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 ~  Abstract
 ~ Introduction
 ~ Patients and Methods
 ~ Results
 ~ Discussion
 ~ Conclusion
 ~  References
 ~  Article Tables

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  Table of Contents  
Year : 2018  |  Volume : 36  |  Issue : 1  |  Page : 97-103

Methicillin-resistant Staphylococcus aureus intracranial abscess: An analytical series and review on molecular, surgical and medical aspects

1 Department of Neuromicrobiology, National Institute of Mental Health and Neurosciences, Bengaluru, Karnataka, India
2 Department of Infectious Diseases, National Institute of Animal Biotechnology, Hyderabad, Telangana, India
3 Department of Neurosurgery, National Institute of Mental Health and Neurosciences, Bengaluru, Karnataka, India

Date of Web Publication2-May-2018

Correspondence Address:
Dr. Veena Kumari Haradara Bahubali
Department of Neuromicrobiology, National Institute of Mental Health and Neurosciences, Bengaluru, Karnataka
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Source of Support: None, Conflict of Interest: None

DOI: 10.4103/ijmm.IJMM_17_41

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 ~ Abstract 

Purpose: Intracranial abscess caused by methicillin-resistant Staphylococcus aureus (MRSA) is rare and unexplored. The aim of the present study is to examine the prevalence, clinical and molecular characteristics, treatment options and outcome of MRSA intracranial abscess over a period of 6 years. Patientsand Methods: A total of 21 patients were included in this retrospective study. The demographic and clinical details of all the patients were collected. Molecular typing including staphylococcal cassette chromosome mec typing, spa typing and polymerase chain reaction of Panton–Valentine leucocidin toxin (PVL) gene for the latter 6 isolates was performed. Results: The paediatric population was the most affected group (33.3%). The primary route of infection was post-operative/trauma in 7 (33.3%) cases. All the patients were treated surgically either by aspiration or excision. Fifteen (71%) patients received anti-MRSA treatment with vancomycin or linezolid, where linezolid-treated patients showed better prognosis. Of the 11 patients who were on follow-up, unfavourable outcome was observed in 3 (27.3%) cases and 8 (72.7%) cases improved. The molecular typing of six isolates revealed four community-associated (CA) MRSA, one each of livestock-associated (LA) and healthcare-associated MRSA with PVL gene noted in all. Conclusion: We propose that timely diagnosis, surgical intervention and appropriate anti-MRSA treatment would contribute to better outcome. The occurrence of CA-MRSA and LA-MRSA infection in the central nervous system signifies the threat from the community and livestock reservoir, thus drawing attention towards surveillance and tracking to understand the epidemiology and implement infection control measures.

Keywords: Anti-methicillin-resistant Staphylococcus aureus therapy, community-associated and livestock-associated methicillin-resistant Staphylococcus aureus, infection control, methicillin-resistant Staphylococcus aureus intracranial abscess, Panton–Valentine leucocidin

How to cite this article:
Bahubali VH, Vijayan P, Bhandari V, Siddaiah N, Srinivas D. Methicillin-resistant Staphylococcus aureus intracranial abscess: An analytical series and review on molecular, surgical and medical aspects. Indian J Med Microbiol 2018;36:97-103

How to cite this URL:
Bahubali VH, Vijayan P, Bhandari V, Siddaiah N, Srinivas D. Methicillin-resistant Staphylococcus aureus intracranial abscess: An analytical series and review on molecular, surgical and medical aspects. Indian J Med Microbiol [serial online] 2018 [cited 2019 Feb 23];36:97-103. Available from:

 ~ Introduction Top

The most common intracranial suppurative lesions include brain abscess, subdural empyema and epidural abscess, characterised by collection of pus enclosed with a well-vascularised capsule, caused by variety of microorganisms. Morbidity and mortality in intracranial abscess are critically dependent on rapid diagnosis and perhaps more importantly, on the timely initiation of suitable antimicrobial therapy.[1],[2] The outcome has noticeably improved due to the advancement in neuroimaging methods aiding in appropriate diagnosis, targeted neurosurgical techniques and newer antibiotics for the better treatment, yet it still remains a clinical challenge with risk of recurrence, serious long-term neurological sequelae with considerable fatality rate when managed improperly.[3]

