Presented at the Neonatal Society 2016 Summer Meeting.
Bilal A1, Taha M-K2, Caeymaex L1,3, Cohen R3, Levy C3, Durrmeyer X1,3 and Members of the National Reference Center for Meningococci
1 Service de Neonatalogie, Centre Hospitalier Intercommunal, 40 avenue de Verdun, 94000 Créteil, France
2 Institut Pasteur, Invasive Bacterial Infections Unit, National Reference Center for meningococci (NRCM), Paris, France
3 Clinical Research Center (CRC), Centre Hospitalier Intercommunal de Créteil, Créteil; France
Background: Neonatal meningitis contributes substantially to neurological disability worldwide. Neonates are at increased risk of sepsis and meningitis than other age groups . Neisseria meningitidis is only occasionally implicated in neonatal bacterial meningitis. The objectify of this study is to describe epidemiological, clinical and bacteriological characteristics of N. meningitidis in France.
Methods: In total, 233 pediatric wards (61% of French pediatric wards) including 45% neonatal units in France participated in this network. All patients ≤ 28 days of age with confirmed bacterial meningitis were included. Isolates were identified in the microbiology laboratory of each hospital. Neonatal meningitis was defined as early-onset (when occurring between days 0 and 4) and late-onset meningitis (when occurring between days 5 and 28). We crosschecked the databases of the (NRCM) for microbiological data and GPIP/ACTIV for clinical data. The data collection was approved by the French National Data Protection Commission (Commission National Informatique et Libertés, CNIL, no. 913006).
Results: Between 2001 and 2013, data for 5,139 cases of bacterial meningitis were collected; 831 cases were neonatal bacterial meningitis (16.2%). Bacterial species implicated in the neonatal period were S. agalactiae (n=464; 55.8%), E. coli (n=232; 27.9%), N. meningitidis (n=23; 2.8%), L. monocytogenes (n=20; 2.4%), S. pneumoniae (n=18, 2.2%), other streptococcus (n=16; 2%), and other bacterial species (n=58; 7%). Among 23 patients with N. meningitidis, 12 were male (52%). The median gestational age at birth was 39.2 weeks. The median age was 17.9 days. Among the 23 cases, only 1 was early-onset (day 4); the remainders were late-onset (96%). Seasonal variation occurred, with the highest proportion of cases reported in winter. At diagnosis, 6 patients (27.3%) presented at least 1 sign of disease severity: all showed signs of shock (27.3%), 3 needed mechanical ventilation (13.6%), 2 were in a coma (9.1%), and 2 presented extensive purpura (9.1%); no seizures were reported. In the 434/807 term-born patients (53.8%) with late-onset meningitis, the proportion of NMM was 5.1% (22/434). N. meningitidis was isolated in 91% in CSF 2 had negative CSF culture (9%), one was diagnosed with positive PCR in CSF and other one had positive antigens. The serogroup distribution was serogroup B for 18 cases (78%), C for 3 cases (13%) and others for 2 cases (9%).The minimum inhibitory concentration was tested for cefotaxime, amoxicillin and penicillin G for 17 strains. All tested isolates were susceptible to cefotaxime. (12%) showed intermediate susceptibility to amoxicillin and penicillin G. Two patients died (both were girls, who showed late-onset meningitis at days 10 and 23, respectively).
Conclusion: Among 831 cases of neonatal bacterial meningitis occurring from 2001 to 2013, Neisseria meningitidis was the third most frequent bacterial species found. All cases occurred only in term neonates and were mainly late-onset. Serogroup B accounted for 78.3% of cases. At diagnosis, 27.3% of cases had at least 1 sign of disease severity. All strains were susceptible to cefotaxime, but 12% showed intermediate susceptibility to penicillin G and to aminopenicillin.
Corresponding author: firstname.lastname@example.org
1. Baud O, Aujard Y. Neonatal bacterial meningitis. Handb Clin Neurol. 2013;112:1109-1113.
2. Barret A, Deghmane A, Lepoutre A, et al. Invasive meningococcal disease in France in 2012: main epidemiological features. http://wwwinvssantefr/beh/2014/1-2/2014_1-2_4html2014.
3. Koplick H. Meningitis in the newborn and in infants under three months of age. Arch Pediatr. 1916:481–500.
4. Shepard CW, Rosenstein NE, Fischer M, Active Bacterial Core Surveillance T. Neonatal meningococcal disease in the United States, 1990 to 1999. Pediatr Infect Dis J. 2003;22:418-422.
5. Wang Y, Guo G, Wang H, et al. Comparative study of bacteriological culture and real-time fluorescence quantitative PCR (RT-PCR) and multiplex PCR-based reverse line blot (mPCR/RLB) hybridization assay in the diagnosis of bacterial neonatal meningitis. BMC Pediatr. 2014;14:224.
6. Kiray Bas E, Bulbul A, Comert S, Uslu S, Arslan S, Nuhoglu A. Neonatal infection with Neisseria meningitidis: analysis of a 97-year period plus case study. J Clin Microbiol. 2014;52:3478-3482.
7. Gaschignard J, Levy C, Romain O, et al. Neonatal Bacterial Meningitis: 444 Cases in 7 Years. Pediatr Infect Dis J. 2011;30:212-217.
8. Levy C, Taha MK, Weil Olivier C, et al. Association of meningococcal phenotypes and genotypes with clinical characteristics and mortality of meningitis in children. Pediatr Infect Dis J. 2010;29:618-623.
9. Maiden MC, Bygraves JA, Feil E, et al. Multilocus sequence typing: a portable approach to the identification of clones within populations of pathogenic microorganisms. Proc Natl Acad Sci U S A. 1998;95:3140-3145.
10. Manchanda V, Gupta S, Bhalla P. Meningococcal disease: history, epidemiology, pathogenesis, clinical manifestations, diagnosis, antimicrobial susceptibility and prevention. Indian J Med Microbiol. 2006;24:7-19.
11. Anonymous. Pregnancy associated and neonatal listeriosis in France: trend from 1984 to 2006. http://wwwinvssantefr/beh/2008/14_15/beh_14_15_2008pdf. 2008.