The UK Joint Specialist Societies Guideline on the Diagnosis and Management of Acute Meningitis and Meningococcal sepsis in

immunocompetent adults.

Fiona McGill, RS Heyderman, BD Michael, S Defres, NJ Beeching, R Borrow, A Miller, L Glennie, O Gaillemin, D Wyncoll, E Kaczmarski, S Nadel, G Thwaites, J Cohen, NWS Davies, A Rhodes, R Read, T Solomon

British Infection AssociationPublic Health EnglandIntensive Care SocietyAssociation of British NeurologistsSociety for Acute MedicineMeningitis Research Foundation

Outline

• Background• Recommendations• Implementation

Background

Why do we need a guideline?

The management of meningitis in the UK is sub-optimal

• Published UK based audits:– Specific diagnostic tests (beyond culture) often

omitted e.g. molecular tests– Considerable variability in dosage of antibiotics

prescribed– Delays in antibiotics and investigations– Inappropriate tests e.g. CT scans

Cullen; Journal of Infection 2005Stockdale; Quarterly Medical Journal 2011

Guidelines may improve outcomes

– Swedish national review after guideline revision• Treatment started earlier• Mortality reduced

– US study comparing 3 time periods• Mortality decreased • “associated with the introduction of recommendations for use

of adjunctive dexamethasone for pneumococcal meningitis”– Dutch historical cohort comparison • Improved outcome and mortality• Follows recommendations for steroids

Glimaker; Clinical Infectious Diseases 2015Castelblanco; Lancet Infectious Diseases 2014Brouwer; Neurology 2010

Our aims:

• to create user-friendly, comprehensive, evidence-based guidelines primarily for hospital-based clinicians in the UK with auditable outcomes.

• Scope: – Adults– suspected and proven acute meningitis and

meningococcal sepsis– pre-hospital care to post-discharge support

Fiona: “when will the meningitis guidelines be revised?”BIA guidelines secretary “Would you like to do it?”

1999

2003

2012

Methods• Working party formed • Identified questions • Literature search • 2-3 authors wrote each section• Whole guideline assimilated and edited• Consultation with stakeholders– Revision and editing

Methods• Working party formed • Identified questions • Literature search • 2-3 authors wrote the relevant section• Whole guideline assimilated and edited• Consultation with stakeholders– Revision and editing

Recommendations

Key Recommendations• Pre-hospital management

• Indications for hospital admission• Clinical signs• Pre admission antibiotics

• Initial hospital assessment• Neuroimaging and lumbar punctures• Bleeding risks and lumbar punctures• Diagnostic Scoring systems• Investigations• Treatment

• Empirical• Definitive• Adjunctive• Outpatient treatment

• Critical Care• Which patients should be

referred to critical care• Other critical care

management issues• Prophylaxis

• Prevention of secondary cases

• Screening for predispositions• Infection control measures

• Follow Up/Sequelae• Viral Meningitis• Audit Tool

Key Recommendations• Pre-hospital management

• Indications for hospital admission• Clinical signs• Pre admission antibiotics

• Initial hospital assessment• Neuroimaging and lumbar punctures• Bleeding risks and lumbar punctures• Diagnostic Scoring systems• Investigations• Treatment

• Empirical• Definitive• Adjunctive• Outpatient treatment

• Critical Care• Which patients should be

referred to critical care• Other critical care

management issues• Prophylaxis

• Prevention of secondary cases

• Screening for predispositions• Infection control measures

• Follow Up/Sequelae• Viral Meningitis• Audit Tool

Antibiotics in the community

• Give to those who have signs of meningococcal disease, severe sepsis or where there might be a delay in getting to hospital

• Patients with known anaphylaxis should not receive antibiotics in the community

Initial hospital assessment

• Action to be taken within the first hour of arriving in hospital– Stabilisation of patient– Blood cultures taken– Lumbar puncture if safe (patients with meningitis)– Treatment commenced– Fluid resuscitation (if signs of sepsis)– Document decision regarding senior review and

need for critical care input

Medical training

• All clinicians managing patients should have training on the initial management of acute bacterial meningitis and meningococcal sepsis

• Patients should be cared for with the input of an infection specialist

Neuroimaging and Lumbar Puncture

Image courtesy of Dr Andrew Dixon, Radiopaedia.org, rID: 32383

Image courtesy of Dr Benedict Michael.

Associations between performing CT scans and: • delays in antibiotics and LP, • worse outcome, • decreased chance of identifying organism

Proulx; Quaterly Journal of Medicine 2005Michael; Emergency Medical Journal 2010Glimaker; Clinical Infectious Diseases 2015

All (n=1117) Had CT (n=901)

Did not have CT (n=216)

P value

Time from admission to LP, median hours (IQR)

16 (6.75,28) 18 (8,29) 10 (4,22) <0.001

Time from admission to antibiotics, median hours (IQR)

3 (1,11) 3 (1,11) 2 (0,10) 0.002

McGill et al, unpublished, UK Meningitis Study

Which patients need a CT scan?Indications for neuroimaging prior to LP in suspected meningitis* Focal neurological signs Presence of papilloedema** Continuous or uncontrolled seizures GCS ≤12****to exclude significant brain swelling and shift that may predispose to cerebral herniation post LP**inability to view the fundus is not a contraindication to LP, especially in patients who have had a short duration of symptoms*** LP may be safe at levels below this

