Lemierre’s Syndrome Caused by MRSA Infection in an Infant

1Evelyne Kalyoussef, MD; 1Chirag Rajan Patel, MD, and 1Huma Quraishi, MD

Contact Information: Evelyne Kalyoussef, MD kalyouev@umdnj.edu

1Department of Otolaryngology – Head & Neck Surgery, University of Medicine and Dentistry of New

Jersey – New Jersey Medical School, Newark, NJ

Objective:

1. Describe an infant with Lemierre’s Syndrome caused by MRSA Sepsis

2. Discuss treatment options and management of IJV Thrombosis and

Lemierre’s Syndrome in Children

Methods:

Lemierre’s Syndrome is usually characterized by recent oropharyngeal infection

complicated by internal jugular vein thrombosis. The main pathogen is usually

Fusobacterium necrophorum. The vast majority of patients affected are young

adults. We present a case of community acquired Methicillin-resistant

Staphylococcus aureus (MRSA) in an eight week old male who was being

breastfed by his mother, who was a MRSA carrier. He presented with a two day

history of fever and left neck swelling and was found to have a deep neck

abscess extending into the mediastinum with internal jugular thrombosis

extending retrograde to involve the sigmoid sinus.

Results:

The infant was taken to the operating room multiple times for incision and

drainage and washout procedures. The internal jugular vein was not ligated;

however, he was treated with anticoagulation with demonstration of

recannulation of the sigmoid sinus. The patient was treated with long term IV

antibiotics. In addition, his mother was treated with Chlorhexidine baths for

MRSA decolonization.

Conclusion:

Classically described in older patients with Fusobacterium infections, there is a

growing body of literature reporting Lemierre’s syndrome secondary to MRSA

infections, particularly in a younger patient population suggesting a changing

demographic as well as a changing microbial pattern. We present the

youngest case of Lemierre’s Syndrome secondary to community acquired

MRSA.

Abstract

Introduction Lemierre’s syndrome (LS) is characterized by septic

thrombophlebitis of the internal jugular vein after an oropharyngeal

infection. Septic emboli can subsequently develop and, in the

preantibiotic era, fatality ensued within a few weeks of onset. This

entity was first described as “post anginal sepsis” in 1900 by

Courmont and Cade but gained it’s moniker after Andre Lemierre’s

extensive description in 19361. It was initially described as the

development of septic thrombophlebitis of the tonsillar and

peritonsillar veins followed by involvement of the parapharyngeal

space and internal jugular vein caused by Bacillus funduliformis

(now known as Fusiformis necrophorus) 2. While Lemierre‘s

syndrome was a frequent complication of deep neck infections in the

pre-antibiotic era, there was a steady decline in the incidence after

the advent of antibiotics and it became known as the “forgotten

disease.”3,4 Today, the incidence is estimated at between 0.6 and 2.3

million.5 However, over the past two decades, there has been an

increase in the number of cases of Lemierre’s being reported in the

literature. Lemierre’s is typically associated with anaerobic

infections in otherwise healthy young adults.2

We present a rare case of Methicillin-resistant Staphylococcus

aureus (MRSA) associated Lemierre’s in an eight week old male.

Case Presentation An eight week old male infant presented to an outside hospital with

a two day history of fever and left neck swelling. He was started on

beta-lactamase stable antibiotics for twenty four hours but was

transferred to our hospital after failing to improve. Prenatal and

medical history was only significant for being breastfed by his

mother who was a MRSA carrier. At presentation to our hospital, the

patient was noted to be very irritable with left sided neck swelling

and erythema, fevers (up to 102.3 F), leukocystosis (white blood

count 25) and decreased urine output. However, the patient was

hemodynamically stable with no evidence of airway instability. A

Computed tomography (CT) Scan of the neck with IV contrast was

obtained and demonstrated a low attenuation fluid collection

involving the retropharyngeal space and a rim enhancing abscess of

the left parapharyngeal space. The patient was taken emergently to

the operating room on Hospital Day #1 for incision and drainage of

the left deep neck abscess. Approximately 5ml of frank pus was

drained from the left parapharyngeal space and left internal jugular

vein thrombosis was identified. A penrose drain was left in place and

the patient was transferred to the Pediatric Intensive Care Unit in

critical condition. Given the patient’s maternal history of multiple

MRSA infections, the infant was empirically started on Vancomycin

and Clindamycin.

