Clostridium septicum brain abscess

Abstract

We present a previously well woman in her 70s who was admitted for 2 weeks of progressively worsening abdominal pain, high fever and drowsiness. She was eventually diagnosed with Clostridium septicum brain abscess, meningoencephalitis and ventriculitis. The diagnosis was challenging as cerebrospinal fluid cultures were negative and a microbiological diagnosis was only obtained on brain biopsy. Despite early initiation of antibiotics that would have been effective against C. septicum, her central nervous system (CNS) infection progressed, and she eventually succumbed to the infection. Infections with C. septicum are typically fulminant and associated with high mortality. In a patient with a CNS infection and concomitant abdominal manifestations, infection with C. septicum should be considered.

Background

Clostridium septicum is a Gram-positive anaerobic bacillus, which is part of normal gut flora.¹ Commonly associated with colonic malignancy, C. septicum gains entry through the breakdown of bowel mucosal barrier and causes spontaneous gas gangrene.² Central nervous system (CNS) infection with C. septicum is rare but carries a high mortality rate.^{2 3} Early initiation of effective parenteral antibiotics with good CNS penetration and prompt surgical drainage of brain abscesses are essential to achieve a good clinical outcome.³ We report a case of C. septicum brain abscess to share the challenges we faced in the evaluation and management of our patient.

Case presentation

A woman in her 70s with no medical history was admitted for 2 weeks of worsening abdominal pain, coupled with high-grade fever and drowsiness. She has a positive family history of colorectal cancer. Her vitals on admission reflected normal blood pressure and heart rate, with a tympanic temperature of 39.9°C. Clinical examination revealed right iliac fossa tenderness without guarding, and she was somnolent with a Glasgow Coma Scale (GCS) of E3V4M6 with bilateral reactive pupils. A CT scan of the abdomen and pelvis revealed a sealed caecal perforation and terminal ileitis. Empirical intravenous ceftriaxone and metronidazole were initiated. Aspiration of the pericaecal collection eventually grew Escherichia coli.

On day 2 of admission, the patient’s level of consciousness deteriorated to a GCS of E1V1M4 with anisocoria; the right pupil measured 3 mm with sluggish response to light and the left pupil measured 5 mm with no response to light. She had positive Babinski’s sign with neck rigidity. The presence of photophobia was difficult to elicit in view of her poor level of consciousness. An emergent CT brain revealed hydrocephalus with no evidence of brain herniation (figure 1); the hydrocephalus was likely non-obstructive as the fourth ventricle was open and no mass effects to account for obstruction. In response, she underwent an emergency right frontal external ventricular drain (EVD) insertion. Intraoperatively, the opening pressures measured 6 mm Hg, and the cerebrospinal fluid (CSF) aspirated was clear. Postoperatively, the patient was kept intubated and transferred to the intensive care unit. The ceftriaxone dosage was adjusted to achieve optimal CNS penetration.

Figure 1.

Image of CT brain performed immediately after patient had a sudden decrease in conscious level with anisocoria. There was evidence of hydrocephalus but no brain herniation at the time of scan.

Investigations

Biochemical investigations revealed raised inflammatory markers—C reactive protein 416 mg/L, procalcitonin 84.7 ng/mL and total white count 15.3×10³ /L with a differential of 90.6% neutrophils. Renal and liver function tests were unremarkable. A contrasted MRI brain scan obtained on day 3 of admission showed basilar meningitis, encephalitis and ventriculitis, and ring-enhancing brain lesions in the left frontal and right parietal lobes concerning for brain abscesses. HIV antigen/antibody test was non-reactive. Multiple sets of blood cultures were unyielding. CSF analysis from samples taken 1 day after empirical antibiotics initiation showed neutrophilic pleocytosis with raised protein (protein 447 mg/dL, 324 cells with 90% neutrophils and 10% lymphocytes, glucose 46.8 mg/dL). Gram stain, bacterial cultures, acid-fast bacilli (AFB) smears, tuberculosis PCR, fungal cultures and a multiplex PCR (BioFire FilmArray Meningitis/Encephalitis panel) performed on the CSF returned negative. 16S ribosomalRNA sequencing of the CSF was unsuccessful. Transthoracic echocardiogram did not identify any vegetation, and CT thorax revealed right lower lobe consolidation with tree-in-bud opacities in bilateral lower lobes of the lungs. A bronchoscopic lavage was performed, but extensive microbiological investigations were similarly unyielding.

Differential diagnosis

In conjunction with an infectious disease specialist, the initial impression was that of a pyogenic brain abscess for which the most common causes are Streptococcus species and Klebsiella pneumoniae. The concomitant caecal perforation and terminal ileitis also raised suspicion for disseminated salmonellosis. However, when all bacterial cultures returned negative, and neurological status remained poor despite empirical ceftriaxone and metronidazole, the diagnosis of CNS TB was considered in view of the constellation of basilar meningitis, terminal ileitis with caecal perforation and tree-in-bud lung opacities.

Treatment

Empirical treatment for CNS TB with isoniazid, rifampicin, pyrazinamide, levofloxacin and adjunctive corticosteroids was added to intravenous ceftriaxone and metronidazole on day 6 of admission while awaiting AFB cultures. Bedside percutaneous tracheostomy was performed on day 9 of admission, and the patient was eventually weaned off the ventilator.

