### Diagnosis Fever, headache and stiff neck are the classic signs and symptoms. Unlike [[encephalitis]], a mental status usually does not change until later in the disease. The sooner you do an LP and get antibiotics started the better. [^1] And the stiff neck. The real deal is ridged. Cannot move at all. As stiff as the proverbial board. Who needs a CT before an LP for community-acquired [[Meningitis]]? Immunocompromised, history of CNS disease, new seizure, altered mental status or focal neurologic exam. [^2] Not that these guidelines are followed. 2/3 of the time a CT is ordered when none are needed, delaying the LP, wasting time and money and not altering management. [^3] But. Not using impaired mental status and immunocompromised state before LP resulted in a prompt LP, earlier therapy and a better outcome. So whose guideline should reign supreme? Having a complication from an LP is quite rare and a CT is only moderately helpful for a contraindication. [^4] Viral cultures of CSF for aseptic [[Meningitis]] in normal people are of extremely low yield; the PCR for enterovirus and [[Herpes]] have a better yield. [^5] Lumbar puncture gives a hint as to the type of [[Meningitis]]: viral/septic, pyogenic/bacterial, granulomatous/fungal/tuberculosis. Remember, the changes in the CSF are not fixed but dynamic based on the course of disease. The numbers rise and fall, the value depending on when the LP is done. Aseptic: 100's of cells, normal glucose, normal to slightly elevated protein. ------------------------- ------------- ------ -----   Enterovirus HSV VZV WBC 51 240 207 Lymph% 91 100 100 Protein mg/L 640 1250 974 CSF/Blood glucose ratio .6 .48 . 55 CRP 15 4.6 6.6 ------------------------- ------------- ------ ----- LP for Enterovirus, HSV, VZV. [^6] If you do not have > 10 WBC in the CSF, it is a waste of money to sent off viral PCRs. [^7] But the smart way to do a spinal tap is to order the cell count, glucose and protein and then add on appropriate tests once you know what the pattern is, instead of the frequent approach of ordering everything like a microencephalopathic. What about 6-10 WBC on a tap? In France, 11 cases (5.6%) were associated with a microbiological diagnoses, one *[[Streptococcus]]* *pneumoniae*, 4 PCR-positive tests for viruses, including three Enterovirus and one herpesvirus type 6, 5 positive for tick borne [[encephalitis]], and one case of rat bite fever. [^8] Viral [[Meningitis]] can give a neutrophilic LP: > "45 (24.7%) had CSF neutrophilic pleocytosis. Enterovirus infections were the cause of 64% of neutrophil-predominant CSF and 33% of lymphocyte-predominant CSF, while [[Herpes]] infections were the cause of 46% of lymphocytic pleocytosis and 20% of neutrophilic pleocytosis (p=0.003). Moreover, neutrophilic pleocytosis was seen more commonly in younger patients (p=0.001), patients with respiratory symptoms (p=0.04), and patients with higher CSF white cell counts (p=0.004)". [^9] Pyogenic (bacterial): thousands of cells, mostly PMN's, low glucose, high protein. If 100's of PMN's and a protein of 500ish or more, think epidural abscess. It is rare, but early in bacterial [[Meningitis]], there can be a lack of WBC on the tap. [^10] Granulomatous: (tuberculosis/Fungal): hundreds of cells, mostly monocytes, low glucose, high protein. In tuberculosis [[Meningitis]] the protein can be so high the CSF will clot, with a spider's web of red cells in it, a rare but characteristic manifestation. [^11] I had one tuberculosis [[Meningitis]] where the CSF was thick as Karo syrup. Cold Karo at that. An elevated CSF lactate is strongly indicative of pyogenic [[Meningitis]] in one meta-analysis: > "CSF lactate was a better marker for distinguishing bacterial [[Meningitis]] from aseptic [[Meningitis]] compared to other conventional markers including CSF glucose, CSF/plasma glucose quotient, CSF protein, and CSF total number of leukocytes...The cut-off value for CSF lactate concentration ranges from 2.1 to 4.44 mmol/L." [^12] A lactate > 3.5 mmol/l is 100% sensitive for bacterial [[Meningitis]]. [^13] The lactate is also valuable for post neurosurgical [[Meningitis]] with cutoff values ranging from 3.45 mmol/L to 5.4 mmol/L. [^14] Although not an approved body fluid, galactomannan (for *[[Aspergillus]]*) and 1-3 beta-D glucan (NOT made by *[[Cryptococcus]]*) are useful for the diagnosis of fungal [[Meningitis]]. [^15] A beta D glucan may be of use in rapid diagnosis of fungal [[Meningitis]], although