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

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)

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)

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

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

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)

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.

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

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

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. 5 méningites bactériennes documentées Hasbun, N Engl J Med 2001

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

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

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)

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

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

Modèle mathématique d'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

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

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

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

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

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

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

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

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

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

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. The one CSF sample that was negative by PCR had gram-negative cocci visible by Gram staining but yielded no bacterial growth. There was a specimen that was positive by PCR for meningococcal IS 1106 but that was negative by culture and Gram staining. Unfortunately, there was no sample available for a confirmatory second PCR with the ctrA primers, and therefore this case did not meet our criteria for meningococcal meningitis. Richardson, J Clin Microbiol 2003

97 cases of suspected bacterial meningitis, with negative CSF culture 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

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%. Our These findings prove that the application of PCR methods is useful for etiological study of aseptic meningitis, and that the vast majority of cases of aseptic meningitis result from viral infection. Hosoya, J Clin Virol 1998

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

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

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