We describe a young man who developed pharyngitis complicated by a septic thrombophlebitis of the jugular vein and embolization to the lungs, findings consistent with Lemierre syndrome. The most common solely isolated organism in this syndrome is Fusobacterium necrophorum. However, in this case, a group C streptococcus identified as Streptococcus anginosus was the cause of illness. To our knowledge, we believe this to be the first report of this species to solely cause Lemierre syndrome.
Department of Internal Medicine, Advocate Lutheran General Hospital, Park Ridge, IL.
Address correspondence and reprint requests to Joyce C. Rii, DO, MA, Department of Internal Medicine, Advocate Lutheran General Hospital, 1775 Dempster Street, Park Ridge, IL 60068. E-mail: Joyce.Rii-DO@advocatehealth.com.
We present a 22-year-old man with a medical history of hepatitis C contracted from intravenous drug use 6 years ago, with a chief concern of pharyngitis, myalgias, and pyrexia. The patient stated that the sore throat and myalgias developed 1 week before admission. This was associated with anorexia and weight loss. The patient also complained of a cough with streaks of blood in the sputum. He was seen at his primary care physician's office at which a rapid streptococcal test and mononucleosis rapid test were performed, both negative. He was prescribed amoxicillin and sent home. The patient continued to have severe throat pain and a daily fever of 40°C for 2 days. On hospital admission, physical examination revealed a young man who was uncomfortable, but not in distress. His temperature was 37.3°C; blood pressure, 113/64 mm Hg; pulse rate, 83 beats per minute; respiratory rate, 20 breaths per minute; and oxygen saturation, 98% while breathing room air. His neck was supple with bilateral anterior cervical lymphadenopathy and tenderness on the right anterior cervical chain. Pharynx was pink with enlarged tonsils but without purulence; however, fresh blood on the tonsils was seen. His lung fields were clear bilaterally, and the heart were in regular rate with no murmurs appreciated. His abdomen was soft. Laboratory tests revealed a leukocyte count of 20,900 cells/μL (94% polysegmented neutrophils, 1% lymphocytes, and 5% monocytes) and 13,000 platelets/mL. Abnormal basic metabolic panel laboratory values were sodium of 128 mEq/L and urea nitrogen and creatinine levels of 50 mg/dL and 2 mg/dL, respectively. Blood cultures were ordered, and the patient was placed on ampicillin-sulbactam empirically.
During the patient's hospitalization, he remained febrile while on antibiotic therapy. On the third day, he complained of shortness of breath, and a splitting of the second heart sound was auscultated. Chest radiograph showed nodular infiltrates in the left and right lungs (Fig. 1B). Previous imaging (Fig. 1A) showed that the lungs were completely clear, and the rapid appearance of the densities suggested septic pulmonary emboli (Fig. 1). A transesophageal echocardiogram was performed with findings of tricuspid valve prolapse, but no evidence of vegetation or thrombus on the heart valves. The results of blood cultures were positive for group C streptococcus, and antibiotic therapy was modified to ceftriaxone.
On the basis of a clinical suspicion of Lemierre syndrome, computed tomography scans of the neck and chest were obtained with the findings of an acute thrombosis of the right common facial vein with thrombus extending to a patent right jugular vein (Fig. 1C). A dense infiltrate adjacent to the left hilum and multiple nodular densities/infiltrates were seen. A dense left upper lobe infiltrate was seen extending to the left hilum.
The organism was finally identified as Streptococcus anginosus. By the sixth day of hospitalization, the patient defervesced and had resolution of dyspnea and pharyngitis. He completed a total of 6 weeks of intravenous antibiotics with ceftriaxone, with complete clinical resolution.
In 1936, an article described 20 cases of an illness that progressed to septicemia within 1 to 2 weeks from the initial onset of a severe pyrexia and rigors.1 Named after the author, Lemierre syndrome is also known as postanginal sepsis and necrobacillosis. Characterized as a pharyngeal infection in young adults, oral floras invade into the head and neck veins and surrounding tissues, creating internal jugular vein septic thrombophlebitis that commonly metastasizes almost always to the lungs and sometimes to the joints. Seventy percent of case reports have attributed Lemierre syndrome to a gram-negative anaerobic bacillus, Fusobacterium necrophorum, as the sole agent.2 However, a literature review finds organisms such as Bacteroides species, Candida species, Eikenella corrodens, Fusobacterium nucleatum, Gemella morbillorum, Klebsiella pneumoniae, Lactobacillus species, Peptostreptococcus species, and Streptococcus viridans in polymicrobial infections.2-4 Recently, a reported case of Lemierre syndrome caused by a sole pathogen identified as an unknown species of a group C streptococcus suspected as Streptococcus equisimilis.5 We report a similar case; yet in our case, we have identified the species as S. anginosus as the sole agent.