somewhat insensitive. [^18] There is pachymeningitis (pachy like elephant skin) a > "focal or diffuse thickening of dura mater visualized on MRI of the brain and/or histologic analysis of dura mater consistent with chronic inflammation." Causes in this review were > "... idiopathic pachymeningitis (n = 18; 30%); granulomatosis with polyangiitis (n = 13; 17%); Erdheim-Chester disease (n = 10; 17%); IgG4-related disease and tuberculosis (n = 3; 5% each); Rosai-Dofman disease, microscopic polyangiitis, and sarcoidosis (n = 2, 3% each); cryptococcal [[Meningitis]], [[Lyme]] disease, ear-nose-throat infection, postlumbar puncture, low spinal-fluid pressure syndrome, and lymphoma (n = 1 each)." [^16] There are a variety of non-culture methods to make a diagnosis, from PCR panels to metagenomic next-generation sequencing (aka magic. "Any sufficiently advanced technology is indistinguishable from magic." Clarke's First Law). If you have them, use them. The sooner you make a diagnosis, the sooner you can start appropriate therapy. [^17] Traumatic tap? At least in kids > "For every 1000 cell increase in CSF red blood cells per mm(3), CSF protein increases by 1.1 mg/dL. [^19] ### Epidemiologic Risks Having a brain. As always in ID, where they have been, what they have been exposed to is the best way to find an odd etiology for the infection. You, taking a careful history. > "...prior head or spine surgery is associated with increased [[Streptococcus]] pneumoniae [[Meningitis]] outside of the postoperative period). Among the cases, only 33.3% had received any prior pneumococcal vaccinations. [^20] > "Patients with bacterial [[Meningitis]] and diabetes mellitus are older, have more comorbidities, and higher mortality. S. pneumoniae and L. monocytogenes are the predominant pathogens, [[Listeria]] being more common...." [^21] ### Microbiology Anything can cause [[Meningitis]], some of the more common etiologies follow. **Aseptic [[Meningitis]]** Common causes include enterovirus in summer/fall, [[Herpes]] simplex often during active genital outbreaks, especially the first outbreak. Patients never volunteer the information and docs never ask. A couple of times a year I get a call from the ER about someone with an aseptic [[Meningitis]]. "Do they have active [[Herpes]]?" I inquire. "Just a sec, I'll ask," they reply. More than a second passes. "Yeah, they got [[Herpes]]. Never had it before." And the moral is, ask the patient with aseptic [[Meningitis]] if the have genital ulcers. VZV. [^22] West Nile virus, syphilis, [[HIV]] (acute illness), Parvovirus, and leptospirosis (which is a very common, but under-recognized, cause). Then there is LCM ([[Lymphocytic Choriomeningitis Virus]]), classically associated with hamster exposure. However, can occur in anyone with contact with the house mouse and around 10% of US citizens and US mice are seropositive. [^23] Recurrent aseptic [[Meningitis]] is usually due to [[Herpes]] 2 (Mollaret's) and if associated with eye/urethra symptoms, think of Bechets. And, for an off the wall cause, chronic strongyloidiasis with human T­-lymphotropic virus type 1 ([PubMed](http://www.ncbi.nlm.nih.gov/pubmed/25548379)). NSAIDs, [[trimethoprim]], and lamotrigine are a few of the drugs that can cause an aseptic [[Meningitis]]. . **Pyogenic (bacterial)** In the US, all age causes are *S*. *pneumoniae* (58.0%), followed by Group B *Streptococci* (18.1%), *N*. *meningitidis* (13.9%), *H*. *influenzae* (6.7%), and *[[Listeria]]* (3.4%). [^24] At least as of 2011. Adults < 55: *S*. *pneumoniae* >> *N*. *meningitidis*. Age > 55: The same as < age 55 except 10% are due to gram-negative rods and they are at risk for *[[Listeria]]*. [^25] The elderly will have a more indolent, less febrile presentation, often with only altered mental status, [^26]and how many of those get admitted a week? [[Meningitis]] can be a direct extension from dental, sinus or ear infections. If otogenic in origin, surgery is more likely than radiology to find a bone defect. [^27] In SE Asia the most common cause is *S*. *suis*, from pigs. [^28] With community-acquired *Enterobacteriaceae* or culture-negative purulent [[Meningitis]] think *Strongiloides* as the reason at least in Japan. [^29] [[Naegleria]] can mimic bacterial [[Meningitis]], the risk is swimming in warm freshwater and using neti pots, especially in the South, although another organism moving north with global warming. Rare and fatal. [^31] **Immunoincompetent** *[[Listeria]]* gets