History

Fact Explanation
Introduction Meninges are the lining that covers the brain and spinal cord. Meningitis is inflammation of the meninges around the brain and spinal cord. It is usually caused by an infectious pathogens such as bacteria, virus, fungi and parasites. Depending on he duration of the symptoms, it can be subdivided into acute and chronic form. Bacterial meningitis is a medical emergency requiring immediate treatment. Streptococcus pneumoniae is the most commonest causative pathogens for bacterial meningitis. [1] There are other streptococcal sp. that can occasionaly cause meningitis such as streptococcus bovis (nonenterococcal, group D streptococcus), [7] streptococcus suis etc. Group A streptococci are an uncommon cause of meningitis. Majority of patients with meningitis due to non-beta-hemolytic streptococci are found to have various underlying diseases.[7] Invasion of the bloodstream can occur directly through skin abrasions or the oral or respiratory route that can results in sepsis and other complications. [5]
Headache Once the organism entered through the blood brain barrier, immune system of the body gets activated to release various cytokines and chemikines. Further it releases reactive oxygen radicals to cause more endothelial and nearby tissue damage. These can cause meningeal irritation, increased intracranial damage and cerebral edema.[5]
Fever [1] Inflammation of the meninges and endothelium releases pyrogens causing fever. [1]
Vomiting Vomiting is a common finding in the meningitis. [6]
Sensitivity to light (photophobia) Inability to tolerate light is due to the meningism that indicates inflammatory activation of the trigeminal sensory nerve fibers in the meninges. [1]
Pain during retraction of the neck [1] Due to the meningeal irritation. [1]
Seizures [1,6] Altered cerebral perfusion pressure can cause reduction of the cerebral blood flow and ischaemia. [1]
Decreased alertness and drowsiness [1] There can be increased intracranial pressure which may be due to the increased blood brain barrier permeability, swelling of the cellular elements of the brain, interstitial edema results from obstruction of flow in normal CSF pathways etc. Neuronal cell death and cerebral edema may also contribute to the drowsiness. [1]
Excessive crying, refusing the feeds Infants and young children present with nonspecific features. [2,6]
Hearing loss Inflammation can extends to the cranial nerves, when the 8th nerve is involved that causes sensorineural type hearing loss. [5]
Visual problems Visual problems Involvement of the optic and other cranial nerves related to the vision can be the cause. [6]
History of immunodeficiency People with immune deficiency [8] like malignancy, chemotherapy, long term steroid use, organ transplant and HIV AIDS are particularly vulnerable for the disease. [3]
Skin infections Group A streptococci are an important causative factors for the soft tissue infections. [4]
Sorethroat and ear discharge Group a beta-hemolytic streptococci are a common cause of pharyngitis and ear infections. [4]
Other organ involvement Streptococci may affect the other organs in the body causing arthritis, pneumonia, endocarditis, endophthalmitis, and spontaneous bacterial peritonitis. [5]
History of handling or eat undercooked pork, e.g., farm workers, butchers, and slaughterhouse workers Streptococcus suis meningitis who handle or eat undercooked pork, e.g., farm workers, butchers, and slaughterhouse workers. [5]
History of maternal pyrexia Mothers of neonates who develop group A streptococcal meningitis are mostly found to have peurperal sepsis and toxic shock syndrome. [6] These mothers transmit the infection to the baby during the delivery : vertical transmission. [6]
References
  1. HOFFMAN O, WEBER RJ. Pathophysiology and Treatment of Bacterial Meningitis Ther Adv Neurol Disord [online] 2009 Nov, 2(6):1-7 [viewed 26 August 2014] Available from: doi:10.1177/1756285609337975
  2. FORD-JONES EL, MACGREGOR D, RICHARDSON S, JAMIESON F, BLASER S, ARTSOB H. Acute childhood encephalitis and meningoencephalitis: Diagnosis and management Paediatr Child Health [online] 1998, 3(1):33-40 [viewed 18 September 2014] Available from: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2851260
  3. TEBRUEGGE M, CURTIS N. Epidemiology, Etiology, Pathogenesis, and Diagnosis of Recurrent Bacterial Meningitis Clin Microbiol Rev [online] 2008 Jul, 21(3):519-537 [viewed 19 September 2014] Available from: doi:10.1128/CMR.00009-08
  4. PATTULLO AL, BOW EJ. A case of group A streptococcal meningitis in an adult Can J Infect Dis [online] 1993, 4(4):223-226 [viewed 23 September 2014] Available from: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3250794
  5. LEE GT, CHIU CY, HALLER BL, DENN PM, HALL CS, GERBERDING JL. Streptococcus suis Meningitis, United States Emerg Infect Dis [online] 2008 Jan, 14(1):183-185 [viewed 23 September 2014] Available from: doi:10.3201/eid1401.070930
  6. LARDHI AMER A. Neonatal group A streptococcal meningitis: a case report and review of the literature. Array [online] 2008 December [viewed 23 September 2014] Available from: doi:10.1186/1757-1626-1-108
  7. GRANT RJ, WHITEHEAD TR, ORR JE. Streptococcus bovis Meningitis in an Infant J Clin Microbiol [online] 2000 Jan, 38(1):462-463 [viewed 23 September 2014] Available from: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC88753

