Bacterial meningitis


7.3 Organisms


In most Western countries, the most common organisms causing neonatal bacterial meningitis are GBS, E. coli, other Gram-negative bacilli, S. pneumoniae and Listeria1,2,21,39 (Table 7.1). In a US study which only reported cases of meningitis in infants <;2 months due to GBS, H. influenzae, S. pneumoniae, N. meningitidis and Listeria, GBS caused 86.1% of cases and Listeria 5%.39 In a French study,21 GBS (59%) and E. coli (28%) were by far the commonest cause of neonatal bacterial meningitis, followed by Gram-negative bacilli other than E. coli (4%), other streptococci (4%), N. meningitidis (3%), and Listeria monocytogenes (1.5%). In early-onset meningitis, GBS caused 77% of cases and E. coli 18%, while in late-onset meningitis GBS caused 50% and E. coli 33%. However, E. coli (45%) was more common than GBS (32%) in pre-term infants and especially in very pre-term infants (54%).21


Table 7.1 Organisms causing neonatal meningitis in Western countriesa.


















Frequency of occurrence Organisms
Common (>10%)* Group B streptococcus (GBS) Escherichia coli
Uncommon (1–10%) Other Gram-negative enteric bacilli
Listeria monocytogenes
Streptococcus pneumoniae
Enterococci (faecal streptococci)
Other streptococci
Rare (<;1%) Coagulase-negative staphylococci
Staphylococcus aureus
Haemophilus influenzae (usually untypeable)
Neisseria meningitidis
Anaerobes
aThe exact proportions vary from country to country, with time, and with the use of intrapartum chemoprophylaxis.

The incidence of GBS in developing countries varies. There were no cases of GBS meningitis in the case series from the Gambia, Ethiopia, Niger, Nigeria, Kenya, the Philippines, Papua New Guinea, Jordan, Saudi Arabia and Panama, summarized in a systematic review.3 However, GBS was the most commonly reported organism causing meningitis in case series from Qatar, the United Arab Emirates, Malawi, Zimbabwe, South Africa and Trinidad, West Indies and was an important cause in case series from Thailand and Kenya.3 It is difficult to know if these differences are because of variations in laboratory techniques or represent genuine differences in incidence (Table 7.2).


Table 7.2 Organisms causing neonatal meningitis in developing countries.


















Frequency of occurrence Organisms
Common (>10%)a Klebsiella species
E. coli
Serratia species
Acinetobacter species
Salmonella (non-typhoidal)
aGBS
aS. aureus
Uncommon (1–10%) Pseudomonas species
Enterobacter species
Other Gram-negative enteric bacilli
bS. pneumoniae
Enterococci (faecal streptococci)
Other streptococci
Rare (<;1%) Coagulase-negative staphylococci
S. aureus
H. influenzae (usually untypeable)
N. meningitidis
Anaerobes
aReported from some countries but not others.
bCan be <;1 month, but more common at age 1–3 months.

Gram-negative enteric bacilli, particularly Klebsiella species, cause early- and late-onset meningitis worldwide. Non-typhoidal salmonellae and S. aureus are reported in some countries but not others. S. pneumoniae is more likely to cause post-neonatal infant meningitis but can also cause neonatal meningitis particularly in Africa.3


7.4 Clinical manifestations


The clinical signs in bacterial meningitis are mostly non-specific (Table 7.3).1-7 However, a bulging fontanelle occurs in about 33% of infants with meningitis, seizures in 30% and neck stiffness in 15%. Opisthotonus (Figure 7.2) is a late and sinister sign.


Table 7.3 Clinical signs and estimated frequency in neonatal meningitis.
















Frequency of signs Clinical signs
Common, non-specific (40–60%) Abnormal temperature (fever or hypothermia)
Abnormal behaviour: lethargy or irritability
Specific (15–33%) Bulging fontanelle (33%)
Seizures (30%)
Neck stiffness (15%)
Non-specific (15–40%) Respiratory symptoms (tachypnoea, distress)
Jaundice
Vomiting or diarrhoea

7.5 Diagnosis


The rationale for immediate LP in suspected sepsis is discussed in Chapter 4 (see Section 4.1.3). The common practice of starting empiric antibiotics without performing an LP and relying on the blood culture result to diagnose meningitis is dangerous: 28–38% of neonates with bacterial meningitis have a negative blood culture.13,19 The risk of LP causing respiratory compromise can be reduced by performing the LP with the infant in a sitting or modified lateral position.40


One paper described the interpretation of CSF results as both art and science, noting that in the second century Galen described CSF as a vaporous humour produced in the ventricles that provided energy to the rest of the body and commenting wryly “such theories have not been universally replaced by rationale.”41 The interpretation of neonatal CSF results is complicated by problems defining normal ranges, problems defining meningitis, interpretation of blood-stained CSF and influence of extraneous factors.


One barrier to defining normal ranges is an ethical problem. Although one 1966 South African study performed LPs on well full-term infants in the first day after birth,41 it is not now considered ethical to LP a normal baby. Therefore in deciding that a baby who received an LP, usually for suspected sepsis, is in fact ‘normal,’ it is imperative to exclude viral or other occult infection, which is impossible in practice. Additionally, CSF parameters vary by gestational age and post-natal age.


The problem defining meningitis relates mainly to growth of possible CSF contaminants and situations where the blood culture grows an organism but the CSF does not, with or without changes in CSF microscopy or biochemistry.


