Bacterial meningitis: An update of new treatment options

Expert Review of Anti-Infective Therapy

Volumn 13, Issue 11, 2015, Pages 1401-1423

  Nau, Roland ^a,b   Djukic, Marija ^a,b   Spreer, Annette ^b   Ribes, Sandra ^b   Eiffert, Helmut ^b  

^a Sleep Laboratory   (Germany)

^b UNIVERSITY OF GÖTTINGEN   (Germany)

Author keywords

Ampicillin; cefepime; ceftazidime; ceftriaxone; clindamycin; complement; daptomycin; eritoran; glycerol; hypothermia; immunotherapy; linezolid; Listeria monocytogenes; monoclonal antibodies; n acetylcysteine; Neisseria meningitidis; palmitoylethanolamide; paracetamol; resveratrol; rifampicin; seliciclib; Streptococcus pneumoniae; vancomycin

Indexed keywords

AMPICILLIN; BETA LACTAM ANTIBIOTIC; CARBAPENEM DERIVATIVE; CEFEPIME; CEFOTAXIME; CEFTAROLINE; CEFTAZIDIME; CEFTOBIPROLE; CEFTRIAXONE; CEPHALOSPORIN; CHLORAMPHENICOL; CORTICOSTEROID; DAPTOMYCIN; DEXAMETHASONE; GENTAMICIN; GLYCYLCYCLINE DERIVATIVE; LINEZOLID; MEROPENEM; METHYLPREDNISOLONE; METRONIDAZOLE; MOXIFLOXACIN; PENICILLIN G; PLACEBO; PNEUMOCOCCUS VACCINE; QUINOLINE DERIVED ANTIINFECTIVE AGENT; TELAVANCIN; TIGECYCLINE; TROVAFLOXACIN; UNINDEXED DRUG; VANCOMYCIN; ANTIINFECTIVE AGENT; MONOCLONAL ANTIBODY; VITAMIN;

ADD ON THERAPY; ANASTOMOSIS; ANTIBIOTIC THERAPY; APHASIA; AREA UNDER THE CURVE; ASEPTIC MENINGITIS; BACTERIAL MENINGITIS; BLOOD BRAIN BARRIER; BRAIN PERFUSION; CENTRAL NERVOUS SYSTEM INFECTION; CEREBROSPINAL FLUID ANALYSIS; CEREBROSPINAL FLUID SHUNTING; CLINICAL FEATURE; COMATOSE PATIENT; COMMUNITY ACQUIRED INFECTION; COMPUTER ASSISTED TOMOGRAPHY; CONFUSION; CONSCIOUSNESS DISORDER; CONTINUOUS INFUSION; DECOMPRESSION SURGERY; DECOMPRESSIVE CRANIECTOMY; DRUG MEGADOSE; DRUG PENETRATION; ENCEPHALITIS; EOSINOPHILIC MENINGITIS; ESCHERICHIA COLI; FACIAL NERVE PARALYSIS; FEVER; GAZE PARALYSIS; GLASGOW OUTCOME SCALE; HEADACHE; HEARING IMPAIRMENT; HUMAN; HYDROCEPHALUS; IMMUNOCOMPROMISED PATIENT; IMMUNOMODULATION; INTRACRANIAL HYPERTENSION; INTRACRANIAL PRESSURE; LIVER TOXICITY; LUMBAR PUNCTURE; MENTAL DISEASE; MINIMUM INHIBITORY CONCENTRATION; MORTALITY; NONHUMAN; PATHOPHYSIOLOGY; PLEOCYTOSIS; REVIEW; SEDATION; SEIZURE; SEPTIC SHOCK; SINGLE DRUG DOSE; STIFF NECK; STREPTOCOCCUS PNEUMONIAE; THERAPEUTIC HYPERVENTILATION; VISUAL FIELD DEFECT; VOLUME OF DISTRIBUTION; CLASSIFICATION; CROSS INFECTION; DEVELOPED COUNTRY; MENINGITIS, BACTERIAL; VACCINATION;

ANTI-BACTERIAL AGENTS; ANTIBODIES, MONOCLONAL; CROSS INFECTION; DEVELOPED COUNTRIES; DEXAMETHASONE; HUMANS; MENINGITIS, BACTERIAL; VACCINATION; VITAMINS;

EID: 84945489396     PISSN: 14787210     EISSN: 17448336     Source Type: Journal    
DOI: 10.1586/14787210.2015.1077700     Document Type: Review

References (238)

1. van de Beek D, de Gans J, Spanjaard L, et al. Clinical features and prognostic factors in adults with bacterial meningitis. N Engl J Med 2004; 351 (18): 1849-59
2. Miller LG, Choi C. Meningitiss in older patients: how to diagnose and treat a deadly infection. Geriatrics 1997; 52 (8): 43-4. 47-50. 55
3. Schwerk C, Tenenbaum T, Kim KS, Schroten H. The choroid plexus-a multi-role player during infectious diseases of the CNS. Frontiers in Cellular Neuroscience 2015; 9: 80
4. Gerber J, Nau R. Mechanisms of injury in bacterial meningitis. Curr Opin Neurol 2013; 23 (3): 312-18
5. van de Beek D, Brouwer MC, Thwaites GE, Tunkel AR. Advances in treatment of bacterial meningitis. Lancet 2012; 380 (9854): 1693-702
6. Nau R, Bruck W. Neuronal injury in bacterial meningitis: mechanisms and implications for therapy. Trends Neurosci 2002; 25 (1): 38-45
7. Engelhardt B, Coisne C. Fluids and barriers of the CNS establish immune privilege by confining immune surveillance to a two-walled castle moat surrounding the CNS castle. Fluids Barriers CNS 2011; 8 (1): 4
8. Ransohoff RM, Cardona AE. The myeloid cells of the central nervous system parenchyma. Nature 2010; 468 (7321): 253-62
9. Mook-Kanamori BB, Geldhoff M, van der Poll T, van de Beek D. Pathogenesis and pathophysiology of pneumococcal meningitis. Clin Microbiol Rev 2011; 24 (3): 557-91
10. Barichello T, Generoso JS, Simoes LR, et al. Role of oxidative stress in the pathophysiology of pneumococcal meningitis. Oxidative Medicine and Cellular Longevity 2013; 2013: 371465
11. Barichello T, Collodel A, Generoso JS, et al. Targets for adjunctive therapy in pneumococcal meningitis. J Neuroimmunol 2015; 278: 262-70
12. Scheld WM, Dacey RG, Winn HR, et al. Cerebrospinal fluid outflow resistance in rabbits with experimental meningitis. Alterations with penicillin and methylprednisolone. J Clin Invest 1980; 66 (2): 243-53
13. Kasanmoentalib ES, Brouwer MC, van der Ende A, van de Beek D. Hydrocephalus in adults with community-acquired bacterial meningitis. Neurology 2010; 75 (10): 918-23
14. Bodilsen J, Schonheyder HC, Nielsen HI. Hydrocephalus is a rare outcome in community-acquired bacterial meningitis in adults: a retrospective analysis. BMC Infect Dis 2013; 13 (1): 321
15. van de Beek D, Brouwer MC, Thwaites GE, Tunkel AR. Advances in treatment of bacterial meningitis. Lancet 2012; 380 (9854): 1693-702
16. Tsilidis KK, Panagiotou OA, Sena ES, et al. Evaluation of excess significance bias in animal studies of neurological diseases. PLoS Biol 2013; 11 (7): e1001609
17. Auburtin M, Wolff M, Charpentier J, et al. Detrimental role of delayed antibiotic administration and penicillin-nonsusceptible strains in adult intensive care unit patients with pneumococcal meningitis: the PNEUMOREA prospective multicenter study. Crit Care Med 2006; 34 (11): 2758-65
18. Koster-Rasmussen R, Korshin A, Meyer CN. Antibiotic treatment delay and outcome in acute bacterial meningitis. J Infect 2008; 57 (6): 449-54
19. Hasbun R, Abrahams J, Jekel J, Quagliarello VJ. Computed tomography of the head before lumbar puncture in adults with suspected meningitis. N Engl J Med 2001; 345 (24): 1727-33 www.dgn.org/images/stories/dgn/leitlinien/LL-2012/pdf/ll-34-ambulant-erworbene-bakterielle-eitrige-meningoenzephalitis.pdf
20. Glimaker M, Johansson B, Grindborg O, et al. Adult bacterial meningitis: earlier treatment and improved outcome following guideline revision promoting prompt lumbar puncture. Clin Infect Dis 2015; 60 (8): 1162-9
