ESCMID guideline: diagnosis and treatment of acute bacterial meningitis.

Bacterial meningitis is a severe infectious disease of the membranes lining the brain resulting in a high mortality and morbidity throughout the world. In the past decades the epidemiology and treatment strategies for community-acquired bacterial meningitis have significantly changed [1McIntyre P.B. O'Brien K.L. Greenwood B. van de Beek D. Effect of vaccines on bacterial meningitis worldwide.Lancet. 2012; 380: 1703-1711Abstract Full Text Full Text PDF PubMed Scopus (70) Google Scholar, 2Brouwer M.C. Tunkel A.R. van de Beek D. Epidemiology, diagnosis, and antimicrobial treatment of acute bacterial meningitis.Clin Microbiol Rev. 2010; 23: 467-492Crossref PubMed Scopus (161) Google Scholar, 3van de Beek D. Brouwer M.C. Thwaites G.E. Tunkel A.R. Advances in treatment of bacterial meningitis.Lancet. 2012; 380: 1693-1702Abstract Full Text Full Text PDF PubMed Scopus (74) Google Scholar]. First, the introduction of conjugate vaccines in Europe resulted in the virtual disappearance of Haemophilus influenzae type b, while conjugate pneumococcal and meningococcal vaccines have substantially reduced the burden of bacterial meningitis [[1]McIntyre P.B. O'Brien K.L. Greenwood B. van de Beek D. Effect of vaccines on bacterial meningitis worldwide.Lancet. 2012; 380: 1703-1711Abstract Full Text Full Text PDF PubMed Scopus (70) Google Scholar]. As a result, community-acquired bacterial meningitis has become a disease that currently affects more adults than infants, with its specific complications and treatment options. A second important development is the increasing rate of reduced susceptibility to common antimicrobial agents among strains of Streptococcus pneumoniae (pneumococcus) and Neisseria meningitidis (meningococcus). Large differences in resistance rates in Europe exist, and empiric antibiotic treatment needs to be adjusted according to regional epidemiology. Finally, several adjunctive treatments have been tested in randomized controlled trials, often with conflicting results [[3]van de Beek D. Brouwer M.C. Thwaites G.E. Tunkel A.R. Advances in treatment of bacterial meningitis.Lancet. 2012; 380: 1693-1702Abstract Full Text Full Text PDF PubMed Scopus (74) Google Scholar]. These developments leave the physician in need of a clear practical guideline, summarizing the available evidence for diagnostic methods, and antimicrobial and adjunctive treatment in bacterial meningitis. To this end the European Society for Clinical Microbiology and Infectious Diseases (ESCMID) promotes guidelines development in the field of infectious diseases. This guideline project was initiated by the ESCMID Study Group for Infections of the Brain (ESGIB). The guideline is aimed at providing guidance in daily practice for diagnosis and treatment of community-acquired bacterial meningitis in hospitals. The conclusions of the guideline provide up-to-date scientific evidence for best medical practice. The recommendations are aimed at explicating this best medical practice and are based on available scientific evidence and the considerations of the guideline committee. The committee formulated ten key questions and several subquestions, which aim to address the full spectrum of current clinical dilemmas in the diagnosis and treatment of community-acquired bacterial meningitis. 1.What are the causative microorganisms of community-acquired bacterial meningitis in specific groups (neonates, children, adults and immunocompromised patients)? 2.What are the clinical characteristics of community-acquired bacterial meningitis, and what is their diagnostic accuracy?3.What is the diagnostic accuracy of algorithms in the distinction between bacterial and viral meningitis?4.Can we use clinical characteristics to predict the absence of intracranial abnormalities associated with increased risk of lumbar puncture?4.1.If lumbar puncture is delayed, should we start treatment? 