Examination

Fact Explanation
Febrile Fever is one of the most common presenting features. This is due to the infection. [1]
Stiff neck Nuchal rigidity is present due to the meningeal irritation. [1]
Kernig sign [1] This is a bedside diagnostic sign used to evaluate suspected cases of meningitis. Patient is kept in supine position, hip and knee are flexed, the knee is slowly extended by the examiner. It is positive if there is a resistance or pain during extension. [2]
Brudzinki sign Another sign of meningeal irritation.[1] First one hand is kept behind the patient's head and the other on chest in order to prevent the patient from rising, passive flexion of the neck produces reflex flexion of the patient's hips and knees in a positive Brudzinski's sign. [2]
Tachycardia and hypotension Fast heart rate is observed in hypotensive, confused patients. [1]
Mental status changes Alteration in mental status is a poor prognostic indicator. [3]
Focal neurological signs Subdural effusion or cerebral-space-occupying lesions such as abscess formation can cause these symptoms. [4]
Buldging of fontanelle Due to the increased intracranial pressure. [6]
Growth retardation and cognitive impairment Ischaemia can cause neuronal cell death and tissue damage, if the developing brain is affected child may ends up with poor growth. Cognitive impairment is most prominent after pneumococcal meningitis. [4]
Sensorineural hearing loss Cranial nerve palsies specially VIII the nerve palsy is the cause for this hearing loss. [1]
Papilloedema This is due to the increased intracranial pressure. [7] Increased blood brain barrier permeability, swelling of the cellular elements of the brain, interstitial edema results from obstruction of flow in normal CSF pathways as in hydrocephalus are the possible causes for the raised intracranial pressure.
Hydrocephalus There can be involvement of the ventricles causing ventriculitis. [2] Inflamed areas are gradually fibrosed with creating an obstruction to the cerebrospinal fluid outflow, leading to hydrocephalus.
Ear discharge/ inflammed pharynx Group a beta-hemolytic streptococci are a common cause of pharyngitis/ upper respiratory tract infections. [1]
Skin sepsis Group a beta-hemolytic streptococci are also responsible for the soft tissue infection. [1]
References
  1. PATTULLO AL, BOW EJ. A case of group A streptococcal meningitis in an adult Can J Infect Dis [online] 1993, 4(4):223-226 [viewed 23 September 2014] Available from: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3250794
  2. MEHNDIRATTA M, NAYAK R, GARG H, KUMAR M, PANDEY S. Appraisal of Kernig's and Brudzinski's sign in meningitis Ann Indian Acad Neurol [online] 2012, 15(4):287-288 [viewed 11 August 2014] Available from: doi:10.4103/0972-2327.104337
  3. TEBRUEGGE M, CURTIS N. Epidemiology, Etiology, Pathogenesis, and Diagnosis of Recurrent Bacterial Meningitis Clin Microbiol Rev [online] 2008 Jul, 21(3):519-537 [viewed 19 September 2014] Available from: doi:10.1128/CMR.00009-08
  4. HOFFMAN O, WEBER RJ. Pathophysiology and Treatment of Bacterial Meningitis Ther Adv Neurol Disord [online] 2009 Nov, 2(6):1-7 [viewed 26 August 2014] Available from: doi:10.1177/1756285609337975
  5. LEE GT, CHIU CY, HALLER BL, DENN PM, HALL CS, GERBERDING JL. Streptococcus suis Meningitis, United States Emerg Infect Dis [online] 2008 Jan, 14(1):183-185 [viewed 23 September 2014] Available from: doi:10.3201/eid1401.070930
  6. GRANT RJ, WHITEHEAD TR, ORR JE. Streptococcus bovis Meningitis in an Infant J Clin Microbiol [online] 2000 Jan, 38(1):462-463 [viewed 23 September 2014] Available from: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC88753
  7. LO S, PHILLIPS DI, PETERS JR, HALL M, HALL R. Papilloedema and cranial nerve palsies complicating apparent benign aseptic meningitis. J R Soc Med [online] 1991 Apr, 84(4):201-202 [viewed 23 September 2014] Available from: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1293181