Bleeding risk and LPs

• Delay LMWH until after LP is performed

• INR<=1.4• Platelets >40• LP should not be

delayed for the results of blood tests unless a high clinical suspicion of a bleeding diathesis

• Other reasons to delay LP:

• Infection at site of LP• Unstable patient• Haemodynamic/respiratory

compromise

Meningitis

Suspected Meningococcal Sepsis

Bloods

Blood CulturesFBC, Urea, creatinine and electrolytes, LFT’s, clotting screen, LactateProcalcitonin (or CRP if unavailable)Meningococcal and Pneumococcal PCRSerology sampleGlucoseHIV Ab/Ag test

CSF

Cell CountOpening PressureMicroscopy, Culture and SensitivityMeningococcal and Pneumococcal PCRProtein, Glucose, Lactate

Throat swab

Bacterial CultureBacterial Culture

Further tests (if no aetiology identified on first panel)

If bacterial meningitis seems likely:16S rRNA PCR on CSF If viral meningitis seems likely:CSF PCR for: HSV 1, HSV 2, VZV and Enterovirus.Stool for Enterovirus PCR Throat swab for Enterovirus PCR

Blood CulturesFBC, Urea, creatinine and electrolytes, LFT’s, clotting screen, LactateProcalcitonin (or CRP if unavailable)Meningococcal and Pneumococcal PCRSerology sampleGlucoseHIV Ab/Ag test

Inve

stiga

tions

Empirical Treatment– Ceftriaxone/Cefotaxime

– Think about penicillin resistance if recent travel – add in IV Vancomycin or Rifampicin

– Add in Amoxicillin if >60 or immunocompromised

– Chloramphenicol if anaphylaxis to penicillins/cephalosporins

Definitive treatment• Guided by microbiological results

– Continue cephalosporin or de-escalate to Benzylpenicillin?

• Consider outpatient therapy

• Aciclovir/valaciclovir not recommended in herpes meningitis

Duration of treatment

Pneumococcal Meningitis

Good Recovery 10 days

Delayed Recovery 14 days

Meningococcal Meningitis/Sepsis

Good recovery 5 days

Delayed Recovery 7 days

No identified pathogen

Good recovery 10 days

Delayed recovery 14 days

Adjunctive treatment

• Dexamethasone 10mg IV 6 hourly – can be given up to 12 hours after antibiotics

• No role for glycerol or therapeutic hypothermia

Critical Care• Involve early• Refer– Those with rapidly evolving rash– Those with GCS of 12 or less– Those requiring monitoring or organ support– Those with uncontrolled seizures

• Intubation strongly considered in those with GCS of 12 or less

• Anyone with severe sepsis should be managed in a critical care setting

Prophylaxis/screening• All patients with meningitis or meningococcal

sepsis should have an HIV test

• Patients with 2 or more episodes (or family history of > 1) should have immunological investigations

• Trauma, neurosurgery or rhino/otorrhoea – investigations for a CSF leak

Follow up/sequelae

• Follow up appointments

• Hearing tests within 4 weeks of being well enough to test

• Fast track assessment for cochlear implant

• Support organisations

Implementation

Implementation

• How do we actually get people to use the guideline?

• How do we assess the effectiveness or otherwise of the guideline?

• Implementation best achieved with a multifaceted approach actively engaging clinicians (Prior; J Eval Clin Pract, 2008)

More effective interventions Less effective interventions

Multifaceted interventions Didactic education

Interactive education Passive dissemination strategies

Clinical reminder systems

Many doctors unaware of the existence of the guidelines

“I know there are guidelines, but and I know that you could probably just Google them and they would probably just be there erm... It is ringing some bells but I couldn't tell you what was on it ((laughs)).” ST3 elderly care

“Erm... there must be some national guidelines, and I do actually need to read them, I have not read any recently erm...“ ST3 gasteroenterology

“Erm… well I know there are some but I don’t, I have never used them.” CT1 Acute Medicine/ A and E

“Yes, I mean I… I have done you know I have done a fair amount of emergency medicine and acute medicine and it [the use of steroids in the management of meningitis] is not something I have really come across, but then how many actual proper bacterial meningitises have I seen.” CT1 Acute Medicine/A and E

How do we actually get people to use the guideline?

• They need to have heard about it– National launch

• Federation of Infection Societies Conference

– Involvement of several societies• Presentations at Intensive Care

Society meeting in December• Write up in the Society for

Acute Medicine’s journal– Algorithm– Audit Tool

How do we actually get people to use the guideline?

• Some other suggestions (for discussion…)– National audit

– Press release

– Editorial

– Apps/easy to navigate ‘clickable’ electronic versions

– Learning modules - BMJ learning

How do we assess the effectiveness or otherwise of the guideline?

• Audit Tool– National audit

• Historical cohort studies

• Other suggestions welcome

Acknowledgements

• All authors• All members of the partner organisations for

comments in the consultation period• Dr Huw Cooper and Professor C H Raine for

advice regarding audiological follow up