added to the list. Transplant patients and [[AIDS]] patients have the same organisms. A nice review of CNS infections in transplant infections here. [^32] **Post Neurosurgical/nosocomial** [^33] *S*. *aureus*, [^34]*S*. *epidermitis*, *[[Pseudomonas]]*. If a shunt or drain in place, *[[Propionibacterium]]* *acnes*. Local flora will vary. **Post spinal anesthesia, LP or similar procedure** Oral *Streptococci* especially *S*. *salivarius*. [^35] Some cases are due to the operator not wearing a mask. [^36] **Basilar skull fracture** *S*. *[[pneumonia]]*, *H*. *i*nfluenzae, group A beta-hemolytic *Streptococci*. **Granulomatous** (tuberculosis/Fungal) *[[Cryptococcus]]*, *Coccidiomycosis*, *Histoplasmosis*, Tuberculosis. *M*. *chimaera* also cause a granulomatous [[encephalitis]] with widespread organ involvement. Molds: [^30] *[[Aspergillus]]*, *[[Fusarium]]*, and *Scedosporium*, *Mucor*, and dematiaceous molds (*Cladophialophora* *bantiana* (also called *Xylohypha* *bantiana*), *Rhinocladiella* *mackenziei*, and *[[Ochroconis]]* *gallopava* (also called *Dactylaria* *gallopava*) and *E*. *rostratum* (with contaminated steroid injections). **Eosinophilic [[Meningitis]]** Can be due to *[[Angiostrongylus]]*, *Coccidiomycosis*, *[[Gnathostoma]]*, *[[Toxocara]]*, *Baylisascariasis*, *[[Paragonimus]]* *westermani*, and *[[Paragonimus]]* *kellicotti* in Missouri, *Schistosoma* *japonicum*, *Taenia* *solium* cysticerci, *Coccidiomycosis*, *tuberculosis*, syphilis. There are non-infectious causes as well: Sarcoidoisis, malignancy, Hodgkin's disease, non-Hodgkin's lymphoma, and eosinophilic leukemia. Medications that have been associated with eosinophlic [[Meningitis]] include [[ciprofloxacin]], ibuprofen, intraventricular [[vancomycin]] and [[gentamicin]]. The rare rupture of a spinal epidermoid cyst; causes a chemical [[Meningitis]]. ### Empiric Therapy Viral: none needed. Everyone (or everyone who matters) will have [[Meningitis]] with genital [[Herpes]], it does not need to be treated nor have there ever been studies to show treatment helps. The best review to date suggests for HSV > "Most patients with HSV [[Meningitis]] rapidly improve, but immunocompromised hosts have more neurologic sequelae and may benefit from antiviral therapy. Our data suggest symptomatic treatment alone for immunocompetent patients with HSV [[Meningitis]], avoiding the cost and side effects of prolonged intravenous [[acyclovir]] therapy; in contrast, immunocompromised patients had improved outcomes and would, therefore, benefit from antiviral therapy." [^37] Not the same as [[Herpes]] [[encephalitis]]. THAT needs therapy. Bacterial: maximum dose [[vancomycin]] (perhaps dosed with a loading dose of 15 mg per kg then continuous infusion of 60 mg per kg per day after which resulted in good CSF levels despite the use of dexamethasone. [^38] This is to cover penicillin intermediate/resistant *S*. *[[pneumonia]]*) PLUS a third-generation cephalosporin at maximum dose (usually [[cefotaxime]] or [[ceftriaxone]] ) PLUS dexamethasone 0.15 mg/kg every 6 h preferably 10-20 min prior to, or at the same time as the first antimicrobial dose, for 2-4 days. In the elderly or the immunoincompetent, add [[ampicillin]] to cover [[Listeria]]. Although as of Dec 2007, what to do is less certain as dexamethasone was not of benefit in adults in Sub Saharan Africa, most of whom were [[HIV]] positive [^39] and in Vietnam was associated with increased death in patients who subsequently found NOT to have bacterial [[Meningitis]]. [^40] A review of steroids in 2013 suggests mostly benefit, [^41]  including less hearing loss. [^42] However, the use of dexamethasone 10 mg q 6 IV for four days lead to an absolute 10% decrease in mortality for pneumococcal [[Meningitis]]. [^43] For meningococcus, the best that can be said is that it doesn't increase harm and decreases the incidence of [[arthritis]]. [^44] Dexamethasone should not be of use for [[Listeria]] [^45] and in one study INCREASED mortality. [^46] In children, glycerol (oral 85% glycerol for 48 h at a dosage of 1.5 g per kg every 6 h; the maximum volume was 25 mL per dose. The first dose was given 15 min prior to [[ceftriaxone]] was superior to dexamethasone. [^48] Or maybe not; one study suggests both glycerol and dexamethasone do nothing. [^49] A 2013 meta-analysis on osmotics in [[Meningitis]] concluded > "The only osmotic diuretic to have undergone randomized evaluation is glycerol. Data from trials to date have