5.What is the optimal type, duration and method of administration of antibiotic treatment when started empirically, after the pathogen has been identified or in culture-negative patients?5.1.Does the addition of vancomycin or rifampicin to a third-generation cephalosporin improve outcome in pneumococcal meningitis patients in the setting of a high resistance rate of pneumococci?6.Does dexamethasone have a beneficial effect on death, functional outcome and hearing loss in adults and children with bacterial meningitis?6.1.Up to what point in time is treatment with dexamethasone indicated if antibiotics are already provided?6.2.Should dexamethasone be stopped if pathogens other than S. pneumoniae are identified?7.Do glycerol, mannitol, acetaminophen/paracetamol, hypothermia, antiepileptic drugs or hypertonic saline have a beneficial effect on death, functional outcome and hearing loss in adults and children with bacterial meningitis?8.Does the use of prophylactic treatment of household contacts decrease carriage or secondary cases?8.1.Is vaccination indicated after community-acquired (pneumococcal) meningitis?9.What complications occur during community-acquired bacterial meningitis, what ancillary investigations are warranted when complications occur and how should they be treated? 10.What follow-up of community-acquired bacterial meningitis patients should be provided (e.g. testing for hearing loss, neuropsychologic evaluation)? Meningococcal disease but also other bacterial infections can present with both meningitis and sepsis. This guideline is not aimed at the urgent recognition and treatment of sepsis patients. Therefore, if e.g. meningococcal sepsis is suspected the physician should refer to other guidelines specific for recognizing children/patients with developing shock who need acute sepsis management (e.g. NICE guidelines, https://www.nice.org.uk/guidance/cg109). This guideline is written for all clinicians involved in diagnosis, treatment and follow-up of bacterial meningitis in adults and children with community-acquired bacterial meningitis in the context of hospital care, including infectious disease specialists, neurologists, intensive care specialists, paediatricians and microbiologists. The initiation of the guideline project was announced at the ESGIB business meetings of 2011 and 2012 during the European Conference on Clinical Microbiology and Infectious Diseases (ECCMID). During this meeting ESGIB members were invited to join the guideline committee by approaching the guideline chairman. In composing the guideline, committee considerations were given to establish a balance in country of origin, gender and medical specialty of the guideline members. After the first meeting the guideline committee was reinforced with two additional members because their specific expertise was originally underrepresented in the committee. After the guideline preparation project was granted ESCMID funding in Summer 2013, a kickoff meeting was staged in Amsterdam (October 2013) at which the key questions and subquestions were formulated and divided between guideline members. A clinical librarian and a research fellow at the chair's institute were appointed to perform the literature searches for each question. Guideline committee members received the identified literature and formulated the answers to the questions, which were discussed during a second meeting held simultaneously with the 2014 ECCMID meeting in Barcelona, Spain. During the meeting consensus was reached for most issues, and unanswered questions were identified and distributed between committee members. The research fellow and chair prepared a draft version of the guideline, which was distributed first to other guidelines members and subsequently to ESGIB members and ESCMID for comments. For the development of a high-quality guideline, patient input is essential, as the treatment has to fulfil the demands and expectations of patients and caregivers. To incorporate these factors into the guideline, the United Kingdom–based Meningitis Research Foundation was approached to participate in the guideline development and provide comments. As preparation for this guideline development project, a search was performed for existing guidelines from guideline institutes (http://www.guideline.gov/, http://www.nice.org.uk/, http://www.sumsearch.org and http://www.sign.ac.uk/) and (inter)national societies for neurologists, paediatricians and infectious disease specialists. Furthermore, systematic reviews were searched in the Cochrane Library and SUMsearch. Subsequently, for all identified questions a specific search was performed in scientific publications using electronic databases PubMed, Medline and Embase (1966–2014). Additional publications were identified by cross-reference checking of identified literature. In the search hierarchy the initial aim was to identify systematic meta-analysis or meta-analyses of