Introduction
Methods
Search strategy
Eligibility criteria
Data extraction
Quality appraisal
Results
Clinical management guidelines
Quality appraisal
Guidelines | Scope and purpose (%) | Stakeholder involvement (%) | Rigour of development (%) | Clarity of presentation (%) | Applicability (%) | Editorial independence (%) | Overall quality |
---|---|---|---|---|---|---|---|
Viral aetiology
| |||||||
IEC | 91.7 | 63.9 | 40.6 | 91.7 | 52.1 | 50.0 | 5 |
EFNS | 83.3 | 52.8 | 55.2 | 91.7 | 47.9 | 25.0 | 5 |
DNS | 38.7 | 27.7 | 22.1 | 41.8 | 16.6 | 0.0 | 3 |
DGN: VM | 69.4 | 44.4 | 50.0 | 75.0 | 20.8 | 66.7 | 5 |
IDSA | 72.2 | 50.0 | 58.3 | 86.1 | 18.8 | 83.3 | 6 |
PHE: VE | 88.9 | 75.0 | 44.8 | 86.1 | 31.3 | 50.0 | 6 |
BIA: ABN | 100 | 83.3 | 94.8 | 94.4 | 47.9 | 66.7 | 6 |
BIA: ABN/BPAIIG | 100 | 83.3 | 74.0 | 91.7 | 54.2 | 0.0 | 6 |
AEPED | 61.1 | 33.3 | 24.0 | 55.6 | 20.8 | 8.3 | 3 |
SPILF | 78 | 41.5 | 45.5 | 75.0 | 4.0 | 8.3 | 4 |
Median | 80.7 | 51.4 | 47.8 | 86.1 | 26.1 | 37.5 | 5.0 |
Range | (39–100) | (22–83) | (22–95) | (42–94) | (17–54) | (0–83) | (3–6) |
Viral and bacterial aetiology
| |||||||
NNF | 75.0 | 52.8 | 37.5 | 88.9 | 6.3 | 29.2 | 4 |
PHE: ME | 97.2 | 69.4 | 28.1 | 94.4 | 43.8 | 83.3 | 5 |
Median | 86.1 | 61.1 | 32.8 | 91.7 | 25.1 | 56.3 | 4.5 |
Range | (75–97) | (52–69) | (28–38) | (89–94) | (6–44) | (29–83) | (4–5) |
Bacterial aetiology
| |||||||
EFNS | 94.4 | 52.8 | 47.9 | 97.2 | 43.8 | 0.0 | 5 |
ESCMID | 100 | 83.3 | 88.5 | 88.9 | 47.9 | 66.7 | 7 |
DSI | 75.0 | 36.1 | 20.8 | 86.1 | 45.8 | 0.0 | 4 |
SPILF | 83.3 | 38.9 | 44.8 | 88.9 | 25.0 | 0.0 | 4 |
DGN: BM | 69.4 | 44.4 | 50.0 | 75.0 | 20.8 | 66.7 | 5 |
HPSC | 100 | 66.7 | 45.8 | 94.4 | 39.6 | 0.0 | 5 |
NVN | 97.2 | 94.4 | 87.6 | 97.2 | 66.7 | 29.2 | 7 |
MHSSE | 100 | 94.4 | 90.6 | 86.1 | 43.8 | 50.0 | 7 |
NICE | 100 | 86.1 | 95.8 | 88.9 | 79.2 | 70.8 | 7 |
UKJSS | 100 | 88.9 | 77.1 | 94.4 | 47.9 | 50.0 | 7 |
SIGN | 91.7 | 91.7 | 79.2 | 86.1 | 37.5 | 45.8 | 7 |
IDSA | 75.0 | 50.0 | 59.4 | 86.1 | 10.4 | 54.2 | 5 |
AEPED | 61.1 | 33.3 | 19.8 | 83.3 | 20.8 | 0.0 | 3 |
MSF | 88.9 | 47.2 | 9.4 | 91.7 | 50.0 | 0.0 | 4 |
Median | 93.1 | 59.8 | 54.7 | 88.9 | 43.8 | 37.5 | 5 |
Range | (61–100) | (33–94) | (9–96) | (75–97) | (10–79) | (0–71) | (3–7) |
Signs and symptoms at presentation
Viral encephalitis/meningoencephalitis
Bacterial CNS infections
| |||||
Neonates/infants (≤ 1 year) (n = 8 CMGs) | Children (< 16–18 years) (n = 10 CMGs) | Adults and unspecified age (n = 10 CMGs) | |||
Signs and symptoms | n (%) | Signs and symptoms | n (%) | Signs and symptoms | n (%) |
Irritability | 8 (100) | Neck stiffness | 10 (100) | Fever | 10 (100) |
Fever | 8 (100) | Headache | 9 (90) | Headache | 10 (100) |
Poor appetite/feeding | 8 (100) | Fever | 9 (90) | Neck stiffness | 10 (100) |
Bulging fontanelle | 6 (75) | Petechial rash/purpura | 8 (80) | AMS/ALOC | 6 (60) |
Petechial rash/purpura | 6 (75) | AMS | 7 (70) | Petechial rash/purpura | 5 (50) |
Lethargy | 6 (75) | Nausea/vomiting | 6 (60) | Focal neurological signs | 5 (50) |
