Abstract
Invasive sinusitis is a rare complication of sinusitis. We present the case of a woman, age 72 years, who presented with acute encephalopathy in the setting of sepsis found to have extensive invasive sinusitis with intracranial extension secondary to Streptococcus intermedius, managed with intravenous antibiotics alone. S. intermedius is a rare cause of acute bacterial sinusitis, associated with infections of relatively greater severity and risk of intracranial spread, often requiring a combination of intravenous antibiotics and surgical debridement for source control. Successful treatment of invasive sinusitis with medical management alone may be achievable if surgical intervention is contraindicated. However, the probability of meaningful recovery without surgical source control is rare and is associated with greater morbidity and mortality. Therefore, factors contributing to the success of medical management alone should be investigated.
Sinusitis is inflammation of one or more of the paranasal sinuses defined as acute (< 4 weeks), subacute (4-8 weeks), chronic (> 8 weeks), and recurrent (≥3 episodes of acute sinusitis in one year).1 The most common clinical presentations include nasal congestion, nasal discharge, facial pain or pressure, and a reduction in or loss of the sense of smell.2 Viral is the most common cause of sinusitis, whereas bacterial sinusitis is relatively uncommon (2% of cases), and fungal sinusitis is rare.2,3 While sinusitis is a common diagnosis, invasive sinusitis is rare (3.7% incidence in patients hospitalized with sinusitis) and can result in neurological complications including brain abscesses, epidural or subdural empyema, preseptal or orbital cellulitis, osteomyelitis, and cavernous sinus thrombosis.4 While rare, bacterial infection is the cause most associated with infectious spread resulting in osteomyelitis and intracranial spread as complications of acute sinusitis.3,4 Haemophilus influenzae, Staphylococcus aureus, Streptococcus pneumoniae, and Moraxella are the most common bacteria that cause invasive sinusitis.5 This case describes a unique presentation of extensive intracranial involvement secondary to Streptococcus intermedius, a rare cause of invasive sinusitis.
Case Presentation
A woman, age 72 years, with a past medical history of recurrent sinusitis and cholecystitis initially presented to an outside hospital with sepsis, back pain, altered mental status (disoriented to time and situation with poor attention), periorbital pain, purulent ocular discharge, and chemosis following a ground-level mechanical fall. According to outside hospital records, the patient’s mentation had slowly declined over several weeks, eventually becoming bed-bound and unable to perform her daily activities, including personal hygiene. The patient began experiencing nasal congestion and rhinorrhea one day prior to admission. Initial imaging included computed tomography of the head and magnetic resonance imaging of the brain, which revealed extensive pansinusitis with near complete opacification of sphenoid sinuses (left worse than right), bilateral orbital inflammation, leptomeningeal enhancement, bilateral superior ophthalmic vein thromboses, right internal jugular vein thromboses, right transverse sinus thrombosis, small right cavernous sinus thrombosis, and central skull base osteomyelitis, along with possible right lateral cerebellar subarachnoid space abscess. The preliminary diagnosis was invasive fungal sinusitis given the insidious onset of symptoms. Blood cultures resulted positive for Streptococcus intermedius, and the patient was initiated on acyclovir, vancomycin, metronidazole, ceftriaxone, and micafungin. The patient’s altered mental status was thought to be most likely due to acute metabolic encephalopathy in the setting of multiple infections. Tests for ingestion and intoxication resulted negative, and there was no evidence of acute intracranial processes suggestive of trauma on imaging. Other laboratory tests obtained included hemoglobin A1c and lactic acid, both within normal limits. The patient was initiated on intravenous dexamethasone per otolaryngology recommendation and transferred to our institution for possible surgical debridement of the sinuses. Initial consultation services included otolaryngology, neurosurgery, ophthalmology, and infectious disease. The patient’s presenting visual acuity was 20/25 in the right eye (OD) and 20/70 in the left eye (OS), with markedly reduced extraocular movements in all cardinal directions, and elevated intraocular pressures to 22 OD and 20 OS. Surgical debridement of the sinuses was recommended given the extent of disease, but was ultimately refused by the patient and her partner due to blood loss risk and the patient being a Jehovah’s Witness. Therefore, a medical management approach was taken and adjustments to the patient’s antimicrobial regimen were made. Intravenous ceftriaxone dose was adjusted to a high-dose regimen of 2 g every 12 hours for