not demonstrated a benefit on death, but it may reduce deafness. Osmotic diuretics, including glycerol, should not be given to adults and children with bacterial [[Meningitis]] unless as part of a carefully conducted randomized controlled trial." [^50] The last sentence the usual Cochrane cluelessness. Inducing hypothermia increases mortality. [^47] Post neurosurgical/Trauma: [[vancomycin]] PLUS [[Ceftazidime]] OR [[cefepime]] OR [[meropenem]]. Obviously, if a specific organism treat accordingly. If cultures are negative at three days it is usually safe to stop antibiotics. [^51] One study suggests intraventricular [[gentamicin]] improves outcomes. [^52] Granulomatous: treatment depends on the organism. Intraventricular doses, adults: [^53] [[Vancomycin]] 5--20 mg; [[gentamicin]] 4--8 mg; [[Amikacin]] 30 mg; polymyxin B 5 mg; [[Colistin]] 10 mg. ### Pearls Recurrent *S*. *pneumoniae*, *H*. *influenzae* or other bacterial, think of CSF leak. [^54] [^55] Pituitary insufficiency may be not uncommon after [[Meningitis]]. [^56] Alcoholics will be more ill, have more seizures, and a worse outcome. [^57] Hearing loss occurs in half of people with pneumococcal [[Meningitis]] and is not suspected at discharge. [^58] If the patient is on anticoagulation, consider holding or reversing it as it increases the risk of hemorrhage and death. [^59] ### Puswhisperers [Leaks](http://www.pusware.com/PW1/Leaks.html) [Audio. The Gobbet 'o Pus Podcast](http://www.pusware.com/gobbet/gop92.mp3) [Prophylaxis?](http://www.pusware.com/PW1/Prophylaxis.html) [Audio. The Gobbet 'o Pus Podcast](http://www.pusware.com/gobbet/gop94.mp3) [Hyperventilation](http:\\www.pusware.com/PW1/Hyperventilation.html) [Audio. The Gobbet 'o Pus Podcast](http://www.pusware.com/gobbet/gop129.mp3) [Swimming in Body Fluids](http://www.pusware.com/PW1/Swimming.html) [Audio. The Gobbet 'o Pus Podcast](http://www.pusware.com/gobbet/gop183.mp3) [Picky Picky](http://www.pusware.com/PW2/PickyPicky.html) [Audio. The Gobbet 'o Pus Podcast](http://www.pusware.com/gobbet/gop299.mp3) [[Meningitis]] and More](http://www.pusware.com/PW/2a032f62) [Audio. The Gobbet 'o Pus Podcast](http://www.pusware.com/gobbet/gop358.mp3) [Not what I had hoped for.](http://www.pusware.com/PW3/NotWhatI.html) [Audio. The Gobbet 'o Pus Podcast](http://www.pusware.com/gobbet/gop367.mp3) [Otitis Gone Bad](http://www.pusware.com/PW3/OtitisGoneBad.html) [Audio. The Gobbet 'o Pus Podcast](http://www.pusware.com/gobbet/gop436.mp3) [[Meningitis]] and Lips](http://www.pusware.com/PW/2a0ede1d ?? [Audio. The Gobbet 'o Pus Podcast](http://www.pusware.com/gobbet/gop493.mp3) [Say it, don't spray it](http://www.pusware.com/PW4/SayIt.html) [Audio. The Gobbet 'o Pus Podcast](http://www.pusware.com/gobbet/gop538.mp3) [There and Back Again](http://www.pusware.com/PW4/ThereAndBack.html) [Audio. The Gobbet 'o Pus Podcast](http://www.puswnare.com/gobbet/gop550.mp3) [Eventually Every Bug Show Up Everywhere](http://www.pusware.com/PW5/Eventually.html) [Audio. The Gobbet 'o Pus Podcast](http://www.pusware.com/gobbet/gop672.mp3) [At the end of the day, safe >>> sorry.](http://www.pusware.com/PW5/AtTheEnd.html) [Audio. The Gobbet 'o Pus Podcast](http://www.pusware.com/gobbet/gop693.mp3) [Better than Expected](http://www.pusware.com/PW6/BetterThanExpected.html) [Audio. The Gobbet 'o Pus Podcast](http://www.pusware.com/gobbet/gop816.mp3) [Not Positive](http://www.pusware.com/PW7/NotPositive.html) [Audio. The Gobbet 'o Pus Podcast](http://www.pusware.com/gobbet/gop940.mp3) [Self-Sealing?](http://www.pusware.com/PW8/SelfSealing.html) [Audio. The Gobbet 'o Pus Podcast](http://www.pusware.com/gobbet/gop1034.mp3) [Calling the Zebra](http://www.pusware.com/PW10/CallingTheZebra.html) [Audio. The Gobbet 'o Pus Podcast](http://www.pusware.com/gobbet/gop1213.mp3) [A Relationship](http://www.pusware.com/PW12/ARelationship.html) [Audio. The Gobbet 'o Pus Podcast](http://www.pusware.com/gobbet/gop1312.mp3) [Wrong Again](http://www.pusware.com/PW13/WrongAgain.html) [Audio. The Gobbet 'o Pus Podcast](http://www.pusware.com/gobbet/gop1367.mp3 ?? ### Rationalizations [^1]: Martin Glimåker, Bibi Johansson, Örjan Grindborg, Matteo Bottai, Lars Lindquist, Jan Sjölin, Adult Bacterial [[Meningitis]]: Earlier Treatment and Improved Outcome Following Guideline Revision Promoting Prompt Lumbar Puncture, _Clinical Infectious Diseases_, Volume 60, Issue 8, 15 April 2015, Pages 1162–1169, [https://doi.org/10.1093/cid/civ011](https://doi.org/10.1093/cid/civ011) [^2]: Allan R. Tunkel, Barry J. Hartman, Sheldon L. Kaplan, Bruce A. Kaufman, Karen L. Roos, W. Michael Scheld, Richard J. Whitley, Practice Guidelines for the Management of Bacterial [[Meningitis]], _Clinical Infectious Diseases_, Volume 39, Issue 9, 1 November 2004, Pages 1267–1284, [https://doi.org/10.1086/425368](https://doi.org/10.1086/425368) [^3]: Salazar L, Hasbun R. Cranial Imaging Before Lumbar Puncture in Adults With Community-Acquired [[Meningitis]]: Clinical Utility and Adherence to the Infectious Diseases Society of America Guidelines. Clin Infect Dis. 2017 Jun 15;64(12):1657-1662. doi: 10.1093/cid/cix240. PMID: 28369295; PMCID: PMC5850549. [^4]: Costerus JM, Brouwer MC, Sprengers MES, Roosendaal SD, van der Ende A, van de Beek D. Cranial Computed Tomography, Lumbar Puncture, and Clinical Deterioration in Bacterial [[Meningitis]]: A Nationwide Cohort Study. Clin Infect Dis. 2018 Aug 31;67(6):920-926. doi: 10.1093/cid/ciy200. PMID: 29522090. [^5]: Polage CR, Petti CA. Assessment of the utility of viral culture of cerebrospinal fluid. Clin Infect Dis. 2006 Dec 15;43(12):1578-9. doi: 10.1086/509581. Epub 2006 Nov 7. PMID: 17109291. [^6]: Ihekwaba UK, Kudesia G, McKendrick MW. Clinical features of viral [[Meningitis]] in adults: significant differences in cerebrospinal fluid findings among [[Herpes]] simplex virus, varicella zoster virus, and enterovirus infections. Clin Infect Dis. 2008 Sep 15;47(6):783-9. doi: 10.1086/591129. PMID: 18680414. [^7]: Wilen CB, Monaco CL, Hoppe-Bauer J, Jackups R Jr, Bucelli RC, Burnham CA. Criteria for reducing unnecessary testing for [[Herpes]] simplex virus, varicella-zoster virus, [[Cytomegalovirus]], and enterovirus in cerebrospinal fluid samples from adults. J Clin Microbiol. 2015 Mar;53(3):887-95. doi: 10.1128/JCM.03161-14. Epub 2015 Jan 7. PMID: 25568435; PMCID: PMC4390640. [^8]: Mathieu Wald, Simona Merisor, Pierre Zachary, Olivier Augereau, Simon Gravier, Benoit Jaulhac, Dominique De Briel, Aurélie Velay, Guillaume Gregorowicz, Martin Martinot, Microbiological Outcomes Associated With Low Leukocyte Counts in Cerebrospinal Fluid, _Open Forum Infectious Diseases_, Volume 8, Issue 2, February 2021, ofaa597, [https://doi.org/10.1093/ofid/ofaa597](https://doi.org/10.1093/ofid/ofaa597) [^9]: Jaijakul S, Salazar L, Wootton SH, Aguilera E, Hasbun R. The clinical significance of neutrophilic pleocytosis in cerebrospinal fluid in patients with viral central nervous system infections. Int J Infect Dis. 2017 Jun;59:77-81. doi: 10.1016/j.ijid.2017.04.010. Epub 2017 Apr 20. PMID: 28435023. [^10]: Hase R, Hosokawa N, Yaegashi M, Muranaka K. Bacterial [[Meningitis]] in the absence of cerebrospinal fluid pleocytosis: A case report and review of the literature. Can J Infect Dis Med Microbiol. 2014 Sep;25(5):249-51. doi: 10.1155/2014/568169. PMID: 25371685; PMCID: PMC4211346. [^11]: TODD RM. Tuberculous [[Meningitis]] in two brothers vaccinated with B.C.G. Arch Dis Child. 1955 Jun;30(151):260-3. doi: 10.1136/adc.30.151.260. PMID: 14388795; PMCID: PMC2011754. [^12]: Huy NT, Thao NT, Diep DT, Kikuchi M, Zamora J, Hirayama K. Cerebrospinal fluid lactate concentration to distinguish bacterial from aseptic [[Meningitis]]: a systemic review and meta-analysis. Crit Care. 2010;14(6):R240. doi: 10.1186/cc9395. Epub 2010 Dec 31. PMID: 21194480; PMCID: PMC3220013. [^13]: Giulieri S, Chapuis-Taillard C, Jaton K, Cometta A, Chuard C, Hugli O, Du Pasquier R, Bille J, Meylan P, Manuel O, Marchetti O. CSF lactate for accurate diagnosis of community-acquired bacterial [[Meningitis]]. Eur J Clin Microbiol Infect Dis. 2015 Oct;34(10):2049-55. doi: 10.1007/s10096-015-2450-6. Epub 2015 Aug 19. PMID: 26282789. [^14]: Xiao X, Zhang Y, Zhang L, Kang P, Ji N. The diagnostic value of cerebrospinal fluid lactate for post-neurosurgical bacterial [[Meningitis]]: a meta-analysis. BMC Infect Dis. 2016 Sep 13;16(1):483. doi: 10.1186/s12879-016-1818-2. PMID: 27618955; PMCID: PMC5020553. [^15]: Chong GM, Maertens JA, Lagrou K, Driessen GJ, Cornelissen JJ, Rijnders BJ. Diagnostic Performance of Galactomannan Antigen Testing in Cerebrospinal Fluid. J Clin Microbiol. 2016 Feb;54(2):428-31. doi: 10.1128/JCM.02913-15. Epub 2015 Dec 9. PMID: 26659218; PMCID: PMC4733214. [^16]: Mekinian A, Maisonobe L, Boukari L, Melenotte C, Terrier B, Ayrignac X, Schleinitz N, Sène D, Hamidou M, Konaté A, Guilpain P, Abisror N, Ghrenassia E, Lachenal F, Cevallos R, Roos-Weil R, Du LTH, Lhote F, Larroche C, Bergmann JF, Humbert S, Fraison JB, Piette JC, Guillevin L, Dhote R, Amoura Z, Haroche J, Fain O. Characteristics, outcome and treatments with cranial pachymeningitis: A multicenter French retrospective study of 60 patients. Medicine (Baltimore). 