21. Tureen JH, Tauber MG, Sande MA. Effect of hydration status on cerebral blood flow and cerebrospinal fluid lactic acidosis in rabbits with experimental meningitis. J Clin Invest 1992; 89 (3): 947-53
22. Maconochie IK, Bhaumik S. Fluid therapy for acute bacterial meningitis. Cochrane Database Syst Rev. Cochrane Database Syst Rev 2014; 5: CD004786
23. Dellinger RP, Levy MM, Rhodes A, et al. Surviving sepsis campaign: international guidelines for management of severe sepsis and septic shock, 2012. Intensive Care Med 2013; 39 (2): 165-228 www.dgn.org/images/stories/dgn/leitlinien/LL-2012/pdf/ll-34-ambulant-erworbene-bakterielle-eitrige-meningoenzephalitis.pdf
24. Glimaker M, Johansson B, Halldorsdottir H, et al. Neuro-intensive treatment targeting intracranial hypertension improves outcome in severe bacterial meningitis: an intervention-control study. PLoS One 2014; 9 (3): e91976
25. Baussart B, Cheisson G, Compain M, et al. Multimodal cerebral monitoring and decompressive surgery for the treatment of severe bacterial meningitis with increased intracranial pressure. Acta Anaesthesiol Scand 2006; 50 (6): 762-5
26. Perin A, Nascimben E, Longatti P. Decompressive craniectomy in a case of intractable intracranial hypertension due to pneumococcal meningitis. Acta Neurochir (Wien) 2008; 150 (8): 837-42
27. Bordes J, Boret H, Lacroix G, et al. Decompressive craniectomy guided by cerebral microdialysis and brain tissue oxygenation in a patient with meningitis. Acta Anaesthesiol Scand 2011; 55 (1): 130-3
28. Imohl M, Reinert RR, Tulkens PM, van der Linden M. Penicillin susceptibility breakpoints for Streptococcus pneumoniae and their effect on susceptibility categorisation in Germany (1997-2013). Eur J Clin Microbiol 2014; 33 (11): 2035-40
29. Imohl M, Reinert RR, van der Linden M. Adult invasive pneumococcal disease between 2003 and 2006 in North-Rhine Westphalia, Germany: serotype distribution before recommendation for general pneumococcal conjugate vaccination for children <2 years of age. Clin Microbiol Infect 2009; 15 (11): 1008-12
30. Erdem H, Elaldi N, Oztoprak N, et al. Mortality indicators in pneumococcal meningitis: therapeutic implications. Int J Infect Dis 2014; 19: 13-19
31. Gouveia EL, Reis JN, Flannery B, et al. Clinical outcome of pneumococcal meningitis during the emergence of pencillin-resistant Streptococcus pneumoniae: an observational study. BMC Infect Dis 2011; 11: 323
32. Vazquez JA, Enriquez R, Abad R, et al. Antibiotic resistant meningococci in Europe: any need to act? FEMS Microbiol Rev 2007; 31 (1): 64-70 Available from: www.dgn.org/images/stories/dgn/leitlinien/LL-2012/pdf/ll-34-ambulant-erworbene-bakterielle-eitrige-meningoenzephalitis.pdf
33. Alvares JR, Mantese OC, Paula A, et al. Prevalence of pneumococcal serotypes and resistance to antimicrobial agents in patients with meningitis: ten-year analysis. Braz J Infect Dis 2011; 15 (1): 22-7
34. Oftadeh S, Gidding HF, Gilbert GL. Laboratory surveillance of invasive pneumococcal disease in New South Wales, Australia, before and after introduction of 7-valent conjugate vaccine: reduced disease, but not antibiotic resistance rates. Epidemiol Infect 2013; 141 (9): 1797-806
35. Linares J, Ardanuy C, Pallares R, Fenoll A. Changes in antimicrobial resistance, serotypes and genotypes in Streptococcus pneumoniae over a 30-year period. Clin Microbiol Infect 2010; 16 (5): 402-10
36. Hsu HE, Shutt KA, Moore MR, et al. Effect of pneumococcal conjugate vaccine on pneumococcal meningitis. N Engl J Med 2009; 360 (3): 244-56
37. Kumari VH, Babu AR, Srinivas D, et al. Methicillin-Resistant Staphylococcus aureus central nervous system infections-Analysis and outcome. British Journal of Neurosurgery 2015; 29: 413-8
38. Konstantelias AA, Vardakas KZ, Polyzos KA, et al. Antimicrobial-impregnated and-coated shunt catheters for prevention of infections in patients with hydrocephalus: a systematic review and meta-analysis. J Neurosurg 2015; 122 (5): 1096-112
39. Wang JS, Muzevich K, Edmond MB, et al. Central nervous system infections due to vancomycin-resistant enterococci: case series and review of the literature. Int J Infect Dis 2014; 25: 26-31
40. Kourbeti IS, Vakis AF, Ziakas P, et al. Infections in patients undergoing craniotomy: risk factors associated with post-craniotomy meningitis. J Neurosurg 2015; 122 (5): 1113-19
41. Huang CR, Lu CH, Chang WN. Adult Enterobacter meningitis: a high incidence of coinfection with other pathogens and frequent association with neurosurgical procedures. Infection 2001; 29 (2): 75-9
42. Pintado V, Pazos R, Jimenez-Mejias ME, et al. Methicillin-resistant Staphylococcus aureus meningitis in adults: a multicenter study of 86 cases. Medicine 2012; 91 (1): 10-17
43. Conde-Pereira C, Rodas-Rodriguez L, Diaz-Paz M, et al. Fatal case of polymicrobial meningitis caused by Cryptococcus liquefaciens and Mycobacterium tuberculosis complex in a human immunodeficiency virus-infected patient. J Clin Microbiol 2015; 53 (8): 2753-5
44. Wang KW, Chang WN, Huang CR, et al. Post-neurosurgical nosocomial bacterial meningitis in adults: microbiology, clinical features, and outcomes. J Clin Neurosci 2005; 12 (6): 647-50
45. Klugman KP, Dagan R. Randomized comparison of meropenem with cefotaxime for treatment of bacterial meningitis. Meropenem meningitis study group. Antimicrob Agents Chemother 1995; 39 (5): 1140-6
46. Schmutzhard E, Williams KJ, Vukmirovits G, et al. A randomised comparison of meropenem with cefotaxime or ceftriaxone for the treatment of bacterial meningitis in adults. Meropenem Meningitis Study Group. J Antimicrob Chemother 1995; 36 (Suppl A): 85-97
47. De Sarro A, Ammendola D, Zappala M, et al. Relationship between structure and convulsant properties of some beta-lactam antibiotics following intracerebroventricular microinjection in rats. Antimicrob Agents Chemother 1995; 39 (1): 232-7
48. Kullar R, Chin JN, Edwards DJ, et al. Pharmacokinetics of single-dose daptomycin in patients with suspected or confirmed neurological infections. Antimicrob Agents Chemother 2011; 55 (7): 3505-9