7.5.1 Cerebrospinal fluid white cell count


A summary of CSF white cell counts from selected studies13,42-48 is given in Table 7.4. There is quite good concordance between the mean or median white cell counts in the studies, which do not seem to vary greatly with gestation. A US study of infants <;1500 g found no correlation between gestational age and CSF white count in infants who had an LP at birth. However, CSF white count decreased with increasing age.49 This information is not useful to the clinician managing an infant with possible meningitis who wants to know “given the CSF findings, is this infant likely to be infected or can I withhold antibiotics?”



Figure 7.2 Bacterial meningitis causing severe opisthotonus (photo reproduced courtesy of Olivia Swann).

c07f002

Table 7.4 Normal values for CSF total white cell count (×106/L or per mm3) from selected studies.


Table07-1


The clinician has a number of questions about CSFs.







Question 1: Is there a safe cerebrospinal fluid white cell count to withhold antibiotics or a critical cerebrospinal fluid white cell count at which antibiotics should always be given?

There is considerable overlap between CSF white cell counts in uninfected infants (the normal reference ranges) and infants with meningitis. For example, in one study the range of CSF white cell counts in children with negative CSF cultures was 0–90 000.13 No one would withhold antibiotics from an infant with a CSF white cell count of 90 000 and almost everyone would treat such an infant empirically with a full course of antibiotics for presumed bacterial meningitis, even if cultures were negative. However, does a CSF white cell count of 20 or 30 or higher indicate likely meningitis, should antibiotics be started and should they be continued if blood and CSF cultures are negative? The literature is not very helpful with these difficult clinical decisions.

A cohort study of neonates <;34 weeks gestation assessed the reliability of CSF parameters in diagnosing meningitis by determining the area under the receiver operating characteristic (ROC) curves.50 These were 0.80 for CSF white cell count, 0.63 for CSF glucose and 0.72 for CSF protein, which prompted the authors to urge caution in interpreting CSF parameters in pre-term neonates and stressed the importance of reliable CSF cultures.51

There are some outlier infants in most studies whose cultures are negative and who do not appear to have meningitis, but who nevertheless have CSF white cell counts as high as 50–90 cells/μL (Table 7.4).42,47,48 An individualized approach is recommended, weighing up risks and benefits of stopping or continuing antibiotics.

Neonatal meningitis is rare. The vast majority of infants with CSF white counts in the ‘reference range’, whether defined as the mean plus 2 SD or the interquartile range around the median, will be uninfected. However, there is overlap and a very small number of babies with CSF counts within the reference range will have bacterial meningitis. Very occasionally a neonate with meningitis will have no white cells on initial CSF microscopy: this was the case in one of 119 infants in one study44 and in 2 of 95 in another (while a further 8 of the 95 had CSF white counts of 1–8 cells).13

The clinician has to weigh the risks and benefits of withholding or starting antibiotics for any given infant. If antibiotics are started and CSF cultures are negative, but the CSF white count is ambiguous, say 20–30, the clinician will need to decide whether or not it is safe to stop antibiotics.

Conclusion: The overlap between CSF white cell counts in infants with meningitis and uninfected infants means the balance of risks and benefits needs to be considered for each individual infant regarding whether or not to start antibiotics and whether to continue antibiotics once started.










Question 2: Is the presence of cerebrospinal fluid neutrophils always abnormal?

Some authorities say that the presence of any neutrophils in the CSF suggest bacterial meningitis. However, studies report that neutrophils comprise 2–61% of the total CSF white cell count in apparently non-infected neonates.41,44 A review of five papers reported a mean absolute CSF neutrophil count of 0.4 (range 0–7) in non-infected term infants aged 0–28 days.47 Another group reported that 5% of non-infected term infants had a neutrophil count >1,41 while another study reported a mean neutrophil count of 2.8 (SD 4.9) in uninfected newborns.50

Conclusion 2: Finding two or three neutrophils in the CSF is common in uninfected newborns and not necessarily abnormal.





CSF microscopy often shows large numbers of red cells, either as a result of a traumatic LP or of intraventricular haemorrhage. It is common practice to correct for the presence of red cells in CSF on the basis of the ratio between red and white cells in peripheral blood. This ratio is about 500–1000 to 1 so, if the red cell count is reported as 30 000 say, the clinician ‘allows’ 30–60 white cells as being introduced into the CSF from the blood, not infection.







Question 3: For traumatic lumbar punctures, should clinicians correct for the number of red cells?

A review of neonatal LPs found that 2519 (39.5%) of 6374 were traumatic, defined as 500 or greater red cells/μL, and 114 infants had meningitis, including 50 with traumatic taps.52 CSF white blood counts were adjusted downward using several commonly used methods and the authors calculated sensitivity, specificity, likelihood ratios and area under the ROC curves for predicting meningitis in neonates with traumatic LPs. The area under the ROC curve was similar for unadjusted or adjusted white cell counts. The authors conclude that adjustment of CSF white cell counts for increased red cells can result in decreased sensitivity with marginal gain in specificity and discouraged correction.

Recommendation 3: CSF white cell counts should not be adjusted for the presence of CSF red cells.










Question 4: How do previous antibiotics affect lumbar puncture culture results?

Clearly, prior antibiotics may sometimes sterilize the CSF. In a US cohort study repeat CSF cultures from 26 (22%) of 118 infants with culture-proven neonatal meningitis, taken after at least 24 hours of antibiotics to monitor disease activity and response to therapy, were positive.53 A study of children with bacterial meningitis examined the effect of the interval between antibiotic administration and CSF culture in infants and children started on empiric parenteral antibiotics. GBS cultures remained positive through the first 8 hours after parenteral antibiotics.54

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Jun 18, 2016 | Posted by in PEDIATRICS | Comments Off on Bacterial meningitis

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