Diagnostic des méningites communautaires

1. Diagnostic des méningites communautaires Bruno Hoen 4ème Journée Maurice Rapin 16 octobre 2003

2. Les étapes du diagnostic des méningites communautaires • Diagnostic positif de méningite • Place de l'imagerie dans la démarche diagnostique initiale • Diagnostic étiologique (bactérie vs. virus)

3. Les étapes du diagnostic des méningites communautaires • Diagnostic positif de méningite • Place de l'imagerie dans la démarche diagnostique initiale • Diagnostic étiologique (bactérie vs. virus)

4. The Diagnostic Accuracy of Kernig’s Sign, Brudzinski’s Sign, and Nuchal Rigidity in Adults with Suspected Meningitis • To determine the diagnostic accuracy of Kernig’s, Brudzinski’s, and nuchal rigidity, 297 adults with suspected meningitis were prospectively evaluated for the presence of these signs before LP. 80 had meningitis (> 5 cells/mm3) • Kernig's, Brudzinski's • Se: 5% • Sp: 95% • PPV: 27% • NPV: 72% • Nuchal rigidity • Se: 30% • Sp: 68% • PPV: 26% • NPV: 73% Thomas, CID 2002

5. The Diagnostic Accuracy of Kernig’s Sign, Brudzinski’s Sign, and Nuchal Rigidity in Adults with Suspected Meningitis • Diagnostic accuracy of Kernig's sign, Brudzinski's sign, and nuchal rigidity in the 29 patients with  100 WBCs/mm3 • Kernig's, Brudzinski's • Se: 9% • Sp: 96% • PPV: 18% • NPV: 91% • Nuchal rigidity • Se: 52% • Sp: 71% • PPV: 16% • NPV: 93% Thomas, CID 2002

6. Les étapes du diagnostic des méningites communautaires • Diagnostic positif de méningite • Place de l'imagerie dans la démarche diagnostique initiale • Diagnostic étiologique (bactérie vs. virus)

7. Conférence de consensus 1996 • A la prise en charge initiale d'une méningite purulente, les indications d'imagerie cérébrale doivent rester très limitées. • L'urgence est à la mise en route de l'antibiothérapie qui doit être précédée d'une ponction lombaire. • Les risques de la PL sont faibles et de loin inférieurs à ceux de la méningite. La réalisation d'un scanner avant la PL expose au risque de retarder la mise en route de l'abthérapie, a un rendement diagnostique faible et a en fait peu d'influence sur la prise en charge thérapeutique initiale. • Pour toutes ces raisons, la PL doit précéder le scanner, même en cas de coma. Ce n'est que devant des signes neurologiques focalisés, faisant évoquer un autre diagnostic ou craindre une complication intracrânienne, que la démar-che diagnostique doit être modifiée.Le scanner suffit pour le diagnostic de la plupart des complications intracrâniennes.

8. CT scan of the head before LP in adults with suspected meningitis Hasbun, N Engl J Med 2001

9. CT scan of the head before LP in adults with suspected meningitis • *characteristics: • > 60 years • immunosuppression • history of a CNS disease • seizure within 1 week before presentation • and the following abnormalities: • abnormal level of consciousness • inability to answer 2 consecutive questions correctly • inability to follow two consecutive commands correctly • gaze palsy • abnormal visual fields, • facial palsy, • arm drift, leg drift, • abnormal language. Hasbun, N Engl J Med 2001

10. 5 méningites bactériennes documentées CT scan of the head before LP in adults with suspected meningitis • Negative predictive value of clinical examination = 97 %. • Of the 3 misclassified patients, only one had a mild mass effect on CT, and all three subsequently underwent LP, with no evidence of brain herniation one week later. • In adults with suspected meningitis, clinical features can be used to identify those who are unlikely to have abnormal findings on CT of the head. Hasbun, N Engl J Med 2001

11. CT scan of the head before LP in adults with suspected meningitis • 75 consecutive cases of pneumococcal meningitis • Cerebral herniation occurred in 10 patients and could not be predicted by: • Focal signs • 3/10 vs 17/65, p=1 • Seizures within past 24 hours • 3/10 vs. 11/65, p=0.38 • GCS < 12 • 7/10 vs. 43/65, p=1 • CT scan abnormalities • 2/10 vs 27/65, p=0.3 Kastenbauer, N Engl J Med 2002