Differential Diagnoses

Fact Explanation
Meningitis due to other infectious causes Neisseria meningitidis and Haemophilus influenzae are the most common causative pathogens for bacterial meningitis. [4] Organisms may differ according to the age of the patient. Eg:- During neonatal period-E.coli, gram negative bacilli, Listeria monocytogens and Group B streptococci, children older than 3 months-Streptococcus pneumoniae, Neisseria meningitidis and Haemophilus influenzae, children between 1-3 months with the organisms from both above mentioned groups. [5]
Chronic meningitis Chronic meningitis is different from acute meningitis as it is an uncommon disease with a gradual onset over 2 weeks or more. Fungal infections are the common cause for chronic meningitis. Cryptococcal meningitis is one of the commonest fungal form of the disease.Cryptococcus neoformans is an encapsulated yeast causingopportunistic life-threatening infections, particularly in immuno-compromised patients. [6]
Encephalitis Encephalitis [1] is an acute, usually diffuse, inflammatory process of the brain. About 90% of cases are associated with herpes simplex virus (HSV-1). [3] They also present with the fever, headache, and clouding of consciousness which may be associated with seizures and focal neurology in some patients. Encephalitis associated with meningitis. Meningoencephalitis may give the same picture as in meningitis making diagnosis difficult. [2]
Encephalopathy due to non infectious causes Same clinical features of encephalitis presents with a history of anoxic/ischaemic damage, nutritional deficiency, alcoholism, critical illness, malignant hypertension, traumatic brain injury or epileptic (non-convulsive status). [2] Fever, headache like features are uncommon in encephalopathy than in encephalitis/ meningitis. Depressed mental status is steadily deteriorating in encephalopathy rather than that may be fluctuating in encephalitis/ meningitis. Focal neurologic signs are uncommon in encephalopathy. Types of seizures are usually generalised.
References
  1. JAKKA S, VEENA S, ATMAKURI R, EISENHUT M. Characteristic abnormalities in cerebrospinal fluid biochemistry in children with cerebral malaria compared to viral encephalitis Cerebrospinal Fluid Res [online] :8 [viewed 16 August 2014] Available from: doi:10.1186/1743-8454-3-8
  2. KENNEDY P. VIRAL ENCEPHALITIS: CAUSES, DIFFERENTIAL DIAGNOSIS, AND MANAGEMENT J Neurol Neurosurg Psychiatry [online] 2004 Mar, 75(Suppl 1):i10-i15 [viewed 11 August 2014] Available from: doi:10.1136/jnnp.2003.034280
  3. BANATVALA JANGU E. Herpes simplex encephalitis. The Lancet Infectious Diseases [online] 2011 February, 11(2):80-81 [viewed 16 August 2014] Available from: doi:10.1016/S1473-3099(11)70012-3 Investigations - for Diagn
  4. HOFFMAN O, WEBER RJ. Pathophysiology and Treatment of Bacterial Meningitis Ther Adv Neurol Disord [online] 2009 Nov, 2(6):1-7 [viewed 26 August 2014] Available from: doi:10.1177/1756285609337975
  5. KLEIN NJ, HEYDERMAN RS, LEVIN M. Antibiotic choices for meningitis beyond the neonatal period. Arch Dis Child [online] 1992 Feb, 67(2):157-159 [viewed 26 August 2014] Available from: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1793401
  6. LEE CH, CHANG TY, LIU JW, CHEN FJ, CHIEN CC, TANG YF, LU CH. Correlation of anti-fungal susceptibility with clinical outcomes in patients with cryptococcal meningitis BMC Infect Dis [online] :361 [viewed 11 August 2014] Available from: doi:10.1186/1471-2334-12-361