49. Cottagnoud P, Pfister M, Acosta F, et al. Daptomycin is highly efficacious against penicillin-resistant and penicillin-and quinolone-resistant pneumococci in experimental meningitis. Antimicrob Agents Chemother 2004; 48 (10): 3928-33
50. Gerber P, Stucki A, Acosta F, et al. Daptomycin is more efficacious than vancomycin against a methicillin-susceptible Staphylococcus aureus in experimental meningitis. J Antimicrob Chemother 2006; 57 (4): 720-3
51. Mook-Kanamori BB, Rouse MS, Kang CI, et al. Daptomycin in experimental murine pneumococcal meningitis. BMC Infect Dis 2009; 9: 50
52. Bardak-Ozcem S, Turhan T, Sipahi OR, et al. Daptomycin versus vancomycin in treatment of methicillin-resistant Staphylococcus aureus meningitis in an experimental rabbit model. Antimicrob Agents Chemother 2013; 57 (3): 1556-8
53. Egermann U, Stanga Z, Ramin A, et al. Combination of daptomycin plus ceftriaxone is more active than vancomycin plus ceftriaxone in experimental meningitis after addition of dexamethasone. Antimicrob Agents Chemother 2009; 53 (7): 3030-3
54. Spanjaard L, Vandenbroucke-Grauls CM. Activity of daptomycin against Listeria monocytogenes isolates from cerebrospinal fluid. Antimicrob Agents Chemother 2008; 52 (5): 1850-1
55. Knoll BM, Hellmann M, Kotton CN. Vancomycin-resistant enterococcus faecium meningitis in adults: case series and review of the literature. Scand J Infect Dis 2013; 45 (2): 131-9
56. Vena A, Falcone M, Comandini E, et al. Daptomycin plus trimethoprim/sulfamethoxazole combination therapy in post-neurosurgical meningitis caused by linezolid-resistant Staphylococcus epidermidis. Diagn Microbiol Infect Dis 2013; 76 (1): 99-102
57. Jaspan HB, Brothers AW, Campbell AJ, et al. Multidrug-resistant Enterococcus faecium meningitis in a toddler: characterization of the organism and successful treatment with intraventricular daptomycin and intravenous tigecycline. Pediatr Infect Dis J 2010; 29 (4): 379-81
58. Erritouni M, Ktaich N, Rahal JJ, et al. Use of daptomycin for the treatment of methicillin-resistant coagulase-negative staphylococcal ventriculitis. Case Rep Med 2012; 2012: 593578
59. Mueller SW, Kiser TH, Anderson TA, Neumann RT. Intraventricular daptomycin and intravenous linezolid for the treatment of external ventricular-drain-associated ventriculitis due to vancomycin-resistant Enterococcus faecium. Ann Pharmacother 2012; 46 (12): e35
60. Alffenaar JW, van Altena R, Bokkerink HJ, et al. Pharmacokinetics of moxifloxacin in cerebrospinal fluid and plasma in patients with tuberculous meningitis. Clin Infect Dis 2009; 49 (7): 1080-2
61. Nau R, Sorgel F, Eiffert H. Penetration of drugs through the blood-cerebrospinal fluid/blood-brain barrier for treatment of central nervous system infections. Clin Microbiol Rev 2010; 23 (4): 858-83
62. Nau R, Schmidt T, Kaye K, et al. Quinolone antibiotics in therapy of experimental pneumococcal meningitis in rabbits. Antimicrob Agents Chemother 1995; 39 (3): 593-7
63. Nau R, Zysk G, Schmidt H, et al. Trovafloxacin delays the antibiotic-induced inflammatory response in experimental pneumococcal meningitis. J Antimicrob Chemother 1997; 39 (6): 781-8
64. Cottagnoud P, Acosta F, Cottagnoud M, et al. Synergy between trovafloxacin and ceftriaxone against penicillin-resistant pneumococci in the rabbit meningitis model and in vitro. Antimicrob Agents Chemother 2000; 44 (8): 2179-81
65. Djukic M, Bottcher T, Wellmer A, et al. Moxifloxacin in experimental Streptococcus pneumoniae cerebritis and meningitis. Neurocrit Care 2005; 2 (3): 325-9
66. Schmidt H, Dalhoff A, Stuertz K, et al. Moxifloxacin in the therapy of experimental pneumococcal meningitis. Antimicrob Agents Chemother 1998; 42 (6): 1397-407
67. Rodriguez-Cerrato V, McCoig CC, Michelow IC, et al. Pharmacodynamics and bactericidal activity of moxifloxacin in experimental Escherichia coli meningitis. Antimicrob Agents Chemother 2001; 45 (11): 3092-7
68. Sipahi OR, Turhan T, Pullukcu H, et al. Moxifloxacin versus ampicillin + gentamicin in the therapy of experimental Listeria monocytogenes meningitis. J Antimicrob Chemother 2008; 61 (3): 670-3
69. Ostergaard C, Sorensen TK, Knudsen JD, Frimodt-Moller N. Evaluation of moxifloxacin, a new 8-methoxyquinolone, for treatment of meningitis caused by a penicillin-resistant pneumococcus in rabbits. Antimicrob Agents Chemother 1998; 42 (7): 1706-12
70. Ruslami R, Ganiem AR, Dian S, et al. Intensified regimen containing rifampicin and moxifloxacin for tuberculous meningitis: an open-label, randomised controlled phase 2 trial. Lancet Infect Dis 2013; 13 (1): 27-35
71. European medicines agency. Available from: www.ema.europa.eu/ema/index.jsp?curl=pages/medicines/human/referrals/Moxifloxacin/human-referral-000114.jsp&mid=WC0b01ac0580024e9a
72. Beer R, Engelhardt KW, Pfausler B, et al. Pharmacokinetics of intravenous linezolid in cerebrospinal fluid and plasma in neurointensive care patients with staphylococcal ventriculitis associated with external ventricular drains. Antimicrob Agents Chemother 2007; 51 (1): 379-82
73. Villani P, Regazzi MB, Marubbi F, et al. Cerebrospinal fluid linezolid concentrations in postneurosurgical central nervous system infections. Antimicrob Agents Chemother 2002; 46 (3): 936-7
74. Peltola H, Anttila M, Renkonen OV. Randomised comparison of chloramphenicol, ampicillin, cefotaxime, and ceftriaxone for childhood bacterial meningitis. Finnish Study Group. Lancet 1989; 1 (8650): 1281-7
75. Rupprecht TA, Pfister HW. Clinical experience with linezolid for the treatment of central nervous system infections. Eur J Neurol 2005; 12 (7): 536-42
76. Sipahi OR, Bardak S, Turhan T, et al. Linezolid in the treatment of methicillin-resistant staphylococcal post-neurosurgical meningitis: a series of 17 cases. Scand J Infect Dis 2011; 43 (10): 757-64
77. Frasca KL, Schuster MG. Vancomycin-resistant enterococcal meningitis in an autologous stem cell transplant recipient cured with linezolid. Transpl Infect Dis 2013; 15 (1): E1-4
78. Morales G, Picazo JJ, Baos E, et al. Resistance to linezolid is mediated by the cfr gene in the first report of an outbreak of linezolid-resistant Staphylococcus aureus. Clin Infect Dis 2010; 50 (6): 821-5