12. Timing of antibiotic administration and mortality in adult acute bacterial meningitis • Retrospective review of 123 cases of AABM • Does increased door-to-antibiotic time (DAT) increase mortality? • 2 independant predictors of mortality • Severely impaired mental status (OR 12.4, p=0.001) • DAT > 6 h (OR 9.7, p= 0.002) • Does CT scan before LP increase DAT? • AB / CT/ LP was associated with the lowest DAT (2.5 h) • CT / LP / AB was associated with the highest DAT (12 h). Proulx, ICAAC 2003, abstract L-614

14. Les étapes du diagnostic des méningites communautaires • Diagnostic positif de méningite • Place de l'imagerie dans la démarche diagnostique initiale • Diagnostic étiologique (bactérie vs. virus)

15. Les caractéristiques du LCR pour le diagnostic étiologique des méningites Hoen, Eur J Clin Microbiol Infect Dis 1995

16. Quelle place pour la détection d’antigènes bactériens dans le LCR ? • Lack of sensitivity of the latex agglutination test to detect bacterial antigen in the CSF of patients with culture-negative meningitis (Tarafdar CID 2001) • Sensitivity 7% • Rapid bacterial antigen detection is not clinically helpful (Perkins, J Clin Microbiol 1995) • Retrospective analysis of positive CSF latex antigen tests • Specificity 71% • GSF Gram stain and/or culture were positive in all cases

17. Modèle mathématiqued'aide au diagnostic • Le modèle • établi sur 500 cas de méningites aiguës primitives • pABM = 1/(1+e-L), où : • L = 32,13 x 10-4 x nb PNN LCR (106 /l)+ 2,365 x protéinorachie (g/l)+ 0,6143 x glycémie (mmol/l)+ 0, 2086 x nb de GB sanguins (109/l) – 11 • Ses performances : pour la valeur de pABM = 0,1 Sensibilité = 97% VPN = 99% Spécificité = 82% VPP = 85% AUCROC = 0,98 Hoen, Eur J Clin Microbiol Infect Dis 1995

18. Prospective Validation of a Diagnosis Model as an Aid to Therapeutic Decision in Acute Meningitis • 109 consecutive patients with acute meningitis and negative cerebrospinal fluid Gram stain. • pABM was computed before therapeutic decision and diagnosis was established in 3 steps • Clinical: before pABM computation, bacterial, viral, uncertain • Computed: viral if pABM<0.1, bacterial otherwise • Definite: bacterial: positive cerebrospinal fluid culture; viral: negative cerebrospinal fluid culture, no other aetiology and no treatment;uncertain: fitting neither of the first two Baty, Eur J Clin Microbiol Infect Dis 2000

19. Prospective Validation of a Diagnosis Model as an Aid to Therapeutic Decision in Acute Meningitis • Computed diagnoses were • viral in 78 of the 80 definite viral cases • bacterial in 4 of the 5 definite bacterial cases. • Negative predictive value of the model was 98.7% • Clinical diagnosis was uncertain in 22 cases • 15 of which were definite viral cases • in all of these 15 cases, computed diagnosis was viral, leading the physician to refrain from starting antibiotics in all of them. • The model is reliable and helps physicians identify patients in whom antibiotics can be avoided safely. Baty et al. Eur J Clin Microbiol Infect Dis 2000

20. Validation of a diagnosis model for differentiating bacterial from viral meningitis in infants and children under 3.5 years of age Distribution of the causative microorganisms in 103 cases of acute meningitis Jaeger et al. Eur J Clin Microbiol Infect Dis 2000

21. Validation of a diagnosis model for differentiating bacterial from viral meningitis in infants and children under 3.5 years of age Performance of the model for different cut-off points of the probability of bacterial meningitis (pABM). Jaeger et al. Eur J Clin Microbiol Infect Dis 2000

22. Measurement of procalcitonin levels in children with bacterial or viral meningitis • CRP: 2 patients with bacterial meningitis and 5 with viral meningitis had overlapping CRP values of 20–50 mg/l. • PCT > 5 mg/l, for diagnosis of bacterial meningitis : • sensitivity 94%, • specificity 100%. Gendrel, CID 1997

