Rare case of bilateral blindness caused by Streptococcus dysgalactiae spp equisimilis endophthalmitis in the setting of meningitis

Abstract

Endogenous endophthalmitis (EE) is a rare infectious disease of the intraocular tissues with a major risk of significant visual loss. We describe a case of a female patient who presented with altered mental status and vision loss. The patient was found to have bacteraemia, meningitis and bilateral EE caused by Streptococcus dysgalactiae spp equisimilis. The patient was clinically stabilised but continued to demonstrate profound visual loss at 5-month follow-up. To our knowledge, this is the first case report of this organism causing meningitis complicated by EE. Furthermore, this infection may have heralded a diagnosis of cancer.

Background

Endophthalmitis is a rare but devastating condition that may have significant consequences for a patient’s vision and overall health. Most cases are usually exogenous in nature, in which microorganisms are inoculated from the external environment. However, endophthalmitis may also occur through endogenous spread of systemic infections in 2%–8% of cases.^{1 2} Endogenous endophthalmitis (EE) is infrequent, but it is known to have a poor visual prognosis.³ Misdiagnosis and delayed diagnosis likely contribute to these poor outcomes. Approximately, 25% of cases of endogenous bacterial endophthalmitis are misdiagnosed on initial evaluation.¹ Early diagnosis and treatment are critical for the preservation of vision and survival.⁴

While haematogenous spread of fungal organisms accounts for the majority of cases of EE, bacterial EE also occurs.^{3 5} There are regional variations in causative organisms, but in most Western countries, gram positives such as Staphylococcal and Streptococcal species are most common—usually following infections of the liver, lung, endocardium or urinary tract.^{1 3 5} Rarely, the infection can originate from the meninges occurring in approximately 5% of cases. Here, we present a case of bilateral EE in the setting of Streptococcus dysgalactiae spp equisimilis (SDSE) meningitis.

In addition to this case’s bilateral eye involvement associated with meningitis, to our knowledge, this is the first reported case of SDSE presenting with both meningitis and EE.^{6 7} SDSE is a group C and G streptococci with increasing global incidence with close genetic and clinical similarity to S. pyogenes.^7–10 Most commonly, SDSE presents with cellulitis and soft tissue infections. Rarely, as in our case, it can cause invasive disease with multiple sites of infection.^{7 9 10} When present, SDSE bacteraemia has a significant risk of mortality and has high association with colorectal cancer.^{10 11}

Case presentation

We report a case of a female patient in her 70s with a previous medical history of bicuspid aortic valve with aortic stenosis status post bovine aortic valve replacement 10 years prior, atrial-ventricular block with dual-chamber pacemaker, paroxysmal atrial fibrillation on warfarin and well-controlled hypertension on lisinopril and metoprolol succinate who presented to our emergency department with lethargy, confusion and fever. The patient lived alone and was previously seen fully functional, working in her garden, with no impaired mentation 2 days prior. She had no history of visual abnormalities or ocular surgery. After 2 days without communication, the family contacted emergency medical services who arrived at the house to find the patient sitting minimally responsive. She was brought to the emergency department by ambulance.

On presentation, the patient was lethargic, confused and febrile with a temperature of 39.6°C. She was normotensive with a heart rate of 81 bpm and an irregular rhythm. External ocular examination showed normal orbits, conjunctiva and sclera. Visual acuity was unable to be accurately assessed at this time due to the patient’s mental status, but her pupils were non-responsive to light. An internal ophthalmic examination was not performed at this time. Additionally, the patient was noted to have a rash consistent with herpes zoster on her back. The patient was subsequently admitted to the Intensive Care Unit.

Investigations

Admission labs were significant for a lactic acidosis of 2.4 mmol/L, C reactive protein of 18.5 mg/dL, and a white blood count of 6.77x10⁹/L. The patient was found to have an acute kidney injury secondary to rhabdomyolysis. CT of the head did not reveal any acute processes. MRI was not performed due to patient’s pacemaker. Urinalysis was negative for nitrites and white blood cells. Cerebrospinal fluid (CSF) studies were obtained revealing normal opening pressure of 13 mm Hg, straw coloured fluid, low glucose of 35 mg/dL, protein elevation of 160 mg/dL, total nucleated cell count of 3414/mm³ with 88% neutrophils and 12% monocytes, red blood cell count of 60/mm³ and negative Herpes Simplex Virus 1 and 2 PCR assay. Gram stain of the fluid showed rare gram-positive cocci and heavy polymorphonuclear leukocytes. Blood and CSF cultures were sent. Blood cultures were positive in 4/4 samples after 6 hours eventually speciating as SDSE with susceptibility to ceftriaxone, penicillin G and vancomycin. CSF culture showed no growth after 2 days. The blood culture results provided a plausible organism for the patient’s meningitis, so no further CSF studies were sent.