2018 Jul;97(30):e11413. doi: 10.1097/MD.0000000000011413. Erratum in: Medicine (Baltimore). 2018 Aug;97(33):e12063. doi: 10.1097/MD.0000000000012063. PMID: 30045263; PMCID: PMC6078725. [^17]: Wilson MR, Sample HA, Zorn KC, Arevalo S, Yu G, Neuhaus J, Federman S, Stryke D, Briggs B, Langelier C, Berger A, Douglas V, Josephson SA, Chow FC, Fulton BD, DeRisi JL, Gelfand JM, Naccache SN, Bender J, Dien Bard J, Murkey J, Carlson M, Vespa PM, Vijayan T, Allyn PR, Campeau S, Humphries RM, Klausner JD, Ganzon CD, Memar F, Ocampo NA, Zimmermann LL, Cohen SH, Polage CR, DeBiasi RL, Haller B, Dallas R, Maron G, Hayden R, Messacar K, Dominguez SR, Miller S, Chiu CY. Clinical Metagenomic Sequencing for Diagnosis of [[Meningitis]] and [[Encephalitis]]. N Engl J Med. 2019 Jun 13;380(24):2327-2340. doi: 10.1056/NEJMoa1803396. PMID: 31189036; PMCID: PMC6764751. [^18]: Davis C, Wheat LJ, Myint T, Boulware DR, Bahr NC. Efficacy of Cerebrospinal Fluid Beta-d-Glucan Diagnostic Testing for Fungal [[Meningitis]]: a Systematic Review. J Clin Microbiol. 2020 Mar 25;58(4):e02094-19. doi: 10.1128/JCM.02094-19. PMID: 31996446; PMCID: PMC7098769. [^19]: Nigrovic LE, Shah SS, Neuman MI. Correction of cerebrospinal fluid protein for the presence of red blood cells in children with a traumatic lumbar puncture. J Pediatr. 2011 Jul;159(1):158-9. doi: 10.1016/j.jpeds.2011.02.038. Epub 2011 Apr 14. PMID: 21492866. [^20]: Chu V, Carpenter DM, Winter K, Harriman K, Glaser C. Increased Risk of Late-onset [[Streptococcus]] pneumoniae [[Meningitis]] in Adults With Prior Head or Spine Surgeries. Clin Infect Dis. 2019 May 30;68(12):2120-2122. doi: 10.1093/cid/ciy974. PMID: 30452617. [^21]: Pomar, V., de Benito, N., Mauri, A. _et al._ Characteristics and outcome of spontaneous bacterial [[Meningitis]] in patients with diabetes mellitus. _BMC Infect Dis_ **20**, 292 (2020). https://doi.org/10.1186/s12879-020-05023-5 [^22]: Becerra JC, Sieber R, Martinetti G, Costa ST, Meylan P, Bernasconi E. Infection of the central nervous system caused by varicella zoster virus reactivation: a retrospective case series study. Int J Infect Dis. 2013 Jul;17(7):e529-34. doi: 10.1016/j.ijid.2013.01.031. Epub 2013 Apr 6. PMID: 23566589. [^23]: Asnis DS, Muana O, Kim DG, Garcia M, Rollin PE, Slavinski S. [[Lymphocytic Choriomeningitis Virus]] [[Meningitis]], New York, NY, USA, 2009. Emerg Infect Dis. 2010 Feb;16(2):328-30. doi: 10.3201/eid1602.091347. PMID: 20113573; PMCID: PMC2958026. [^24]: Thigpen MC, Whitney CG, Messonnier NE, Zell ER, Lynfield R, Hadler JL, Harrison LH, Farley MM, Reingold A, Bennett NM, Craig AS, Schaffner W, Thomas A, Lewis MM, Scallan E, Schuchat A; Emerging Infections Programs Network. Bacterial [[Meningitis]] in the United States, 1998-2007. N Engl J Med. 2011 May 26;364(21):2016-25. doi: 10.1056/NEJMoa1005384. PMID: 21612470. [^25]: Lorber B. Community-acquired [[Listeria]] monocytogenes [[Meningitis]] in adults. Clin Infect Dis. 2007 Mar 1;44(5):765-6. doi: 10.1086/511695. PMID: 17278080. [^26]: Domingo, P., Pomar, V., de Benito, N. _et al._ The spectrum of acute bacterial [[Meningitis]] in elderly patients. _BMC Infect Dis_ **13**, 108 (2013). https://doi.org/10.1186/1471-2334-13-108 [^27]: Bruschini L, Fortunato S, Tascini C, Ciabotti A, Leonildi A, Bini B, Giuliano S, Abbruzzese A, Berrettini S, Menichetti F; GISA (Italian Group for Antimicrobial Stewardship) [[Meningitis]] Study Group. Otogenic [[Meningitis]]: A Comparison of Diagnostic Performance of Surgery and Radiology. Open Forum Infect Dis. 2017 Apr 6;4(2):ofx069. doi: 10.1093/ofid/ofx069. PMID: 28534037; PMCID: PMC5434250. [^28]: Wertheim HF, Nghia HD, Taylor W, Schultsz C. [[Streptococcus]] suis: an emerging human pathogen. Clin Infect Dis. 2009 Mar 1;48(5):617-25. doi: 10.1086/596763. PMID: 19191650. [^29]: Mukaigawara M, Nakayama I, Gibo K. Strongyloidiasis and Culture-Negative Suppurative [[Meningitis]], Japan, 1993–2015. _Emerging Infectious Diseases_. 