Point-of-Care Guides

Predicting the Likelihood of Bacterial Meningitis in Children



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Am Fam Physician. 2007 Feb 15;75(4):533-535.

Clinical Question

Is it possible to predict the likelihood of bacterial meningitis in children with suspected meningitis?

Evidence Summary

Although the incidence of bacterial meningitis has dropped with increased immunization against Haemophilus influenzae, meningitis remains a devastating illness. For every child with meningeal signs and symptoms who is diagnosed with bacterial meningitis after lumbar puncture, many more undergo the procedure to rule out the disease. Therefore, researchers have attempted to identify predictors of bacterial meningitis to allow physicians to estimate risk and avoid unnecessary testing while correctly identifying children who need urgent intravenous antibiotics.

Clinical decision rules for diagnosing bacterial meningitis in children vary in several ways (Table 1).110 Some include complex multivariate models that require the use of a computer and do not allow the physician to easily see why a particular prediction is made. Others use a simple scoring system that assigns points to certain signs and symptoms and are easier to use at the point of care. Some rules require cerebrospinal fluid (CSF) findings, making them unsuitable for determining whether lumbar puncture should be performed. In addition, the rules have been prospectively validated to differing degrees.

TABLE 1

Summary of Studies Used to Develop and Validate Clinical Decision Rules for the Diagnosis of Bacterial Meningitis in Children

Study Age group studied Prospectively validated Clinical decision rule CSF findings required

Lindquist, et al., 19881

Children and adults

No

Multivariate model

Yes

Spanos, et al., 19892

Children and adults

No

Multivariate model

Yes

Hoen, et al., 19953

3.5 years or younger

Yes

Multivariate model

Yes

Jaeger, et al., 20004

Freedman, et al., 20015

2 months to 17 years

Yes

Point score

Yes

Nigrovic, et al., 20026

1 month to 19 years

Yes

Point score

Yes

Oostenbrink, et al., 20027

1 month to 15 years

Yes

Point score

No (includes follow-up score that requires CSF findings)

Oostenbrink, et al., 20048

Bonsu, et al., 20049

1 month to 18 years

Yes

Multivariate model

Yes

Nigrovic, et al., 200710

1 month to 19 years

Yes

Point score

Yes


CSF = cerebrospinal fluid.

Information from references 1 through 10.

TABLE 1   Summary of Studies Used to Develop and Validate Clinical Decision Rules for the Diagnosis of Bacterial Meningitis in Children

View Table

TABLE 1

Summary of Studies Used to Develop and Validate Clinical Decision Rules for the Diagnosis of Bacterial Meningitis in Children

Study Age group studied Prospectively validated Clinical decision rule CSF findings required

Lindquist, et al., 19881

Children and adults

No

Multivariate model

Yes

Spanos, et al., 19892

Children and adults

No

Multivariate model

Yes

Hoen, et al., 19953

3.5 years or younger

Yes

Multivariate model

Yes

Jaeger, et al., 20004

Freedman, et al., 20015

2 months to 17 years

Yes

Point score

Yes

Nigrovic, et al., 20026

1 month to 19 years

Yes

Point score

Yes

Oostenbrink, et al., 20027

1 month to 15 years

Yes

Point score

No (includes follow-up score that requires CSF findings)

Oostenbrink, et al., 20048

Bonsu, et al., 20049

1 month to 18 years

Yes

Multivariate model

Yes

Nigrovic, et al., 200710

1 month to 19 years

Yes

Point score

Yes


CSF = cerebrospinal fluid.

Information from references 1 through 10.