Figure 2. CT Neck with IV contrast obtained on Hospital Day #4 demonstrating progression of the fluid collections surrounding the left carotid sheath

Figure 1. CT Neck with IV contrast obtained on Hospital Day #1 demonstrating left paraphyargeal abscess, retropharygeal phelgmon and left internal jugular vein thrombosis (blue arrow).

Table 1. Cases of Staphylococcus aureus related Lemierre’s Syndrome. MRSA= methicillin resistant Staphylococcus aureus ; MSSA= methicillin sensitive Staphylococcus aureus

Conclusions

References

Lemierre syndrome is a rare but potentially life threatening infection which is on

the rise today, with a changing demographic as well as a changing microbial

pattern. Without awareness of MRSA as a causative agent, appropriate antibiotic

coverage may be delayed. Early diagnosis and intervention is essential. We

present the youngest cases of Lemierre’s Syndrome secondary to community

acquired MRSA.

Discussion Lemierre’s syndrome typically occurs in otherwise healthy young adults secondary to an

oropharyngeal infection. Internal jugular vein septic thrombosis develops and septic emboli

can lead to pulmonary and joint involvement.4 LS is typically associated with anaerobic

organisms: Fusobacterium necrphorum (57%), Fusobacterium species (30%) and

Fusobacterium nucleatum (3%) followed by anaerobic streptococci and other miscellaneous

Gram-negative anaerobes (10%).6 Staphylococcus aureus is not usually a cause of

Lemierre’s syndrome.

Classically described in older patients with Fusobacterium infections, there is a growing

body of literature reporting Lemierre’s syndrome secondary to MRSA infections, particularly

in a younger patient population suggesting a changing demographic as well as a changing

microbial pattern7,8. Since 2002, there have been 13 cases of septic internal jugular vein

thrombophlebitis secondary to staphylococcus aureus unrelated to catheter placement

reported in the literature.9-19 No reports were identified in the preceding 20 years. Nine of

these cases were caused by methicillin resistant staph aureus.9-13, 16-17 Five of these cases

occurred in pediatric patients (age range 3 months to 16 yrs), and three of these pts were

less than one year of age.3,9,10 The clinical presentation varied among the patients. Most

presented with facial or neck swelling and fever. All three children under 12 months of age,

presented with rapid onset neck swelling, fever and deep neck abscess formation.3,9,10 All

three of these patients underwent incision and drainage and prolonged treatment with IV

antibiotics and did well.3,9,10

Staphylococcus aureus is the most commonly isolated human bacterial pathogen. 6,20,21

Methicillin- resistant Staphylococcus aureus (MRSA) is increasingly prevalent in the United

States. There has been a dramatic increase in the number of both hospital acquired and

community acquired MRSA infections.20,21 MRSA related Lemierre’s Syndrome appears to

be more virulent and affecting a younger population of patients.13 Early diagnosis with

aggressive antimicrobial therapy and surgical intervention is key to effective treatment of

Lemierre syndrome and prevention of septic emboli.

Internal jugular vein thrombophelbitis usually manifests as unilateral swelling and pain at the

angle of the mandible and along the sternocleidomastoid muscle with associated trismus.

Although rare, Lemierre syndrome has the potential for significant morbidity and possibly

mortality. Early recognition and aggressive treatment are important in preventing severe

systemic manifestations. We recommend CT scan imaging with IV contrast or ultrasound

imaging for diagnosis. Empiric broad spectrum antibiotics should be started as soon as

possible. MRSA should be considered in all patients not responding to beta lactamase

stable conventional antibiotic therapy. While the effectiveness of anticoagulation is still

unclear, anticoagulation to prevent progression of thrombus or development of septic emboli

may be considered in the treatment algorithm of Lemierre’s. Anticoagulation therapy is thus

based on individual patient cases and physician preferences rather than firm evidence.

