Bacterial Meningitis - Infections of the CNS

Infections of the CNS

Bacterial Meningitis

Signs and Symptoms

·        Rapid onset of: 

o  Meningism: Headaches, photophobia, stiff neck. Kernig‟s sign: Pain on straightening knee with hip flexed 

o  ­ICP: Headache, irritable, drowsy, vomiting, fits, ¯pulse, ­¯BP, ¯LOC, pin-point pupils, papilloedema (late sign), tense fontanelle 

o   Septicaemia: fever, arthritis, DIC, ¯BP, ­pulse, tachycardia, rash (ultimately 80% will have a purpuric rash, 10 – 15% will have a maculo-papular or urticarial rash, 5 – 10% will have no rash)

·        In different age groups: 

o  Infants/toddlers: fever, lethargy, poor feeding, vomiting, toxic (drowsy, pallor), rash. Only 30 – 50% have signs of meningism Þ absence doesn‟t exclude. Bulging anterior fontanelle – but if vomiting may be normal or reduced 

o   Children > 3: fever, headache, vomiting, photophobia, stiff neck, confusion (may be combative), non-blanching rash (initially blotchy macular rash that rapidly becomes petechial or purpuric)

o  Adolescents: may present as acute mania or appearance of drug induced psychosis

Pathogenesis

·        Organisms: 

o  Neonates: E. Coli, b-haemolytic streptococci Group B (eg streptococcus agalactiae – normal vaginal flora), rarely listeria 

o  Children < 14 years: H. Influenza (if < 4 and not immunised), Neisseria Meningitidia Type B, Strep Pneumoniae, Tb 

o  Adults: Neisseria Meningitidia Type B, Strep Pneumoniae, maybe staph aureus or Cryptococcus neoformans

o  Elderly, Immunocompromised: Pneumococcal, Listeria, Tb, G –ive, Cryptococcus Neoformans

·        Pathogenesis:

o  Pathology: inflammation of pia mater and arachnoid

o  Most common are N Meningitidis and S pneumoniae 

o  Nasopharynx®blood®subarachnoid space (via choroid plexus): N meningitides, HIB, S. pneumoniae 

o  Middle ear®blood®subarachnoid space: S Pneumoniae, HIB

o  Congential abnormalities (eg spina bifida): coliform bacilli, pseudomonas, Strep agalactiae

o  Trauma: Skull fracture + CSF leak, CNS surgery, shunts: Staph aureus

o  Depressed immunity: listeria monocytogenes, cryptococcus neoformans

o  Neonatal meningitis from vaginal flora (especially with prematurity, prolonged ROM, delayed 2^nd stage): Strep agalactiae, coliforms (E coli), listeria monocytogenes

·        If recurrent:

o  Consider immunosuppression (eg hypogammaglobulinaemia or complement deficiency)

o  Look for lumbosacral defects, especially if enteric bacteria or S aureus

Investigations

·        Do blood culture before presumptive treatment if possible, but NOTHING should delay presumptive treatment. Tell lab about antibiotics

·        Must do:

o  Blood cultures

o  CSF via lumbar puncture unless contraindicated (see below)

o  Urine: supra-pubic aspiration or catheter

o  If antibiotics have already been administered:

§  Needle aspirate purpuric lesions for gram stain and culture

§  Throat swab

·        Bloods:

o  Blood Glucose sample – may be hypoglycaemic [ABC = Airway, breathing, circulation. DEFG =

o   Don‟t Ever Forget Glucose]

o  FBC, electrolytes, clotting time, ABGs

·        Lumbar puncture:

o   Contraindicated if: 

§  Signs of ­ICP (all meningitis will have ­ICP) causing cerebral herniation (eg very ¯LOC, very bad headache, focal signs including abnormal papillary reflexes, tonic seizures, decerebrate or decorticate posturing, irregular respirations, bradycardia, papilloedema). If in doubt then CT 

§  Severe cardiovascular compromise with DIC/coagulopathy (eg fulminant sepsis)