Investigations - for Diagnosis

Fact Explanation
Lumbar puncture Opening pressure will be elevated in meningitis. Regarding the protein content in the CSF, in bacterial meningitis there is markedly elevated protein (< 1 g/l), where as in other types that may be less prominent. CSF glucose level is decreased. [2] Markedly elevated white blood cell count with predominant neutrophils is seen in streptococcal meningitis. [1] Bacterial antigen detection in the CSF for Streptococcus pneumoniae will be positive. [2]
Blood culture [1] Is done if the patient seems to be septic or lumbar puncture can not be done safely due to the possibility of increased intracranial pressure before the antibiotics. [1] Blood culture will isolate gram-positive cocci in pairs and chains. [3]
Full blood count There can be elevated lymphocytes/leucocytes in the blood. [2]
Gram stain of the ear discharge Ear discharge analysis will show a small amount of pus cells and large numbers of Gram-positive cocci. [2]
Computer tomography(CT) scan of the head and Magnetic Resonance Imaging(MRI) CT scan will be even better as the first investigation specially to rule out the possibility of increased intracranial pressure before doing lumbar puncture. MRI will demonstrate the inflammatory dural meningeal process with enhanced uptake over the affected areas. This also show the intracranial complications such as brain edema, hydrocephalus and infarcts. [1]
References
  1. HOFFMAN O, WEBER RJ. Pathophysiology and Treatment of Bacterial Meningitis Ther Adv Neurol Disord [online] 2009 Nov, 2(6):1-7 [viewed 26 August 2014] Available from: doi:10.1177/1756285609337975
  2. PATTULLO AL, BOW EJ. A case of group A streptococcal meningitis in an adult Can J Infect Dis [online] 1993, 4(4):223-226 [viewed 23 September 2014] Available from: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3250794
  3. LEE GT, CHIU CY, HALLER BL, DENN PM, HALL CS, GERBERDING JL. Streptococcus suis Meningitis, United States Emerg Infect Dis [online] 2008 Jan, 14(1):183-185 [viewed 23 September 2014] Available from: doi:10.3201/eid1401.070930

Investigations - Fitness for Management

Fact Explanation
Erythrocyte sedimentation rate(ESR) and C Reactive protein(CRP) Is elevated due to the inflammation. [1]
Renal functions and serum electrolytes Syndrome of inappropriate Antidiuretic Hormone secretion is a complication of meningitis. This can cause hyponatraemia. [5] Reduced intake of fluids can cause electrolyte imbalances. Medications may alter the renal functions and therefore baseline value is also needed.
Liver function tests Medications may alter the liver functions and therefore baseline value is needed before the treatment. [3]
Random blood sugar Should be done immediately especially if the patient is drowsy, to rule out the hypoglycaemia. [4]
References
  1. HOFFMAN O, WEBER RJ. Pathophysiology and Treatment of Bacterial Meningitis Ther Adv Neurol Disord [online] 2009 Nov, 2(6):1-7 [viewed 26 August 2014] Available from: doi:10.1177/1756285609337975
  2. PATTULLO AL, BOW EJ. A case of group A streptococcal meningitis in an adult Can J Infect Dis [online] 1993, 4(4):223-226 [viewed 23 September 2014] Available from: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3250794
  3. ELWIR SM, SHAFFER CC, ARVAN SW, KUPERMAN EF. Disseminated Varicella Zoster Virus Infection with Encephalitis in a UC Patient Receiving Infliximab Gastroenterol Hepatol (N Y) [online] 2013 Jan, 9(1):54-56 [viewed 18 September 2014] Available from: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3975981
  4. BRACKENRIDGE A, WALLBANK H, LAWRENSON RA, RUSSELL‐JONES D. Emergency management of diabetes and hypoglycaemia Emerg Med J [online] 2006 Mar, 23(3):183-185 [viewed 18 September 2014] Available from: doi:10.1136/emj.2005.026252
  5. PILLAI BP, UNNIKRISHNAN AG, PAVITHRAN PV. Syndrome of inappropriate antidiuretic hormone secretion: Revisiting a classical endocrine disorder Indian J Endocrinol Metab [online] 2011 Sep, 15(Suppl3):S208-S215 [viewed 23 September 2014] Available from: doi:10.4103/2230-8210.84870