A B

A B

A B

B

Reference for case (Year)

Age of Patient

Bacterium

Complications

Intervention for Thrombosis

Kalyoussef et al (2012) 2 month old MRSA Medistinal abscess,sigmoid sinus thrombosis Heparin/Enoxaparin

Fleish et al. (2007) 3 month old MRSA Mediastinal abscess Enoxaparin

Hoehn et al. (2010) 7 month old MRSA Septic pulmonary emboili, epyema, pneumothorax, hemorrhagic pericardial effuusion Enoxaparin/Heparin

Fong and Watson (2002) 7month old MRSA Septic pulmonary emboili, cervical abscess, mastoiditis None Bently and Brennan (2009) 8yr MRSA Multiple pulmonary nodules ASA Kadhiravan et al. (2008) 16 yr MRSA

Septic pulmonary emboil, cavitation, pleural effusion, hemoptysis None

Chanin et al (2011) 22yr MRSA Necrotizing pneumonia and cerebral infarcts None Puymirat et al. (2008) 22yr MSSA

Multiple pulmonary nodules, cavitation, cavernous sinus thrombosis Heparin, ligation of IJ/EJ

Boga et al. (2007) 22yr MRSA Multiple small nodular lung densities, pleural effusion Heparin

Bilal et al. (2009) 30yr MRSA Multiple pulmonary nodules, pleural effusion, cavernous sinus thrombosis, cranial nerve palsies Heparin/Warfarin

Shivashakar et al. (2008) 32yr MSSA

Pulmonary nodules/abscesses, cavernous sinus thrombosis, cerebral infarcts

Heparin/Warfarin/Activated Protein C

Herek et al. (2010) 33yr MRSA Multiple septic pulmonary emboli, necrotizing pneumonia None

Ceylan et al. (2009) 80yr MSSA Pulmonary nodular infiltrates, pleural effusions None

Lemierre A: On certain septicemias due to anaerobic organisms. Lancet. 1936; 1: 701-703.

Ridgway JM, Parikh DA, Wright R, et al. Lemierre syndrome: a pediatric case series and review of literature. American Journal of Otolaryngology-Head and Neck Medicine and Surgery. 2010; 31:

38-45.

Hoehn KS, Capouya JD, Daum RS, et al: Lemierre-like syndrome caused by community-associated methicillin-resistant Staphylococcus aureus complicated by hemorrhagic pericarditis. Pediatr

Crit Care Med. 2010; 11:e32-e35.

Mohamed BP, Carr L. Neurological complications in two children with Lemierre syndrome. Developmental Medicine & Child Neurology 2010; 52; 779-781.

Syed MI, Baring D, Addibdle M, et al. Lemierre syndrome: two cases and a review. Laryngoscope. 2007; 117:1605-10.

Karkos PD, Asrani S, Karkos CD, et al. Lemierre’s Syndrome: A Systematic Review. Laryngoscope. 2009; 119: 1552-1559.

Hagelskajaer LH, Prag J, Malczynski J, et al. Incidence and clinical epidemiology of necrobacillosis, including Lemierre’s syndrome, in Denmark 1990-1995. Eur J Clin Microbiol Infect Dis. 1998;

17: 561-565.

Chirinos JA, Lichstein DM, Garcia J, et al. The evolution of Lemierre syndrome: report of 2 cases and review of literature. Medicine. 2002; 81: 458-465.

Fleisch AF, Nolan S, Gerber JG, et al. Methicillin-Resistant Staphylococcus aureus as a cause of extensive retropharyngeal abscess in two infants. The Pediatric Infectious Disease Journal. 2007;

26 (12): 1161-1163.

Fong SM, Watson M. Lemierre syndrome due to non-multiresistant methicillin-resistant Staphylococcus aureus. J Paediatr Child Health. 2002; 38: 305-307.

