When a Stroke is not Just a Stroke: Escherichia coli Meningitis with Ventriculitis and Vasculitis: A Case Report

Pyogenic ventriculitis is defined as the presence of suppurative fluid in the cerebral ventricular system [1,2]. It is usually a complication of neurosurgical procedures, ruptured brain abscesses, or head injury [1, 2, 3]. Cases of community-acquired ventriculitis are rare, with only a few cases due to Escherichia coli (E. coli) reported in the literature[2,3]. Bacteria can cause an acute septic process in the brain and the surrounding meninges, leading to cerebral vasculitis [4]. Mortality associated with E. coli central nervous system (CNS) infections is high (47%), and it can be greater than 85% when associated with specific risk factors [5]. The emergence of extended-spectrum beta-lactamase (ESBL) producing Enterobacteriaceae also poses a significant challenge to the management of these cases [6,7].

A 58-year old Caucasian British female presented to the emergency department (ED), Colchester General Hospital, Colchester, UK in October 2018, after she was found unresponsive by relatives. She had complained of sudden onset headache the night before admission and had attended the same ED days previously with symptoms suggesting a urinary tract infection (UTI), for which she was given unspecified oral treatment and discharged. A mid-stream urine sample obtained at that time was reported later as positive for E. coli, as were samples from previous years.

Initial findings included a Glasgow Coma Score (GCS) of 6/15 (scores of 2, 1 and 3 for eye, verbal and motor responses, respectively), right-sided weakness and facial droop. She was afebrile, without neck stiffness but myoclonic jerks in both arms were noted. Past medical and social history included anxiety, treated with sertraline. She smoked approximately thirty cigarettes per day and alcohol intake of seven units per day. There was no recent history of travel, trauma or surgery.

She was intubated in the ED and transferred to the Intensive Care Unit (ICU). The initial working diagnosis was of stroke, however considering a possible CNS infection, ceftriaxone 2 grams 12-hourly (Wockhardt UK Ltd, Wrexham, UK) and aciclovir 640 miligrams 12-hourly (Hospira UK Limited, Hurley, UK) were promptly started. Results of blood tests on admission are summarised in Table 1.

At the time of admission, a computerised tomography (CT) of the brain showed signs of a left-sided middle cerebral artery (MCA) infarct, but no hydrocephalus. On the same day, a magnetic resonance imaging (MRI) of the brain showed a right internal capsule acute infarct and debris in the ventricles suggestive of ventriculitis (Figure 1).

Fig. 1

Two sets of blood cultures taken on the day of admission to hospital were later reported as having grown E. coli, with similar sensitivities to isolates from other fluid samples.

A lumbar puncture (LP) was performed, and cerebrospinal fluid (CSF) results are shown in Table 2.

CSF gram-stain analysis revealed that gram-negative organisms and culture results were later reported as Escherichia coli (Figures 2 and 3), susceptible to ceftriaxone. An unenhanced CT brain seven days after admission confirmed a recent right internal capsule infarct (Figure 4).

Fig. 2

Fig. 3

Fig. 4

A repeat LP, on day 11, post-admission, showed marked improvement (Table 3), with no further bacterial growth.

The patient had a prolonged stay in ICU, requiring mechanical ventilation for twenty-seven days. Therefore a reliable neurological examination was only possible after sedation hold. Marked left-sided hemiparesis was evident. Ceftriaxone was continued at the same dose and frequency until day 25 of admission, when dose was reduced to 2 grams daily. Aciclovir was stopped following the CSF microscopy report.

Strongyloides, human immunodeficiency virus (HIV), Hepatitis B and C serologies were reported negative. Renal tract ultrasound showed no evidence of hydronephrosis or collection. A transthoracic echocardiogram was reported as normal.

On day 27 of hospital admission, an MRI brain with contrast, showed persistent features of ventriclitis, a subacute infarct in the right internal capsule and trapped occipital horn of the right lateral ventricle (Figure 5). A tracheostomy was performed due to marked global weakness. The patient was successfully decannulated in ICU and stepped-down to the Stroke ward 29 days after hospital admission, requiring intensive physiotherapy and neuro-rehabilitation. On day forty-one post-admission, an MRI brain showed a mild reduction of a ring-enhancing lesion in the right lateral ventricle, but persistent ventricular debris (Figure 6).

Fig. 5

Fig. 6

The patient was discharged to a rehabilitation facility after fifty-eight days in the hospital and eight weeks of intravenous antibiotics. Follow-up imaging at four months showed significant regression of the findings previously noted.