The Oostenbrink rule (Table 211) is potentially the most useful for physicians because it is simple and can guide decisions about performing a lumbar puncture and about treating patients empirically with antibiotics.7,8 When originally developed, the rule stated that patients with a score of 9.5 or more should have a lumbar puncture.7 A prospective validation study in four Dutch hospitals applied the rule to 226 children.8 The study showed that two out of 25 children with bacterial meningitis had a score less than 9.5; the diagnosis would have been missed in these patients. One of the two children had meningeal signs and two protracted seizures, whereas the other was a 34-day-old premature infant who probably did not meet the minimum age cutoff of one month.8 The authors then used a lower cutoff of 8.5 points and applied it to the original study population (360 children) and the validation study population (226 children). None of the 205 children (95% CI, 0 to 2) with a score less than 8.5 points had bacterial meningitis; 13 percent (95% CI, 9 to 17) with a score of 8.5 to 14.9 had the disease; 52 percent (95% CI, 39 to 65) with a score of 15.0 to 19.9 had the disease; and 87 percent (95% CI, 79 to 95) with a score of 20.0 or more had the disease.8

TABLE 2

Oostenbrink Clinical Decision Rule for Predicting Bacterial Meningitis Risk in Children with Meningeal Signs

Risk factor Points

Duration of main problem in patient history

1.0 per day (maximum 10)

History of vomiting

2.0

Physical examination findings:

Cyanosis

6.5

Disturbed consciousness

8.0

Meningeal irritation*

7.5

Petechiae

4.0

Serum C-reactive protein level, mg per dL (mg per L)

< 5.0 (50)

0

5.0 to 9.9 (50 to 99)

0.5

10.0 to 14.9 (100 to 149)

1.0

15.0 to 19.9 (150 to 199)

1.5

≥ 20.0 (200)

2.0

Total:

__________


note: Rule applies to children one month to 15 years of age. Children with a score of 8.5 or more should receive a lumbar puncture; see Table 3 for interpreting cerebrospinal fluid findings.

*— Brudzinski's sign (passive flexion of the neck toward the chest causes flexion of the knees and hips); Kernig's sign (extension of the lower leg is limited by pain when the thigh is flexed at a 90 degree angle to the trunk); tripod position (legs flexed and arms out-stretched at the elbow) while sitting; or neck stiffness. Irritability during movement of the head or legs or a bulging fontanel also may be signs in children younger than one year.

Adapted with permission from Oostenbrink R, Moons KG, Donders AR, Grobbee DE, Moll HA. Prediction of bacterial meningitis in children with meningeal signs: reduction of lumbar punctures. Acta Paediatr 2001;90:613.

TABLE 2   Oostenbrink Clinical Decision Rule for Predicting Bacterial Meningitis Risk in Children with Meningeal Signs

View Table

TABLE 2

Oostenbrink Clinical Decision Rule for Predicting Bacterial Meningitis Risk in Children with Meningeal Signs

Risk factor Points

Duration of main problem in patient history

1.0 per day (maximum 10)

History of vomiting

2.0

Physical examination findings:

Cyanosis

6.5

Disturbed consciousness

8.0

Meningeal irritation*

7.5

Petechiae

4.0

Serum C-reactive protein level, mg per dL (mg per L)

< 5.0 (50)

0

5.0 to 9.9 (50 to 99)

0.5

10.0 to 14.9 (100 to 149)

1.0

15.0 to 19.9 (150 to 199)

1.5

≥ 20.0 (200)

2.0

Total:

__________


note: Rule applies to children one month to 15 years of age. Children with a score of 8.5 or more should receive a lumbar puncture; see Table 3 for interpreting cerebrospinal fluid findings.

*— Brudzinski's sign (passive flexion of the neck toward the chest causes flexion of the knees and hips); Kernig's sign (extension of the lower leg is limited by pain when the thigh is flexed at a 90 degree angle to the trunk); tripod position (legs flexed and arms out-stretched at the elbow) while sitting; or neck stiffness. Irritability during movement of the head or legs or a bulging fontanel also may be signs in children younger than one year.

Adapted with permission from Oostenbrink R, Moons KG, Donders AR, Grobbee DE, Moll HA. Prediction of bacterial meningitis in children with meningeal signs: reduction of lumbar punctures. Acta Paediatr 2001;90:613.