Nausea/vomiting | 5 (63) | Photophobia | 6 (60) | Seizures | 4 (40) |
Neck stiffness | 5 (63) | Kernig’s sign | 5 (50) | Photophobia | 3 (30) |
Seizures | 4 (50) | Brudzinski’s sign | 5 (50) | Nausea/vomiting | 3 (30) |
Apnoea or respiratory distress | 4 (50) | Cold hands/feet | 4 (40) | ||
Hypothermia | 4 (50) | Abnormal skin colour | 4 (40) | ||
Confusion | 3 (38) | Focal neurological signs | 3 (30) | ||
Photophobia | 3 (38) | Poor appetite | 3 (30) | ||
Abnormal skin colour | 3 (38) | Leg pain | 2 (20) | ||
Kernig’s sign | 2 (25) | Lethargy | 2 (20) | ||
Brudzinski’s sign | 2 (25) | Irritability | 2 (20) | ||
Viral CNS infections
| |||||
Children (n = 4 CMGs) | Adults and unspecified age (n = 10 CMGs) | ||||
Signs and symptoms | n (%) | Signs and symptoms | n (%) | ||
Seizures | 4 (100) | Seizures | 10 (100) | ||
Focal neurological signs | 4 (100) | Focal neurological signs | 10 (100) | ||
Fever | 4 (100) | Fever | 9 (90) | ||
ALOC | 4 (100) | ALOC | 9 (90) | ||
Changes in personality or behaviour | 4 (100) | Changes in personality or behaviour | 8 (80) | ||
Headache | 1 (25) | Rash | 5 (50) | ||
Headache | 4 (40) | ||||
Vomiting | 1 (10) | ||||
Memory changes | 1 (10) |
Bacterial meningitis
Diagnostic methods
Viral encephalitis/meningoencephalitis
Bacterial meningitis
Differential diagnostics
Viral encephalitis/meningoencephalitis
CMG | Differential diagnostic recommendations |
---|---|
IEC* | Children: HSV-1, HSV-2, enteroviruses, EBV, parechovirus (< 3 years), Mycoplasma pneumoniae, TBEV, WNV (S. Europe), TOSV (S. Europe) Adults: HSV-1, HSV-2, enteroviruses, VZV, Treponema pallidum, Cryptococcus, HIV, TBEV, WNV (S. Europe), TOSV (S. Europe) Others based on epidemiological and clinical features. |
EFNS^ | Unspecified: HSV-1, HSV-2, VZV, HHV 6/7, CMV, EBV, JCV, Dengue virus, respiratory viruses, RSV, HIV, adenovirus, influenza A and B, rotavirus, Coxsackie B5, non-typed enterovirus, Parainfluenza 1 virus |
DNS | Unspecified: HSV, VZV, HIV, EBV/CMV, syphilis, HHV 6–7, toxoplasma |
DGN: VM | Unspecified: HSV, VZV, CMV, coxsackievirus, echovirus, adenovirus, phlebovirus, measles, TBE, mumps, EBV, rubella, enterovirus 71, HIV, parvovirus B19, HHV-6, Dengue virus, FSME, rabies, vaccinia, Lassa virus, Japanese encephalitis, WNV, polioviruses, hantavirus, filovirus Others based on epidemiological and clinical features. |
IDSA* | Neonates: HSV 2, CMV, rubella virus, L. monocytogenes, T. pallidum, Toxoplasma gondii Infants and Children: Eastern equine encephalitis virus, Japanese encephalitis virus, Murray Valley encephalitis virus, influenza virus, La Crosse virus Unspecified: HSV, WNV, TBEV, A. phagocytophilum, B.burgdorferi Elderly: Eastern equine encephalitis virus, St. Louis encephalitis virus, WNV, sporadic Creutzfeldt-Jakob Disease, L. monocytogenes Person-to-person transmission: VZV, Venezuelan equine encephalitis virus (rare), poliovirus, non-polio enteroviruses, measles virus, mumps virus, rubella virus, EBV, HHV 6, B virus, WNV (transfusion transplantation, breast feeding), HIV, Nipah virus, rabies virus (transplantation), influenza virus, M. pneumoniae, Mycobacterium tuberculosis, T. pallidum. Others based on specific clinical findings, epidemiology and risk factors. |