Pyogenic ventriculitis is a known complication of meningitis and especially following neurosurgical interventions (e.g. shunts), trauma or CSF leak [3,5]. Spontaneous, community-acquired gram-negative bacilli CNS infections are reported as rare, representing 8.7% of all cases of meningitis. E. coli was reported in nearly 42% of cases [5]. A recent literature review suggested the main risk factors for community-acquired E. coli meningitis are chronic alcoholism and cirrhosis, diabetes mellitus, disseminated strongyloidiasis, HIV and chronic obstructive pulmonary disease. The same review suggested bacteraemia is the most common route of dissemination, followed by UTI and pneumonia.

E. coli is a well-known commensal in the human gastrointestinal (GI) tract [8,9]. These strains rarely cause disease, unless the host is immunocompromised or there is GI barrier incompetence due to peritonitis.

Three main categories of E. coli pathotypes have been described, causing enteric/diarrhoeal disease, urinary tract infections and sepsis/meningitis [8,9]. UTIs are the commonest extra-intestinal infections. Uropathogenic E. coli (UPEC) causes approximately 80% of UTIs, but it can also cause septicaemia [8, 9, 10]. Cases of meningitis and sepsis-associated E.coli (MNEC) have become increasingly common [8, 9, 10]. E. coli pathotypes share common mechanisms, including effective colonisation of the mucosa, evasion of the host’s immune system, multiplication and host damage. They can also acquire genetic elements that ensure their adaptation to new niches [9,10]. UPEC migrates from the GI tract and enters the genitourinary tract. Adhesion to the uroepithelium is facilitated by fimbrial adhesion H (fimH), and interaction with integrins allows internalisation of bacteria that can then enter the bladder and ascend to the kidneys. Toxins, such as haemolysin, can damage the renal epithelium, and once the glomeruli and tubules are affected, bacteria can enter the circulation [8, 9, 10]. In order to cause meningitis, bacteria must cross the blood-brain barrier and proteins such as the outer membrane protein A (OmpA) and K1 capsule play a role in causing damage to the brain tissue [8,9,11]. The formation of a ‘biofilm’ contributes to immune evasion and act as a reservoir for recurrent infections [8,10], whereas genomic plasticity contributes to the development of antibiotic resistance [11].

Recent case reports and reviews on primary ventriculitis question the true prevalence of the condition [2,6]. As clinical presentation can be non-specific, the diagnosis relies essentially on neuroimaging. The current patient did not present with neck stiffness, which is consistent with findings reported by Gronthoud et al. (2017)[3] and Kasimahanti et al. (2018)[6].

A high level of suspicion is needed, and an MRI of the brain is the most sensitive tool for early diagnosis [2]. The presence of irregular debris on MRI is specific for pus, according to Fukui et al. (2001) [12]. Recently, Vale et al. (2019) [13] published a case of community-acquired E.coli meningitis in a patient with spondylodiscitis and discoid lupus erythematosus. The current case differs from that one in so far as the current patient did not have any significant co-morbidities. As CSF, blood and urine cultures grew the same micro-organism, they lead us to hypothesise that a UTI was the likely source of E. coli infection, with later systemic dissemination.

Cerebral vasculitis has been reported as a complication of both pneumococcal meningitis and meningococcal ventriculitis [2], supporting the current findings. Meningeal inflammation can cause infiltration of inflammatory cells within the vessel walls, leading to vessel damage [4]. This report appears to be the first documented case of E. coli meningitis/ventriculitis with associated vasculitis.

The different vascular territories affected, left MCA on initial imaging, right internal capsule on subsequent scans, possibly reflected the evolution of the inflammatory response and CNS infection.

There are no specific recommendations for the management of patients with community-acquired ventriculitis [2,5]. An early neurosurgical opinion should be sought; however, the optimal duration for antimicrobial treatment is not well defined [2,3]. Given the potential high mortality and morbidity, longer duration of antibiotics should be considered (6-12 weeks) [2, 5].

Decision-making, during the management of the current patient, was multidisciplinary, and the teams involved included neurosurgery, critical care, microbiology and stroke. Persistent evidence of intra-ventricular debris on imaging was the primary concern and rationale for a long course of antibiotics.

This case report illustrates the unique features of a case of community-acquired E. coli meningitis with ventriculitis and cerebral vasculitis, in a patient with no significant co-morbidities. UTIs are recognised risk factor, and the belief was that this was the initial condition leading to disseminated E. coli disease. Obtaining early samples for culture, especially CSF, is vital to the identification of the causative agent and guide treatment. Prompt treatment is required, given the severity of the disease. A multidisciplinary approach is essential to the management of such complex cases.

Universal agreement and recommendation regarding the duration of antibiotic treatment in such cases is required.