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Good outcomes with the intraventricular vancomycin therapy in a patient with ruptured brain abscesses

Brain abscesses are associated with high morbidity and mortality rates. In particular, patients with intraventricular rupture of brain abscess (IVROBA) exhibit mortality rates up to 85%. Treatment options are lacking for IVROBA, once patients become refractory to intravenous antibiotics and surgical drainage. Limited data exist regarding the risks and benefits of intraventricular therapy in such a scenario. We report a patient with IVROBA, who deteriorated while on systemic antibiotics; once intraventricular vancomycin was employed, the patient demonstrated remarkable improvement without perceivable side effects. This case suggests that intraventricular vancomycin may be a safe, effective, and viable option for the treatment of IVROBA, especially for patients becoming refractory to systemic antibiotics.


Introduction
Brain abscesses are associated with high morbidity and mortality rates. [1] In particular, patients with intraventricular rupture of brain abscess (IVROBA) exhibit mortality rates up to 85%. [1][2][3][4][5][6] Currently, standard treatment involves surgical drainage and intravenous (IV) antibiotics. [1,[4][5][6] Sparse articles have documented good outcomes associated with intraventricular antibiotics for patients refractory to systematic treatment; [6][7][8][9] trialed antibiotics have included gentamicin, colistin, tobramycin, and ampicillin. [6,7,9] In general, intraventricular vancomycin has predominantly been directed at ventriculitis and shunt infections; [10][11][12][13] its use appears safe and effective. [10,11] Only one article has described the administration of intraventricular vancomycin as a treatment for IVROBA. [14] Given the paucity of literature, skepticism persists regarding the employment of intraventricular antibiotics specifically for the treatment of IVROBA. To our knowledge, this is the second report involving intraventricular vancomycin for the treatment of IVROBA in a patient persistently having positive cerebrospinal fluid (CSF) cultures despite prolonged use of IV antibiotics; once intraventricular vancomycin was employed, the patient demonstrated remarkable improvement without perceivable side effects.

Case Report
A 64-year-old male, with a history of poorly controlled Type II diabetes mellitus (HbA1c = 16), presented with right arm weakness, visual disturbance, expressive aphasia, and confusion. Magnetic resonance imaging (MRI) of the brain revealed multifocal brain abscesses (right frontal lobe, right occipital lobe, and left parietal lobe) [ Figure 1]. The patient was started on IV vancomycin, ceftriaxone, and metronidazole on the day of admission. The right occipital abscess was needle-tapped the next day, which grew Streptococcus intermedius; unfortunately, antibiotic susceptibilities could not be extracted due to inadequate growth. Despite treatment with systemic, broad-spectrum antibiotics for more than a month, the patient deteriorated into a comatose state, requiring intubation for airway protection. A repeat MRI of the brain showed IVROBA and associated ventriculitis [ Figure 2]. An external ventricular drain was placed [ Figure 3]. The patient underwent further needle drainage of the right frontal and left parietal abscesses. Daily CSF Gram-stain remained positive for Gram-positive cocci despite prolonged treatment with IV antibiotics. Due to continual clinical decline, intraventricular vancomycin therapy was initiated. The patient was given 10-20 mg of intraventricular vancomycin daily, through the external ventricular drain; dosages were adjusted to achieve the CSF vancomycin therapeutic trough level of 20-25 mg/L. [15][16][17] A week later, IV rifampin was added to the antibiotic regimen and ceftriaxone was switched to cefotaxime 2 g every 4 h. The CSF Gram-stain turned negative after 11 days of intraventricular therapy, and 5 days after the CSF, vancomycin level became therapeutic. On the same day, the patient gradually became more alert. The patient received intraventricular vancomycin for a total of 30 days. He was discharged on 2 months after his initial presentation. At discharge, the patient could follow simple commands, exhibit a steady gait, and demonstrate full strength in all extremities; although he still had expressive aphasia, his speech was improving. More recently, the patient was employed at a rehabilitation facility.

Discussion
The overall morbidity and mortality rates from brain abscess have progressively improved over the last several decades. [6] However, the most feared sequela of brain abscess is IVROBA, which can rapidly lead to death without an aggressive therapy. Successful treatments of IVROBA with systemic therapies have been reported, albeit with small sample sizes. [2,[18][19][20] It has been suggested that there is a higher chance for success in the treatment of IVROBA with systemic therapy if patients had been receiving antibiotics prior to the intraventricular rupture; [7] this may be due to the excellent vancomycin penetration of the brain abscess with systemic treatment, as abscess levels can reach up to 86% of serum levels. [21] In fact, CNS infection may facilitate vancomycin CSF penetration, as a higher level of CSF vancomycin was achieved in patients with meningitis compared to those without meningitis. [22] Kao et al. identified diabetes mellitus as the leading, underlying comorbidity associated with brain abscess in their series of 53 patients. [23] As such, our patient had a significant risk factor given his high HgbA1c. Although S. intermedius was identified from the initial biopsy, the susceptibility study was not achievable due to the lack of bacterial growth. This finding is not uncommon; the incidence of a sterile biopsy from a brain abscess ranges from 0% to 43%. [24][25][26] Antibiotic administration before biopsy is known to decrease the yield of laboratory cultures; [24] our patient received broad-spectrum antibiotics a day before the biopsy, and this may have suppressed the bacterial growth required for the susceptibility study.
Despite treatment with broad-spectrum IV antibiotics for over a month, our patient demonstrated disease progression, as he exhibited clinical decline associated with IVROBA and persistently having positive CSF cultures. In comparison, negative CSF cultures were noted 11 days after initiation of intraventricular vancomycin therapy. Once purulent material occupies the ventricular system, diffuse inflammation can follow, leading to ventricular f a e septation and organized debris; this cascade elicits barriers that impede the penetration of IV antibiotics to the ventricular system, where infectious nidus may exist. [27] This may explain the persistently positive CSF cultures despite prolonged IV antibiotics. With intraventricular vancomycin, the antibiotic comes into direct contact with the intraventricular infection [ Figures 2 and 3]. The administration of intraventricular antibiotics can control infection, reduce inflammation, and prevent ventricular septation. [8] Clinically, our patient improved gradually with the commencement of intraventricular therapy, and the infection was eventually eradicated.

Conclusion
IVROBA is unlikely to be effectively treated without intraventricular antibiotics. The intraventricular infection creates barriers that prevent the penetration of IV antibiotics to the ventricular system, where infectious nidus may exist. This case suggests that intraventricular vancomycin may be a safe, effective, and viable option for the treatment of IVROBA, especially for patients becoming refractory to systemic antibiotics.

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Conflicts of interest
There are no conflicts of interest.