randomized controlled trials (RCTs). In the absence of RCTs a further search was performed for prospective controlled studies. Key questions were formulated in a PICO format (Population, Intervention, Control, Outcome) when appropriate. Search strategies were developed by a clinical librarian at the chair's institute (AMC, Amsterdam, Netherlands) for all PICO formatted questions (Appendix). The literature was selected by the committee members and was graded for quality on the basis of the ESCMID quality-of-evidence system (Table 1.1). The quality of used articles to substantiate the conclusions by the committee is provided with the concluding answer to each question. The scientific evidence is summarized in a conclusion, in which references to the key literature are provided.Table 1.1Quality of evidenceClassConclusions based on:1Evidence from at least one properly designed randomized controlled trial.2Evidence from at least one well-designed clinical trial, without randomization; from cohort or case–control analytic studies (preferably from >1 centre); from multiple time series; or from dramatic results of uncontrolled experiments.3Evidence from opinions of respected authorities, based on clinical experience, descriptive case studies. Open table in a new tab On the basis of the identified literature the committee reached consensus on a recommendation for or against use of diagnostic methods or treatment. The strength of the recommendation is expressed using the ESCMID strength of recommendation system (Table 1.2) and does not link with the quality of evidence. High quality of evidence may result in marginal support for use, while low-quality evidence may result in a strong recommendation for use.Table 1.2Strength of recommendationGradeRecommendationAESCMID strongly supports recommendation for use.BESCMID moderately supports recommendation for use.CESCMID marginally supports recommendation for use.DESCMID supports recommendation against use. Open table in a new tab We will disseminate and promote the guideline by publication in a peer-reviewed journal and active promotion of the guideline to all European national organizations of infectious disease specialists, intensive care specialists, neurologists, microbiologists and paediatricians. Members of the guideline committee will be asked to gather local, regional and/or national treatment guidelines from their home country (and if possible for other countries) to assess whether these have been updated to include evidence provided by the ESCMID guidelines. We aim to have at least half of the European national guidelines adapted to the ESCMID European guideline recommendations within 2 years. This will be assessed on a biannual basis and presented at the ESGIB meeting at the ECCMID. Two members of the guideline committee (the chair plus one other) will give a yearly update on developments in the field of meningitis research applicable to the guideline and will assess the need for updating the guidelines. This update will be provided during the ESGIB business meeting at the ECCMID. Significant amendments or updates to the guideline will be submitted for publication. The ultimate date of updating the protocol will be 4 years after the final version is published. Guidelines do not contain legal regulations but provide evidence-based recommendations. Clinicians may strive to provide optimal care by adhering to the guideline. Because the guideline is based on general evidence of optimal care and the guideline committee's expert opinion, physicians may choose to deviate from the guideline on the basis of their professional autonomy when necessary in individual patients. Deviating from the guideline may in fact be required in specific situations. When deviating from advice provided in the guideline, it is advisable to document the considerations for doing so. Key Question 1. What are the causative microorganisms of community-acquired bacterial meningitis in specific groups (neonates, children, adults and immunocompromised patients)? Key Question 1. What are the causative microorganisms of community-acquired bacterial meningitis in specific groups (neonates, children, adults and immunocompromised patients)? The epidemiology of community-acquired bacterial meningitis worldwide has changed in the past decades as a result of the introduction of conjugated vaccines against H. influenzae type b, N. meningitidis serogroup C and 7-, 10- and 13-valent pneumococcal conjugate vaccines [[1]McIntyre P.B. O'Brien K.L. Greenwood B. van de Beek D. Effect of vaccines on bacterial meningitis worldwide.Lancet. 