Lemierre Syndrome Caused by MRSA In an Infant

AFFILIATION:
Department of Pediatrics, University of Texas Southwestern, Dallas, Texas

CITATION:
Roy M, Yang K, Patel A. Lemierre syndrome caused by MRSA in an infant. Consultant. 2023;63(4):e7. doi:10.25270/con.2022.10.000002

Received April 7, 2022. Accepted April 26, 2022. Published online September 30, 2022.

DISCLOSURES:
The authors report no relevant financial relationships.

DISCLAIMER:

The authors report that informed parental consent was obtained for publication of the images used herein.

CORRESPONDENCE:
Amee Patel, University of Texas Southwestern, 5323 Harry Hines Blvd Dallas, TX 75390 (amee.patel@utsouthwestern.edu)

Abstract

Lemierre syndrome is a rare disease that results in bacteremia, internal jugular vein thrombophlebitis, and septic emboli. Classically defined as an infection of the posterior compartment of the lateral pharyngeal space by Fusobacterium necrophorum affecting adolescents and young adults, there is considerable morbidity and mortality if appropriate antibiotics are not initiated. Despite becoming a “forgotten disease'' after the introduction of antibiotics, there has been a recent resurgence of cases within the last 20 years. Therefore, it is crucial that clinicians are educated on the clinical features of this rare yet serious condition so that they can appropriately diagnose and treat it in a timely fashion. We describe a case of a 9-month-old infant who presented with acute onset right neck and chest swelling ultimately found to have methicillin-resistant Staphylococcus aureus (MRSA) bacteremia and a right internal jugular vein thrombus consistent with Lemierre syndrome. Our case highlights an evolving diversity of aerobic organisms involved with the syndrome, concerning trends of increasing rates in younger pediatric populations, the therapeutic role of surgical intervention in addition to antibiotics, and the utility of long-term anticoagulation in the setting of lacking evidence.

Key words: Lemierre syndrome, pediatrics, thrombophlebitis, MRSA, antibiotics, anticoagulation

Case Presentation

A 9-month-old girl presented to our emergency room with an atraumatic right-sided neck mass that was tender to palpation. She was otherwise healthy when the initial symptoms of low-grade fevers and erythematous nonpruritic skin changes began 1 week prior, for which she was evaluated in the emergency department (ED) and given antipyretics and hydrocortisone cream. Her parent was instructed on supportive care measures. Over the next few days, however, she developed hardened nodules on her lateral neck, decreased neck movement secondary to pain, progressively higher fevers, irritability, drooling, and decreased oral intake. 

Initial vital signs showed the following: temperature of 37.8°C, heart rate of 163 beats/min, respiratory rate of 34 breaths/min, and blood pressure of 90/53 mm Hg. In the ED, the infant was started on intravenous clindamycin and fluids. Laboratory testing showed elevated inflammatory markers, and hypoalbuminemia. An ultrasound of the swollen area of the neck demonstrated nonspecific soft tissue swelling. A complete blood count showed a slight neutrophil predominance and bandemia. Urine culture and blood culture were collected. 

However, upon admission to the pediatric hospital medicine floor, evaluation showed an acute clinical change within 12 hours. The patient had an overall toxic appearance with fussiness, nuchal rigidity, and extensive right neck and clavicular swelling. She was also noted to have a 3- by 4-inch indurated nodule in the right cervical region without overlying erythema and 2 small satellite modules measuring 1 cm in the posterior chain. These findings, coupled with early growth of gram-positive cocci in pairs and clusters on blood cultures, led to expanding empiric coverage with intravenous vancomycin and ceftriaxone. Computed tomography of the neck showed extensive right neck edema extending into the supraclavicular region and anterior chest and a focal filling defect in the right proximal internal jugular vein (Figure 1). Guidance from infectious disease and hematology teams was requested. Anticoagulation with enoxaparin sodium was initiated due to an intramural thrombus, with a goal anti-Xa level of 0.5 to 1 unit/mL. Once blood cultures resulted in methicillin-resistant Staphylococcus aureus (MRSA), ceftriaxone was discontinued.

Figure 1. Computed tomography of the neck with contrast in sagittal view. The arrow points to the filling defect in the right internal jugular vein.

Approximately 48 hours into initiating antibiotics, the patient’s fever curve, inflammatory markers, duration between blood culture MRSA positivity, and clinical examination improved. However, on day 7, clinical status worsened with decreased oral intake, irritability, tachycardia, and recurrent fevers. Physical examination findings at this time demonstrated an overall improvement in edema, however, a focal fluctuant mass had overtaken the originally indurated nodule. These findings, in combination with persistent MRSA blood cultures, led us to pursue further imaging with magnetic resonance imaging of the neck to evaluate for an abscess as a source for continual nidus of bacteremia. Results showed phlegmonous changes within the right lower cervical soft tissues, early abscess formation in the subcutaneous fat overlying the right pectoralis muscle measuring 1.5 × 2.9 cm, and interval resolution of right internal jugular vein thrombus (Figure 2). Additional evaluation for septic emboli was done with a liver ultrasound, which was within normal limits. 

Figure 2. Magnetic resonance venography of the neck with contrast in coronal view. This image demonstrates interval resolution of the right internal jugular vein filling defect.

On day 10, the patient was taken for incision and drainage of her chest wall abscess under sedation. Approximately 5 cc of purulent discharge was expressed, and wound cultures grew MRSA. She tolerated the procedure well, and a vessiloop drain was put in place for 1 week. The following day her vital signs stabilized, and her constitutional symptoms and swelling resolved. Her subsequent blood cultures no longer had growth. Given the drastic improvement with surgical intervention and culture susceptibility, she was switched to oral clindamycin. Once stable on oral antibiotics for 48 hours, she was cleared for discharge with instruction to follow-up with infectious disease and hematology specialists. No other complications were reported after discharge. The patient’s hospital course and fever curve during her admission is summarized in Figure 3.

