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How Do I Perform a Lumbar Puncture and Analyze the Results to ...

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DIAGNOSING BACTERIAL MENINGITIS BY LUMBAR PUNCTURE<br />

blood cells. 2 He also states that a single<br />

polymorphonuclear cell in <strong>the</strong> CSF with<br />

a white blood cell count of less than 5<br />

µL is considered normal. Steele <strong>and</strong> colleagues<br />

suggest rapid analysis of CSF<br />

<strong>and</strong> noted that neutrophil counts can<br />

decrease by 50% within 2 hours of<br />

collection. 59<br />

We found 3 studies that met <strong>the</strong> inclusion<br />

criteria <strong>and</strong> that described <strong>the</strong><br />

accuracy of CSF Gram stain for diagnosing<br />

bacterial meningitis. 53-55 None<br />

of <strong>the</strong>se studies appeared <strong>to</strong> be prospective.<br />

All studies reported sensitivity<br />

of Gram stain <strong>and</strong> 1 study reported<br />

specificity of this test 53 (TABLE 3). If bacteria<br />

are seen on Gram stain, it helps<br />

diagnose bacterial meningitis but if this<br />

test is negative, bacterial meningitis cannot<br />

be ruled out.<br />

We identified 4 studies that met <strong>the</strong><br />

inclusion criteria <strong>and</strong> that reported on<br />

<strong>the</strong> accuracy of biochemical analysis of<br />

CSF in patients with suspected central<br />

nervous system infection 55-58 (Table 2<br />

<strong>and</strong> TABLE 4). Only 1 study of CSF<br />

white blood cell counts met our strict<br />

inclusion criteria. A CSF white blood<br />

cell count of 500/µL or higher increases<br />

<strong>the</strong> likelihood of meningitis (LR,<br />

15; 95% CI, 10-22), whereas a count<br />

less than 500/µL lowers <strong>the</strong> likelihood<br />

(LR, 0.3; 95% CI, 0.2-0.4). 56<br />

A CSF–blood glucose ratio of 0.4 or<br />

less was accurate for diagnosing bacterial<br />

meningitis (LR, 18; 95% CI, 12-<br />

27), whereas a normal CSF–blood glucose<br />

ratio made this diagnosis less likely<br />

(LR, 0.31; 95% CI, 0.21-0.45). 56,57 A<br />

CSF lactate level of 31.53 mg/dL or<br />

more (3.5 mmol/L) was accurate for<br />

diagnosing bacterial meningitis (LR, 21;<br />

95% CI, 14-32 55-57 ; Table 4), whereas<br />

a CSF lactate level of less than 31.53<br />

mg/dL (3.5 mmol/L) makes <strong>the</strong> diagnosis<br />

of bacterial meningitis less likely<br />

(LR, 0.12; 95% CI, 0.07-0.23).<br />

Prediction Models<br />

Spanos <strong>and</strong> colleagues 60 developed a<br />

prediction rule for diagnosing bacterial<br />

meningitis. This rule (TABLE 5) was<br />

derived from a retrospective chart review<br />

of patients with a final diagnosis<br />

of acute meningitis. The sample was divided<br />

in<strong>to</strong> a derivation <strong>and</strong> validation<br />

set, but data from a large number of<br />

charts (94/214) in <strong>the</strong> derivation set had<br />

missing data <strong>and</strong> were excluded from<br />

<strong>the</strong> analysis. And, <strong>the</strong> technique used<br />

for CSF cell count changed during <strong>the</strong><br />

study period, which could influence <strong>the</strong><br />

results of this study. The accuracy as<br />

measured by <strong>the</strong> area under <strong>the</strong> receiver<br />

operating curve (AUC) was 0.97<br />

for <strong>the</strong> validation set.<br />

Hoen <strong>and</strong> colleagues 61 attempted <strong>to</strong><br />

validate <strong>the</strong> above rule in a retrospective<br />

review <strong>and</strong> used <strong>the</strong> same data <strong>to</strong><br />

generate <strong>the</strong>ir own decision rule<br />

(Table 5) that included 4 different clinical<br />

variables. In <strong>the</strong>ir validation of <strong>the</strong><br />

work by Spanos <strong>and</strong> colleagues, <strong>the</strong> AUC<br />

was 0.98 while that for <strong>the</strong>ir derived<br />

equation was 0.99. In ano<strong>the</strong>r retrospective<br />

review of patients with meningitis,<br />

Leblebicioglu <strong>and</strong> colleagues 62 assessed<br />

<strong>the</strong> rules by Hoen <strong>and</strong> Spanos <strong>and</strong> <strong>the</strong><br />