improved central nervous system coverage and S. intermedius bacteremia. Intravenous micafungin was transitioned to intravenous amphotericin for better central nervous system penetration and fungal coverage. Intravenous metronidazole was continued for cholecystitis coverage. Intravenous acyclovir was discontinued, as herpes simplex virus encephalitis was of low concern. Vancomycin was also discontinued given negative methicillin-resistant Staphylococcus aureus nucleic acid amplification test. Ophthalmology initiated erythromycin ointment in both eyes. Repeat blood cultures were negative. A biopsy of the left nasal turbinate was obtained and resulted negative for fungus and anaerobic/aerobic growth but did reveal chronic inflammation. A lumbar puncture revealed cerebral spinal fluid with low glucose (69 mg/dL [normal 60% of serum/plasma glucose]), elevated protein (80 mg/dL [normal 15-45 mg/dL]), elevated RBC (3/μL [normal 0/μL]) and elevated nucleated cell count (27/μL [normal 0-5/μL]). The cerebral spinal fluid was negative for cryptococcus antigen and herpes simplex virus by polymerase chain reaction. Cerebral spinal fluid cultures were negative for aerobic bacteria, fungus, or acid-fast bacilli. The patient improved significantly from her baseline presentation just 2 days after medical management regimen adjustment, with vision improving to 20/25 in both eyes (OU), normal extraocular movements and intraocular pressures, minimal chemosis and injection, and no ocular pain. Additionally, mentation had improved with consistent orientation to self and familiarity to place and time with assistance. Given the rapid improvement and negative KOH (potassium hydroxide) prep for fungus, a fungal cause was thought to be unlikely. Therefore, amphotericin was discontinued. Intravenous dexamethasone was held for elevating blood sugars, possibility of steroid contribution to patient’s continued altered mental status and unclear benefit of steroid use. Intravenous metronidazole was also discontinued. However, 2 days following cessation of these medications, an acute worsening of the patient’s condition occurred with increased chemosis, eye pain, headache, and worsening altered mental status. Intravenous dexamethasone was re-initiated for concern of elevating intracranial pressure versus symptom rebound following rapid steroid discontinuation. Repeat magnetic resonance imaging of the brain with and without contrast, magnetic resonance venography with and without contrast, computed tomography stealth sinuses were obtained, which appeared overall stable from previous findings (Figure 1). The antibiotic regimen was expanded to resume vancomycin and metronidazole. Ceftriaxone was transitioned to cefepime. Amphotericin was not restarted as clinical rapid worsening in this manner would be uncharacteristic for a fungal infection. Mentation improved significantly after one day on this regimen.
Results from repeat MR Brain, MRV Brain, and CT Stealth Sinuses. (A) MR Brain and MRV with arrows indicating markedly dilated bilateral superior ophthalmic veins. (B) MR Brain and MRV with measure marker indicating 12.5 mm nonspecific right lateral cerebellar lesion interpreted as possible subarachnoid space abscess. (C) and (D) CT Sinus with arrow heads indicating bony dehiscence along posterolateral wall of left sphenoid sinus.
Over the course of the next 2 weeks, the patient steadily improved in mentation to be consistently oriented to self and situation. The patient’s ophthalmic examination remained unchanged from a presumed baseline of 20/25 OU. Antibiotics were de-escalated to ampicillin-sulbactam only, along with a long oral steroid taper. After 40 days of hospitalization, the patient remained stable, completing nearly 6 weeks of ampicillin-sulbactam to target skull base osteomyelitis. The patient was transferred to a rehabilitation center with continued plan to complete a total of 2-month steroid taper. Patient was transitioned to oral amoxicillin and clavulanate for the final 4 days of the 6-week antibiotic treatment for ease of medication administration due to transfer out of hospital. Patient was instructed to initiate apixaban once antibiotics were completed to address dural sinus thromboses.
Scheduled outpatient appointments for otolaryngology and neurology were made. At 7 days after hospital discharge, the patient completed outpatient follow-up with otolaryngology, who noted concern for odontogenic rhinitis upon review of imaging and identified poor dentition on physical examination. Patient was instructed to have carious teeth extracted. The patient’s mental status examination was similar to that at time of hospital discharge. The patient was taking prednisone and apixaban at the time of appointment but had completed all antibiotics 5 days prior to appointment.
The patient has not been evaluated since her otolaryngology appointment, because she was a no show to her neurology appointment, and a follow-up appointment with ophthalmology was never scheduled.
