.) Gates RL, Caniano DA, Hayes JR, Area MJ. Does VATS provide optimal treatment of empyema in children? A systematic review. J Pediatr Surg 2004; 39:381-386.

(6.) Luh SP, Chou MC, Wang LS, Chen JY, Tsai TE Video-assisted thoracoscopic surgery in the treatment of complicated para-pneumonic effusions or empyemas: outcome of 234 patients. Chest 2005; 127:1427-1432.

(7.) Ramirez S, Hild TG, Rudolph CN, Sty JR, Kehl SC, Havens P et al. Increased diagnosis of Lemierre syndrome and other Fusobacterium necrophorum infections at a Children's Hospital. Pediatrics 2003; 112:e380.

(8.) Briggs S, Pappachan J, Argent J, McGill N, Marsh M. Lemierre disease in the pediatric intensive care unit, clinical course, and the use of high-frequency oscillatory ventilation. Pediatr Crit Care Med 2003; 4:107-110.

(9.) Riordan T, Wilson M. Lemierre's syndrome: more than a historical curiosa. Postgrad Med J 2004; 80:328-334.

(10.) Chirinos JA, Lichtstein DM, Garcia J, Tamariz LJ. The evolution of Lemierre syndrome: report of 2 cases and review of the literature. Medicine (Baltimore) 2002; 81:458-465.

(11.) Alvarez A, Schreiber JR. Lemierre's syndrome in adolescent children-anaerobic sepsis with internal jugular vein thrombophlebitis following pharyngitis. Pediatrics 1995; 96:354-359.

(12.) Forrester LJ, Campbell BJ, Berg JN, Barrett JT Aggregation of platelets by Fusobacterium necrophorum. J Clin Microbiol 1985;22:245-249.

(13.) Dool H, Soetekouw R, van Zanten M, Grooters E. Lemierre's syndrome: three cases and a review. Fur Arch Otorhinolaryngol 2005; 262:651-654.

(14.) Sonsale PD, Philipson MR, Bowskill J. Septic arthritis of the knee due to Fusobacterium necrophorum. J Clin Microbiol 2004; 42:3369-3370.

(15.) Stuart G, Wren C. Endocarditis with acute mitral regurgitation caused by Fusobacterium necrophorum. Pediatr Cardiol 1992; 13:230-232.

(16.) Jaremko JL, Kirton A, Brenner JL. A 12-year-old girl with pharyngitis, meningitis and sinovenous thrombosis. CMAJ 2003; 169:811-812.

(17.) Kuduvalli PM, Jukka CM, Stallwood M, Battersby C, Neal T, Masterson G et al. Fusobacterium necrophorum-induced sepsis: an unusual case of Lemierre's syndrome. Acta Anaesthesiol Scand 2005; 49:572-575.

(18.) Haasper C, Tecklenburg FW, Cochran JB, Habib DM, Smith CD. A pain in the neck can lead to pain in the belly: Lemierre's Syndrome. International Pediatrics 2004; 19:185-187.

(19.) Ahkee S, Srinath L, Huang A, Raff MJ, Ramirez JA. Lemierre's syndrome: postanginal sepsis due to anaerobic oropharyngeal infection. Ann Otol Rhinol Laryngol 1994; 103:208-210.

(20.) Screaton NJ, Ravenel JG, Lehner PJ, Heitzman ER, Flower CD. Lemierre syndrome: forgotten but not extinct-report of four cases. Radiology 1999; 213:369-374.

(21.) Chang PS, Harris JP, Bhumbra N, Puczynski M, Kherallah N, Lewis TJ et al. Index of suspicion. Pediatr Rev 2006; 27:73-78.

(22.) Mancao M, Manci E, Figarola M, Estrada B. Fusobacterium necrophorum mediastinal abscess presenting as an anterior chest wall mass in a child: a case report. Clin Pediatr (Phila) 2005; 44:73-75.

D. WANG *, A. K. PRICE ([dagger]), K. K. LEITCH ([double dagger]), M. SALVADORI ([section]), R. N. SINGH **, A. KORNECKI ([dagger][dagger]), S. D. McKILLOP ([double dagger][double dagger]), D. D. FRASER ([section][section])

Children's Hospital of Western Ontario, University of Western Ontario, London, Ontario, Canada

*B.Sc., Medical Student, Schulich School of Medicine.

[dagger] M.D., F.R.C.P.C., Consultant, Department of Paediatrics.

[double dagger] M.D., F.R.C.S.C., Consultant, Department of Surgery.

[section] M.D., F.R.C.P.C., Consultant, Department of Paediatrics.

** M.B., B.S., F.R.C.P.C., Consultant, Department of Paediatrics, University of Western Ontario and Children's Health Research Institute and Centre for Critical Illness Research.

[dagger][dagger] M.D., Consultant, Department of Paediatrics, University of Western Ontario and Children's Health Research Institute and Centre for Critical Illness Research.

[double dagger][double dagger] M.D., F.R.C.P.C., Consultant, Departments of Paediatrics and Radiology.