AUC was 0.99 <strong>and</strong> 0.95, respectively.<br />

McKinney <strong>and</strong> colleagues 63 obtained<br />

similar results in <strong>the</strong>ir retrospective<br />

review.<br />

In <strong>the</strong> only prospective validation<br />

that we were able <strong>to</strong> identify, Baty <strong>and</strong><br />

colleagues 64 assessed Hoen’s rule in a<br />

sample of 109 patients aged 1 <strong>to</strong> 85<br />

years with acute community-acquired<br />

meningitis. Data are only available in<br />

patients with bacterial <strong>and</strong> viral meningitis,<br />

<strong>and</strong> thus <strong>the</strong> specificity of <strong>the</strong><br />

model cannot be calculated. The sensitivity<br />

of <strong>the</strong>ir computed model was<br />

80% for <strong>the</strong> diagnosis of bacterial meningitis.<br />

For this decision rule <strong>to</strong> be recommended<br />

in clinical practice, it needs<br />

<strong>to</strong> be validated prospectively in larger<br />

populations with broader disease<br />

spectrum. 65<br />

Brivet <strong>and</strong> colleagues 66 completed a<br />

retrospective study <strong>and</strong> found that <strong>the</strong><br />

presence of at least 1 sign of severity of<br />

disease at <strong>the</strong> time referral <strong>and</strong> a CSF<br />

neutrophil count of more than 1000/µL<br />

Table 2. Studies Assessing Cerebrospinal Fluid Analysis in Patients With Suspected Central<br />

Nervous System Infection<br />

Source Study Design Sample Size Age Reference St<strong>and</strong>ard<br />

Dunbar et al, 53<br />

1998<br />

Wasilauskas <strong>and</strong><br />

Hamp<strong>to</strong>n, 54<br />

1982<br />

Lannigan et al, 55<br />

1980<br />

Lindquist et al, 56<br />

1988<br />

Briem, 57 1983<br />

Retrospective<br />

Retrospective<br />

Cohort<br />

(not clear if<br />

prospective)<br />

Prospective<br />

cohort<br />

Cohort<br />

(not clear if<br />

prospective)<br />

2635 CSF<br />

samples<br />

80 CSF<br />

samples<br />

Adults<br />

Adults<br />

Positive CSF culture<br />

Positive CSF culture<br />

or bacterial antigen<br />

434 16-86 y Positive CSF culture<br />

710 2 mobut<br />

majority adults<br />

Positive CSF culture<br />

or bacterial antigen<br />

266 90% 15 y or older Positive CSF culture<br />

or bacterial antigen<br />

Komorowski Retrospective 562 Adults Positive CSF culture<br />

et al, 58 1986<br />

Abbreviation: CSF, cerebrospinal fluid.<br />

Table 3. Accuracy of Cerebrospinal Gram Stain in Patients With Suspected Bacterial<br />

Meningitis*<br />

Study<br />

Sensitivity, %<br />

(95% CI)<br />

Specificity, %<br />

(95% CI)<br />

Likelihood<br />

Ratio for<br />

Positive Test<br />

(95% CI)<br />

Likelihood<br />

Ratio for<br />

Negative Test<br />

(95% CI)<br />

Dunbar et al, 53 1998 86 (74-92.6) 100 (lower 95 737 (230-2295) 0.14 (0.08-0.27)<br />

confidence<br />

limit 99.7)<br />

Wasilauskas <strong>and</strong> 60 (47-71) . . . . . . . . .<br />

Hamp<strong>to</strong>n, 54 1982<br />

Lannigan et al, 55 1980 56 (34-75) . . . . . . . . .<br />

Abbreviation: CI, confidence interval.<br />

*Ellipses indicate that data are not available.<br />

©2006 American Medical Association. All rights reserved. (Reprinted) JAMA, Oc<strong>to</strong>ber 25, 2006—Vol 296, No. 16 2017<br />

<strong>Do</strong>wnloaded from www.jama.com at University of Alabama-Birmingham, on November 8, 2006

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