Symptoms of meningism and raised numbers of cells in the CSF with a sterile bacterial culture.

Transcription

1 Table 1. Definitions. Meningism Meningitis Sepsis Severe sepsis Septic shock Meningococcal sepsis Invasive meningococcal disease (IMD) Encephalitis Meningoencephalitis Aseptic Meningitis Symptoms associated with meningitis including headache, neck stiffness and photophobia Inflammation of the meninges Strictly a pathological diagnosis Cerebrospinal fluid white cell count and protein are normally used as indicators of inflammation Meningeal enhancement may be seen on contrast enhanced CT or MRI Presence of infection with systemic manifestations such as: Fever or hypothermia Tachycardia Tachypnoea Altered mental state (see the surviving sepsis guidelines for a full list of potential manifestations of sepsis (42)) Acute organ dysfunction secondary to documented or suspected infection Severe sepsis plus hypotension not reversed with fluid resuscitation Evidence of a systemic inflammatory response with or without a characteristic petechial/ purpuric skin rash and hypoperfusion. Neisseria meningitidis may be identified from blood,csf or skin lesions (culture or PCR). Invasion of any normally sterile site by Neisseria meningitidis including meningitis and bacteraemia Inflammation of the brain parenchyma Strictly a pathological diagnosis Cerebrospinal fluid white cell count and protein normally used as proxies to indicate inflammation Parenchymal inflammation may be seen on MRI Inflammation of the meninges and adjoining brain parenchyma Symptoms of meningism and raised numbers of cells in the CSF with a sterile bacterial culture.

2 Table 2. Key aetiological considerations Young adults Older adults Skull fracture/csf leak Previous lymphocytic meningitis Rash Co-existing upper respiratory tract infection e.g. otitis media, sinusitis HIV Positive Other immunocompromised Travel history Viral Meningitis more common than bacterial, especially in women in their 20s-40s. Second peak of Meningococcal disease in late teens/early 20s Pneumococcal disease more common in over 50s Listeria commoner in over 60s but remains rare. Pneumococcal meningitis and a risk factor for recurrent meningitis HSV-2 is the commonest cause of recurrent lymphocytic meningitis Meningococcal meningitis more likely to present with a rash than pneumococcal meningitis Pneumococcal meningitis is often associated with an upper respiratory tract infection Cryptococcal meningitis commonest in those with a CD4 count <100 x 10 6 but should be considered in anyone with a CD4 count of <200 x 10 6 or <14%. TB meningitis an important consideration at all CD4 counts Pneumococcal meningitis also increased Asplenic individuals are at increased risk from all encapsulated bacteria e.g. Streptococcus pneumoniae, Neisseria meningitidis and Haemophilus influenza Complement deficiency increases risk of meningococcal disease An appropriate travel history may determine other rarer causes including Toscana Virus (Mediterranean), Tick Borne Encephalitis Virus (Central and Eastern Europe), Parasitic meningitis (such as Naegleri fowleri - following visits to warm, fresh or brackish water, of trypanosomiasis South America or parts of Africa), Other Meningococcal (meningitis belt in Africa), Amoebic, West Nile Virus (USA), Lyme disease (appropriate exposure in Europe or USA).

3 Table 3. GRADE rating system for the strength of the guidelines recommendations and the quality of the evidence(23) Strength of the Recommendation Quality of the Evidence 1 Strongly recommended A High Quality RCT, metanalysis 2 Weakly recommended B Moderate Quality down graded RCT or an upgraded observational study C Low Quality Observational Study D Very low quality down graded observational study. Table 3a. Factors that may influence the grading of quality of evidence Factors that might decrease the quality of Factors that might in increase the quality of evidence evidence Study Limitations Large magnitude of effect Inconsistency of results Plausible confounding, which would reduce a demonstrated effect Indirectness of evidence Dose-response gradient Imprecision Publication bias Table 3b. Factors that determine the strength of a recommendation Balance between desirable and undesirable effects Quality of evidence Values and Preferences Costs of the intervention

4 Table 4. Classical CSF Features of the different causes of meningitis Normal Bacterial Viral Tuberculous Fungal Opening Pressure Raised Normal/mildly Raised Raised (cm CSF) raised Appearance Clear Turbid, cloudy, purulent Clear Clear or cloudy Clear or cloudy CSF WCC (cells/ul) <5 Raised (normally >100) Raised (normally <1000) Raised (normally <500) Raised (normally <500)* Predominant cell n/a Neutrophils** Lymphocytes # Lymphocytes Lymphocytes type CSF protein (g/l) <0.4 Raised, Mildly raised Markedly Raised normally>1.0 (0.5-1) raised CSF glucose < 2.5 Normal/slightl < 2.5 Low (mmol) y low CSF/ plasma glucose ratio >0.66 Very low Normal/slightl y low Very low Low CSF cerebrospinal fluid; WCC white cell count Local laboratory ranges for biochemical tests should be consulted and may vary from these quoted here. A traumatic lumbar puncture will affect the results by falsely elevating the white cells due to excessive red cells. A common correction factor used is 1:1000. *Occasionally the CSF WCC may be normal (especially in immunodeficiency or TB). ** May be lymphocytic if antibiotics given before lumbar puncture (partially treated bacterial meningitis), or with certain bacteria e.g. Listeria monocytogenes # May be neutrophilic in enteroviral meningitis (especially early in disease) May be neutrophils early on in the course of disease