Despite concurrent treatment for both pyogenic and TB brain abscesses, the patient’s neurological status remained poor. Interval CT scan performed on day 11 of admission showed an increase in size of the right parietal lobe abscess and stable size of left frontal lobe abscess. Surgical aspiration of the abscesses was recommended, but the family opted to continue antibiotics due to concerns of neurosurgical risks. When the EVD was found to be obstructed on day 15 of admission, the patient underwent change of EVD and aspiration of the left frontal lobe abscess, which yielded 20 mL of frank pus. Bacterial cultures eventually grew C. septicum sensitive to clindamycin, metronidazole and penicillin G on day 18 of admission, and a diagnosis of C. septicum meningoencephalitis, ventriculitis and brain abscess was made. A postoperative MRI brain showed an increase in size of the existing intracranial abscesses and interval development of new loculated intracranial abscesses with extensive meningoencephalitis, ventriculitis and right-ward midline shift of 0.5 cm (figure 2).

Figure 2.

MRI brain T1 with contrast axial images demonstrating multiple intracranial abscesses. (A) Intracranial abscesses present in bilateral parietal lobes and right frontal lobe, (B) as well as in the genu of the corpus callosum and left frontal lobe. The largest intracranial abscess was in the right parietal lobe measuring 3.2×2.8 cm. In addition, the images revealed right-ward midline shift 0.5 cm, and extensive leptomeningeal enhancement and thickening.

Outcome and follow-up

As the multiple brain abscesses were in surgically challenging locations, the neurosurgical team felt that further surgical intervention was not feasible and recommended for treatment with parenteral antibiotic therapy alone. On day 21 of hospital admission, the patient suffered a cardiorespiratory arrest with severe hypoxic-ischaemic encephalopathy. The family was updated on the poor prognosis and requested for terminal extubation in view of medical futility. The patient was terminally extubated and demised on day 23 of hospital admission. The cause of death was reported as acute myocardial infarction contributed by meningoencephalitis.

Discussion

C. septicum is a rare cause of CNS infection in adults, with less than 20 published cases thus far.³ The organism is typically associated with colonic malignancy that compromises the bowel mucosal barrier, resulting in haematogenous spread to the brain causing meningoencephalitis or brain abscesses.^{2 4} The disease prognosis is poor, with mortality rates exceeding 70% based on published studies.^{3 5} The treatment of C. septicum meningoencephalitis involves parenteral antibiotic therapy and aspiration of brain abscesses where possible.^{2 3 6}

While our patient had been on ceftriaxone since admission, which has activity against C. septicum, the initial lack of a microbiological diagnosis and the delay in surgical drainage likely contributed to our patient’s poor outcome. Although multiple blood and CSF cultures were taken, the aetiological agent C. septicum was not identified, likely due to empirical antibiotics. Moreover, our patient did not have pneumocephalus, a feature commonly seen in other cases of C. septicum infection. When clinical response was poor, surgical drainage of the abscesses was recommended for diagnosis and source control. An earlier surgical drainage might have improved the patient’s outcome, though such a procedure would risk incurring surrounding brain injury. Antibiotic penetration into the brain abscesses was suboptimal, as C. septicum still grew from the brain abscess aspirate despite 15 days of antibiotics.

When CSF cultures remained negative, TB treatment was initiated with adjunctive steroids, which might have further impaired antibiotic penetration into the CNS. As there was a compatible clinical syndrome that suggested disseminated TB, we decided to administer adjunctive dexamethasone with empirical TB treatment as steroid treatment confers survival benefits in patients with TB meningitis. At the same time, empirical antibiotics against pyogenic bacteria were continued while attempts were made to establish a microbiological diagnosis through obtaining more CSF for cultures, prolonged incubation of cultures, molecular diagnostics and aspiration of the brain abscess. The plan was to adjust antimicrobials and steroids quickly once a microbiological diagnosis was secured. The patient was never clinically stable enough to undergo endoscopic evaluations for the sealed perforation in the caecum, which in retrospect may be due to an undiagnosed colonic malignancy.

In conclusion, C. septicum CNS infection is rare but should be considered when there is concomitant suspicion for colonic malignancy. In cases of brain abscesses where clinical response is poor, early surgical drainage should be considered to obtain a microbiological diagnosis and achieve source control due to suboptimal antibiotic penetration.

Patient’s perspective.

Patient’s daughter—I am grateful for all the support that the medical team has given to my mother and family. It has been a challenging period for all of us. Eventually, the medical team was able to identify the rare bacteria infecting her brain. Through this case report, I hope that my mother’s case can be of help to others in the future.

Learning points.

• In a patient with a central nervous system (CNS) infection and concomitant abdominal manifestations suspicious for colonic malignancy, infection with Clostridium septicum should be considered.

• Prognosis of CNS infection with C. septicum is poor, with a high mortality rate.

• Antibiotics with good CNS penetration and early, aggressive surgical drainage of brain abscesses are important in the management of CNS infection with C. septicum.

Ethics statements

Patient consent for publication

Consent obtained from next of kin.