Lemierre’s Syndrome Due to Methicillin-Resistant Staphylococcus aureus

Lemierre’s syndrome is an uncommon and potentially fatal complication of oropharyngeal and facial infections. It involves an associated septic thrombophlebitis, bacteremia, and septic emboli. Traditionally, compromise of the internal jugular vein has been described in conjunction with an infection caused by anaerobes, especially, Fusobacterium necrophorum. In recent years, however, variant forms have been appearing, including other vessel compromise and other etiologic agents. We present the case of Lemierre’s syndrome in a 31-year-old male with facial vein thrombosis, septic emboli to the lungs, and bacteremia caused by methicillin-resistant Staphylococcus aureus. We hope that this case will raise awareness about variant presentations and promote a timely diagnosis and appropriate treatment of this potentially fatal infection.


Introduction
In 1936, André Lemierre published the original description of what later became known as Lemierre's syndrome. 1 He described a septicemia produced by an anaerobic infection followed by local thrombophlebitis and septic emboli. Subsequently, with the advent of antimicrobials, the prevalence of this syndrome significantly decreased and became a "forgotten disease." 2 More recently, however, there appears to be a resurgence with atypical presentations and etiologies. 3 In this article, we report a case of Lemierre's syndrome caused by methicillin-resistant Staphylococcus aureus (MRSA) and discuss the changing aspect of this fascinating infection.

Case
A 31-year-old male was admitted to the hospital with a 4-day history of fever, diaphoresis, and right submandibular edema. He also complained of sore throat, dyspnea, and pleuritic chest pain. He had a past history of HIV infection since 2017 and genital chlamydia infection. He was not taking antiretrovirals due to lack of compliance with his regular follow-up visits and medications. He endorsed alcohol, tobacco, and marijuana use but denied other illicit or intravenous drug use. On physical examination, he appeared acutely ill. He was febrile (39.4°C), tachycardic (143 heart rate), normotensive (121/66 mm Hg), and tachypneic (28 respiratory rate). Oxygen saturation was 99% on room air. He had right submandibular edema and a small orolabial ulcer with mild purulent drainage ( Figure 1). Bilateral tonsillar hypertrophy without exudates was also noted. There were no signs of dental or periodontal infection. Pulmonary examination revealed decreased breath sounds in the left lower lung field and bibasilar crackles. The rest of his examination was unremarkable. Laboratory studies revealed a white blood cell count of 26 200 cells/µL (85% neutrophils, 8% bands). Arterial blood gases and routine chemistries were normal. CD4 count was 356 cells/µL. Chest X-ray showed bilateral nodular opacities and a small left pleural effusion. Computed tomography (CT) scan of the neck showed right-sided submandibular inflammation, facial vein thrombosis, and reactive cervical lymphadenopathy ( Figure 2). CT scan of the chest revealed numerous subpleural and intraparenchymal pulmonary nodules, some with spiculated cavitation (Figure 3). Small bilateral pleural effusions, a large consolidative opacification in the left lower lobe, and bibasilar ground glass opacities were also noted. CT angiogram showed partial filling defects The patient was started on intravenous vancomycin and piperacillin/tazobactam. Piperacillin/tazobactam was discontinued after isolation of MRSA from blood cultures with no gram-negative or anaerobic growth. MRSA was also isolated from a drainage culture of the superficial orofacial ulcer. A transthoracic echocardiogram showed no valvular lesions or signs suggestive of infectious endocarditis. He initially received anticoagulation with intravenous heparin for 5 days and then oral apixaban for 5 additional days, but it was later discontinued.
The patient responded well to treatment, and after 1 week, his submandibular edema subsided ( Figure 4). He was discharged from the hospital after receiving 2 weeks of intravenous vancomycin and completed a 4-week course as an outpatient. This was administered via a peripherally inserted    central catheter at a skilled nursing facility with monitoring of routine laboratories and vancomycin levels. At a 2-month follow-up outpatient appointment, he was doing well. He was instructed to keep regular follow-up visits for his HIV care.

Discussion
Our case had features consistent with Lemierre's syndrome including right submandibular inflammation, facial vein thrombosis, bacteremia, and metastatic pulmonary emboli. This syndrome has traditionally been described as an internal jugular vein septic thrombophlebitis, septicemia, and distant septic emboli (usually involving the lungs) in association with an oropharyngeal infection. 4 Variations to this presentation, however, can occur. In his original description, 1 Lemierre himself mentioned that the primary infection might arise from other sites, including inflammatory lesions of the mouth and jaw, as it was seen in our case. In addition, the internal jugular may not be the primary vein involved. Facial vein thrombosis has been described especially in infections of oropharyngeal or facial origin, as was also seen in our case. To our knowledge, only 6 cases of Lemierre's syndrome presenting with facial vein involvement have been reported ( Table 1).
The etiologic agent isolated in our case was atypical. Lemierre originally described several species of anaerobes that live as saprophytes in various cavities of the body, including the mouth and pharynx, as the primary pathogens implicated, and in particular, Fusobacterium necrophorum. 1 Other pathogens including non-anaerobic species are implicated less frequently. We conducted a MEDLINE search using the terms "Lemierre's syndrome" and "Staphylococcus aureus" and identified 15 additional cases, all reported since 2010. These data suggest that S aureus may have become an important cause of Lemierre's syndrome in recent years. It is unclear if decreased frequency of traditional more susceptible pathogens or an emergence of S. aureus has played a role. Definite conclusions cannot be drawn based on the limited data available. However, it is worth noting that this organism is known to promote coagulation by secreting 2 coagulases, staphylocoagulase and von Willebrand factor binding protein that activate prothrombin to generate fibrin. This coagulase activity is essential for the formation of S. aureus-fibrin-platelet microaggregates and for the homing of the organism to the vascular wall under flow. These mechanisms contribute to immune evasion and disease pathogenesis. 7 Molloy et al stated that despite often being described as a condition of the pre-antibiotic era, it now seems that Lemierre's syndrome belongs to our modern era of increasingly virulent and antibiotic-resistant organisms. 8 Sherer and Mishal stated in their editorial "The Changing Face of Lemierre's Syndrome" 3 that in this post-antimicrobial era, some of the classical characteristics of the disease have changed. They also concluded after analyzing several cases that one should expect "variations or incomplete forms" of the disease due to the widespread use of antibiotics. Chirinos et al 5 similarly stated that the typical course of this syndrome has changed since Lemierre's original description, most likely as a consequence of widespread antibiotic usage in pharyngeal infections.
We believe that increased awareness about atypical presentations and adding empiric antimicrobial coverage against MRSA should be considered whenever there is suspicion of Lemierre's syndrome.

Conclusion
Our case illustrates an atypical presentation of Lemierre's syndrome due to MRSA. Clinicians should be aware of the changing clinical features of this syndrome as earlier recognition and pathogen-specific antimicrobial treatment will lead to improved outcomes.

Declaration of Conflicting Interests
The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Funding
The author(s) received no financial support for the research, authorship, and/or publication of this article.

Ethics Approval
Our institution does not require ethical approval for reporting individual cases or case series.

Informed Consent
Verbal informed consent was obtained from the patient for their anonymized information to be published in this article.