Brain abscess usually results by contiguous spread of pathogen to brain, by systemic route, post-operative or traumatic, all of these acting as predisposing factors. With the changing epidemiology of brain abscess, it is noted that compared to otogenic abscesses, the incidence of brain abscess in immunocompromised host, post-traumatic or post-operative cases, has increased in the past 10–15 years.[4]

Abscess formation occurring after neurosurgical procedures or head trauma is often caused by skin-colonising bacteria, such as Staphylococcus aureus and Staphylococcus epidermidis. A progressive shift from sensitive S. aureus to highly resistant and often potentially destructive methicillin-resistant S. aureus (MRSA) in the central nervous system (CNS) infections has been observed.[5],[6] The infections by these resistant strains in a unique environment such as CNS reduce the treatment options and also the prognosis. We experienced a series of MRSA intracranial abscess in our institute, an alarming situation not frequently reported in literature.

In this study, we performed a retrospective analysis of intracranial abscess episodes for 6 years in our institute and explored the epidemiology, pre-disposing factors, clinical, microbiological findings and treatment outcome of 21 cases of MRSA intracranial abscess and compared with available literature on MRSA abscess. Molecular characterisation of few of the recent isolates was also carried out providing insight for optimal management and infection control.

 ~ Patients and Methods Top

The medical records of neurosurgical patients diagnosed with intracerebral abscess between January 2010 and December 2015 were retrospectively reviewed, and data of 21 patients who had MRSA infections were sorted out. The following information was documented: age, sex, medical history, clinical presentation, neurological status, associated predisposing factors, radiological and microbiological investigations, therapeutic management and outcome.

A standard algorithm for treatment of focal infective brain lesions has been followed in our institute.

Clinical diagnosis

All the patients initially underwent cerebral computerised tomography (CT) scan, which formed the basis of the diagnosis and evaluated by the presence of a space-occupying lesion with or without mass effect/surrounding oedema/ring enhancement after contrast. Magnetic resonance imaging (MRI) was performed during diagnostic dilemma.

Treatment procedures

The patients were managed conservatively or underwent surgery by aspiration via burr hole or complete excision/evacuation via craniotomy or craniectomy. A post-operative CT was performed on all patients, usually within 48 h of surgery. In case of aspiration, imaging was done frequently to look for the reduction in size, and repeat aspirations or excision was performed on residual abscess/empyema or deterioration while on antibiotic therapy.

All recurrences were detected within 2 weeks post-operatively, which was the usual time of discharge. Patients were discharged after a minimum of 2 weeks in-hospital intravenous (IV) antibiotics, only after CT showed no residual lesion and neurologically intact with follow-up at variable intervals. All patients who had chronic suppurative otitis media or sinusitis as the source of the abscess were referred to an otologist for further management.

The empirical antimicrobial therapy comprising of ceftriaxone, amikacin and metronidazole was administered as per the hospital antibiotic policy and then switched over to culture-driven definitive therapy.

In culture-negative cases, the empiric regimen was continued for 6 weeks subject to upgradation based on serial CT scans showing any re-accumulation of pus or febrile or poor neurological status. In culture-positive cases with clinical improvement by the end of 2 weeks of IV antibiotic therapy, switch over to oral antibiotics or continuation on IV in case of insensitivity to oral antibiotics for 4 weeks was made. Altogether, patients received 6 weeks of antibiotic therapy.

Laboratory findings

The aspirated or excised abscess specimen and other specimens such as ear swab, surgery site swabs, blood and cerebrospinal fluid (CSF) were subjected to microbiological investigations. The excised abscess material was sent for pathological analysis.

The abscess pus was subjected to Gram staining, Ziehl–Neelsen staining and India ink staining and cultured in both aerobic and anaerobic conditions; also for mycobacterial and fungal culture. The organisms were identified and reported as per the Clinical and Laboratory Standards Institute guidelines.

