Table 6.

Laboratory Diagnosis of Meningitis

Etiologic Agents	Diagnostic Procedures	Optimum Specimens	Transport Issues and Optimal Transport Time
Bacterial
Streptococcus pneumoniae  Neisseria meningitidis  Listeria monocytogenes  Streptococcus agalactiae  Haemophilus influenzae  Escherichia coli  Other Enterobacteriaceae  Elizabethkingia meningoseptica  Citrobacter diversus	Gram staina Aerobic bacterial cultureBlood cultures	CSFBlood, 2–4 sets	Sterile container, RT, immediatelyBlood culture bottles, RT, 2 h
Mycobacterium tuberculosis	AFB smear AFB culture	CSF (≥5 mL)	Sterile container, RT, 2 h
	Mycobacterium tuberculosis NAATb	CSF	Sterile container, RT, 2 h
Spirochetal
Treponema pallidum (syphilis)	VDRL, FTA-ABS	CSF	Sterile container, RT, 2 h
	Traditional: RPR screening test with positive RPR confirmed by TPPA test or other treponemal confirmatory test Reverse sequence: EIA or chemiluminescent immunoassay treponemal screening test with positive confirmed by RPR (negative RPR reflexed to TPPA)	Serum	Clot tube, RT, 2 h
Borrelia burgdorferi (Lyme disease)	B. burgdorferi antibodies, IgM and IgG with Western blot assay confirmationc	Serum	Clot tube, RT, 2 h
		CSF	Closed container, RT, 2 h
	B. burgdorferi NAAT (low sensitivity)	CSF	Sterile container, RT, 2 h
Leptospira spp	Leptospira NAATd	Blood	EDTA or sodium citrate tube, RT, 2 h
		CSF, urine	Sterile container, RT, 2 h
	Leptospira culture (special media required; rarely available in routine laboratories)	First week of illness: CSF, 10 mL blood	Sterile container, heparin or citrate tube, RT, immediately
		After first week of illness: 10 mL urine (neutralized)	Sterile container, RT, immediately
	Leptospira antibody, microscopic agglutination test	Serum	Clot tube, RT, 2 h
Fungal
Cryptococcus neoformans	Cryptococcus antigen test	CSF	Closed container, RT, 2 h
Cryptococcus gattii	Gram stain Aerobic bacterial culture (faster growth on blood agar medium) Fungal culture	CSF	Sterile container, RT, 2 h
Coccidioides spp	Coccidioides antibody, complement fixation, and immunodiffusioneCalcofluor stain and Fungal culture	CSFSerumCSF	Closed container, RT, 2 hClot tube, RT, 2 hSterile container, RT, 2 h
Parasitic
Acanthamoeba spp  Naegleria fowleri	See Table 7
Viral
Enteroviruses (nonpolio)	Enterovirus NAAT	CSF	Sterile container, RT, 2 h
Parechoviruses	Parechovirus NAAT	CSF	Sterile container, RT, 2 h
Herpes simplex virus	HSV-1 and HSV-2 NAAT	CSF	Sterile container, RT, 2 h
Varicella zoster virus	VZV NAAT	CSF	Sterile container, RT, 2 h
LCM virus	LCM antibodies, IgM and IgG, IFA	CSF	Closed container, RT, 2 h
		Serum	Clot tube, RT, 2 h
Mumps virus	Mumps virus antibodies, IgM and IgG	Serum	Clot tube, RT, 2 h
		CSF	Closed container, RT, 2 h
	Mumps culture and NAAT	CSF	Sterile container, on ice, immediately
		Buccal or oral swabf	Viral transport device, on ice, immediately
HIV	g

Abbreviations: AFB, acid-fast bacilli; CSF, cerebrospinal fluid; EDTA, ethylenediaminetetraacetic acid; EIA, enzyme immunoassay; FTA-ABS, fluorescent treponemal antibody–absorbed; HIV, human immunodeficiency virus; HSV, herpes simplex virus; IFA, indirect fluorescent antibody; IgG, immunoglobulin G; IgM, immunoglobulin M; LCM, lymphocytic choriomeningitis virus; NAAT, nucleic acid amplification test; RPR, rapid plasma reagin; RT, room temperature; TPPA, Treponema pallidum particle agglutination assay; VDRL, Venereal Disease Research Laboratory; VZV, varicella zoster virus.

^aGram stains may be performed on uncentrifuged specimens when the CSF is visibly turbid.

^bA negative result does not rule out Mycobacterium tuberculosis.

^cInclude a CSF index: simultaneous CSF:serum ratio of Borrelia burgdorferi antibodies with normalized protein amounts.

^dThe Centers for Disease Control and Prevention accepts specimens referred by state or local public health laboratories (https://www.cdc.gov/laboratory/specimen-submission/index.html).

^eComplement fixation on CSF is optimal test; serum complement fixation antibody may reflect a remote rather than an active infection.

^fSpecimen collection instructions available at https://www.cdc.gov/mumps/lab/specimen-collect.html.

^gThe diagnosis of acute meningitis due to HIV, a condition that often arises during the early stages of the HIV retroviral syndrome, is best established based on compatible CSF findings (ie, a mild CSF lymphocytosis with a mildly elevated CSF protein level and normal glucose) combined with definitive evidence of recent HIV infection (see Section XIV, HIV diagnosis).