PHE: VE* | Children and adults: HSV-1, HSV-2, VZV, enteroviruses, parechovirus (< 3 years), HHV-6 (< 3 years), mumps (if epidemic), Influenza A, B (if epidemic), HIV, Others based on specific epidemiology and risk factors |
BIA/ABN | Adults: HSV-1, HSV-2, VZV, enteroviruses, parechovirus, measles virus, mumps virus, TBEV (eastern Europe), WNV (southern Europe), HIV, EBV (immunocompromised), CMV (immunocompromised) influenza virus (rare), adenovirus (rare), Erythrovirus B19 (rare), lymphocytic choreomeningitis virus (rare), rubella virus (rare) Others based on epidemiological and clinical features. |
BIA/ABN/BPAIIG | Children: HSV-1, HSV-2, VZV, enteroviruses, parechovirus, HHV 6/7, measles virus, mumps virus, rotavirus, HIV, TBEV (eastern Europe), WNV (southern Europe), HIV, EBV (immunocompromised), CMV (immunocompromised) influenza virus (rare), adenovirus (rare), Erythrovirus B19 (rare), lymphocytic choreomeningitis virus (rare), rubella virus (rare) Others based on epidemiological and clinical features. |
AEPED* | Congenital: Lymphocytic Choriomeningitis virus, CMV, measles virus, T. gondii, T. pallidum, Neonates (< 1 month): HSV, enteroviruses, adenovirus, Citrobacter spp., GBS, L. monocytogenes Infants and children > 1 month: HSV, enteroviruses, arboviruses, EBV, adenovirus, HIV, M. pneumoniae, Borrelia burgdorferi, Bartonella henselae, Rickettsia rickettsii. Others based on epidemiological and clinical features. |
SPILF*^ | Adults (metropolitan France): HSV, VZV, HIV, enterovirus, L. monocytogenes (higher risk > 65 years), M. tuberculosis (higher risk > 75 years) |
NNF* | Unspecified: HSV-1, HSV-2, VZV, EBV, HHV-6, enteroviruses, parechovirus (children), adenovirus, Influenza A, measles, mumps, rubella, HIV, Hepatitis E, Japanese B, WNV, rabies virus, TBE, Eastern equine encephalitis, S. pneumoniae, B. burgdorferi, M. pneumoniae, Chlamydia trachomatis, L. monocytogenes, M. tuberculosis, cerebral malaria, Cystericosis. Others based on immune status. |
PHE: ME* | Unspecified: HIV, HSV-1, HSV-2, VZV, enteroviruses, parechovirus (< 3 years), N. meningitidis, S. pneumoniae, H. influenzae, E. coli, L. monocytogenes, GBS |
Bacterial meningitis
Pathogen | Age group | EFNS Europe | ESCMID Europe | DSI Denmark | SPILF France | DGN: BM^ Germany | HPSC Ireland | NVN Netherlands | NICE UK | UKJSS^^ UK | IDSA USA/Global | AEPED Spain | MSF Global | NNF^^ | PHE: ME |
---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
S. pneumoniae
| Neonates | (very rare) | N | N | > 7 days | NS | |||||||||
Paediatric | P | P | P | P | NS | 1–12 months | ≥ 3 months | P | P | > 3 months | > 2 years | NS | |||
Adults | A | A | A | A | A | NS | A | A | A | A | A | NS | |||
N. meningitidis
| Neonates | N | NS | ||||||||||||
Paediatric | P | P | P | P | NS | > 12 months | ≥ 3 months | P | P | > 3 months | > 2 years | NS | |||
Adults | A | (less common) | A | A | A | NS | A | A | A | A | A | NS | |||