79. Rodvold KA, Gotfried MH, Cwik M, et al. Serum, tissue and body fluid concentrations of tigecycline after a single 100 mg dose. J Antimicrob Chemother 2006; 58 (6): 1221-9
80. Ray L, Levasseur K, Nicolau DP, Scheetz MH. Cerebral spinal fluid penetration of tigecycline in a patient with Acinetobacter baumannii cerebritis. Ann Pharmacother 2010; 44 (3): 582-6
81. Lengerke C, Haap M, Mayer F, et al. Low tigecycline concentrations in the cerebrospinal fluid of a neutropenic patient with inflamed meninges. Antimicrob Agents Chemother 2011; 55 (1): 449-50
82. Tutuncu EE, Kuscu F, Gurbuz Y, et al. Tigecycline use in two cases with multidrug-resistant Acinetobacter baumannii meningitis. Int J Infect Dis 2010; 14 Suppl 3: e224-6
83. Garrison MW, Kawamura NM, Wen MM. Ceftaroline fosamil: a new cephalosporin active against resistant Gram-positive organisms including MRSA. Expert Rev Anti Infect Ther 2012; 10 (10): 1087-103
84. Patel SN, Pillai DR, Pong-Porter S, et al. In vitro activity of ceftaroline, ceftobiprole and cethromycin against clinical isolates of streptococcus pneumoniae collected from across Canada between 2003 and 2008. J Antimicrob Chemother 2009; 64 (3): 659-60
85. Stucki A, Cottagnoud M, Acosta F, et al. Evaluation of ceftobiprole activity against a variety of gram-negative pathogens, including Escherichia coli, Haemophilus influenzae (beta-lactamase positive and beta-lactamase negative), and Klebsiella pneumoniae, in a rabbit meningitis model. Antimicrob Agents Chemother 2012; 56 (2): 921-5
86. Balouch MA, Bajwa RJ, Hassoun A. Successful use of ceftaroline for the treatment of MRSA meningitis secondary to an infectious complication of lumbar spine surgery. J Antimicrob Chemother 2015; 70 (2): 624-5
87. Kuriakose SS, Rabbat M, Gallagher JC. Ceftaroline CSF concentrations in a patient with ventriculoperitoneal shunt-related meningitis. J Antimicrob Chemother 2015; 70 (3): 953-4
88. Stucki A, Gerber P, Acosta F, et al. Efficacy of telavancin against penicillin-resistant pneumococci and Staphylococcus aureus in a rabbit meningitis model and determination of kinetic parameters. Antimicrob Agents Chemother 2006; 50 (2): 770-3
89. Nnedu ON, Pankey GA. Update on the emerging role of telavancin in hospital-acquired infections. Therapeutics and Clinical Risk Management 2015; 11: 605-10
90. Pelkonen T, Roine I, Cruzeiro ML, et al. Slow initial beta-lactam infusion and oral paracetamol to treat childhood bacterial meningitis: a randomised, controlled trial. Lancet Infect Dis 2011; 11 (8): 613-21
91. Roberts JA, Boots R, Rickard CM, et al. Is continuous infusion ceftriaxone better than once-a-day dosing in intensive care? A randomized controlled pilot study. J Antimicrob Chemother 2007; 59 (2): 285-91
92. Nau R, Prange HW, Muth P, et al. Passage of cefotaxime and ceftriaxone into cerebrospinal fluid of patients with uninflamed meninges. Antimicrob Agents Chemother 1993; 37 (7): 1518-24
93. Stuertz K, Schmidt H, Eiffert H, et al. Differential release of lipoteichoic and teichoic acids from Streptococcus pneumoniae as a result of exposure to beta-lactam antibiotics, rifamycins, trovafloxacin, and quinupristin-dalfopristin. Antimicrob Agents Chemother 1998; 42 (2): 277-81
94. Shiu J, Wang E, Tejani AM, Wasdell M. Continuous versus intermittent infusions of antibiotics for the treatment of severe acute infections. Cochrane Database Syst Rev 2013; 3: CD008481
95. Webster DP, Griffiths S, Bowler IC. Failure of linezolid therapy for post-neurosurgical meningitis due to Enterococcus faecium. J Antimicrob Chemother 2009; 63 (3): 622-3
96. Vivas M, Force E, Garrigos C, et al. Experimental study of the efficacy of daptomycin for the treatment of cephalosporin-resistant pneumococcal meningitis. J Antimicrob Chemother 2014; 69 (11): 3020-6
97. Kim BN, Peleg AY, Lodise TP, et al. Management of meningitis due to antibiotic-resistant acinetobacter species. Lancet Infect Dis 2009; 9 (4): 245-55
98. Antachopoulos C, Karvanen M, Iosifidis E, et al. Serum and cerebrospinal fluid levels of colistin in pediatric patients. Antimicrob Agents Chemother 2010; 54 (9): 3985-7
99. Garnacho-Montero J, Amaya-Villar R. Multiresistant acinetobacter baumannii infections: epidemiology and management. Curr Opin Infect Dis 2010; 23 (4): 332-9
100. Karaiskos I, Galani L, Baziaka F, Giamarellou H. Intraventricular and intrathecal colistin as the last therapeutic resort for the treatment of multidrug-resistant and extensively drug-resistant Acinetobacter baumannii ventriculitis and meningitis: a literature review. Int J Antimicrob Agents 2013; 41 (6): 499-508
101. Hanninen P, Rossi T. Penetration of sulbactam into cerebrospinal fluid of patients with viral meningitis or without meningitis. Rev Infect Dis 1986; 8 Suppl 5: S609-11
102. Stahl JP, Bru JP, Fredj G, et al. Penetration of sulbactam into the cerebrospinal fluid of patients with bacterial meningitis receiving ampicillin therapy. Rev Infect Dis 1986; 8 Suppl 5: S612-16
103. Foulds G, McBride TJ, Knirsch AK, et al. Penetration of sulbactam and ampicillin into cerebrospinal fluid of infants and young children with meningitis. Antimicrob Agents Chemother 1987; 31 (11): 1703-5
104. Jimenez-Mejias ME, Pachon J, Becerril B, et al. Treatment of multidrug-resistant Acinetobacter baumannii meningitis with ampicillin/sulbactam. Clin Infect Dis 1997; 24 (5): 932-5
105. Cawley MJ, Suh C, Lee S, Ackerman BH. Nontraditional dosing of ampicillin-sulbactam for multidrug-resistant acinetobacter baumannii meningitis. Pharmacotherapy 2002; 22 (4): 527-32
106. McCracken GH Jr, Mize SG, Threlkeld N. Intraventricular gentamicin therapy in gram-negative bacillary meningitis of infancy. Report of the Second Neonatal Meningitis Cooperative Study Group. Lancet 1980; 1 (8172): 787-91
107. Odio CM, Faingezicht I, Paris M, et al. The beneficial effects of early dexamethasone administration in infants and children with bacterial meningitis. N Engl J Med 1991; 324 (22): 1525-31
108. Scheld WM, Brodeur JP. Effect of methylprednisolone on entry of ampicillin and gentamicin into cerebrospinal fluid in experimental pneumococcal and Escherichia coli meningitis. Antimicrob Agents Chemother 1983; 23 (1): 108-12
