Intracranial thrombosis associated with MSSA bacteraemia in the setting of influenza A

Abstract

The authors present a case of a 42-year-old previously healthy man who presented in sepsis, with right lateral gaze palsy. He was found to have bilateral cavernous sinus thrombosis (CST) and bilateral internal jugular thrombosis in the setting of Staphylococcus aureus bacteraemia. The patient was successfully treated and recovered from his illness after a protracted stay in the medical intensive care unit. We go over the treatment course and follow-up of this patient and discuss the need to have a high degree of clinical suspicion for CST and suppurative thrombophlebitis of the internal jugular veins. We also discuss the possible role of the Panton-Valentine leukocidin in causing thrombotic complications of S. aureus bacteraemia.

Background

The 30-day mortality of Staphylococcus aureus bacteraemia remains high at close to 20% despite recent advances in medicine.¹ Certain highly pathogenic strains of this bacteria have been associated with thrombotic complications including suppurative thrombophlebitis and cavernous sinus thrombosis (CST).²

Case presentation

A 42-year-old man with no prior medical history presented to the emergency department with a 1-week history of fever, chills, night sweats and myalgias. On further questioning, he described that his illness started with a pimple in his nose which, after manipulation, became progressively red and swollen, which spread into his left eye. In addition, he reported productive cough for the same duration of time. He had no history of tobacco, illicit drugs or alcohol abuse and no contact with animals or pets. He was born in Mexico, migrated to the USA>20 years before with no recent travel history. He was taking no prescribed or over the counter medications. He worked as an active labourer in a dry cleaner store. He had an exposure to two close friends with active tuberculosis (TB) approximately 20 years ago.

The patient appeared ill. He had a temperature of 37.1°C, heart rate of 142 bpm, blood pressure of 116/76 mm Hg, respiratory rate of 42 bpm and pulse oximetry of 96% on room air. Eye examination revealed left eyelid erythema and swelling with intact extraocular movements. Lung examination was positive for bilateral diffuse ronchi. The rest of the examination was otherwise normal.

Investigations

Initial laboratory tests revealed a white cell count of 3.800 g/L (reference range (RR) 4.4–10.6) with 71% band cells, platelet count of 92 g/L (RR 161–369), creatinine of 1.7 mg/dL (RR 0.6–1.4), serum albumin of 2.3 g/dL (RR 3.8–5.2), aspartate aminotransferase of 258 U/L (RR 0–40), alanine aminotransferase of 128 U/L (RR 5–35), lactate dehydrogenase of 419 U/L (RR 85–210), creatine kinase of 1866 U/L (RR 0–163), blood lactate of 6.5 mmol/L (RR 0.5–1.6) and a corrected anion gap of 21. A CT scan of the chest revealed multiple bilateral pulmonary opacities, some with central cavitation, along with prominent mediastinal and right hilar lymphadenopathy. Rapid influenza test was positive for influenza A. Blood and sputum cultures were collected at admission. The rest of routine laboratory tests including HIV were within normal RRs.

Clinical course prior to diagnosis

The patient was admitted to the general medical wards, received intravenous fluid resuscitation and was started on cefepime, vancomycin and oseltamivir. His acute kidney injury and lactic acidosis improved after fluid resuscitation. However, on day 2 of admission, he developed hypoxemia and increased work of breathing, requiring supplemental oxygen through nasal canula. In addition, he also developed lateral gaze palsy in the right eye. He was transferred to the intensive care unit and urgent imaging was planned.

Differential diagnosis

1. Influenza pneumonia with viral sepsis and orbital cellulitis.

2. Influenza pneumonia with bacterial superinfection, sepsis, infective endocarditis and embolic stroke.

3. Influenza pneumonia with bacterial superinfection, sepsis and intracranial suppurative thromboses.

4. Acute miliary TB with tuberculous meningitis.

5. Influenza pneumonia with bacterial superinfection, sepsis and pyomyositis of extraocular muscles.

Further diagnostic workup

Blood and sputum cultures were positive for methicillin-sensitive S. aureus (MSSA). MRI of the brain and neck with angiography and venography (see figure 1A–D) revealed extensive bilateral CST with clot propagation into the bilateral superior ophthalmic, facial and other adjacent small veins, pachymeningitis of the middle cranial and posterior fossa and bilateral internal jugular vein thrombosis without definite fluid collections. Transthoracic and transesophageal echocardiogram was normal. Following the above workup, our diagnosis was MSSA bacteraemia complicated by bilateral internal jugular vein and CST, leading to septic pulmonary emboli.