Discussion
This is a unique case presentation of extensive invasive sinusitis resulting in pansinusitis, bilateral superior ophthalmic vein thrombosis, bilateral orbital cellulitis, dural sinus thrombosis, internal jugular vein thrombosis, central skull base osteomyelitis, and right lateral cerebellar subarachnoid space abscess due to S. intermedius, which was managed medically. Of patients hospitalized with sinusitis, 3.7% develop bacterial invasive sinusitis.4 Proposed mechanisms of intracranial spread include retrograde spread through diploic valves, which drain the paranasal mucosa and connect to dural sinuses, leading to venous thrombophlebitis or through contiguous spread through bone.6 In this case, both are likely mechanisms for bacterial invasion, which led to extensive intracranial pathology. Per initial radiology read of imaging, the likely nidi of infection were the paranasal sinuses with a presumed pathway of infectious spread through a defect in the posterior wall of the left sphenoid sinus into the cavernous sinus. However, upon further review of computed tomography of the sinuses by otolaryngology during patient’s outpatient visit, multiple left-sided dental peri-apical lucencies were noted, suggestive of odontogenic sinusitis. This odontoid infection was the likely source of infection leading to sinusitis with intracranial spread along with suprahyoid deep neck space infection, which was noted on magnetic resonance imaging of the brain during hospital course.
The bacterium identified as the most likely cause of infection, S. intermedius, was a major contributor to the extent of bacterial invasion and severity of disease. S. intermedius is a bacterium within the Streptococcus anginosus group (SAG), which are primarily commensal bacteria of mucosal membranes. This group of bacteria is considered highly pyogenic due to enzymes such as hyaluronate lyase and chondroitin sulphatase, which can destroy the extracellular matrix leading to tissue destruction and invasive spread of the bacteria.7 There has been documentation of pediatric cases of invasive rhinosinusitis showing that infection with SAG leads to a more severe infection. These patients were more likely to require neurosurgical intervention and more likely to develop complications such as meningitis or permanent neurological deficits.8 Most case reports of invasive rhinosinusitis related to SAG infections occur in pediatric patients, which contrasts to our case of an adult patient with extensive invasive sinusitis of the same infectious etiology.
Therapeutic options for S. intermedius infection include penicillin or ceftriaxone. However, in the setting of intracranial spread, specifically with brain abscess formation, cefotaxime and metronidazole should be the regimen of choice along with surgical intervention.9 In our case, the patient was initially treated with a broad spectrum of antimicrobials to cover S. intermedius and presumed fungal infection. The third-generation cephalosporin, ceftriaxone, and metronidazole were included in this regimen, with transition to 2 weeks of a fourth-generation cephalosporin, cefepime, followed by eventual de-escalation to ampicillin-sulbactam for 6 weeks. Despite the multiple changes in antibiotics, the antibiotic regimen utilized for eradication of S. intermedius skull base osteomyelitis was ampicillin-sulbactam, suggesting this may be a beneficial antibiotic regimen for intracranial involvement of SAG infections.
The treatment for invasive sinusitis complicated by intracranial spread typically involves surgery. Specifically for intracranial abscesses, early aggressive treatment with abscess drainage and endoscopic sinus drainage has been shown to decrease the need for repeated craniotomies and is associated with a decreased length of hospital stay. Treatment with antibiotics alone is associated with up to a 50% treatment failure rate.10,11 Therefore, the standard of care is neurosurgical drainage for intracranial abscesses that develop as a complication of invasive sinusitis. Additionally, literature has shown surgical or endoscopic resection and sinus debridement results in an increase in meaningful recovery for patients along with decreased morbidity and mortality.12,13 In our case, surgical intervention was not pursued due to the patient’s religious values. However, despite forgoing surgical debridement and pursuing medical management only, the outcome for this patient was considered positive. The patient’s visual acuity improved from 20/70 OS with markedly reduced extraocular movements to 20/25 OS with normal extraocular movements at time of hospital discharge. Additionally, the patient had relative improvement in mentation at hospital discharge as compared to initial presentation. Given there has been no documentation in the electronic health system for the previous 20 years, it is difficult to determine if the patient has returned to her baseline mentation status.
Conclusion
This is a unique case of severe invasive sinusitis resulting in extensive thrombophlebitis of the bilateral superior ophthalmic veins, right internal jugular vein, right cavernous sinus and right transverse sinus along with orbital cellulitis, central skull base osteomyelitis, and right lateral cerebellar subarachnoid space abscess due to Streptococcus intermedius, successfully treated with medical management only. Given the bacterium’s virulence factors, the severity of complications, and thus overall prognosis, invasive sinusitis due to S. intermedius tends to be worse than other causes of sinusitis. Early identification of the pathogen and prompt treatment, including surgical intervention, of invasive sinusitis are likely the biggest factors that will lead to improved patient outcomes. However, this case suggests the possibility of successful medical management if surgical intervention is contraindicated. The probability of meaningful recovery without surgical source control is rare and is associated with greater morbidity and mortality. Therefore, factors contributing to success of medical management alone should be investigated.
- Received May 19, 2024.
- Revision received August 5, 2024.
- Accepted August 19, 2024.
References
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