A recent study attempted to validate five clinical decision rules3,57,9 using a retrospective database.12 The study showed that the Nigrovic,6 Freedman,5 and Bonsu9 rules had 100 percent sensitivity for detecting children with bacterial meningitis, although the Freedman rule5 was only 12 percent specific.12 The authors conclude that the Nigrovic rule6  (Table 36,10,12) is preferred because it is easy to use and has a good specificity of 66 percent. Two out of 12 children with a score less than 8.5 using the Oostenbrink rule had bacterial meningitis.12 However, retrospective chart reviews, such as the Oostenbrink rule, typically underestimate the accuracy of clinical decision rules because consistent documentation of symptoms in medical records is unreliable.

TABLE 3

Nigrovic Clinical Decision Rule for Predicting Bacterial Meningitis in Children Using CSF Findings

Risk factor

Positive CSF Gram stain

CSF protein level ≥ 80 mg per dL (800 mg per L)

Peripheral absolute neutrophil count ≥ 10,000 cells per mm3 (10 × 109 per L)

Seizure at or before presentation

CSF absolute neutrophil count ≥ 1,000 cells per mm3 (1 × 109 per L)

Cases of bacterial meningitis/total patients (%)


Number of risk factors Nigrovic, et al., 20026 Dubos, et al., 200612 Nigrovic, et al., 200710

0

0/144 (0)

0/86 (0)

2/1,714 (0.1)

1 or more

38/90 (42)

20/65 (31)

119/1,189 (10)


CSF = cerebrospinal fluid.

Adapted with permission from Nigrovic LE, Kuppermann N, Malley R. Development and validation of a multivariable predictive model to distinguish bacterial from aseptic meningitis in children in the post–Haemophilus influenzae era. Pediatrics 2002;110:715, with additional information from references 10 and 12.

TABLE 3   Nigrovic Clinical Decision Rule for Predicting Bacterial Meningitis in Children Using CSF Findings

View Table

TABLE 3

Nigrovic Clinical Decision Rule for Predicting Bacterial Meningitis in Children Using CSF Findings

Risk factor

Positive CSF Gram stain

CSF protein level ≥ 80 mg per dL (800 mg per L)

Peripheral absolute neutrophil count ≥ 10,000 cells per mm3 (10 × 109 per L)

Seizure at or before presentation

CSF absolute neutrophil count ≥ 1,000 cells per mm3 (1 × 109 per L)

Cases of bacterial meningitis/total patients (%)


Number of risk factors Nigrovic, et al., 20026 Dubos, et al., 200612 Nigrovic, et al., 200710

0

0/144 (0)

0/86 (0)

2/1,714 (0.1)

1 or more

38/90 (42)

20/65 (31)

119/1,189 (10)


CSF = cerebrospinal fluid.

Adapted with permission from Nigrovic LE, Kuppermann N, Malley R. Development and validation of a multivariable predictive model to distinguish bacterial from aseptic meningitis in children in the post–Haemophilus influenzae era. Pediatrics 2002;110:715, with additional information from references 10 and 12.

The Nigrovic and Oostenbrink rules provide the best balance between prospective validation and ease of use. These rules should not be applied strictly. For example, seizure is relatively rare and does not meet statistical criteria for inclusion in the Oostenbrink rule; nevertheless, any child with suspected meningitis and seizure should undergo lumbar puncture. All children with suspected meningitis should have close follow-up, whether or not they have received lumbar puncture or empiric treatment.

Applying the Evidence

A four-year-old boy with signs of meningeal irritation has been sick for two days. He has vomited twice but does not have cyanosis, disturbed consciousness, or petechiae. His serum C-reactive protein level is 1.0 mg per dL (10 mg per L). Should he undergo lumbar puncture? If so, how should the results be interpreted?