5 Table 5. Empirical Antibiotic choices Preferred Choice Adults <60 years of age* Cefotaxime 2g 6 Ceftriaxone 2g 12 Adults 60 years of age* Cefotaxime 2g 6 Ceftriaxone 2g 12 AND Amoxicillin 2g 4 Alternative Chloramphenicol 25mg/kg 6 Chloramphenicol 25mg/kg 6 AND Co-trimoxazole 10-20mg/kg in four divided doses(of the trimethoprim component) *add in IV Vancomycin 15-20mg/kg bd or Rifampicin 600mg bd if penicillin resistance is suspected e.g. patient has recently arrived from a country where penicillin resistant pneumococci is prevalent (if unsure, check with local infectious diseases/microbiology expertise) Serum vancomycin trough concentrations of 15-20ug/ml should be aimed for

6 Table 6.Definitive antibiotic treatment Aetiology Antibiotic (s) Dose Alternative antibiotic choices Neisseria meningitidis Streptococcus pneumoniae (sensitivities unknown or penicillin resistant, cephalosporin sensitive) Streptococcus pneumoniae (penicillin sensitive, MIC 0.06) Streptococcus pneumoniae (penicillin and cephalosporin nonsusceptible, penicillin MIC>0.06 or cefotaxime/cef triaxone MIC >0.5) Listeria monocytogene s Haemophilus influenzae Cefotaxime Ceftriaxone Cefotaxime* Ceftriaxone* Benzylpenicilli n Cefotaxime Ceftriaxone*** Cefotaxime Ceftriaxone AND Vancomycin Rifampicin 2g 6 / 2g 12 2g 6 2g g 4 2g 6 / 2g 12 2g 6 2g mg/kg g 12 (adjustin g accordin g to serum trough levels) 600mg bd Amoxicillin 2g 4 Cefotaxime Ceftriaxone 2g 6 2g 12 Chloramphenicol (if anaphylaxis) Benzylpenicillin Dose 25mg/kg 6 2.4g 4 Chloramphenicol 25mg/kg 6 Chloramphenicol 25mg/kg 6 Chloramphenicol 25mg/kg 6 Duration* * 5 days 10 days (if stable) Up to 14 days if taking longer to respond 10 days (if stable) Up to 14 days if taking longer to respond 14 days Co-Trimoxazole 10-20mg/kg (of the trimethopri m component) 21 days Moxifloxacin 400mg od 10 days

7 *add in IV Vancomycin 15-20mg/kg bd or Rifampicin 600mg bd if penicillin resistance is suspected e.g. patient has recently arrived from a country where penicillin resistant pneumococci is prevalent (if unsure, check with local infectious diseases/microbiology expertise **treatment durations may need to be extended if patient is not responding ***if low risk of Clostridium difficile infection and/or requiring outpatient therapy Serum vancomycin trough concentrations of 15-20ug/ml should be aimed for

8 Box 1. Key Changes since Consensus Document in 1999 Updated epidemiology Change in recommendations regarding pre-hospital antibiotics Clear guidance on when to perform a CT scan Recommended durations of antibiotics and adjunctive treatment including the removal of activated protein C. Updated recommendations on empirical antibiotics Recommendations regarding outpatient treatment Updated guidance on prophylaxis for contacts Infection control advice The addition of a section on viral meningitis Audit Tool Box 2. Guidelines which may be of use in other settings. Infectious Diseases Society of America Patient_Care/PDF_Library/Bacterial%20Meningitis%281%29.pdf European Federation of Neurological Sciences European Society for Clinical Medicine and Infectious Diseases (to be published mid-late 2015) Federation of Infectious Diseases Society of Southern Africa Ministry of Health, Social Services and Quality, Spain.