By the second morning of hospitalisation, the patient was stabilised and her mentation had improved. She was found to have vision limited to light perception in both eyes. Examination showed bilaterally dilated pupils to 8 mm that were non-responsive to light. Ophthalmology was promptly consulted, and on examination, the patient was found to have moderate nuclear sclerosis and severe vitritis, which prevented full visualisation of the posterior chamber. Intraocular pressure was normal in both eyes. Extraocular motility and external structures were normal. A bilateral vitreous tap was performed and intravitreal antibiotic were injected. Due to this being unsuccessful oculus sinister (OS), aqueous sampling was performed instead. These were cultured, eventually showing heavy SDSE in the intravitreal culture and no growth within 2 days in the aqueous tap.

Additional evaluation was performed to assess for other niduses of infection. Abdominal and renal ultrasounds showed no evidence of abscesses. Transthoracic echocardiogram was negative for vegetations. Transesophageal echocardiogram also revealed no signs of infective endocarditis. A positron emission tomography (PET) scan was obtained prior to discharge to assess for involvement of the patient’s pacemaker and spine. There was no significant uptake in these regions, but the PET-CT revealed hypermetabolic activity in the aortic valve of unclear aetiology as well as findings consistent with possible metastatic rectal carcinoma. Additionally, images of the brain showed uptake in the R temporal lobe and posterior cranial fossa (figure 1).

Figure 1.

Positron emission tomography scan of the patient’s brain showing asymmetric activity in the right temporal lobe and symmetrical activity in the posterior cranial fossa.

Treatment

On arrival to the emergency department, the patient was initially suspected to have severe sepsis of unclear aetiology and was started on intravenous vancomycin and intravenous piperacillin/tazobactam, however, when the diagnosis of meningitis was entertained, antibiotic therapy was adjusted to intravenous vancomycin, intravenous ceftriaxone and intravenous ampicillin. When blood culture results were finalised including antimicrobial susceptibility testing, antibiotic therapy was de-escalated to intravenous ceftriaxone 2 g every 12 hours. The patient was also started on valacyclovir for her zoster infection. Following the vitreous tap, the patient received oculus uterque (OU) intravitreal vancomycin and ceftazidime. She additionally received OU prednisolone eye drops. The patient was discharged on intravenous ceftriaxone to complete a 6-week course. Additionally, 2 weeks after hospitalisation, the patient was treated with sub-Tenon’s Kenalog injections bilaterally due to persistent inflammation and impaired vision.

Outcome and follow-up

The patient did not experience improvement of vision. In outpatient follow-up, persistent, dense vitritis was noted on examination, which was further exemplified via B-scan ultrasonography (figure 2). Following limited improvement with sub-Tenon’s Kenalog, the patient subsequently underwent pars plana vitrectomy (PPV) oculus dexter (OD) in a week and a half later. Multiple retinal breaks and a detachment were noted and repaired with the placement of silicone oil. A vitrectomy was not performed OS due to guarded visual prognosis. Despite intravitreal antibiotics and PPV, the patient remained only having light perception OD and no light perception OS. The patient survived the acute infection with completion of antibiotics; however, the incidentally found rectal mass was found by biopsy to be an advanced stage rectal adenocarcinoma for which she is currently being treated.

Figure 2.

B-scan ultrasound demonstrating scattered vitreous opacities one time per day and dense vitreous debris oculus sinister (OS).

Discussion

EE is a condition associated with significant vision loss.¹ We presented a case of this rare condition in the setting of bacteraemia and meningitis caused by the SDSE. While SDSE typically presents with soft tissue infections, it can occasionally present with invasive disease such as bacteraemia and multifocal metastatic infection.^{6 9} Endophthalmitis and meningitis are both extremely rare manifestations of SDSE infection with only 24 reported cases of group C streptococcus (GCS) leading to EE in a recent review and similarly low reports of meningitis.^{6 7} As a result, little is known about the specific treatment, presentation and outcomes of SDSE EE and meningitis. To our knowledge, this is the first reported case of SDSE presenting with both these conditions, although a few cases have implicated other GCS.¹²