[section][section] M.D., Ph.D., F.R.C.P.C., Consultant, Departments of Paediatrics, Physiology/Pharmacology and Clinical Neurological Sciences, University of Western Ontario and Children's Health Research Institute and Centre for Critical Illness Research.

Address for reprints: Dr D. D. Fraser, Paediatric Critical Care Medicine Office, Room C2-C82, Children's Hospital of Western Ontario, 800 Commissioners Road East, London, ON, N6C 2V5, Canada.
TABLE 1
A summary of paediatric patients (< 18 years of age) reported in
the literature with disseminated F. necrophorum infection

Case Age Gender Presenting Source
 complaints

1 2 M Lethargy, Unclear
1992 (15) anorexia,
 pallor, fever

2 14 F Sore throat, Oropharynx
1994 (19) fever,
 malaise,
 diarrhoea

3 14 F Sore throat, Oropharynx
1995 (11) fever,
 headache,
 cough

4 17 F Sore throat, Tonsillar
1999 (20) fever, neck
 pain

5 14 F Headache, Tonsillar/
2003 (8) photophobia, peritonsillar
 Myalgia infection
 fever,
 vomiting,
 diarrhoea

6 12 F Rigors, sore Oropharynx
2003 (16) throat, neck
 pain and
 swelling,
 headache,
 fever

7 15 F Fever, sore Pharynx
2006 (21) throat,
 vomiting,
 abdominal
 pain

Case Complications Antibiotic Time to
 therapy diagnosis

1 Pneumonia, lung Gentamicin, Two days
1992 (15) abscesses, mitral Azlocillin,
 valve and chordae Vancomycin,
 rupture Ceftazidime,
 Metronidazole

2 Pneumonia, Penicillin, Unclear
1994 (19) pleural effusions, Ticarcillin-
 Lemierre's Clavulanate,
 syndrome Amoxyicillin-
 Clavulanate

3 Pneumonia, Cefaclor, Eight
1995 (11) pleural effusions, Ampicillin- days
 Lemierre's Sulbactam,
 syndrome Erythromycin,
 Penicillin

4 Lemierre's Erythromycin, Unclear
1999 (20) syndrome, Cefotaxime,
 pulmonary Metronidazole
 cavitations,
 empyema

5 Pulmonary Cefotaxime, Seven
2003 (8) cavitations, Flucloxacillin, days
 acute respiratory Metronidazole,
 distress syndrome, Rifampicin
 Lemierre's
 syndorme

6 Meningitis, Vancomycin, Three
2003 (16) Lemierre's Cefotaxime, days
 syndrome Eiprofloxacin,
 Piperacillin-
 tazomycin

7 Pulmonary Ceftriaxone, Unclear
2006 (21) infiltrates and Azithromycin,
 cavitation, sepsis, Penicillin
 liver failure,
 Lemierre's
 syndrome

Case Other Outcome
 interventions

1 Mechanical Recovered
1992 (15) ventilation,
 mitral valve
 replacement

2 Heparin Recovered
1994 (19)

3 Unclear Recovered
1995 (11)

4 Heparin, Recovered
1999 (20) decortication

5 Mechnical Recovered
2003 (8) ventilation
 with HFO,
 nitric oxide

6 Heparin Recovered
2003 (16)

7 Unclear Unclear
2006 (21)

Additional cases of F. necrophorum infection have been reported
with localised tissue infections or strictly Lemierre's
syndrome (7,9,10,14,20,22). Cases of disseminated F. necrophorum
infection prior to 1990 have been summarised previously (11). One
other reported case of disseminated F. necrophorum infection was
found (7) but there was insufficient information provided for
inclusion in the table. HFO: high frequency oscillation.
COPYRIGHT 2007 Australian Society of Anaesthetists
No portion of this article can be reproduced without the express written permission from the copyright holder.
Copyright 2007 Gale, Cengage Learning. All rights reserved.

Article Details
Printer friendly Cite/link Email Feedback
Author:Wang, D.; Price, A.K.; Leitch, K.K.; Salvadori, M.; Singh, R.N.; Kornecki, A.; Mckillop, S. D.; Fras
Publication:Anaesthesia and Intensive Care
Article Type:Clinical report
Geographic Code:1CANA
Date:Oct 1, 2007
Words:3251
Previous Article:Early autonomic dysreflexia in acute paraplegia following anterior spinal artery thrombosis.
Next Article:Hypotension and anaemia--a blinding combination.
Topics:


Related Articles
Taking the shock out of septic shock.
Lemierre's Syndrome.
Bilateral Lemierre's syndrome: a case report and literature review. (Original Article).
Prevent foot rot in your goats. (The goat barn).
Otogenic Fusobacterium meningitis, sepsis, and mastoiditis in an adolescent.
FP-3. Lemierre disease: case report.
Lemierre's syndrome.
Sigmoid sinus thrombosis secondary to Lemierre's syndrome.
Lemierre syndrome complicating a subcutaneous neck abscess.
Thrombocytopenia in septic shock patients--a prospective observational study of incidence, risk factors and correlation with clinical outcome.

Terms of use | Copyright © 2018 Farlex, Inc. | Feedback | For webmasters