Answer: Using the Oostenbrink rule (Table 211), the patient receives 11.5 points (2 points for duration of illness, 2 for vomiting, and 7.5 for meningeal irritation) and, therefore, should undergo lumbar puncture. The lumbar puncture findings include a negative CSF Gram stain, a CSF protein level of 60 mg per dL (600 mg per L; normal range: 10 to 40 mg per dL [100 to 400 mg per L]), a peripheral absolute neutrophil count of 6,500 cells per mm3 (6.5 × 109 per L; normal range: 4,000 to 10,000 cells per mm3 [4 to 10 × 109 per L]), and a CSF absolute neutrophil count of 1,400 cells per mm3 (1.4 ×109 per L; normal range: 0 to 5 cells per mm3 [0 to 0.005 × 109 per L]). Therefore, the patient has a significant risk of bacterial meningitis based on the Nigrovic validation studies (Table 36,10,12) and should receive empiric treatment while awaiting culture results.

Address correspondence to Mark H. Ebell, M.D., M.S., at ebell@msu.edu. Reprints are not available from the author.

REFERENCES

1. Lindquist L, Linne T, Hansson LO, Kalin M, Axelsson G. Value of cerebrospinal fluid analysis in the differential diagnosis of meningitis: a study in 710 patients with suspected central nervous system infection. Eur J Clin Microbiol Infect Dis. 1988;7:374–80.

2. Spanos A, Harrell FE Jr, Durack DT. Differential diagnosis of acute meningitis. An analysis of the predictive value of initial observations. JAMA. 1989;262:2700–7.

3. Hoen B, Viel JF, Paquot C, Gerard A, Canton P. Multivariate approach to differential diagnosis of acute meningitis. Eur J Clin Microbiol Infect Dis. 1995;14:267–74.

4. Jaeger F, Leroy J, Duchene F, Baty V, Baillet S, Estavoyer JM, et al. Validation of a diagnosis model for differentiating bacterial from viral meningitis in infants and children under 3.5 years of age. Eur J Clin Microbiol Infect Dis. 2000;19:418–21.

5. Freedman SB, Marrocco A, Pirie J, Dick PT. Predictors of bacterial meningitis in the era after Haemophilus influenzae. Arch Pediatr Adolesc Med. 2001;155:1301–6.

6. Nigrovic LE, Kuppermann N, Malley R. Development and validation of a multivariable predictive model to distinguish bacterial from aseptic meningitis in children in the post–Haemophilus influenzae era. Pediatrics. 2002;110:712–9.

7. Oostenbrink R, Moons KG, Twijnstra MJ, Grobbee DE, Moll HA. Children with meningeal signs: predicting who needs empiric antibiotic treatment. Arch Pediatr Adolesc Med. 2002;156:1189–94.

8. Oostenbrink R, Moons KG, Derksen-Lubsen AG, Grobbee DE, Moll HA. A diagnostic decision rule for management of children with meningeal signs [Published correction appears in Eur J Epidemiol 2004;19:1137]. Eur J Epidemiol. 2004;19:109–16.

9. Bonsu BK, Harper MB. Differentiating acute bacterial meningitis from acute viral meningitis among children with cerebrospinal fluid pleocytosis: a multivariable regression model. Pediatr Infect Dis J. 2004;23:511–7.

10. Nigrovic LE, Kuppermann N, Macias CG, Cannavino CR, Moro-Sutherland DM, Schremmer RD, et al. Clinical prediction rule for identifying children with cerebrospinal fluid pleocytosis at very low risk of bacterial meningitis. JAMA. 2007;297:52–60.

11. Oostenbrink R, Moons KG, Donders AR, Grobbee DE, Moll HA. Prediction of bacterial meningitis in children with meningeal signs: reduction of lumbar punctures. Acta Paediatr. 2001;90:611–7.

12. Dubos F, Lamotte B, Bibi-Triki F, Moulin F, Raymond J, Gendrel D, et al. Clinical decision rules to distinguish between bacterial and aseptic meningitis. Arch Dis Child. 2006;91:647–50.

This guide is one in a series that offers evidence-based tools to assist family physicians in improving their decision making at the point of care.



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