ESPID 2012 N°655
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Meningococcal genotype ST-11 and corticosteroids therapy: which impact on pediatric invasive meningococcal infections?
A CT I V
Fouad Madhi1,2,3, Corinne Levy3,4, Stéphane Béchet4, Ala Eddine Deghmane5, Robert Cohen1,2,3,4 and Muhamed-Kheir Taha5 1Service
de Pédiatrie, Centre Hospitalier Intercommunal, Créteil, France ; 2Inserm U955, équipe 11, Faculté de médecine, Université Paris-Est, Créteil, France ; 3GPIP Groupe de Pathologie Infectieuse Pédiatrique, SFP Société Française de Pédiatrie, Paris, France ; 4ACTIV (Association Clinique et Thérapeutique Infantile du Val de Marne), Paris, France; 5 Invasive Bacterial Infections Unit, National Reference Center for Neisseria meningitidis (NRCM), Institut Pasteur, Paris, France
Introduction Corticosteroids in bacterial meningitis as an adjuvant therapy are still a matter of debate in particular in meningococcal disease. Several bacterial components induce an intense host inflammatory response during invasive meningococcal infections (IMI) provoked by Neisseria meningitidis (Nm) that cause an induction of proinflammatory cytokines (particularly TNF-alpha and IL-1). Regulation of the other cytokines production, such as IL-1ß, interleukin-1 receptor antagonist (IL-1RA), IL-6 and IL-10, and the regulation of the soluble receptors of TNF-α play a key role in the outcome of meningococcal sepsis [1]. An association between fatal meningococcal disease and meningococcal isolates of the genotype ST-11 (clonal complex) was observed in N. meningitis [2]. Isolates of this genotype are able to induce apoptosis through modulation of NF-κB and the expression of soluble receptors of TNF-α [3]. Corticosteroids in IMI are expected to reduce the inflammatory response and thus improve prognosis. To explain the variable response to corticosteroids in IMI, we hypothesize that there may be a benefit from corticosteroids when highly pro-inflammatory genotypes such as ST-11 isolates are involved.
Patients and Methods From January 2001 to December 2009, 259 pediatric wards working with 168 microbiology laboratories throughout France prospectively enrolled all reported cases of community-acquired meningococcal meningitis in children aged from 1 day to 18 years. For meningitis, inclusion criteria were a clinical meningeal syndrome, cerebrospinal fluid (CSF) pleiocytosis (> 10 cells/µL) and at least one positive microbiological test, consisting of direct detection or culture of Gramnegative cocci in CSF, CSF capsular antigen detection (N. meningitidis serogroups A, B, C, Y, W-135 and miscellaneous), CSF PCR, and/or blood culture. Serogroups were determined by agglutination using specific in-house rabbit antibodies to N. meningitidis. Isolates were genotyped by multilocus sequence typing (MLST). Alleles, sequence types and clonal complexes were assigned using the Neisseria MLST database (available on http://neisseria.org). For the present study, we analysed both databases (NRCM and ACTIV) for cases of meningococcal meningitis and purpura fulminans (PF). The use of corticosteroids was analysed regardless of the time of administration. Severe cases were defined as at least one of the following criteria: shock, PF, coma, mechanical ventilation or seizures. Data were double-entered using 4D software (version 6.4), and analyzed using Stata SE 11.1 (Stata Corp., College Station, TX, USA).
Results 1 885 meningococcal infections were identified. Among them, 805 cases (meningitis, 88.4%, PF, 11.6%) were analysed. Serogroup B accounted for 68.9% of cases, followed by serogroup C 27.0%, serogroup W135 was involved in 2.4% of cases, and serogroup Y in 0.6% of cases (in 1.1% of cases, serogroup was not available). Corticosteroids treatment was reported in 33.5% of all cases (Table 1). In the absence of corticosteroids, significant higher risk of death was observed to be related to ST-11 isolates compared to cases caused by isolates belonging to other genotypes (OR=4.68, 95% CI [1.91; 11.46], p=0.001) (Table 2). For children who received corticosteroids, no significant difference was observed according to the genotype regardless the severity of the infection. However, 41.7% of severe cases received a corticosteroids treatment versus 25.8% for other cases (p