MRSA was reported by the growth and morphology on blood agar plate, Gram staining, catalase test, coagulase test and resistance to 30 μg cefoxitin disc on Mueller–Hinton agar. The latter six MRSA isolates collected during 2014 and 2015 were stored in brain–heart infusion media with glycerol and maintained at −80°C for further use.

Molecular characterisation of methicillin-resistantStaphylococcus aureus isolates

DNA was extracted from the MRSA isolates using the standard phenol-chloroform method. The extracted DNA was suspended in 50 μl of buffer and used for all the polymerase chain reaction (PCR)-based methods. A triplex PCR assay targeting 16srRNA (genus-specific), nuc (species-specific), mecA (methicillin resistance), a multiplex PCR to determine the staphylococcal cassette chromosome mec (SCCmec) types and a simplex PCR for the presence of Panton–Valentine leucocidin (PVL) toxin and spa typing were performed.[7],[8],[9],[10]

Statistical analysis

The data were analysed using SPSS Version 11.0 statistical software. Qualitative variables were analysed with Fisher's exact test. All P≤ 0.05 was considered statistically significant.

 ~ Results Top

A total of 769 patients were admitted for intracranial abscess between 2010 and 2015, of which 21 (2.7%) were diagnosed with MRSA infection: 18 brain abscess, two subdural empyema and one epidural abscess. There were 18 (85.7%) males and three females (14.3%), with a wide age range of 4 weeks to 73 years. Seven patients (33.3%) belonged to paediatric group, and all were below 2 years.

Clinical presentation

The mean duration of symptoms was 24 days, with a median of 15 days (range: 2–120 days). The Glasgow coma score (GCS) at the time of admission was 12–15 in 19 patients and <9 in two patients. The most common symptom was fever (42.9%) followed by headache (38.1%). Focal neurological deficits were also noted in 38.1% of patients (visual deficits in 2, hemiparesis in 2, hemiplegia in 2 and ataxia in 2). Other symptoms included vomiting, seizures, meningeal irritation, altered sensorium, giddiness, ear discharge, increased head size and papilloedema.

The demographic, epidemiological details and clinical presentations are depicted in [Table 1].
Table 1: Demographic and epidemiological data (n=21)

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Aetiology and comorbidity

The primary source of infection was identified in 13 patients (62%). The common cause in the study population was post-operative or trauma in 7 (33.3%) patients, followed by contiguous spread seen in five (23.8%) and haematogenous spread noted in 1 (4.9%). Of the remaining 8 (38%) patients, four patients were noted to be immunosuppressed: two had diabetes with pulmonary tuberculosis and one each with malignant tumour, and leprosy and in four cases, primary source of infection was not identified.

Radiological investigation and abscess characteristics

Primary neuroimaging was done by CT in all patients while cerebral MRI was performed only in one case.

There were 11 cases of solitary abscess (52.4%), seven multiple abscess (33.3%), two subdural empyema (9.5%) and one epidural abscess (4.8%).

The location and possible source of the abscess are shown in [Table 2].
Table 2: Aetiology and location of the abscess (n=21)

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Microbiological findings

All the 21 abscess pus samples yielded MRSA. In addition, other clinical samples such as three wound swabs from surgical site, one each of sinus mucosa, ear swab, bone flap, CSF and subdural fluid, also yielded MRSA with same antibiotic sensitivity pattern as that of the isolate from the corresponding abscess sample. The antibiotic sensitivity revealed 100% sensitivity to vancomycin and linezolid. The sensitivity pattern for other antibiotics is shown in [Table 3].
Table 3: Antibiotic sensitivity pattern (n=21)

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Molecular characterisation

Molecular typing revealed five MRSA isolates carrying SCCmec Type V and one isolate belonged to SCCmec Type III. PVL PCR was positive in all the isolates. Spa typing revealed t024, t030, t567, t657 types in these isolates [Table 4].
Table 4: Molecular pattern of the methicillin-resistant Staphylococcus aureus isolates

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Patient management

Surgical intervention was attempted in all patients, either by burr hole and aspiration or by craniotomy/craniectomy and excision/evacuation. Stereotactic aspiration was preferred as the first choice in 10 cases (47.6%), whereas excision/evacuation was performed in 11 cases (52.4%). Repeat aspiration or excision had to be performed in eight of the 10 cases (80%) from the aspiration group as compared to the other group (P = 0.007), due to re-accumulation of abscess or due to worsening of the patient's condition. None of them underwent re-exploration from the open-surgery category.