Figure 1.

(A) MRI post-contrast demonstrating confluent central areas of non-enhancement in both cavernous sinuses. (B) MRI post-contrast demonstrating clot propagation into the superior ophthalmic veins. (C) MRI post-contrast demonstrating abnormal enhancement of both abducens nerves. (D) MRV demonstrating a filling defect in the left internal jugular vein.

Treatment

Antibiotic treatment was narrowed to intravenous oxacillin for MSSA bacteraemia and therapeutic anticoagulation with heparin infusion was started for extensive venous thrombosis. The patient’s clinical condition deteriorated further requiring mechanical ventilation and vasopressor support. Given persistent bacteraemia, intravenous clindamycin was added. By day 13 of hospital stay, his blood cultures became negative; however, he developed further complications with acute anaemia, thrombocytopenia, multiple intramuscular haematomas of the thighs and gluteus, necrotising pneumonia and a left-sided loculated pneumothorax and empyema requiring a tube thoracostomy and eventually partial lung decortication. He underwent a tracheostomy and percutaneous endoscopic gastrostomy (PEG) tube placement for continued ventilatory and nutritional support. He was eventually weaned off mechanical ventilation and, after 53 days of hospital stay, was transferred to a long-term care facility to complete intravenous antibiotic therapy. Two months after discharge, the patient was readmitted for persistent painful fluid collections in the right gluteus and thigh requiring CT-guided drainage with negative cultures. At that time, a contrast-enhanced CT of the brain and neck demonstrated no evidence of thrombosis. In total, he received 6 weeks of intravenous antibiotic therapy after drainage of the last fluid collection. Given severe deconditioning, attempts were made to discharge the patient to a rehabilitation facility, however, given insurance limitations, he was ultimately discharged home with family support.

Outcome and follow-up

The patient has been followed up till 5 months after his discharge and has no residual symptoms of his infection. He has had his PEG tube removed and is tolerating an oral diet well. He is following with the department of otorhinolaryngology for care of his tracheostomy with plans for revision of the scar in the future. He is receiving outpatient physical and occupational therapy and is currently able to ambulate without an assistive device.

Discussion

Suppurative thrombophlebitis of the internal jugular veins (Lemierre’s syndrome) and CST are dreaded endovascular complications of bacteraemia. The combination of the two, although rare, has been reported in the literature, mostly by intraoral flora.^{3 4} S. aureus has also been reported to cause this same condition.⁵

Panton-Valentine leukocidin (PVL) producing S. aureus has been reported to cause thrombotic complications including Lemierre’s syndrome and CST.^{6 7} PVL is an exotoxin produced by some strains of S. aureus, which has necrotic, proinflammatory and prothrombotic properties.⁸ Although, our patient’s bacterial strain was not tested for the presence of the toxin, it is likely that he was infected by a toxin-producing strain. Evidence on managing PVL-producing S. aureus bacteraemia is sparse, but it has been argued that the use of clindamycin (aiming to inhibit toxin synthesis) and anticoagulation should be strongly considered.⁸

Our patient may have had a furuncle caused by S. aureus, which on manipulation can lead to transient bacteraemia. Furuncles in the ‘danger area’ of the face have been associated with intracranial thrombosis, including CST.⁹ Influenza A has been shown to predispose people to secondary bacterial infections as well, including MSSA.¹⁰

Anticoagulation is controversial in the setting of intracranial thrombotic infections; however, it is the only definitive way of achieving source control from endovascular infections in these patients. A high degree of clinical suspicion is needed to suspect intracranial suppurative thromboses, and prompt imaging must be obtained. Neurological deficits suggestive of possible cranial nerve palsies are frequent presentations of this condition.

Persistent S. aureus bacteraemia is a condition associated with significant morbidity and mortality. The ideal choice of other agents to add to betalactam antibiotics for synergistic purposes is still unclear and further research in this area is needed.¹¹

Learning points.

• Cavernous sinus thrombosis is a dreaded condition and must be suspected in septic individuals presenting with extraocular ophthalmoplegia; prompt imaging must be obtained to ascertain the diagnosis.

• Suppurative thrombophlebitis of the internal jugulars must be suspected in patients presenting with evidence of septic pulmonary emboli.

• Further research is warranted into the role of testing for Panton-Valentine leukocidin in patient with Staphylococcus aureus bacteraemia and thrombotic complications; a case can be made for the use of clindamycin to suppress toxin production if the bacteria are found to produce this toxin.