SDSE is a common coloniser of the skin, gastrointestinal tract and female genitourinary system.⁷ SDSE is associated with cancer as well as cirrhosis, alcohol abuse, immunosuppression, cardiovascular disease and skin breakdown in up to 90% of patients.⁹ The initial nidus of infection in our patient is unclear. One possibility is that the bacteria were introduced through damaged skin related to her gardening wound or zoster infection. Later discussion with the patient revealed that she had scratched her arm on a wooden fence. Notably, however, the patient was discovered to have rectal cancer, which has a 21%–65% association with SDSE.¹¹ In this situation, her infection may have acted as a herald sign of this malignancy. Interestingly, the patient did not have signs of cardiac involvement on transesophageal echocardiogram (TEE) despite the presence of a prosthetic heart valve and a pacemaker which has been frequently reported, especially in SDSE EE. Endocarditis in our case could not be fully excluded given the patients non-specific cardiac PET findings. In GCS-related EE, endocarditis has been noted in up to 44% of cases.⁶

Typically, EE occurs via bacteraemia, leading to septic emboli in vasculature of the posterior segment of the eye. This subsequently spreads across the blood-ocular barrier and through the structures of the eye anteriorly.³ Resultant ocular damage occurs from inflammation and microbial proliferation as well as through toxin-induced damage.

Rapid diagnosis and early treatment of EE are critical to minimising damage to vision and the need for more drastic measures such as enucleation and evisceration.^{1 3 4} Our case demonstrates some of the difficulty with establishing the diagnosis, such as delayed visual assessment in the setting of altered mental status. EE is known to be a difficult diagnosis with common misdiagnosis and diagnostic delays.^{1 3 13} In part, this is due to the rarity of the condition. Additionally, EE can present in numerous ways, including with unilateral or bilateral disease and variable symptoms at onset, with some patients experiencing pain, vision loss, blurriness or floaters.³ Diagnosis may remain difficult even once suspected. Our case highlights the imprecision of the diagnostic testing. Anterior chamber aqueous sampling and vitreous sampling have a low yield of 22% and 32%, respectively.¹⁴ Vitrectomy has a higher diagnostic yield, thought to be in part due to localised infection near the retinal surface.³ CSF cultures for SDSE can similarly have limited positivity, especially after the initiation of antimicrobial therapy.^{11 15} While cultures certainly have a diagnostic role, clinical diagnosis should be established based on ophthalmic examination.

Standard treatment for EE includes broad-spectrum intravitreal antibiotics as well as systemic antibiotics initiated within 24 hours.^{1 3 4} The incidence of SDSE-specific EE and meningitis limits study on specific treatments, but intravenous penicillin G tends to be the therapy of choice for SDSE infections, including EE, with third-generation cephalosporins as reasonable alternatives.^{7 9} Vancomycin is appropriate for patients with severe penicillin allergies.⁷ Meanwhile, intravitreal ceftazidime and vancomycin are first line for suspected bacterial infections of the eye.^{1 3}

Surgical intervention with PPV should also be considered. This intervention has the benefit of confirming infection and providing antimicrobial susceptibilities as well as functioning as source control.³ There is no established criteria for when this is necessary, and it is up to clinical judgement.³ In our case, the patient’s right eye continued to exhibit significant vitreous inflammation on examination. PPV was performed OD to minimise intraocular inflammation and with hopes of improving visual prognosis. PPV was not performed OS due to poor visual prognosis in the setting of no light perception. While intravitreal or sub-Tenon’s steroids are another potential treatment modality, studies have not definitively shown benefit, although there is theoretically protection from inflammatory damage, tissue destruction and prolonging antibiotic half-life.^{1 4}

Our case is one of only a few reported EE cases caused by SDSE and likewise one of few reported cases of EE in the setting of bacterial meningitis. EE is known to be a challenging diagnosis.^{1 3 13} Given the importance of early intervention, it is critical to suspect this disease in any bacteremic patient with ocular symptoms.⁴ Special care should be taken as many patients with severe sepsis and bacteraemia may be unresponsive and unable to convey new vision changes.¹⁶ Clinicians should be vigilant and have a low threshold to consult for urgent ophthalmic assessment.

Learning points.

• Endogenous endophthalmitis (EE) is an extremely dangerous condition that clinicians should consider in any bacteremic patient with ocular symptoms.

• There are significant rates of misdiagnosis and delayed diagnosis for EE. Early systemic and intravitreal antibiotics are critical for minimising vision loss and mortality.

• There is an association between Streptococcus dysgalactiae spp equisimilis (SDSE) and cancer. Clinicians should consider this with any invasive infections of this organism.

• Vitreous and meningeal fluid cultures can have low diagnostic yield, especially for SDSE. A negative culture does not preclude these diagnoses.

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