Investigations - Followup

Fact Explanation
Lumbar puncture Lumbar puncture Is done during the follow up and when the response is poor to the current treatment within 48 hours of treatment. [1,2]
CT imaging CT imaging is performed if there is poor response within 48 hours of antibiotic treatment. [2] This may be due to the potential complications of the disease.
References
  1. CRUM-CIANFLONE N, TRUETT A, WALLACE MR. Cryptococcal Meningitis Manifesting as a Large Abdominal Cyst in a HIV-Infected Patient with a Robust CD4 Count AIDS Patient Care STDS [online] 2008 May, 22(5):359-363 [viewed 11 August 2014] Available from: doi:10.1089/apc.2007.0085
  2. HOFFMAN O, WEBER RJ. Pathophysiology and Treatment of Bacterial Meningitis Ther Adv Neurol Disord [online] 2009 Nov, 2(6):1-7 [viewed 26 August 2014] Available from: doi:10.1177/1756285609337975

Investigations - Screening/Staging

Fact Explanation
MRI/CT brain Increased intracranial pressure is evident on MRI by severe sulcal effacement and midline shift on brain imaging. [1] Therefore cranial CT should be done before the lumbar puncture, specially in those present with focal neurological deficits or seizures and those who have a disturbed consciousness due to the possible risk of cerebral herniation due to raised intracranial pressure.[1]
References
  1. HOFFMAN O, WEBER RJ. Pathophysiology and Treatment of Bacterial Meningitis Ther Adv Neurol Disord [online] 2009 Nov, 2(6):1-7 [viewed 26 August 2014] Available from: doi:10.1177/1756285609337975

Management - General Measures

Fact Explanation
Immediate management This is particularly important if the patient presents with confusion and drowsiness. Airway, breathing, circulation, disability and environment need to be attended. Random blood sugar is done to exclude hypoglycaemia. [4] Lumbar puncture needs to be done before the antibiotics [5] started ( if the possibility of increased intracranial pressure can be rule out) If it is not safe to do the LP blood culture is done and antibiotics are started as soon as possible without delay.
Supportive management Antipyretics (i.e. acetaminophen) and antiemetics, (i.e.promethazine) may be given. Hydration should be checked and due to the possibility of syndrome of inappropriate Antidiuretic hormone, 2/3 of maintenance is preferable. Usual recommended fluid intake is less than 800 mg/day. [1] Monitoring of the vital parameters should be done during the initial period.
Management of the complications Ventriculoperitoneal (VP) shunt is placed for the symptomatic improvement in hydrocephalus. If there are seizures, anticonvulsants should be continued and close follow-up should be done. If there is of rapidly increasing intracranial pressure with clinical deterioration where medical treatment failed, surgical decompression has to be considered as a life saving measure. [2] Extracranial complications such as sepsis, disseminated coagulopathy, multiorgan failure, arthritis and electrolyte imbalance, can occur due to the usually syndrome of inappropriate antidiuretic hormone (SIADH) secretion. [1]
Management of associated streptococcal infections Group A streptococci may be involved in the causation of the pharyngitis and skin infections. [7] Appropriate antibiotics with penicilllin and wound care are needed.
Follow up As they are vulnerable for complications such as hearing loss, [6] vision problems, growth retardation, learning disability they need to be followed up with hearing, vision and growth assessment. [4]
References
  1. PILLAI BP, UNNIKRISHNAN AG, PAVITHRAN PV. Syndrome of inappropriate antidiuretic hormone secretion: Revisiting a classical endocrine disorder Indian J Endocrinol Metab [online] 2011 Sep, 15(Suppl3):S208-S215 [viewed 23 September 2014] Available from: doi:10.4103/2230-8210.84870
  2. KENNEDY P. VIRAL ENCEPHALITIS: CAUSES, DIFFERENTIAL DIAGNOSIS, AND MANAGEMENT J Neurol Neurosurg Psychiatry [online] 2004 Mar, 75(Suppl 1):i10-i15 [viewed 11 August 2014] Available from: doi:10.1136/jnnp.2003.034280
  3. FLORET D. [Suppurative meningitis in infants and in children: adjuvant treatments and treatments of neurological forms]. Pediatrie [online] 1993, 48(1):21-7 [viewed 19 September 2014] Available from: http://www.ncbi.nlm.nih.gov/pubmed/8392687
  4. FORD-JONES EL, MACGREGOR D, RICHARDSON S, JAMIESON F, BLASER S, ARTSOB H. Acute childhood encephalitis and meningoencephalitis: Diagnosis and management Paediatr Child Health [online] 1998, 3(1):33-40 [viewed 18 September 2014] Available from: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2851260
  5. TEBRUEGGE M, CURTIS N. Epidemiology, Etiology, Pathogenesis, and Diagnosis of Recurrent Bacterial Meningitis Clin Microbiol Rev [online] 2008 Jul, 21(3):519-537 [viewed 19 September 2014] Available from: doi:10.1128/CMR.00009-08
  6. LEE GT, CHIU CY, HALLER BL, DENN PM, HALL CS, GERBERDING JL. Streptococcus suis Meningitis, United States Emerg Infect Dis [online] 2008 Jan, 14(1):183-185 [viewed 23 September 2014] Available from: doi:10.3201/eid1401.070930
  7. PATTULLO AL, BOW EJ. A case of group A streptococcal meningitis in an adult Can J Infect Dis [online] 1993, 4(4):223-226 [viewed 23 September 2014] Available from: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3250794