Bentley TP, Brennan DF. Lemierre’s syndrome: methicillin- resistant Staphylococcus aureus (MRSA) finds a new home. The Journal of Emergency Medicine. 2009; 37 (2): 131-134.

Kadhiravan T, Piramanayagam P, Banga A, et al. Lemierre’s syndrome due to community acquired methicillin-resistant Staphylococcus aureus infection and presenting with orbital cellulitis: a

case report. Journal of Medical Case Reports. 2008; 3: 374-377.

Chanin JM, Marcos LA, Thompson BM, et al. Methicillin- resistant Staphylococcus aureus USA 300 Clone as a cause of Lemierre’s Syndrome. Journal of Clinical Microbiology. 2011; 49 (5): 2063-

2066.

Boga C, Ozdogu H, Diri B, et al. Lemierre syndrome variant: Staphylococcus aureus associated with thrombosis of both the right internal jugular vein and the splenic vein after the exploration of a

river cave. J Thromb Thrombolysis. 2007; 23: 151-154.

Shivasankar GH, Murukesh N, Varma MPS, et al. Infection by panton-valentine leukocidin-producing Staphylococcus aureus clinically mimicking Lemierre’s syndrome. Journal of Medical

Microbiology. 2008; 57: 118-120.

Bilal M, Cleveland KO, Gelfand MS. Community –acquired methicillin-resistatn Staphylococcus aureus and Lemierre Syndrome. Am J Med Sci. 2009; 338 (4): 326-327.

Herek PA, lewis T, Bailitz JM. An unusual case of Lemierre’s Syndrome due to methicillin- resistant Staphylococcus aureus. The Journal of Emergency Medicine. 2010; 39 (5): 644-646.

Puymirat E, Biais M, Camou F, et al. A Lemierre Syndrome variant caused by Staphylococcus aureus. 2008; 26: 380.e5-380. e7.

Ceylan BG, Yavuz L, Baydar CL, et al. Lemierre Syndrome: a case of rarely isolated microorganism, Staphylococcus aureus. Med Sci MOnit. 2009: 15 (3): CS58-61.

Lowy FD: Staphylococcus aureus infections. N Engl J Med. 1998; 339: 520-532.

David MZ, Glikman D, Crawford SE, et al: What is community-associated methicillin resistant Staphylococcus aureus? J infect Dis. 200l; 197: 1235-1243.

The patient improved slightly but had persistent purulent drainage through the penrose

drain and remained febrile. Repeat magnetic resonance imaging was ordered to

evaluate whether the fluid collections were adequately being drained by the penrose

drain however the patient developed worsening cellulitis with progression to the

contralateral side. The patient became hemodynamically unstable in the MRI suite with

evidence of septic shock. He was taken back to the intensive care unit where he was

stabilized. Repeat CT imaging was obtained the following day when the patient was

hemodynamically stable. Repeat imaging demonstrated some progression of the fluid

collection surrounding the left carotid sheath, peripheral rim enhancement surrounding

the thymus and anterior mediastinum as well as progression of the left internal jugular

thrombosis into the chest and retrograde to involve the sigmoid sinus. The patient was

taken back to the Operating Room on Hospital Day # 4 for neck re-exploration and

drainage of the retropharyngeal abscess as well as drainage of mediastinal abscess by

Pediatric Surgery. Multiple passive drains were placed in the wound and patient was

monitored closely postoperatively. The internal jugular vein was not ligated as the

thrombosis extended beyond the neck. Instead, the patient was started on a heparin

drip after his second operative trip and transitioned to Enoxaparin (1mg/kg per dose

subcutaneously every 12hours). Repeat imaging demonstrated recannulation and

complete resolution of the transverse and sigmoid sinus blood thrombi. Wound cultures

were consistent with MRSA.

The patient was treated with IV antibiotics (Vancomycin and Rifampin) for a total of 15

days. He was discharged home on Bactrim for two additional weeks and left the

hospitable in stable condition without any long term sequelae. The family and his

patient were also treated with daily chlorhexidine baths.