9 Box 3 Key Questions What are the indications for hospital admission? What should the pre-hospital management be? What are the clinical signs to look for including early recognition? What is the initial assessment and immediate action? Are prognostic or diagnostic scores of any value? What are the contraindication to LP? What are the indications for imaging? What investigations should be requested? o Microbiological o Biochemical o Haematological o Others (including travel related) When should an HIV test be offered? What treatment should be given? o Empirical o Directed o Adjunctive What is the role of steroids? What is the role of Glycerol? When should you refer to specialists/intensive care? What is the role for fluid management, inotropes and indications for ventilation? What should the Intensive Care management be? What preventative measures should/can be taken? (including notification and primary and secondary prevention) What are the appropriate infection control measures? Who should be screened for predisposing factors? What should follow up look like? (including the role of support services) How should viral meningitis be investigated and treated? What are the auditable measures? (to include an audit tool) When should this guideline be reviewed?

10 Box 4. Risk factors for a fatal outcome in meningococcal disease Rapidly progressing rash Coma Hypotension and Shock Lactate >4mmol/L Low/normal peripheral white blood cell count Low acute phase reactants Low platelets Coagulopathy Absence of meningitis Box 5. Indications for neuroimaging 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 Box 6. Initial therapeutic endpoints in the resuscitation of septic shock (42) Capillary refill time less than 2 seconds Normal blood pressure for age (in adults > 65mmHg mean BP) Normal pulses with no differential between peripheral and central pulses Warm extremities Urine output >0.5 ml/kg/hour (A urinary catheter is required) Normal mental status CVP 8-12mmHg Lactate < 2mmol/L

11 Box 7. Methods to reduce post lumbar puncture headache Definition and aetiology Headache following a LP that is typically a low-pressure phenotype; i.e. worse upright and better lying flat. This low-pressure headache is typically caused by a dural tear sustained at the time of performing the LP rather than due to the volume of CSF taken. It is usually self-limiting although a few patients may require a blood patch for persistent headache and rarely the low pressure may be associated with the development of subdural haematomas. Practices associated with reduced risk of post LP headache 1. Finer gauge needles(266, 267) a. Risk of headache decreases with smaller gauge needles but this needs to be balanced with the length of time the proceudure will take with very fine needles. A 22G needle is probably the smallest that can be used for a diagnostic needle. 2. Perpendicular orientation of the bevel of the needle(268,269) a. Although this is probably less important if an atraumatic needle is being used. 3. Non-traumatic (less traumatic) needles(267,270) a. Paraesthesia rate and failure rate may be higher with these needles 4. Replacement of the stylet before withdrawing the needle(271) 5. Procedural skill and number of attempts at lumbar puncture(272) a. The number of dural punctures directly relates to the size of the dural damage, making fewer attempts at dural puncture could be associated with lesser incidence of headache after lumbar puncture. However, no studies have been conducted. Practices NOT proven to reduce risk of post LP headache 1. Reducing the volume of CSF taken(273) a. There is no evidence that the amount of CSF removed influences the incidence of post LP headache 2. Bed rest(274,275) a. Patients are often advised to lie recumbent for a period of time after a lumbar puncture but there is no evidence that this reduces the risk of post LP headache. 3. Hydration (276) a. There has only been one study looking at fluid post LP as a preventative strategy and it showed no difference between those who took 1.5 litre and those who had 3 litres post LP. 4. Caffeine a. There have been some experiments looking at IV caffeine to treat post LP headache but there is no evidence that either oral or IV caffeine can prevent the headache.

12 Box 8. Selected countries with penicillin resistance (refer to (277) for a complete list) Canada China Croatia Greece Italy Mexico Pakistan Poland Spain Turkey USA

13 Box 9. Outpatient Therapy (OPAT) of Meningitis and Meningococcal disease 7a. Indications where outpatient therapy may be appropriate The decision to commence OPAT must be made by a physician familiar with OPAT and should be carried out by a specialist OPAT team and include regular review of cases by a physician Patient should be afebrile and clinically improving The patient should have received 5 days of inpatient therapy and monitoring (?shorter) The patient should have reliable intravenous access The patient should be able to access medical advice/care from the OPAT team or delegated individuals 24 hours a day. The patient and family/carer must be willing to participate in OPAT The patient should have no other acute medical needs other than the need for parenteral antimicrobials 7b. Regimes that could be used in the community Ceftriaxone 2 g bd IV (4g od IV can be used after the first 24 hours of therapy) Ceftriaxone 2g bd IV and Rifampicin 600mg bd PO for penicillin resistant pneumococci

14 Box 10. Complications of acute meningitis and meningococcal sepsis. Complication Warning Signs Action Meningitis Subdural collection Persistent fever New focal neurology Urgent imaging WITH contrast Neurosurgical opinion Seizures Hydrocephalus Meningococcal Sepsis Purpura fulminans Rapidly progressive rash Septic shock Cold peripheries Refractory hypotension EEG monitoring Neuroimaging and neurosurgical opinion Ensure on appropriate antibiotics Involve critical care and infection specialist ASAP Ensure on appropriate antibiotic therapy Involve critical care and infection specialist ASAP

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