Management - Specific Treatments

Fact Explanation
Antibiotic therapy [2] Aims of the therapy would be to treat the infection and prevention of long-term central nervous system sequelae. Diagnostic delays should not be a cause fro delaying the immediate antibiotic therapy. [1] Emperical treatment is started usually with the ceftriaxone, vancomycin, and ampicillin [2,3] and then changed according to the culture results with antibiotic sensitivity report. Targeted antimicrobial therapy would be penicillin G, 24 million units intravenously per day. [2] But currently it has been suggested third generation cephalosphorins as the first line drug in pneumococcal meningitis due to the resistance of organism to the penicillin and inadequate penetration into the central nervous system to target these resistant organisms. [4] Other antibiotics that can be use to treat the streptococcal meningitis are amino glycosides, second and third generation cephalosporin, and vancomycin. [3]
Steroids Dexamethasone (4 mg every six hours) is given to reduce the inflammatory response occur during the anti microbial treatment. Dexamethasone may reduce the incidence of hearing loss in some patients. [2]
Pneumococcal conjugate vaccine Pneumococcal conjugate vaccine is important in preventing the invasive pneumococcal diseases. [4] It is a10 valen congugated pneumococcal and some countries have included it in the routine immunization progrrame. [4]
References
  1. KLEIN NJ, HEYDERMAN RS, LEVIN M. Antibiotic choices for meningitis beyond the neonatal period. Arch Dis Child [online] 1992 Feb, 67(2):157-159 [viewed 26 August 2014] Available from: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1793401
  2. LEE GT, CHIU CY, HALLER BL, DENN PM, HALL CS, GERBERDING JL. Streptococcus suis Meningitis, United States Emerg Infect Dis [online] 2008 Jan, 14(1):183-185 [viewed 23 September 2014] Available from: doi:10.3201/eid1401.070930
  3. LARDHI AMER A. Neonatal group A streptococcal meningitis: a case report and review of the literature. Array [online] 2008 December [viewed 23 September 2014] Available from: doi:10.1186/1757-1626-1-108
  4. GOUVEIA EDILANE L, REIS JOICE N, FLANNERY BRENDAN, CORDEIRO SORAIA M, LIMA JOSILENE BT, PINHEIRO RICARDO M, SALGADO KáTIA, MASCARENHAS ANA, CARVALHO M GLORIA, BEALL BERNARD W, REIS MITERMAYER G, KO ALBERT I. Clinical outcome of pneumococcal meningitis during the emergence of pencillin-resistant Streptococcus pneumoniae: an observational study. Array [online] 2011 December [viewed 23 September 2014] Available from: doi:10.1186/1471-2334-11-323