2012; 380: 1703-1711Abstract Full Text Full Text PDF PubMed Scopus (70) Google Scholar]. This resulted in a dramatic reduction of the incidence of bacterial meningitis in children [[4]Netherlands Reference Laboratory for Bacterial Meningitis (AMC/RIVM) Bacterial meningitis in the Netherlands annual report 2010. University of Amsterdam, Amsterdam2011Google Scholar], and currently the majority of patients are adults. The causative pathogens of bacterial meningitis depend on the age of the patient and predisposing factors. Bacterial meningitis in the neonatal period is considered early when occurring during the first week of life and late when occurring between the second and sixth weeks [[5]Garges H.P. Moody M.A. Cotten C.M. Smith P.B. Tiffany K.F. Lenfestey R. et al.Neonatal meningitis: what is the correlation among cerebrospinal fluid cultures, blood cultures, and cerebrospinal fluid parameters?.Pediatrics. 2006; 117: 1094-1100Crossref PubMed Scopus (112) Google Scholar]. In early neonatal meningitis the primary mode of infection is by vertical transmission (mother to child) through the birth canal, whereas in late neonatal meningitis transmission is nosocomial or horizontal (person to person). The most common pathogens in neonatal meningitis are Streptococcus agalactiae (group B streptococcus, GBS) and Escherichia coli, causing two thirds of all cases (Table 2.1).Table 2.1Causative organisms of neonatal meningitisaStudies were performed in different time periods, with varying vaccination strategies per country.CountryUnited Kingdom [12]Okike I.O. Johnson A.P. Henderson K.L. Blackburn R.M. Muller-Pebody B. Ladhani S.N. et al.Incidence, etiology, and outcome of bacterial meningitis in infants aged <90 days in the United kingdom and Republic of Ireland: prospective, enhanced, national population-based surveillance.Clin Infect Dis. 2014; 59: e150-e157Crossref PubMed Scopus (16) Google ScholarFrance [13]Gaschignard J. Levy C. Romain O. Cohen R. Bingen E. Aujard Y. et al.Neonatal bacterial meningitis: 444 cases in 7 years.Pediatr Infect Dis J. 2011; 30: 212-217Crossref PubMed Scopus (52) Google ScholarSpain [14][Neonatal meningitis. Epidemiological study of the Grupo de Hospitales Castrillo].An Esp Pediatr. 2002; 56: 556-563Crossref PubMed Google ScholarNetherlands [4]Netherlands Reference Laboratory for Bacterial Meningitis (AMC/RIVM) Bacterial meningitis in the Netherlands annual report 2010. University of Amsterdam, Amsterdam2011Google ScholarTotalObservation period2010–20112001–20071997–19982006–2012Streptococcus agalactiae1502586988565 (58%)Escherichia coli411231227203 (21%)Listeria monocytogenes1170119 (2%)Streptococcus pneumoniae2880339 (4%)Other72432214156 (16%)Total30244466133982a Studies were performed in different time periods, with varying vaccination strategies per country. Open table in a new tab Preventive penicillin in women colonized with S. agalactiae has been implemented as a measure to decrease the incidence of GBS meningitis in neonates following positive trials and meta-analyses [[6]Allen U.D. Navas L. King S.M. Effectiveness of intrapartum penicillin prophylaxis in preventing early-onset group B streptococcal infection: results of a meta-analysis.CMAJ. 1993; 149: 1659-1665PubMed Google Scholar]. Initially this was reported to result in a strong decrease in GBS neonatal disease in the 1990s [7Andersen J. Christensen R. Hertel J. Clinical features and epidemiology of septicaemia and meningitis in neonates due to Streptococcus agalactiae in Copenhagen County, Denmark: a 10 year survey from 1992 to 2001.Acta Paediatr. 2004; 93: 1334-1339Crossref PubMed Google Scholar, 8Schrag S.J. Zywicki S. Farley M.M. Reingold A.L. Harrison L.H. Lefkowitz L.B. et al.Group B streptococcal disease in the era of intrapartum antibiotic prophylaxis.N Engl J Med. 2000; 342: 15-20Crossref PubMed Scopus (644) Google Scholar]. However, recent studies from the United Kingdom and the United States showed increased incidence rates in the 2000s [9Centers for Disease Control and Prevention Trends in perinatal group B streptococcal disease—United States, 2000–2006.MMWR Morb Mortal Wkly Rep. 2009; 58: 109-112PubMed Google Scholar, 10Lamagni T.L. Keshishian C. Efstratiou A. Guy R. Henderson K.L. Broughton K. et al.Emerging trends in the epidemiology