109. Paris MM, Hickey SM, Trujillo M, et al. Evaluation of CP-99,219, a new fluoroquinolone, for treatment of experimental penicillin-and cephalosporin-resistant pneumococcal meningitis. Antimicrob Agents Chemother 1995; 39 (6): 1243-6
110. Paris MM, Hickey SM, Uscher MI, et al. Effect of dexamethasone on therapy of experimental penicillin-and cephalosporin-resistant pneumococcal meningitis. Antimicrob Agents Chemother 1994; 38 (6): 1320-4
111. Ricard JD, Wolff M, Lacherade JC, et al. Levels of vancomycin in cerebrospinal fluid of adult patients receiving adjunctive corticosteroids to treat pneumococcal meningitis: a prospective multicenter observational study. Clin Infect Dis 2007; 44 (2): 250-5
112. Nau R, Wellmer A, Soto A, et al. Rifampin reduces early mortality in experimental Streptococcus pneumoniae meningitis. J Infect Dis 1999; 179 (6): 1557-60
113. Focke NK, Kallenberg K, Mohr A, et al. Distributed, Limbic Gray Matter Atrophy in Patients after Bacterial Meningitis. AJNR Am J Neuroradiol 2012; 34 (6): 1164-7
114. Schmidt H, Heimann B, Djukic M, et al. Neuropsychological sequelae of bacterial and viral meningitis. Brain 2006; 129 (Pt 2): 333-45
115. Nau R, Schmidt H. Long-term neuropsychological deficits after central nervous system infections despite adequate therapy. J Neurol 2007; 254 (Suppl 2): II80-3
116. Zysk G, Bruck W, Gerber J, et al. Anti-inflammatory treatment influences neuronal apoptotic cell death in the dentate gyrus in experimental pneumococcal meningitis. J Neuropathol Exp Neurol 1996; 55 (6): 722-8
117. Leib SL, Kim YS, Chow LL, et al. Reactive oxygen intermediates contribute to necrotic and apoptotic neuronal injury in an infant rat model of bacterial meningitis due to group B streptococci. J Clin Invest 1996; 98 (11): 2632-9
118. Leib SL, Heimgartner C, Bifrare YD, et al. Dexamethasone aggravates hippocampal apoptosis and learning deficiency in pneumococcal meningitis in infant rats. Pediatr Res 2003; 54 (3): 353-7
119. Weisfelt M, Hoogman M, van de Beek D, et al. Dexamethasone and long-term outcome in adults with bacterial meningitis. Ann Neurol 2006; 60 (4): 456-68
120. de Gans J, van de Beek D. European Dexamethasone in Adulthood Bacterial Meningitis Study I. Dexamethasone in adults with bacterial meningitis. N Engl J Med 2002; 347 (20): 1549-56
121. van de Beek D, Farrar JJ, de Gans J, et al. Adjunctive dexamethasone in bacterial meningitis: a meta-analysis of individual patient data. Lancet Neurol 2010; 9 (3): 254-63
122. Esposito S, Semino M, Picciolli I, Principi N. Should corticosteroids be used in bacterial meningitis in children? Eur J Paediatr Neurol 2013; 17 (1): 24-8
123. Brouwer MC, Tunkel AR, van de Beek D. Epidemiology, diagnosis, and antimicrobial treatment of acute bacterial meningitis. Clin Microbiol Rev 2010; 23 (3): 467-92
124. Heckenberg SG, Brouwer MC, van der Ende A, van de Beek D. Adjunctive dexamethasone in adults with meningococcal meningitis. Neurology 2012; 79 (15): 1563-9
125. Brouwer MC, McIntyre P, Prasad K, van de Beek D. Corticosteroids for acute bacterial meningitis. Cochrane Database Syst Rev 2013; 6: CD004405
126. Ambulant erworbene bakterielle (eitrige) Meningoenzephalitis. Available from: www.dgn.org/component/content/article/45-leitlinien-der-dgn-2012/2398-ll-34-ambulant-erworbene-bakterielle-eitrige-meningoenzephalitis.html?q=meningoenzephalitis
127. Nau R. Osmotherapy for elevated intracranial pressure: a critical reappraisal. Clin Pharmacokinet 2000; 38 (1): 23-40
128. Singhi S, Jarvinen A, Peltola H. Increase in serum osmolality is possible mechanism for the beneficial effects of glycerol in childhood bacterial meningitis. Pediatr Infect Dis J 2008; 27 (10): 892-6
129. Schmidt H, Stuertz K, Chen V, et al. Glycerol does not reduce neuronal damage in experimental Streptococcus pneumoniae meningitis in rabbits. Inflammopharmacology 1998; 6 (1): 19-26
130. Blaser C, Klein M, Grandgirard D, et al. Adjuvant glycerol is not beneficial in experimental pneumococcal meningitis. BMC Infect Dis 2010; 10: 84
131. Peltola H, Roine I, Fernandez J, et al. Adjuvant glycerol and/or dexamethasone to improve the outcomes of childhood bacterial meningitis: a prospective, randomized, double-blind, placebo-controlled trial. Clin Infect Dis 2007; 45 (10): 1277-86
132. Ajdukiewicz KM, Cartwright KE, Scarborough M, et al. Glycerol adjuvant therapy in adults with bacterial meningitis in a high HIV seroprevalence setting in Malawi: a double-blind, randomised controlled trial. Lancet Infect Dis 2011; 11 (4): 293-300
133. Molyneux EM, Kawaza K, Phiri A, et al. Glycerol and acetaminophen as adjuvant therapy did not affect the outcome of bacterial meningitis in Malawian children. Pediatr Infect Dis J 2014; 33 (2): 214-16
134. Wall EC, Ajdukiewicz KM, Heyderman RS, Garner P. Osmotic therapies added to antibiotics for acute bacterial meningitis. Cochrane Database Syst Rev 2013; 3: CD008806
135. Nau R, Soto A, Bruck W. Apoptosis of neurons in the dentate gyrus in humans suffering from bacterial meningitis. J Neuropathol Exp Neurol 1999; 58 (3): 265-74
136. Edwards GE. The use of hypothermia in a case of measles meningo-encephalitis. J Ir Med Assoc 1958; 42 (252): 181-3
137. Robinson A, Buckler JM. Emergency hypothermia in meningococcal meningitis. Lancet 1965; 1 (7376): 81-3
138. Veghelyi PV. Emergency hypothermic in meningococcal meningitis. Lancet 1965; 1 (7387): 710
139. Cuthbertson BH, Dickson R, Mackenzie A. Intracranial pressure measurement, induced hypothermia and barbiturate coma in meningitis associated with intractable raised intracranial pressure. Anaesthesia 2004; 59 (9): 908-11
140. Lepur D, Kutlesa M, Barsic B. Induced hypothermia in adult community-acquired bacterial meningitis-more than just a possibility? J Infect 2011; 62 (2): 172-7
141. Irazuzta JE, Pretzlaff RK, Zingarelli B, et al. Modulation of nuclear factor-kappaB activation and decreased markers of neurological injury associated with hypothermic therapy in experimental bacterial meningitis. Crit Care Med 2002; 30 (11): 2553-9
142. Angstwurm K, Reuss S, Freyer D, et al. Induced hypothermia in experimental pneumococcal meningitis. J Cereb Blood Flow Metab 2000; 20 (5): 834-8