23. High Sensitivity and Specificity of Serum Procalcitonin Levels in Adults withBacterial Meningitis • Prospective study of 105 consecutive adult patients admitted to an emergency care unit for suspicion of acute meningitis. Viallon, CID 1999

24. High Sensitivity and Specificity of Serum Procalcitonin Levels in Adults withBacterial Meningitis Viallon et al., Clin Iinfect Dis 1999

25. Damien, 15 ans, collégien • 1 octobre 2003 : syndrome méningé aigu fébrile évoluant depuis 8 heures au moment de la PL – pas de purpura • PL: LCR clair, 185 GB/mm3, 70% PNN, P 0.7 g/l, G 3.1 mmol/l • GB : 15000/mm3, 91% PNN, CRP 15 mg/l • Procalcitonine : 5 ng/ml • pABMhoen = 0,06 • Traitement par Ceftriaxone, en attendant PCR/LCR • J5 : cholécystite aiguë • J7 : diagnostic étiologique • Recherche virus gorge et selles positive à enterovirus. • PCR méningocoque négative

26. Evaluation of a Rapid PCR Assay for Diagnosis of Meningococcal Meningitis • 281 patients with suspected bacterial meningitis • 38 met the criteria for meningococcal meningitis • clinical signs and symptoms of meningitis, and • pleocytosis (> 10 cells/mm3), and • positive CSF or blood culture for N. meningitidis, or • CSF Gram stain positive with Gram-negative diplococci, or • positive PCR assay of CSF for meningococcal IS 1106, confirmed by a second test • 65 had other bacteria identified • Streptococcus pneumoniae: n = 45 • 178 had no bacteria identified • PCR assay was performed in all 281 CSF samples Richardson, J Clin Microbiol 2003

27. Evaluation of a Rapid PCR Assay for Diagnosis of Meningococcal Meningitis • Comparison of accuracy of diagnostic methods in the 38 cases of meningococcal meningitis • PCR was negative in all other CSF samples • Duration of PCR assay: 2 hours. Richardson, J Clin Microbiol 2003

28. Use of universal PCR on CSF to diagnose bacterial meningitis in culture-negative patients • 97 cases of suspected bacterial meningitis, with negative CSF culture • All negative controls negative by PCR • All positive controls positive by PCR Margall Coscojuela, Eur J Clin Microbiol Infect Dis 2002

29. Application of PCR for various neurotropic viruses on the diagnosis of viral meningitis • CSF samples were collected from 73 children suspected of having meningitis from November 1991 to December 1994. • The samples were examined for infectious viruses by cell culture and for viral genomes by multiple PCR. • 45 diagnoses of aseptic meningitis – positive PCR results for: • Enterovirus : 25 • Mumps virus : 14 • Cytomegalovirus : 1 • Varicella-zoster virus : 1 • Diagnosis sensitivity • PCR alone: 91.1% • PCR + conventional virological methods: 97.8%. Hosoya, J Clin Virol 1998

30. Evaluation of a rapid real-time RT-PCR assay for detection of enterovirus RNA in CSF specimens • 251 CSF specimens with a differential diagnosis including viral meningitis from 03/00 to 11/01. Sensitivity: 57.4% 72.6% Verstrepen, J Clin Virol 2002

31. Impact of rapid PCR results on management of pediatric patients with enteroviral meningitis • CSF specimens from 113 patients with suspected EV meningitis were submitted for EV PCR • 50 of 113 (44%) were positive. • 17 of 50 (34%) had results available in <24 h • 33 of 50 (66%) had results available in >24 h. • Patients with EV-positive results reported <24 h after specimen collection had • 20 h less of antibiotic use (P = 0.006) and • 2798 USD less in hospital charges (P = 0.001) Robinson, Pediatr Infect Dis J 2002

32. OUI NON Abth PL CT scan Formule de MB Formule ? Formule de MV PL PCT et/ou pABM Abth No tt Formule de MB Formule de MV MB+ MB Culture + PCR si Culture  • PCR HSV • PCR multiplex Abth No tt PCR si culture  PCR Multiplex ? Syndrome méningé fébrile sans purpura Existe-t-il des signes neurologiques en foyer ?