Antibiotic treatment

Following microbiological confirmation, 15 (71%) of the patients had switched from empiric regimen to culture-driven definitive anti-MRSA therapy with either vancomycin or linezolid; seven received vancomycin and four of them received linezolid, and in four cases, there was a switch over from vancomycin to linezolid. Six (29%) patients were discharged against medical advice before administering specific therapy and were lost to follow-up.

Complications, outcome and mortality

The patients were discharged following improvement though one patient was severely disabled during discharge. Eleven of 15 (73%) treated patients were on follow-up. The mean follow-up period was 3.4 months (range: 1–10 months). Mortality was noted in two, severe disability (significant neurological deficit interfering daily activities, as per the Glasgow outcome score) in one, complications such as abscess recurrence and bone flap osteomyelitis were observed in two which were accordingly managed, one each showed residual morbidities such as persistent weakness, seizures, subdural collection with ventriculomegaly and three showed complete resolution of abscess with no neurological sequelae.

 ~ Discussion Top

The study highlights the fact that intracranial abscess continues to be a significant CNS infection; as per our data, a total of 769 cases encountered in 6 years with a mean of 128 as against studies from developing countries mainly in India have reported a mean of 15,[11] 21[12] and 41[3] cases per year.

The incidence of intracranial MRSA infection is difficult to establish as it is a rare manifestation. MRSA intracranial abscess has not been explored in detail with literature search revealing only sporadic case reports and ours being the first largest series of its kind, to the best of our knowledge. In the study period, MRSA abscess accounted for 2.7% of the total cases. The higher rate of intracranial abscess and MRSA abscess per se in our institute might be due to the reason that it is a tertiary neurocare referral centre treating diverse population.

According to the Centers for Disease Control and Prevention, community-associated (CA) MRSA infections continue to be still on the rise,[13] and as CA-MRSA CNS infections are significantly noted,[14] the need to study these infections to meet the growing challenge to eradicate such life-threatening superbug is need of the hour.

Brain abscess is infrequent in paediatric population. In contrast, the paediatric age group was the most affected in this study, and 33.3% (7 cases) were below 2 years. The recent case reports have noted MRSA brain abscess in preterm low-weight infants.[15],[16],[17] We also noted a higher incidence of infection in patients aged >50 years.

The mean duration of symptoms in patients with brain abscess has been reported to be 8.3 days in a recent meta-analysis.[18] The delayed presentation in our series with a mean of 24 days and a median of 15 days may be ascribed to paucity in referring the patients from other centres, which also points towards the increased morbidity in our patients.

The clinical features of abscess are variable and non-specific, leading to delay in diagnosis, as the symptoms are mainly based on the underlying condition of the patient, size and location of the abscess. The clinical presentation of MRSA intracranial abscess was not different from other organisms causing brain abscess.[19] Fever was the single most common symptom (50%) in our study, and majority of the reported cases of MRSA brain abscess too presented with fever followed by headache and focal neurological deficits.

Due to the changing epidemiology, the proportion of brain abscess due to middle ear infection is decreasing compared to surgical aetiology and immunocompromised status.[3],[20] Múñez et al. noted that 50% of post-neurosurgical infections resulting in intracranial abscess or meningitis are caused by S. aureus, one-third of them are methicillin resistant.[21] Supported by the fact that staphylococci are the common causative agents in intracranial infections occurring after neurosurgery or penetrating cranial trauma, our study also evidenced post-neurosurgical infection as the predominant primary source of MRSA intracranial abscess, noted in seven out of 21 cases (33.3%). A study on the post-craniotomy subdural empyemas and epidural abscesses from Japan found MRSA infection in 50% of the cases.[22] This emphasises the need for continuous monitoring and efficient management of perioperative patients to control infection.