143. Mourvillier B, Tubach F, van de Beek D, et al. Induced hypothermia in severe bacterial meningitis: a randomized clinical trial. JAMA 2013; 310 (20): 2174-83
144. Kuikka A, Sivonen A, Emelianova A, Valtonen VV. Prognostic factors associated with improved outcome of Escherichia coli bacteremia in a Finnish university hospital. Eur J Clin Microbiol 1997; 16 (2): 125-34
145. Kuikka A, Valtonen VV. Factors associated with improved outcome of Pseudomonas aeruginosa bacteremia in a Finnish university hospital. Eur J Clin Microbiol 1998; 17 (10): 701-8
146. Roine I, Peltola H, Fernandez J, et al. Influence of admission findings on death and neurological outcome from childhood bacterial meningitis. Clin Infect Dis 2008; 46 (8): 1248-52
147. ARRIVE guidelines. Available from: www.nc3rs.org.uk/arrive-guidelines
148. Tauber SC, Stadelmann C, Spreer A, et al. Increased expression of BDNF and proliferation of dentate granule cells after bacterial meningitis. J Neuropathol Exp Neurol 2005; 64 (9): 806-15
149. Barichello T, Generoso JS, Simoes LR, et al. Vitamin B6 prevents cognitive impairment in experimental pneumococcal meningitis. Exp Biol Med 2014; 239 (10): 1360-5
150. Zysset-Burri DC, Bellac CL, Leib SL, Wittwer M. Vitamin B6 reduces hippocampal apoptosis in experimental pneumococcal meningitis. BMC Infect Dis 2013; 13: 393
151. Barichello T, Generoso JS, Simoes LR, et al. Folic acid prevented cognitive impairment in experimental pneumococcal meningitis. J Neural Transm 2015; 122 (5): 643-51
152. Djukic M, Onken ML, Schutze S, et al. Vitamin d deficiency reduces the immune response, phagocytosis rate, and intracellular killing rate of microglial cells. Infect Immun 2014; 82 (6): 2585-94
153. Djukic M, Sostmann N, Bertsch T, et al. Vitamin D deficiency decreases survival of bacterial meningoencephalitis in mice. J Neuroinflammation 2015; 12 (1): 208
154. Gerber J, Redlich S, Ribes S, et al. Intrathecal treatment with the anti-phosphorylcholine monoclonal antibody TEPC-15 decreases neuronal damage in experimental pneumococcal meningitis. Chemotherapy 2012; 58 (3): 212-16
155. Nataf S, Stahel PF, Davoust N, Barnum SR. Complement anaphylatoxin receptors on neurons: new tricks for old receptors? Trends Neurosci 1999; 22 (9): 397-402
156. Mabbott NA, Bruce ME, Botto M, et al. Temporary depletion of complement component C3 or genetic deficiency of C1q significantly delays onset of scrapie. Nat Med 2001; 7 (4): 485-7
157. Tuomanen E, Hengstler B, Zak O, Tomasz A. The role of complement in inflammation during experimental pneumococcal meningitis. Microb Pathog 1986; 1 (1): 15-32
158. Woehrl B, Brouwer MC, Murr C, et al. Complement component 5 contributes to poor disease outcome in humans and mice with pneumococcal meningitis. J Clin Invest 2011; 121 (10): 3943-53
159. Nau R, Eiffert H. Modulation of release of proinflammatory bacterial compounds by antibacterials: potential impact on course of inflammation and outcome in sepsis and meningitis. Clin Microbiol Rev 2002; 15 (1): 95-110
160. Ribes S, Adam N, Schutze S, et al. The nucleotide-binding oligomerization domain-containing-2 ligand muramyl dipeptide enhances phagocytosis and intracellular killing of Escherichia coli K1 by Toll-like receptor agonists in microglial cells. J Neuroimmunol 2012; 252 (1-2): 16-23
161. Jarisch A. Therapeutische Versuche bei Syphilis. Wien Med Wochenschr 1895; 45: 721-4
162. Herxheimer K, Krause K. Über eine bei Syphilitischen vorkommende Quecksilberreaktion. Dtsch Med Wochenschr 1902; 28: 895-7
163. Hopkin DA. Frapper fort ou frapper doucement: a gram-negative dilemma. Lancet 1978; 2 (8101): 1193-4
164. Ahmed A, Jafri H, Lutsar I, et al. Pharmacodynamics of vancomycin for the treatment of experimental penicillin-and cephalosporin-resistant pneumococcal meningitis. Antimicrob Agents Chemother 1999; 43 (4): 876-81
165. Spreer A, Lugert R, Stoltefaut V, et al. Short-term rifampicin pretreatment reduces inflammation and neuronal cell death in a rabbit model of bacterial meningitis. Crit Care Med 2009; 37 (7): 2253-8
166. Schneider O, Michel U, Zysk G, et al. Clinical outcome in pneumococcal meningitis correlates with CSF lipoteichoic acid concentrations. Neurology 1999; 53 (7): 1584-7
167. Aubry-Damon H, Soussy CJ, Courvalin P. Characterization of mutations in the rpoB gene that confer rifampin resistance in Staphylococcus aureus. Antimicrob Agents Chemother 1998; 42 (10): 2590-4
168. Enright M, Zawadski P, Pickerill P, Dowson CG. Molecular evolution of rifampicin resistance in Streptococcus pneumoniae. Microb Drug Resist 1998; 4 (1): 65-70
169. Gerber J, Pohl K, Sander V, et al. Rifampin followed by ceftriaxone for experimental meningitis decreases lipoteichoic acid concentrations in cerebrospinal fluid and reduces neuronal damage in comparison to ceftriaxone alone. Antimicrob Agents Chemother 2003; 47 (4): 1313-17
170. Spreer A, Kerstan H, Bottcher T, et al. Reduced release of pneumolysin by streptococcus pneumoniae in vitro and in vivo after treatment with nonbacteriolytic antibiotics in comparison to ceftriaxone. Antimicrob Agents Chemother 2003; 47 (8): 2649-54
171. Azeh I, Gerber J, Wellmer A, et al. Protein synthesis inhibiting clindamycin improves outcome in a mouse model of staphylococcus aureus sepsis compared with the cell wall active ceftriaxone. Crit Care Med 2002; 30 (7): 1560-4
172. Bottcher T, Ren H, Goiny M, et al. Clindamycin is neuroprotective in experimental Streptococcus pneumoniae meningitis compared with ceftriaxone. J Neurochem 2004; 91 (6): 1450-60
173. Grandgirard D, Burri M, Agyeman P, Leib SL. Adjunctive daptomycin attenuates brain damage and hearing loss more efficiently than rifampin in infant rat pneumococcal meningitis. Antimicrob Agents Chemother 2012; 56 (8): 4289-95
174. Grandgirard D, Schurch C, Cottagnoud P, Leib SL. Prevention of brain injury by the nonbacteriolytic antibiotic daptomycin in experimental pneumococcal meningitis. Antimicrob Agents Chemother 2007; 51 (6): 2173-8
175. Barichello T, Goncalves JC, Generoso JS, et al. Attenuation of cognitive impairment by the nonbacteriolytic antibiotic daptomycin in Wistar rats submitted to pneumococcal meningitis. BMC Neurosci 2013; 14: 42