§  Infection over the injection site 

o   Tests of CSF: Gram stain, Tb, cytology, virology, glucose, protein, India ink (Cryptococcus), culture (if clear then ?virus), antigen testing (especially if partially treated)

o   May be normal, repeat if symptoms persist

o   Typical CSF (lots of variation):

§  NB: early viral meningitis may have predominantly polymorphs

§  RBCs: None. If there are then either traumatic (more in 1^st of 3 tubes) or bleed (new if red, yellow if old – zathachromia)

o   Appearance on Gram stain:

§  N Meningitidis: G –ive diplococci

§  H influenzae: Pleomorphic G –ive bacilli

§  S pneumoniae & S agalactiae: G +ive diplococci

§  Listeria: G +ive bacilli

§  TB: Acid fast bacilli very scant – take at least 5 mls of CSF

§  Cryptococcus neoformans: Indian ink stain shows capsules 

·        Imaging: To identify subdural collections, abscess, hydrocephalus, thrombosis and infarction. Only if LP contraindicated and suspected mass lesion or persistent or focal neuro signs

Management

·        Management (based on protocol for a child):

o   Standard infection control precautions plus surgical mask when examining throat, intubating etc

o   ICU if:

§  Coma

§  Circulatory collapse

§  Persistent, recurrent seizures

§  SIADH with cerebral oedema or seizures 

o   Shock or ­ICP is what kills

o   Maintain perfusion:

§  Colloid bolus (20 – 40 ml/kg 4% albumen iv), then colloid + glucose

§  Inotrope eg dobutamine (10 mg/kg/min) 

§  Watch for ­ ADH secretion ® hyponatraemia and cerebral oedema if too much fluid given

§  Check Na 6 – 12 hourly.  If Na < 135 mmol/l then ¯iv rate.  If Na > 145 then ­rate

o   Respiratory support:

§  O2 

§  Early elective intubation if persistent shock (but may exacerbate hypotension due to vasodilation and ¯sympathetic drive) 

§  Immediate intubation if ­ICP, hypoxia and/or respiratory failure, pulmonary oedema or hypotension (uncompensated shock) 

o   Correct abnormalities: anaemia, hypoglycaemia, coagulopathy (FFP), acidosis (NaHCO₃), hypokalaemia

o   Seizures: anticonvulsants 

o   Watch for ­ICP:

§  ¯Conscious state, focal neuro signs, abnormal pupils, hypertension and relative bradycardia.

§  Treatment: ICU, ¯PCO2, diuretics (Mannitol, frusemide), head up, deep sedation, inotropes. But priority is to correct the shock (CBF = MAP – ICP) 

o  Weight and measure head daily in an infant

o  Isolate patient, ensure analgesia 

o  Dexamethasone treatment controversial (most benefit in HIB). Not routinely used. Reduces fever and gives misleading impression of clinical improvement

·        Antibiotic regimes:

o  Empiric antibiotic treatment: 

§  Neonate – 3 mths: Amoxycillin 50 mg/kg (for listeria) + Ceftriaxone 50 mg/kg (E coli and Strep). 2 weeks for G +ive, 3 weeks for G –ive.

§  Older child:

·        Cefotaxime 50 mg/kg/6hr, max 2 g, iv for 7 – 10 days or

·        Ceftriaxone 50 mg/kg/12hr, max 2 g, iv for 7 – 10 days or

·        Penicillin G 50 mg/kg/4hr iv for 7 – 10 days 

§  If strep pneumonia suspected: Vancomycin 15 mg/kg/6hr, max 500 mg, iv + cefotaxime/ceftriaxone – synergistic, necessary due to ­resistance to 3^rd generation cephalosporins 

§  If still failing consider adding Rifampicin

o  Specific Treatment according to culture and susceptibility results: 

§  N Meningitidis, S agalactiae: Penicillin (Cefotaxime if allergic to penicillin) for 5-7 days. For meningococcaemia only can use penicillin or cefotaxime

§  S pneumonia:

·        Penicillin susceptible: penicillin (but 20% are resistant) for 7 – 10 days

·        Penicillin resistant, 3^rd generation susceptible: Cefotaxime

·        Penicillin and 3^rd generation resistant: Cefotaxime + Vancomycin

§  H Influenza: Cefotaxime, Ceftriaxone

§  L Monocytogenes: amoxycillin

§  Staph Aureus: Flucloxacillin

§  M Tuberculosis: Rifampicin, Isoniazid, Pyrazinamide, Ethambutol

§  Coliforms: 3^rd generation Cephalosporin (ie Cefotaxime, Ceftazidime)

§  Pseudomonas: Ceftazidime

§  Cryptococcus Neoformans: fluconazole or amphotericin B

§  NB: Erythromycin and gentamycin don‟t have good CSF penetration 

o  If not responding, or non-susceptible strain of pneumococci or receiving dexamethasone than repeat LP after 24 – 48 hours 

·        Complications:

o  Seizures:

§  First suspicion should be hyponatraemia (also hypoglycaemia): 

·        SIADH (Na < 130 and urine Na > 20) ® exacerbates cerebral oedema

·        Prevent by restricting fluids to 50% of maintenance 

·        Treatment: severe fluid restriction (10 ml/kg/day), in an emergency consider hypertonic saline, Mannitol or frusemide 

§  Hypoventilation can further ­ ICP ® hypoxia, hypercapnea, acidosis

§  Anticonvulsants can also exacerbate these metabolic changes 

§  Management options: diazepam, clonazepam, phenobarbitone, dextrose to control hypoglycaemia, intubation and ventilation 

o  Major disability in 15%: Deafness, brain damage, peripheral necrosis, etc. All cases should have audiologist check within 6 – 8 weeks of discharge

o  Death in 5%, 10 –15% pneumococcal meningitis, 20% in fulminant meningococcaemia

Meningococcal Disease

·        Cause: Neisseria Meningitidia

·        Epidemiology: 

o  10-year epidemic started in 1990 with about 50 reported cases. Since then 3696 cases and 163 deaths. Current case fatality rate is 3 – 5 %

o  Leading infectious cause of death in children

o  500 reported cases in 2000.  NZ rate is 13.3 per 100,000. UK rate is 4 per 100,000

o  Regional variation: East Cape and Central North Island the highest

o  Rates per 100,000 < 1 year olds:

§  Pacific Island: 570

§  Maori: 230

§  European: 80

·        Healthy people can be carriers

·        Transfer via respiratory secretions

·        Kids and teenagers more susceptible than adults

·        Not a cause of Otitis media 

·        Pathogenesis: endotoxins (lipopolysaccharides in the cell wall) activate complement and release of PAF causing endothelial injury ® immune activation and ­vascular permeability

·        Notifiable to public health (as is HIB) 

·        Prophylaxis to stop nasal carriage of the bug – not to cure incubating illness. Nasal carriage higher in adults than children 

o   Rifampicin: 4 doses, 600 mg bd for adults, 10 mg/kg bd for kids (very high dose). Broad spectrum antibiotic 

o   Offer to index case (if only treated with penicillin), all intimate, household and day-care contacts during last 10 days

o   Contraindications: pregnancy (use single dose ceftriaxone), liver disease. 

o   Side effects: nausea, vomiting, diarrhoea (GI effects), turns urine/tears/sweat orange/red (will stain contacts) 

o   Interactions: asthma, blood clotting and oral contraceptives (continue pill, use barrier method until 7 days after antibiotics finished)

TB Meningitis

·        Rare

·        Most common < 5 years

·        Slow onset: malaise and fever progressing to drowsiness, neck stiffness and seizures over 2 weeks

·        Mantoux testing may be normal, and CXR normal in ½ of cases

·        Investigations:

o   Gastric lavage, urine and CSF for Acid fast stain and culture

o   CT

·        Treatment: isoniazid, rifampicin, pyrazinamide

·        Notifiable disease