We had contiguous spread of infection as the second possible source of infection seen in 23.8% of the patients. This may be due to the reason that most of our patients were in the first two decades of age where mastoid infections are common.[23] In developing countries like India, ear infections are often neglected and not treated promptly and aggressively to impede further spread of infection.

In addition to definite focus of infection, certain medical conditions pose increased risk of infection as these underlying comorbidities reduce the immune response.[4] In our study, there were eight cryptogenic cases with unknown source of infection; three adults and five paediatric cases. Among them, four (3 adults and 1 paediatric) cases were noted to be immunocompromised: two had diabetes with tuberculosis infection and 1 each had malignancy and leprosy. However, an underlying comorbidity did not result in unfavourable outcome in this series (P = 1.00) although studies have shown that diabetes was associated with high mortality acting as an independent pre-disposing factor in cryptogenic abscesses.[24] In the remaining four paediatric patients, there was no evidence of clear source of infection or significant risk factors and previous hospitalisation. In these cases, the etiological role of CA-MRSA could be anticipated due to its widespread occurrence in the community. As molecular typing is a recent initiative in our institute, it was not possible to prove the above assumption for these older isolates. Two recent case reports of CA-MRSA brain abscess of idiopathic nature in a 2-year-old child in India and in an 11-month-old child in the UK [25],[26] signify the ability of the CA-MRSA to cause life-threatening CNS infections, a potential risk to the public health.

Published MRSA brain abscess case reports showed that the isolates harboured either SCCmec Type IV-USA 300[14],[25],[26],[27],[28],[29],[30] or SCCmec Type V [31] or SCCmec II.[32] Molecular characterisation of our six intracranial MRSA isolates over a period of 2 years showed that four were harbouring SCCmec Type V which is traditionally associated with CA-MRSA, one was Type III, which is healthcare-associated MRSA (HA-MRSA), and one strain was Type V with spa Type t567, which is a surrogate marker of ST398 representing livestock-associated MRSA (LA-MRSA);[33],[34] hence, the isolate was considered as LA-MRSA. Of the four CA-MRSA infected patients; three were epidemiologically classified as hospital acquired, i.e., post-operative infection along with absence of MRSA nasal carriage at the time of admission before surgery. The above association of carriage of SCCmec Type V in health-care infection cases explains the infiltration and circulation of community strains in the hospital setting. A large-scale prospective molecular study on epidemiologically characterised hospital-acquired MRSA strains is under process which might help us ascertain the CA-MRSA invasion and establishment of these clones in our hospital, as reports on CA-MRSA lineages with increased antibiotic resistance invading the healthcare system, contributing to nosocomial infections, are noted in abundance.[35] Although ST398 LA-MRSA human infection has been noted in many European countries, it is not common and has never been reported in Asia.[36] Hence, our report on LA-MRSA CNS infection holds a worthwhile significance and suggests a need for better understanding of the epidemiology and transmission of LA-MRSA.

Most of the virulent strains of CA-MRSA are positive for PVL, a pore-forming leucotoxin which is considered important for S. aureus immune evasion and its role in skin and soft tissue infections and necrotising pneumonia.[37] All the four CA-MRSA isolates in our study carried PVL toxin gene similar to the literature which also revealed the same in all the CA-MRSA.[14],[25],[26],[29],[30],[31] We also found HA-MRSA and LA-MRSA strains to be positive for this toxin which deserves mention. The presence of PVL might predict the invasive potential of these strains to infect CNS though the actual role of PVL in CNS infection is not explored in detail.