176. Vivas M, Force E, Tubau F, et al. Effect of dexamethasone on the efficacy of daptomycin in the therapy of experimental pneumococcal meningitis. Int J Antimicrob Agents 2015; 46 (1): 28-32
177. Malley R, Henneke P, Morse SC, et al. Recognition of pneumolysin by Toll-like receptor 4 confers resistance to pneumococcal infection. Proc Natl Acad Sci USA 2003; 100 (4): 1966-71
178. Ebert S, Gerber J, Bader S, et al. Dose-dependent activation of microglial cells by Toll-like receptor agonists alone and in combination. J Neuroimmunol 2005; 159 (1-2): 87-96
179. Hanke ML, Kielian T. Toll-like receptors in health and disease in the brain: mechanisms and therapeutic potential. Clin Sci (Lond) 2011; 121 (9): 367-87
180. Shirey KA, Lai W, Scott AJ, et al. The TLR4 antagonist Eritoran protects mice from lethal influenza infection. Nature 2013; 497 (7450): 498-502
181. Goos M, Lange P, Hanisch UK, et al. Fibronectin is elevated in the cerebrospinal fluid of patients suffering from bacterial meningitis and enhances inflammation caused by bacterial products in primary mouse microglial cell cultures. J Neurochem 2007; 102 (6): 2049-60
182. Opal SM, Laterre PF, Francois B, et al. Effect of eritoran, an antagonist of MD2-TLR4, on mortality in patients with severe sepsis: the ACCESS randomized trial. JAMA 2013; 309 (11): 1154-62
183. Azeh I, Mader M, Smirnov A, et al. Experimental pneumococcal meningitis in rabbits: the increase of matrix metalloproteinase-9 in cerebrospinal fluid correlates with leucocyte invasion. Neurosci Lett 1998; 256 (3): 127-30
184. Leppert D, Leib SL, Grygar C, et al. Matrix metalloproteinase (MMP)-8 and MMP-9 in cerebrospinal fluid during bacterial meningitis: association with blood-brain barrier damage and neurological sequelae. Clin Infect Dis 2000; 31 (1): 80-4
185. Ricci S, Grandgirard D, Wenzel M, et al. Inhibition of matrix metalloproteinases attenuates brain damage in experimental meningococcal meningitis. BMC Infect Dis 2014; 14 (1): 3853
186. Baranger K, Rivera S, Liechti FD, et al. Endogenous and synthetic MMP inhibitors in CNS physiopathology. Prog Brain Res 2014; 214: 313-51
187. Liechti FD, Bachtold F, Grandgirard D, et al. The matrix metalloproteinase inhibitor RS-130830 attenuates brain injury in experimental pneumococcal meningitis. J Neuroinflammation 2015; 12 (1): 43
188. Liechti FD, Grandgirard D, Leppert D, Leib SL. Matrix metalloproteinase inhibition lowers mortality and brain injury in experimental pneumococcal meningitis. Infect Immun 2014; 82 (4): 1710-18
189. Barichello T, Generoso JS, Michelon CM, et al. Inhibition of matrix metalloproteinases-2 and-9 prevents cognitive impairment induced by pneumococcal meningitis in Wistar rats. Exp Biol Med 2014; 239 (2): 225-31
190. Koedel U, Pfister HW. Protective effect of the antioxidant N-acetyl-L-cysteine in pneumococcal meningitis in the rat. Neurosci Lett 1997; 225 (1): 33-6
191. Auer M, Pfister LA, Leppert D, et al. Effects of clinically used antioxidants in experimental pneumococcal meningitis. J Infect Dis 2000; 182 (1): 347-50
192. Klein M, Koedel U, Pfister HW, Kastenbauer S. Meningitis-associated hearing loss: protection by adjunctive antioxidant therapy. Ann Neurol 2003; 54 (4): 451-8
193. Hogen T, Demel C, Giese A, et al. Adjunctive N-acetyl-L-cysteine in murine pneumococcal meningitis. Antimicrob Agents Chemother 2013; 57 (10): 4825-30
194. Sheu JN, Liao WC, Wu UI, et al. Resveratrol suppresses calcium-mediated microglial activation and rescues hippocampal neurons of adult rats following acute bacterial meningitis. Comp Immunol Microbiol Infect Dis 2013; 36 (2): 137-48
195. Gerber J, Lotz M, Ebert S, et al. Melatonin is neuroprotective in experimental Streptococcus pneumoniae meningitis. J Infect Dis 2005; 191 (5): 783-90
196. Wu UI, Mai FD, Sheu JN, et al. Melatonin inhibits microglial activation, reduces pro-inflammatory cytokine levels, and rescues hippocampal neurons of adult rats with acute Klebsiella pneumoniae meningitis. J Pineal Res 2011; 50 (2): 159-70
197. Spreer A, Gerber J, Baake D, et al. Antiinflammatory but no neuroprotective effects of melatonin under clinical treatment conditions in rabbit models of bacterial meningitis. J Neurosci Res 2006; 84 (7): 1575-9
198. Barichello T, Ceretta RA, Generoso JS, et al. Cannabidiol reduces host immune response and prevents cognitive impairments in Wistar rats submitted to pneumococcal meningitis. Eur J Pharmacol 2012; 697 (1-3): 158-64
199. Nau R, Zettl U, Gerber J, et al. Granulocytes in the subarachnoid space of humans and rabbits with bacterial meningitis undergo apoptosis and are eliminated by macrophages. Acta Neuropathol 1998; 96 (5): 472-80
200. Koedel U, Frankenberg T, Kirschnek S, et al. Apoptosis is essential for neutrophil functional shutdown and determines tissue damage in experimental pneumococcal meningitis. PLoS Pathog 2009; 5 (5): e1000461
201. Hoogendijk AJ, Roelofs JJ, Duitman J, et al. R-roscovitine reduces lung inflammation induced by lipoteichoic acid and Streptococcus pneumoniae. Mol Med 2012; 18: 1086-95
202. Krystof V, Uldrijan S. Cyclin-dependent kinase inhibitors as anticancer drugs. Curr Drug Targets 2010; 11 (3): 291-302
203. Wache C, Klein M, Ostergaard C, et al. Myeloid-Related Protein 14 Promotes Inflammation and Injury in Meningitis. J Infect Dis 2015; 212 (2): 247-57
204. Hohne C, Wenzel M, Angele B, et al. High mobility group box 1 prolongs inflammation and worsens disease in pneumococcal meningitis. Brain 2013; 136 (Pt 6): 1746-59
205. Gerber J, Bottcher T, Bering J, et al. Increased neurogenesis after experimental Streptococcus pneumoniae meningitis. J Neurosci Res 2003; 73 (4): 441-6
206. Gerber J, Tauber SC, Armbrecht I, et al. Increased neuronal proliferation in human bacterial meningitis. Neurology 2009; 73 (13): 1026-32
207. Liebetanz D, Gerber J, Schiffner C, et al. Pre-infection physical exercise decreases mortality and stimulates neurogenesis in bacterial meningitis. J Neuroinflammation 2012; 9: 168
208. Barichello T, Fagundes GD, Generoso JS, et al. Environmental enrichment restores cognitive deficits induced by experimental childhood meningitis. Revista Brasileira de Psiquiatria 2014; 36 (4): 322-9