of invasive group B streptococcal disease in England and Wales, 1991–2010.Clin Infect Dis. 2013; 57: 682-688Crossref PubMed Scopus (22) Google Scholar]. A recent epidemiologic study from the Netherlands showed similar incidence rates of GBS meningitis over the past 25 years [[11]Bekker V. Bijlsma M.W. van de Beek D. Kuijpers T.W. van der Ende A. Increasing incidence and pathogen genotype redistribution of invasive group B streptococcal disease in newborns: a 25-year nationwide surveillance study in the Netherlands.Lancet Infect Dis. 2014; 14: 1083-1089Abstract Full Text Full Text PDF PubMed Scopus (11) Google Scholar]. Historically Listeria monocytogenes has been considered an important cause of neonatal meningitis [[2]Brouwer M.C. Tunkel A.R. van de Beek D. Epidemiology, diagnosis, and antimicrobial treatment of acute bacterial meningitis.Clin Microbiol Rev. 2010; 23: 467-492Crossref PubMed Scopus (161) Google Scholar], but recent cohort studies and surveillance data identified L. monocytogenes in only a minority of cases. Streptococcus pneumoniae, the primary causative organism of bacterial meningitis in patients beyond the neonatal age, is only incidentally found in neonates. Historically the three main pathogens causing bacterial meningitis in children beyond the neonatal age were H. influenzae type b, N. meningitidis and S. pneumoniae. After vaccination against H. influenzae type b was introduced in the 1990s this pathogen has virtually disappeared as a major cause of bacterial meningitis in children [[2]Brouwer M.C. Tunkel A.R. van de Beek D. Epidemiology, diagnosis, and antimicrobial treatment of acute bacterial meningitis.Clin Microbiol Rev. 2010; 23: 467-492Crossref PubMed Scopus (161) Google Scholar]. H. influenzae meningitis currently occurs incidentally in unvaccinated children or may be due to serotypes other than b [[15]Levy C. de La Rocque F. Cohen R. [Epidemiology of pediatric bacterial meningitis in France].Med Mal Infect. 2009; 39: 419-431Crossref PubMed Scopus (13) Google Scholar]. After a peak in incidence of serogroup C meningococcal meningitis in the early 2000s, several countries introduced the Men C vaccine in their vaccination programs [16Bijlsma M.W. Brouwer M.C. Spanjaard L. van de Beek D. van der Ende A. A decade of herd protection after introduction of meningococcal serogroup C conjugate vaccination.Clin Infect Dis. 2014; 59: 1216-1221Crossref PubMed Scopus (14) Google Scholar, 17Maiden M.C. Ibarz-Pavon A.B. Urwin R. Gray S.J. Andrews N.J. Clarke S.C. et al.Impact of meningococcal serogroup C conjugate vaccines on carriage and herd immunity.J Infect Dis. 2008; 197: 737-743Crossref PubMed Scopus (229) Google Scholar]. This resulted in a sharp decrease in serogroup C meningococcal meningitis cases and provided long-term herd immunity [16Bijlsma M.W. Brouwer M.C. Spanjaard L. van de Beek D. van der Ende A. A decade of herd protection after introduction of meningococcal serogroup C conjugate vaccination.Clin Infect Dis. 2014; 59: 1216-1221Crossref PubMed Scopus (14) Google Scholar, 17Maiden M.C. Ibarz-Pavon A.B. Urwin R. Gray S.J. Andrews N.J. Clarke S.C. et al.Impact of meningococcal serogroup C conjugate vaccines on carriage and herd immunity.J Infect Dis. 2008; 197: 737-743Crossref PubMed Scopus (229) Google Scholar]. Currently serogroup B causes most meningococcal meningitis cases in both children and adults [[18]Bijlsma M.W. Bekker V. Brouwer M.C. Spanjaard L. van de Beek D. van der Ende A. Epidemiology of invasive meningococcal disease in the Netherlands, 1960–2012: an analysis of national surveillance data.Lancet Infect Dis. 2014; 14: 805-812Abstract Full Text Full Text PDF PubMed Google Scholar]. The incidence of meningococcal meningitis due to serogroup B has decreased in some countries in the past decade, which is probably due to stochastic variation [[19]Martin N.G. Sadarangani M. Pollard A.J. Goldacre M.J. Hospital admission rates for meningitis and septicaemia caused by Haemophilus influenzae, Neisseria meningitidis, and Streptococcus pneumoniae in children in England over five decades: a population-based observational study.Lancet Infect Dis. 2014; 14: 397-405Abstract Full Text Full Text PDF PubMed Scopus (25) Google Scholar]. Due to this decrease pneumococcal meningitis is now as common as meningococcal meningitis in children beyond the neonatal age, and reductions in incidence rates have been achieved following introduction of pneumococcal