Figure 3. Hospital course timeline and fever curve of the patient.

Discussion

Lemierre syndrome (LS) is named after Dr Andre Lemierre, who published a report in 1936 detailing 20 cases of patients with pharyngotonsillitis or peritonsillar abscesses who developed neck swelling, tenderness, septic thrombophlebitis of the internal jugular vein, metastatic abscesses, and anaerobic septicemia.^1,2 The syndrome was rare but fatal, with 18 of the 20 patients succumbing to the disease.² The prevalence of LS decreased drastically after the development of antibiotics; however, there has been an increase in cases over the past few decades, possibly caused by antibiotic resistance or changes in antibiotic prescription patterns.³ One study, for example, found the overall incidence in Denmark increased from 0.8 cases per million per year in 1998 to 3.6 cases per million per year in 2008.⁴

The syndrome most commonly presents in the second decade of life. However, about 8% of patients are younger than 10 years old.³ In addition, there has been an increasing incidence of S aureus, rather than the classic Fusobacterium necrophorum, as the causative organism for this disease in the pediatric population.⁵ This underscores the evolving microbiologic profile of this disease. Jariwala and colleagues and Hameed and colleagues present cases of a 13-month-old child and a 4-year-old child, respectively, who were isolated with S aureus.^6,7 Our patient presented at 9 months of age with fevers, neck swelling, MRSA bacteremia, an internal jugular vein thrombus, and a chest wall abscess requiring an interdisciplinary approach to treatment with surgical incision and drainage, prolonged antibiotics, and anticoagulation.

Presentation

While the presentation of LS is variable, there are some common findings that point health care providers to the diagnosis. The table below lists the most common symptoms in LS and their estimated frequency.^3,5,8,9 Many of these common examination findings are nonspecific, but signs such as neck pain and swelling and internal jugular vein thrombosis should raise clinical suspicion for LS.

Table. Commonly Reported Symptoms in Lemierre Syndrome

Diagnosis

The diagnosis of LS can be challenging as it is rare, and there exists no universal consensus regarding its diagnosis.¹⁰. Historically, three criteria are used to diagnose LS: 

1. Primary infection source originating from the head or neck

2. Thrombus in the internal jugular vein or another vein of the head or neck

3. Identification of F necrophorum from the blood culture 

These criteria are not strict rules but guidelines due to numerous exceptions. For example, some researchers suggest that identifying an internal jugular vein thrombosis may not be required, as it can be easily missed and is not always present throughout the whole disease course.¹⁰ In addition, as our case highlights, F necrophorum is not the only organism to cause LS. A systematic review by Johannesen and Bodtger⁸ noted only 47 of 137 patients with LS were confirmed to be infected with F necrophorum. Therefore, the diagnosis of LS should not be excluded if F necrophorum is not identified in the patient. There has been a shift in the microbiome that causes LS. Although F necrophorum is the predominant etiology of LS, recent studies have identified more cases infected with Streptococcus and Staphylococcus than in the past.^5-7,11

Treatment

Treatment for LS is tailored to the specific bacterial source. Because most instances of LS are caused by F necrophorum, most antibiotic courses involve monotherapy with carbapenems or piperacillin-tazobactam with metronidazole.⁸ However, because our patient had MRSA, she was treated with vancomycin that was later narrowed to clindamycin after identifying sensitivities culminating in a total of 3 weeks of therapy. A variety of treatment lengths are reported in the literature ranging from 1.5 to 6 weeks, with the average length of treatment found to be 4 weeks.^2,7,8,14 Our patient was followed by our infectious disease specialists and showed improvement with no signs of disease recurrence. Her case emphasizes the importance of considering broader antibiotic coverage for pediatric patients with LS when an organism is not yet identified. 

Another important aspect of our patient’s case was the decision to start anticoagulation therapy, as it is still an area of debate for patients with LS. Our patient was discharged with instructions to complete 12 weeks of enoxaparin sodium therapy for her internal jugular vein thrombus. One review found that of the 137 patients diagnosed with LS, 64% were treated with therapeutic anticoagulation. ⁸ Only two of the patients treated with anticoagulation experienced an adverse drug reaction. Based on their review, the authors concluded that anticoagulation neither supported nor aided the resolution of LS.^8,9 A retrospective study by Cupit-Link and colleagues found that anticoagulation in LS has not been shown to affect thrombus outcomes; however, most patients in this study who received anticoagulation were pediatric patients.¹² Since there has not yet been a study examining the role of anticoagulation specifically for pediatric patients with LS, further research is needed.  

A review by Patel and colleagues found that in pediatric patients with LS, 66.3% had at least one incidence of surgical management, ranging from debridement and drainage to exploratory laparotomy.⁵ Surgical management is usually recommended in instances of empyema, tissue necrosis, and mediastinitis, and it may be required in those with abscess formation, pulmonary thrombosis, or cerebral thrombosis to clear the nidus of infection.^13,14 Surgical treatment for infected clots is usually reserved for prolonged cases of sepsis, bacteremia, or septic emboli despite antibiotic treatment.^13,15 Our patient required incision and drainage of her chest wall abscess to resolve her persistent bacteremia, after which she showed clinical improvement. Thus, incision and drainage should be strongly considered in other patients with a similar presentation.

Rapid identification and initiation of appropriate management of LS in the pediatric population is critical to recovery. A multidisciplinary approach with the help of infectious disease, hematology, and surgery colleagues is important for appropriate care of this complex disease. Further research targeting pediatric populations is needed to better understand the increasing biodiversity in bacterial organisms causing LS, the role of earlier surgical management, and the utility of anticoagulation.