Group C streptococci are divided into 2 classes based on colony size: small/minute (<0.5 mm in diameter) and large colony (>0.5 mm in diameter). Large-colony group C streptococci have traditionally been divided into 4 species: Streptococcus dysgalactiae, S. equisimilis, Streptococcus zooepidemicus, and Streptococcus equi. Similarities have been reported between species, suggesting that they represent a single genotype.6 However, differences in fermentation patterns have changed the nomenclature of S. zooepidemicus to S. equi subsp zooepidemicus and S. equisimilis to S. dysgalactiae subsp equisimilis.
The small-colony group C streptococcus comprised 3 species: Streptococcus intermedius, Streptococcus constellatus, and S. anginosus, collectively known as S. anginosus group, previously known as Streptococcus milleri when named by Guthof in 1956 after W. D. Miller, an oral microbiologist.7 This group requires a microaerobic or anaerobic environment for growth and produces a caramel-like odor on agar plates.
Streptococcus intermedius colonizes the mouth, upper respiratory, and intestinal tract. It is known to cause pyogenic infections of the skin, soft tissues, intra-abdominal structures, and bone and possesses particular tropism for the brain and liver.8 Streptococcus constellatus contains 2 subspecies: S. constellatus subsp constellatus and S. constellatus subsp pharyngitis. This pathogen is usually isolated from lower respiratory tract infections, empyema, and thoracic abscesses. Streptococcus anginosus is found in the mouth, upper respiratory tract, gastrointestinal tract, and vagina. This pathogen can cause suppurative infections of the brain, lung, abdomen, pelvic, and soft tissue.9 Incidences of pleural empyema, spondylodiscitis, meningitis, peritonitis, endocarditis, and osteomyelitis have also been reported.10 However, one author found S. anginosus the least likely to be associated with abscess when compared with S. intermedius and S. constellatus.
In 1947, a prospective study of 3000 US army recruits hospitalized for respiratory tract infections reported 7 patients with positive cultures for group C streptococcal infections.11 Since publication, the role of β-hemolytic group C streptococci as a pathogen in pharyngitis has been debated. An epidemiological study by Turner et al12-14 found significant isolation of S. dysgalactiae subsp equisimilis and S. anginosus from cultures of throat swabs from patients with exudative pharyngitis compared with the cultures of throat swabs from healthy controls.15 However, the author concludes by stating that S. anginosus does not play a prominent role in the clinical syndrome of acute pharyngitis in young adults because of differences in isolation rates between S. anginosus (8%) and S.dysgalactiae subsp equisimilis (11%).14 Contradictory studies have shown that S. anginosus may be more commonly found. Lawrence16, Lebrun et al,17 and Ruoff et al18 found more isolates of S. anginosus than S. dysgalactiae subsp equisimilis from various clinical sources at rates of 56%, 73%, and 75%, respectively.11,19 Lewis and Balfour11 isolated group C streptococci in 4.4% of throat swabs sent for bacteriological examination in young adults with complaints of pharyngitis. Species identification found that 38% belonged to S. dysgalactiae subsp equisimilis and 53% to S. anginosus. The virulence of S. anginosus in pharyngitis seems less than group B streptococci, causing less pyrexia, tonsillar enlargement, lymphadenopathy, and pharyngeal exudates.14,15
The predominant treatment of Lemierre syndrome has been antibiotic therapy tailored to organisms isolated in culture. Clarridge et al20 reported S. anginosus group to be susceptible to penicillin, amoxicillin, cefotaxime, and ceftriaxone, but variable susceptibilities to tetracycline, clindamycin, and erythromycin. One author reports that the initial selection of antibiotic therapy and susceptibilities did not depend on the identification of the group C streptococcus to the species level.21 Many clinicians have added coverage to include F. necrophorum because of its prominence in this syndrome. Anecdotal evidence suggests that patients will respond to antibiotics alone; however, literature review by Armstrong et al2 found 21% of case reports receiving anticoagulation therapy. One author reserves anticoagulation for patients with propagation of the internal jugular vein thrombophlebitis toward the cavernous sinus, a regimen consisting of 1 week of heparin and 3 months of coumadin.22,23 Surgical interventions such as ligation of the internal jugular vein are recommended only in patients who have persistent fevers, increasing thrombus size, recurrent septic emboli, or uncontrolled sepsis after 48 to 72 hours of intravenous antibiotic therapy.23,24
In summary, this case highlights S. anginosus as the sole etiological agent in Lemierre syndrome and the importance to recognize it as a potential pathogen in the role of pharyngitis. Although F. necrophorum is a well-known causative agent of Lemierre syndrome, group C streptococci must now be included in the differential diagnosis.
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