conjugated vaccines (PCVs) against 7, 11 or 13 pneumococcal serotypes [[19]Martin N.G. Sadarangani M. Pollard A.J. Goldacre M.J. Hospital admission rates for meningitis and septicaemia caused by Haemophilus influenzae, Neisseria meningitidis, and Streptococcus pneumoniae in children in England over five decades: a population-based observational study.Lancet Infect Dis. 2014; 14: 397-405Abstract Full Text Full Text PDF PubMed Scopus (25) Google Scholar]. The majority of bacterial meningitis cases in adults is caused by S. pneumoniae (Table 2.3). After the introduction of PCVs a reduction in cases has been observed as a result of a reduction of disease due to serotypes included in the vaccine. In adults serotype replacement has also been observed, and continuous surveillance and vaccine development remains important [[23]Ardanuy C. Tubau F. Pallares R. Calatayud L. Domínguez M.A. Rolo D. et al.Epidemiology of invasive pneumococcal disease among adult patients in barcelona before and after pediatric 7-valent pneumococcal conjugate vaccine introduction, 1997–2007.Clin Infect Dis. 2009; 48: 57-64Crossref PubMed Scopus (119) Google Scholar]. Meningococcal meningitis in adults is mostly found in adolescents and is mostly caused by serogroup B. Similar to the paediatric population, the incidence of meningococcal meningitis has declined in the past decade [[18]Bijlsma M.W. Bekker V. Brouwer M.C. Spanjaard L. van de Beek D. van der Ende A. Epidemiology of invasive meningococcal disease in the Netherlands, 1960–2012: an analysis of national surveillance data.Lancet Infect Dis. 2014; 14: 805-812Abstract Full Text Full Text PDF PubMed Google Scholar]. L. monocytogenes is the third most common cause of meningitis in adults and is commonly associated with old age and an immunocompromised state [[24]Koopmans M.M. Brouwer M.C. Bijlsma M.W. Bovenkerk S. Keijzers W. van der Ende A. et al.Listeria monocytogenes sequence type 6 and increased rate of unfavorable outcome in meningitis: epidemiologic cohort study.Clin Infect Dis. 2013; 57: 247-253Crossref PubMed Scopus (19) Google Scholar]. Haemophilus influenzae and Staphylococcus aureus are found in 1–2% of adult cases and are associated with specific underlying conditions such as otitis and sinusitis (H. influenzae) or endocarditis (S. aureus).Table 2.2Causative organisms of paediatric meningitis beyond neonatal ageCountryFrance [20]Levy C. Bingen E. Aujard Y. Boucherat M. Floret D. Gendrel D. et al.[Surveillance network of bacterial meningitis in children, 7 years of survey in France].Arch Pediatr. 2008; 15: S99-S104Crossref PubMed Scopus (15) Google ScholarDenmark [21]Howitz M. Hartvig C.A. Harboe Z.B. Molbak K. Surveillance of bacterial meningitis in children under 2 y of age in Denmark, 1997–2006.Scand J Infect Dis. 2008; 40: 881-887Crossref PubMed Scopus (9) Google ScholarFrance [22]Bargui F. D’Agostino I. Mariani-Kurkdjian P. Alberti C. Doit C. Bellier N. et al.Factors influencing neurological outcome of children with bacterial meningitis at the emergency department.Eur J Pediatr. 2012; 171: 1365-1371Crossref PubMed Google ScholarNetherlands [4]Netherlands Reference Laboratory for Bacterial Meningitis (AMC/RIVM) Bacterial meningitis in the Netherlands annual report 2010. University of Amsterdam, Amsterdam2011Google ScholarTotalObservation period2001–20071997–20061995–20042006–2012Neisseria meningitidis1303159353081805 (50%)Streptococcus pneumoniae802195353101342 (37%)Haemophilus influenzae7881173170 (5%)Other137568101302 (8%)Total2320418897923619 Open table in a new tab Table 2.3Causative organisms of adult bacterial meningitisCountryDenmark [25]Bodilsen J. Dalager-Pedersen M. Schonheyder H.C. Nielsen H. Dexamethasone treatment and prognostic factors in community-acquired bacterial meningitis: a Danish retrospective population-based cohort study.Scand J Infect Dis. 2014; 46: 418-425Crossref PubMed Google ScholarTurkey [26]Arda B. Sipahi O.R. Atalay S. Ulusoy S. Pooled analysis of 2,408 cases of acute adult purulent meningitis from Turkey.Med Princ Pract. 2008; 17: 76-79Crossref PubMed Scopus (21) Google ScholarUnited Kingdom [27]Gjini A.B. Stuart J.M. Lawlor D.A. Cartwright K.A. Christensen H. Ramsay M. et al.Changing epidemiology of bacterial meningitis among adults in England and Wales 1991–2002.Epidemiol Infect. 