2018;24(12):2378-2380. doi:10.3201/eid2412.180375. [^30]: McCarthy M, Rosengart A, Schuetz AN, Kontoyiannis DP, Walsh TJ. Mold infections of the central nervous system. N Engl J Med. 2014 Jul 10;371(2):150-60. doi: 10.1056/NEJMra1216008. PMID: 25006721; PMCID: PMC4840461. [^31]: Centers for Disease Control and Prevention (CDC). Primary amebic meningoencephalitis--Arizona, Florida, and Texas, 2007. MMWR Morb Mortal Wkly Rep. 2008 May 30;57(21):573-7. PMID: 18509301. [^32]: Alissa J. Wright, Jay A. Fishman, Central Nervous System Syndromes in Solid Organ Transplant Recipients, _Clinical Infectious Diseases_, Volume 59, Issue 7, 1 October 2014, Pages 1001–1011, [https://doi.org/10.1093/cid/ciu428](https://doi.org/10.1093/cid/ciu428) [^33]: van de Beek D, Drake JM, Tunkel AR. Nosocomial bacterial [[Meningitis]]. N Engl J Med. 2010 Jan 14;362(2):146-54. doi: 10.1056/NEJMra0804573. PMID: 20071704. [^34]: - Aguilar, Javier MD; Urday-Cornejo, Varinia MD; Donabedian, Susan MPH; Perri, Mary MT; Tibbetts, Robert PhD; Zervos, Marcus MD. [[Staphylococcus]] aureus [[Meningitis]]: Case Series and Literature Review. Medicine 89(2):p 117-125, March 2010. | DOI: 10.1097/MD.0b013e3181d5453d [^35]: Wilson M, Martin R, Walk ST, Young C, Grossman S, McKean EL, Aronoff DM. Clinical and laboratory features of [[Streptococcus]] salivarius [[Meningitis]]: a case report and literature review. Clin Med Res. 2012 Feb;10(1):15-25. doi: 10.3121/cmr.2011.1001. Epub 2011 Aug 4. PMID: 21817122; PMCID: PMC3280456. [^36]: Centers for Disease Control and Prevention (CDC). Bacterial [[Meningitis]] after intrapartum spinal anesthesia - New York and Ohio, 2008-2009. MMWR Morb Mortal Wkly Rep. 2010 Jan 29;59(3):65-9. PMID: 20110933. [^37]: Amanda Noska, Ramona Kyrillos, Glen Hansen, Diane Hirigoyen, David N. Williams, The Role of Antiviral Therapy in Immunocompromised Patients With [[Herpes]] Simplex Virus [[Meningitis]], _Clinical Infectious Diseases_, Volume 60, Issue 2, 15 January 2015, Pages 237–242, [https://doi.org/10.1093/cid/ciu772](https://doi.org/10.1093/cid/ciu772) [^38]: Ricard JD, Wolff M, Lacherade JC, Mourvillier B, Hidri N, Barnaud G, Chevrel G, Bouadma L, Dreyfuss D. 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 Jan 15;44(2):250-5. doi: 10.1086/510390. Epub 2006 Dec 15. PMID: 17173226. [^39]: Scarborough M, Gordon SB, Whitty CJ, French N, Njalale Y, Chitani A, Peto TE, Lalloo DG, Zijlstra EE. Corticosteroids for bacterial [[Meningitis]] in adults in sub-Saharan Africa. N Engl J Med. 2007 Dec 13;357(24):2441-50. doi: 10.1056/NEJMoa065711. PMID: 18077809; PMCID: PMC5068549. [^40]: Nguyen TH, Tran TH, Thwaites G, Ly VC, Dinh XS, Ho Dang TN, Dang QT, Nguyen DP, Nguyen HP, To SD, Nguyen vV, Nguyen MD, Campbell J, Schultsz C, Parry C, Torok ME, White N, Nguyen TC, Tran TH, Stepniewska K, Farrar JJ. Dexamethasone in Vietnamese adolescents and adults with bacterial [[Meningitis]]. N Engl J Med. 2007 Dec 13;357(24):2431-40. doi: 10.1056/NEJMoa070852. PMID: 18077808. [^41]: Brouwer MC, McIntyre P, Prasad K, van de Beek D. Corticosteroids for acute bacterial [[Meningitis]]. Cochrane Database Syst Rev. 2013 Jun 4;(6):CD004405. doi: 10.1002/14651858.CD004405.pub4. Update in: Cochrane Database Syst Rev. 2015 Sep 12;(9):CD004405. doi: 10.1002/14651858.CD004405.pub5. PMID: 23733364. [^42]: Rayanakorn A, Ser HL, Pusparajah P, Chan KG, Goh BH, Khan TM, Saokaew S, Lee SWH, Lee LH. Comparative efficacy of antibiotic(s) alone or in combination of corticosteroids in adults with acute bacterial [[Meningitis]]: A systematic review and network meta-analysis. PLoS One. 2020 May 29;15(5):e0232947. doi: 10.1371/journal.pone.0232947. PMID: 32469959; PMCID: PMC7259733.(PubMed) [^43]: Peltola H, Roine I, Fernández J, Zavala I, Ayala SG, Mata AG, Arbo A, Bologna R, Miño G, Goyo J, López E, de Andrade SD, Sarna S. 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 Nov 15;45(10):1277-86. doi: 10.1086/522534. Epub 2007 Oct 15. PMID: 17968821. [^44]: Heckenberg SG, Brouwer MC, van der Ende A, van de Beek D. Adjunctive dexamethasone in adults with meningococcal [[Meningitis]]. Neurology. 2012 Oct 9;79(15):1563-9. doi: 10.1212/WNL.0b013e31826e2684. Epub 2012 Sep 12. PMID: 22972648. [^45]: Koopmans MM, Brouwer MC, Bijlsma MW, Bovenkerk S, Keijzers W, van der Ende A, van de Beek D. [[Listeria]] monocytogenes sequence type 6 and increased rate of unfavorable outcome in [[Meningitis]]: epidemiologic cohort study. Clin Infect Dis. 2013 Jul;57(2):247-53. doi: 10.1093/cid/cit250. Epub 2013 Apr 16. PMID: 23592828. [^46]: Charlier C, Perrodeau É, Leclercq A, Cazenave B, Pilmis B, Henry B, Lopes A, Maury MM, Moura A, Goffinet F, Dieye HB, Thouvenot P, Ungeheuer MN, Tourdjman M, Goulet V, de Valk H, Lortholary O, Ravaud P, Lecuit M; MONALISA study group. Clinical features and