S. agalactiae
| Neonates | N | N | N | N | N | N | N | ≤ 7 days | NS | |||||
Paediatric | < 3 months | < 24 months | < 3 months | NS | |||||||||||
Adults | A | (rare) | A | NS | |||||||||||
H. influenzae
| Neonates | NS | |||||||||||||
Paediatric | P | (unvaccinated) | NS | ≥ 3 months | < 24 months | 3 months to 5 years | NS | ||||||||
Adults | (rare) | (rare) | A | (rare) | A | NS | A | A | NS | ||||||
L. monocytogenes
| Neonates | (rare) | N | N | N | N | N | > 7 days | NS | ||||||
Paediatric | P | ≤ 3 months | NS | ||||||||||||
Adults | A | > 50 years | A | (rare) | A | A | > 60 years | > 50 years | > 50 years | NS | |||||
E. coli
| Neonates | N | N | N | N | N | N | ≤ 7 days | NS | ||||||
Paediatric | P | < 3 months (rare) | < 24 months | NS | |||||||||||
Adults | A | A | > 50# | NS | |||||||||||
Klebsiella spp. | Neonates | N | ≤ 7 days | NS | |||||||||||
Paediatric | P | ||||||||||||||
Adults | A | A^ | |||||||||||||
Enterobacter spp. | Neonates | ||||||||||||||
Paediatric | P | ||||||||||||||
Adults | A | A | A | ||||||||||||
Pseudomonas aeruginosa
| Neonates | ≤ 7 days | |||||||||||||
Paediatric | P | ||||||||||||||
Adults | A | A | A^ | A | |||||||||||
Proteus mirabilis
| Neonates | ||||||||||||||
Paediatric | P | ||||||||||||||
Adults | A | ||||||||||||||
Salmonella spp. | Neonates | ≤ 7 days | |||||||||||||
Paediatric | |||||||||||||||
Adults | |||||||||||||||
S. aureus
| Neonates | (very rare) | |||||||||||||
Paediatric | P | ||||||||||||||
Adults | A | A (rare) | A | A |
Empirical treatment
Viral encephalitis/meningoencephalitis
Bacterial meningitis
Initial treatment recommendations* | |||||
---|---|---|---|---|---|
CMG | 3rd-generation cephalosporin (ceftriaxone^ or cefotaxime) | 3rd generation-cephalosporin (ceftriaxone^ or cefotaxime) plus a penicillin (amoxicillin, ampicillin or penicillin) | Aminoglycoside (gentamicin) plus a penicillin (amoxicillin or ampicillin) | Add: glycopeptide (vancomycin) | Add: corticosteroids (before or with first dose of antibiotics) |
EFNS Europe | P, A | E | Older children and adults** | Yes | |
ESCMID Europe | P, A | N, A > 50 years, or if risk factor for L. monocytogenes | N | **,^ | Yes^ up to 4 h post-antibiotics |
DSI Denmark | A | A if risk of L. monocytogenes | Yes | ||
SPILF France | P, A | P, A if suspected L. monocytogenes° | If S. pneumoniae | Yes″ | |
DGN: BM Germany | A | A | A** | Yes | |
HPSC Ireland | P > 2 m, A | N, P < 2 months | N, P < 2 months | **,^ | Yes up to 24 h post-antibiotics |
NVN Netherlands | P, A | N, A | Yes | ||
MHSSE# Spain | P | Yes | |||
NICE UK | P > 3 m | N, P < 3 months | If travel outside of the UK | Yes^^ up to 12 h post-antibiotics | |
UKJSS UK | A | A > 60 years | Pending travel history | Yes up to 12 h post-antibiotics | |
SIGN# Scotland | P > 3 m | N, P ≤ 3 months | Yes up to 24 h post-antibiotics | ||
IDSA USA/Global | P, A | N, A > 50 years | N | P, A | P^, infants if Hib, A |
AEPED Spain | P | N, P ≤ 3 months | **,^ | Yes | |
MSF Global | P > 3 m, A | N, P ≤ 3 months | N, P ≤ 3 months | Yes^ | |
NNF Norway | NS | NS | Yes |