2006; 134: 567-569Crossref PubMed Scopus (16) Google ScholarCzech Republic [28]Dzupova O. Rozsypal H. Prochazka B. Benes J. Acute bacterial meningitis in adults: predictors of outcome.Scand J Infect Dis. 2009; 41: 348-354Crossref PubMed Scopus (21) Google ScholarNetherlands [4]Netherlands Reference Laboratory for Bacterial Meningitis (AMC/RIVM) Bacterial meningitis in the Netherlands annual report 2010. University of Amsterdam, Amsterdam2011Google ScholarTotalObservation period1998–20121994–20031997–20021997–20042006–2012Neisseria meningitidis42251550751711089 (27%)Streptococcus pneumoniae924575258210012157 (53%)Haemophilus influenzae3248356112 (3%)Listeria monocytogenes56482174154 (4%)Other306812435291548 (13%)Total172784129521615934060 Open table in a new tab The spectrum of causative pathogens that needs to be considered is different when the patient has certain specific medical conditions. Deficiencies of the immune system, which may be iatrogenic (e.g. use of immunosuppressive medication or splenectomy), due to diseases influencing the immune system (e.g. cancer, diabetes mellitus, alcoholism, human immunodeficiency virus (HIV) infection) or hereditary (e.g. hypogammaglobulinaemia, late complement component deficiency, common variable immunodeficiency), increase the risk of bacterial meningitis [[2]Brouwer M.C. Tunkel A.R. van de Beek D. Epidemiology, diagnosis, and antimicrobial treatment of acute bacterial meningitis.Clin Microbiol Rev. 2010; 23: 467-492Crossref PubMed Scopus (161) Google Scholar]. The incidence of pneumococcal meningitis is increased in patients after splenectomy or with a hyposplenic state [[29]Adriani K.S. Brouwer M.C. van der Ende A. van de Beek D. Bacterial meningitis in adults after splenectomy and hyposplenic states.Mayo Clin Proc. 2013; 88: 571-578Abstract Full Text Full Text PDF PubMed Google Scholar], chronic kidney or liver disease [[30]Cabellos C. Viladrich P.F. Ariza J. Maiques J.M. Verdaguer R. Gudiol F. Community-acquired bacterial meningitis in cirrhotic patients.Clin Microbiol Infect. 2008; 14: 35-40Abstract Full Text Full Text PDF PubMed Scopus (17) Google Scholar], HIV infection [[31]Domingo P. Suarez-Lozano I. Torres F. Pomar V. Ribera E. Galindo M.J. et al.Bacterial meningitis in HIV-1-infected patients in the era of highly active antiretroviral therapy.J Acquir Immune Defic Syndr. 2009; 51: 582-587Crossref PubMed Scopus (12) Google Scholar], alcoholism, hypogammaglobulinaemia, diabetes mellitus and patients using immunosuppressive drugs [[2]Brouwer M.C. Tunkel A.R. van de Beek D. Epidemiology, diagnosis, and antimicrobial treatment of acute bacterial meningitis.Clin Microbiol Rev. 2010; 23: 467-492Crossref PubMed Scopus (161) Google Scholar]. Patients with complement system deficiencies have been identified to have a strongly increased risk of meningococcal meningitis [[32]Brouwer M.C. de Gans J. Heckenberg S.G. Zwinderman A.H. van der Poll T. van de Beek D. Host genetic susceptibility to pneumococcal and meningococcal disease: a systematic review and meta-analysis.Lancet Infect Dis. 2009; 9: 31-44Abstract Full Text Full Text PDF PubMed Scopus (117) Google Scholar]. Predisposing conditions associated with H. influenzae meningitis include diabetes mellitus, alcoholism, splenectomy or asplenic states, multiple myeloma and immune deficiency such as hypogammaglobulinaemia [[2]Brouwer M.C. Tunkel A.R. van de Beek D. Epidemiology, diagnosis, and antimicrobial treatment of acute bacterial meningitis.Clin Microbiol Rev. 2010; 23: 467-492Crossref PubMed Scopus (161) Google Scholar]. L. monocytogenes meningitis is more often found in elderly patients (>60 years) and those with acquired immunodeficiencies, such as diabetes, cancer and use of immunosuppressive drugs [[24]Koopmans M.M. Brouwer M.C. Bijlsma M.W. Bovenkerk S. Keijzers W. van der Ende A. et al.Listeria monocytogenes sequence type 6 and increased rate of unfavorable outcome in meningitis: epidemiologic cohort study.Clin Infect Dis. 2013; 57: 247-253Crossref PubMed Scopus (19) Google Scholar]. Tabled 1Level 2Most common causative pathogens in neonatal meningitis are Streptococcus agalactiae and Escherichia coli. Open table in a new tab Tabled 1Level 2Most common causative pathogens in children beyond the neonatal age are Neisseria meningitidis and Streptococcus pneumoniae. Open table in a new tab Tabled 1Level 2Most common causative pathogens in adults are Streptococcus pneumoniae and Neisseria meningitidis. Another important causative microorganism in adults is Listeria monocytogenes. Open table in a new tab