209. Tauber SC, Harms K, Falkenburger B, et al. Modulation of hippocampal neuroplasticity by Fas/CD95 regulatory protein 2 (Faim2) in the course of bacterial meningitis. J Neuropathol Exp Neurol 2014; 73 (1): 2-13
210. Schmidt AK, Reich A, Falkenburger B, et al. Adjuvant granulocyte colony-stimulating factor therapy results in improved spatial learning and stimulates hippocampal neurogenesis in a mouse model of pneumococcal meningitis. J Neuropathol Exp Neurol 2015; 74 (1): 85-94
211. Adams WG, Deaver KA, Cochi SL, et al. Decline of childhood Haemophilus influenzae type b (Hib) disease in the Hib vaccine era. JAMA 1993; 269 (2): 221-6
212. Hak E, Grobbee DE, Sanders EA, et al. Rationale and design of CAPITA: a RCT of 13-valent conjugated pneumococcal vaccine efficacy among older adults. Neth J Med 2008; 66 (9): 378-83
213. Davis S, Feikin D, Johnson HL. The effect of Haemophilus influenzae type B and pneumococcal conjugate vaccines on childhood meningitis mortality: a systematic review. BMC Public Health 2013; 13 Suppl 3: S21
214. Campbell H, Andrews N, Borrow R, et al. Updated postlicensure surveillance of the meningococcal C conjugate vaccine in England and Wales: effectiveness, validation of serological correlates of protection, and modeling predictions of the duration of herd immunity. Clin Vaccine Immunol 2010; 17 (5): 840-7
215. Ladhani SN, Flood JS, Ramsay ME, et al. Invasive meningococcal disease in England and Wales: implications for the introduction of new vaccines. Vaccine 2012; 30 (24): 3710-16
216. Leca M, Bornet C, Montana M, et al. Meningococcal vaccines: Current state and future outlook. Pathol Biol (Paris) 2015; 63 (3): 144-51
217. Gossger N, Snape MD, Yu LM, et al. Immunogenicity and tolerability of recombinant serogroup B meningococcal vaccine administered with or without routine infant vaccinations according to different immunization schedules: a randomized controlled trial. JAMA 2012; 307 (6): 573-82
218. Read RC, Baxter D, Chadwick DR, et al. Effect of a quadrivalent meningococcal ACWY glycoconjugate or a serogroup B meningococcal vaccine on meningococcal carriage: an observer-blind, phase 3 randomised clinical trial. Lancet 2014; 384 (9960): 2123-31
219. Block SL, Szenborn L, Daly W, et al. A comparative evaluation of two investigational meningococcal ABCWY vaccine formulations: Results of a phase 2 randomized, controlled trial. Vaccine 2015; 33 (21): 2500-10
220. Gamez G, Hammerschmidt S. Combat pneumococcal infections: adhesins as candidates for protein-based vaccine development. Curr Drug Targets 2012; 13 (3): 323-37
221. Ribes S, Riegelmann J, Redlich S, et al. Multivalent choline dendrimers phagocytosis of Streptococcus pneumoniae R6 by microglial cells. Chemotherapy 2013; 59 (2): 138-42
222. Ratilal BO, Costa J, Pappamikail L, Sampaio C. Antibiotic prophylaxis for preventing meningitis in patients with basilar skull fractures. Cochrane Database Syst Rev 2015; 4: CD004884
223. Kim KS. Current concepts on the pathogenesis of Escherichia coli meningitis: implications for therapy and prevention. Curr Opin Infect Dis 2012; 25 (3): 273-8
224. Tan YC, Gill AK, Kim KS. Treatment strategies for central nervous system infections: an update. Expert Opin Pharmacother 2015; 16 (2): 187-203
225. Ribes S, Ebert S, Regen T, et al. Toll-like receptor stimulation enhances phagocytosis and intracellular killing of nonencapsulated and encapsulated Streptococcus pneumoniae by murine microglia. Infect Immun 2010; 78 (2): 865-71
226. Ribes S, Adam N, Schutze S, et al. The nucleotide-binding oligomerization domain-containing-2 ligand muramyl dipeptide enhances phagocytosis and intracellular killing of Escherichia coli K1 by Toll-like receptor agonists in microglial cells. J Neuroimmunol 2012; 252 (1-2): 16-23
227. Ribes S, Meister T, Ott M, et al. Intraperitoneal prophylaxis with CpG oligodeoxynucleotides protects neutropenic mice against intracerebral Escherichia coli K1 infection. J Neuroinflammation 2014; 11: 14
228. Muccioli GG, Stella N. Microglia produce and hydrolyze palmitoylethanolamide. Neuropharmacology 2008; 54 (1): 16-22
229. De Petrocellis L, Davis JB, Di Marzo V. Palmitoylethanolamide enhances anandamide stimulation of human vanilloid VR1 receptors. FEBS Lett 2001; 506 (3): 253-6
230. Lo Verme J, Fu J, Astarita G, et al. The nuclear receptor peroxisome proliferator-activated receptor-alpha mediates the anti-inflammatory actions of palmitoylethanolamide. Mol Pharmacol 2005; 67 (1): 15-19
231. LoVerme J, Russo R, La Rana G, et al. Rapid broad-spectrum analgesia through activation of peroxisome proliferator-activated receptor-alpha. J Pharmacol Exp Ther 2006; 319 (3): 1051-61
232. Ryberg E, Larsson N, Sjogren S, et al. The orphan receptor GPR55 is a novel cannabinoid receptor. Br J Pharmacol 2007; 152 (7): 1092-101
233. Loria F, Petrosino S, Mestre L, et al. Study of the regulation of the endocannabinoid system in a virus model of multiple sclerosis reveals a therapeutic effect of palmitoylethanolamide. Eur J Neurosci 2008; 28 (4): 633-41
234. Redlich S, Ribes S, Schutze S, et al. Palmitoylethanolamide stimulates phagocytosis of Escherichia coli K1 and Streptococcus pneumoniae R6 by microglial cells. J Neuroimmunol 2012; 244 (1-2): 32-4
235. Redlich S, Ribes S, Schutze S, Nau R. Palmitoylethanolamide stimulates phagocytosis of Escherichia coli K1 by macrophages and increases the resistance of mice against infections. J Neuroinflammation 2014; 11: 108
236. Kahlich R, Klima J, Cihla F, et al. Studies on prophylactic efficacy of N-2-hydroxyethyl palmitamide (Impulsin) in acute respiratory infections. Serologically controlled field trials. J Hyg Epidemiol Microbiol Immunol 1979; 23 (1): 11-24
237. Keppel Hesslink MJ. New targets in pain, non-neuronal cells, and role of palmitoylethanolamide. Open Pain J 2012 (5): 12-23
238. Nau R, Ribes S, Djukic M, Eiffert H. Strategies to increase the activity of microglia as efficient protectors of the brain against infections. Frontiers in Cellular Neuroscience 2014; 8: 138 Available from: www.dgn.org/images/stories/dgn/leitlinien/LL-2012/pdf/ll-34-ambulant-erworbene-bakterielle-eitrige-meningoenzephalitis.pdf