prognostic factors of listeriosis: the MONALISA national prospective cohort study. Lancet Infect Dis. 2017 May;17(5):510-519. doi: 10.1016/S1473-3099(16)30521-7. Epub 2017 Jan 28. Erratum in: Lancet Infect Dis. 2017 Sep;17(9):897. doi: 10.1016/S1473-3099(17)30440-1. PMID: 28139432. [^47]: Mourvillier B, Tubach F, van de Beek D, Garot D, Pichon N, Georges H, Lefevre LM, Bollaert PE, Boulain T, Luis D, Cariou A, Girardie P, Chelha R, Megarbane B, Delahaye A, Chalumeau-Lemoine L, Legriel S, Beuret P, Brivet F, Bruel C, Camou F, Chatellier D, Chillet P, Clair B, Constantin JM, Duguet A, Galliot R, Bayle F, Hyvernat H, Ouchenir K, Plantefeve G, Quenot JP, Richecoeur J, Schwebel C, Sirodot M, Esposito-Farèse M, Le Tulzo Y, Wolff M. Induced hypothermia in severe bacterial [[Meningitis]]: a randomized clinical trial. JAMA. 2013 Nov 27;310(20):2174-83. doi: 10.1001/jama.2013.280506. PMID: 24105303. [^48]: Peltola H, Roine I, Fernández J, Zavala I, Ayala SG, Mata AG, Arbo A, Bologna R, Miño G, Goyo J, López E, de Andrade SD, Sarna S. 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 Nov 15;45(10):1277-86. doi: 10.1086/522534. Epub 2007 Oct 15. PMID: 17968821. [^49]: Peltola H, Roine I, Fernández J, González Mata A, Zavala I, Gonzalez Ayala S, Arbo A, Bologna R, Goyo J, López E, Miño G, Dourado de Andrade S, Sarna S, Jauhiainen T. Hearing impairment in childhood bacterial [[Meningitis]] is little relieved by dexamethasone or glycerol. Pediatrics. 2010 Jan;125(1):e1-8. doi: 10.1542/peds.2009-0395. Epub 2009 Dec 14. PMID: 20008417. [^50]: Wall EC, Ajdukiewicz KM, Heyderman RS, Garner P. Osmotic therapies added to antibiotics for acute bacterial [[Meningitis]]. Cochrane Database Syst Rev. 2013 Mar 28;3(3):CD008806. doi: 10.1002/14651858.CD008806.pub2. Update in: Cochrane Database Syst Rev. 2018 Feb 06;2:CD008806. doi: 10.1002/14651858.CD008806.pub3. PMID: 23543568; PMCID: PMC3996551. [^51]: Zarrouk V, Vassor I, Bert F, Bouccara D, Kalamarides M, Bendersky N, Redondo A, Sterkers O, Fantin B. Evaluation of the management of postoperative aseptic [[Meningitis]]. Clin Infect Dis. 2007 Jun 15;44(12):1555-9. doi: 10.1086/518169. Epub 2007 May 2. PMID: 17516398. [^52]: Tängdén T, Enblad P, Ullberg M, Sjölin J. Neurosurgical gram-negative bacillary ventriculitis and [[Meningitis]]: a retrospective study evaluating the efficacy of intraventricular [[gentamicin]] therapy in 31 consecutive cases. Clin Infect Dis. 2011 Jun;52(11):1310-6. doi: 10.1093/cid/cir197. Epub 2011 May 2. PMID: 21540208. [^53]: van de Beek D, Drake JM, Tunkel AR. Nosocomial bacterial [[Meningitis]]. N Engl J Med. 2010 Jan 14;362(2):146-54. doi: 10.1056/NEJMra0804573. PMID: 20071704. [^54]: Liora ter Horst, Matthijs C Brouwer, Arie van der Ende, Diederik van de Beek, Community-acquired Bacterial [[Meningitis]] in Adults With Cerebrospinal Fluid Leakage, _Clinical Infectious Diseases_, Volume 70, Issue 11, 1 June 2020, Pages 2256–2261, [https://doi.org/10.1093/cid/ciz649](https://doi.org/10.1093/cid/ciz649) [^55]: Adriani KS, van de Beek D, Brouwer MC, Spanjaard L, de Gans J. Community-acquired recurrent bacterial [[Meningitis]] in adults. Clin Infect Dis. 2007 Sep 1;45(5):e46-51. doi: 10.1086/520682. Epub 2007 Jul 23. PMID: 17682979. [^56]: Tsiakalos A, Xynos ID, Sipsas NV, Kaltsas G. Pituitary insufficiency after infectious [[Meningitis]]: a prospective study. J Clin Endocrinol Metab. 2010 Jul;95(7):3277-81. doi: 10.1210/jc.2010-0144. Epub 2010 Apr 28. PMID: 20427491. [^57]: Paciorek M, Bednarska A, Krogulec D, Makowiecki M, Kowalska JD, Bursa D, Świderska A, Puła J, Raczyńska J, Skrzat-Klapaczyńska A, Zielenkiewicz M, Radkowski M, Laskus T, Horban A. Chronic alcohol abuse affects the clinical course and outcome of community-acquired bacterial [[Meningitis]]. Eur J Clin Microbiol Infect Dis. 2019 Nov;38(11):2171-2176. doi: 10.1007/s10096-019-03661-5. Epub 2019 Aug 7. PMID: 31392446; PMCID: PMC6800865. [^58]: Worsøe L, Cayé-Thomasen P, Brandt CT, Thomsen J, Østergaard C. Factors associated with the occurrence of hearing loss after pneumococcal [[Meningitis]]. Clin Infect Dis. 2010 Oct 15;51(8):917-24. doi: 10.1086/656409. PMID: 20815735. [^59]: Mook-Kanamori BB, Fritz D, Brouwer MC, van der Ende A, van de Beek D. Intracerebral hemorrhages in adults with community associated bacterial [[Meningitis]] in adults: should we reconsider anticoagulant therapy? PLoS One. 2012;7(9):e45271. doi: 10.1371/journal.pone.0045271. Epub 2012 Sep 13. PMID: 23028898; PMCID: PMC3441739.