As regards the management, removal of abscess helps in reduction of the bacterial load in the abscess cavity and also in microbial identification and its susceptibility to antibiotics. The indications for burr hole and aspiration of the abscess as the primary procedures included a poorly formed abscess wall, a poor GCS score at presentation, rapid neurological deterioration and severe anaemia.[38] In our series, all the patients had surgical removal of the abscess either by aspiration or by excision. There are no prospective randomised controlled studies comparing the efficacy of these two methods though the available studies suggest excision better than aspiration in terms of improvement of neurological status, need for repeat surgeries, duration of antibiotic use, length of hospital stay and overall cost of treatment, with no significant difference in morbidity and mortality.[39],[40] We did not find any significant difference between the outcome of these two surgical methods during discharge (P = 1.00), but burr hole and aspiration were associated with more surgical procedures for an individual patient (P = 0.007) as against the excision group, as 80% of the patients who underwent aspiration on the first hand needed repeat aspiration or excision. Well-timed surgical management is very important to avoid the delay in culture-driven appropriate antibiotic therapy.

CNS infections caused by MRSA are truly a therapeutic challenge; first due to the inadequate drug penetration to attain enough concentration in the CNS, and second, a very limited treatment of choice.[41] Clinical Practice Guidelines by the Infectious Diseases Society of America for the treatment of MRSA in adults and children recommends the use of IV vancomycin alone or along with rifampicin or alternatives such as linezolid or co-trimoxazole for CNS infections.[42]

Although essentially bactericidal drugs are indicated in MRSA CNS infections, considerable data suggest the successful use of linezolid, a bacteriostatic antibiotic as a safe alternative to vancomycin,[43],[44] because of its good CSF penetration, effectiveness, high oral bioavailability, few side effects and low cost.[45] While reviewing the MRSA intracranial abscess case reports, it was noted that anti-MRSA treatment with linezolid or combination therapy with linezolid or switch over to linezolid from vancomycin [17],[26],[27],[46],[47],[48] resulted in favourable outcome compared to vancomycin alone or combination therapy with vancomycin.[14],[15],[16],[25],[28],[29],[30],[31],[32],[49],[50],[51] In the present study, 71% of the cases underwent anti-MRSA treatment either with vancomycin or with linezolid. During follow-up, of the seven patients who received vancomycin, the rate of treatment failure (culture/radiographic/clinical evidence of infection within 60 days of the completion of antibiotic therapy) was 43% which included death, recurrence and bone flap osteomyelitis, whereas in linezolid, it was 25% (1 of 4) with one mortality. It was not possible to compare the efficacy of vancomycin with that of linezolid on long-term basis as many patients who received linezolid were not available for details. However, the data indicate that unfavourable outcome was higher in vancomycin-treated patients compared to linezolid both in our series as well as in the case reports. A study on efficacy of vancomycin as monotherapy or in combination therapy showed a failure rate of 28% in epidural abscess.[52] However, linezolid over vancomycin as the first choice has to be supported with ample evidence and randomised controlled trials.

The clinical impact of MRSA brain abscess has not been explored in expanse. A significant proportion of patients on appropriate treatment recover completely, but intellectual impairment, behavioural disturbances and other neurological sequelae in children and young patients also have been trailed.[53],[54] As we encountered a predominant paediatric population, a long-term follow-up would have provided information on the outcome and treatment efficacy, which is the shortcoming of this study though not an unusual feature in developing countries.

 ~ Conclusion Top

The study implicates timely diagnosis, surgical intervention and appropriate anti-MRSA treatment aid in infection clearance though some residual neurological symptoms are inevitable.

The occurrence of CA-MRSA in the CNS infection signifies the threat of infiltration of these strains to the hospital and their potential to invade CNS which has to be addressed without delay. The episode of LA-MRSA implies a significant risk from the livestock reservoir to community and hospitals, thus drawing attention towards surveillance, tracking and modes of inter transmission, for a better understanding of the epidemiology and implementation of infection control measures.


Priya Vijayan acknowledges the University Grants Commission, India for NET- JRF. We thank Dr. P. Marimuthu, Department of Biostatistics, NIMHANS, for his assistance in statistical methods used in the study.

Financial support and sponsorship


Conflicts of interest

There are no conflicts of interest.

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  [Table 1], [Table 2], [Table 3], [Table 4]


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2004 - Indian Journal of Medical Microbiology
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