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Applying the bacterial meningitis score in children with cerebrospinal fluid pleocytosis: a single center's experience

Purpose The widespread introduction of bacterial conjugate vaccines has decreased the risk of cerebrospinal fluid (CSF) pleocytosis due to bacterial meningitis (BM) in children. However, most patients with CSF pleocytosis are hospitalized and treated with parenteral antibiotics for several days. The bacterial meningitis score (BMS) is a validated multivariate model derived from a pediatric population in the postconjugate vaccine era and has been evaluated in several studies. In the present study, we examined the usefulness of BMS in South Korean patients. Methods This study included 1,063 patients with CSF pleocytosis aged between 2 months and 18 years. The BMS was calculated for all patients, and the sensitivity and negative predictive value (NPV) of the test were evaluated. Results Of 1,063 patients, 1,059 (99.6%) had aseptic meningitis (AM). Only four patients (0.4%) had BM. The majority of patients (98%) had a BMS of ≤1, indicating a diagnosis of AM. The BMS was 0 in 635 patients (60%) and 1 in 405 patients (38%). All four BM patients had a BMS of ≥4. Conclusion To our knowledge, this is the first study to investigate the diagnostic strength of the BMS in South Korea. In our study, the BMS showed 100% sensitivity and 100% NPV. Therefore, we believe that the BMS is a good clinical prediction rule to identify children with CSF pleocytosis who are at a risk of BM.

Nevertheless, BM is still an important cause of morbidity and mortality in pediatric patients. In its initial stage, it is difficult to distinguish BM from AM, because the clinical presentations and laboratory results overlap. Additionally, it is difficult to understand or assess the clinical features that infants or children are actually experiencing.
Given the similar presentations between BM and AM, most pediatricians empirically treat with parenteral antibiotics for two to three days until negative culture results rule out BM 4,18) . In most cases, this means that patients are treated with antibiotics and are hospitalized unnecessarily. This overuse of medicine not only increases the risks of patients developing adverse effects to treatment and acquiring nosocomial infections, but also is wasteful in terms of medical cost. Unfortunately, there is not currently a single clinical symptom or laboratory finding that distinguishes BM from AM. Many researchers have investigated several clinical prediction rules (CPRs) to discriminate these two etiologies. The bacterial meningitis score (BMS) 1,5) , introduced by Nigrovic et al. 1) , is the first validated model that was derived from a pediatric population in the postconjugate vaccination era and has been applied to the largest number of pediatric patients worldwide 1,3,4,[19][20][21][22][23] . A meta-analysis was also carried out in 2012 5) . The BMS has been used as a guide in the Emergency Department to help exclude BM. The purpose of this study was to explore the usefulness of BMS in South Korean patients, and to introduce BMS as a CPR.

Patients
A total of 1,363 patients who received a diagnosis including the term 'meningitis' or 'encephalitis' between the ages of two months and 18 years from January 2006 to December 2012 at Severance Hospital, Seoul, South Korea were included in this study. Three hundred patients were excluded with regard to the following criteria: CSF pleocytosis with cell count <10 cells/mm 3 (n=143), CSF red blood cell (RBC) count of ≥10,000 cells/mm 3 (n=44), a diagnosis that was more likely encephalitis than meningitis (n=42), positive CSF culture results with suspicion of contamination (n=8), critical illness or immunosuppressed patients (n=7), central nervous system (CNS) device or recent neurosurgery (n=8), presence of other bacterial infections (n=48). A total of 1,063 patients were ultimately included.

Bacterial meningitis score
The variables in the BMS include a positive CSF Gram stain, CSF absolute neutrophil count (ANC) ≥1,000 cells/mm 3 , CSF protein ≥80 mg/dL, peripheral blood ANC ≥10,000 cells/mm 3 , and a history of seizure with the illness. A positive CSF Gram stain corresponds to 2 points and the other criteria correspond to 1 point each; therefore, the BMS ranges from 0 to 6 points ( Table 1). Children who scored 0 were classified as having 'very low risk' and those with a score above 0 were classified as 'not low risk' for BM.

Exclusion criteria
This study excluded patients who had CSF pleocytosis WBC<10 cells/mm 3 , CSF RBC of ≥10,000 cells/mm 3 , a diagnosis that was more likely encephalitis than was meningitis, positive CSF culture results with signs of contamination (e.g., Staphylococcus epider midis), critical illness or immunosuppression (intensive care unit care status, altered mental status, clinical sepsis, or chemotherapy), CNS device or recent neurosurgery, and other bacterial infections.

Statistical methods
Statistical analyses were performed with the IBM SPSS Statistics ver. 20.0 (IBM Co., Armonk, NY, USA). Group differ ences and associations between categorical variables were assessed using nonparametric statistical tests such as the Mann-Whitney U test and Fisher exact test, as appropriated. Bayes' Theorem was used to calculate positive predictive value and negative predictive value (NPV). Korean J Pediatr 2015;58 (7):251-255 enteroviral season, which lasts from June 1 to October 31. There were significant differences in CSF WBC, ANC, glucose, and protein between the two groups. Only four patients had a positive CSF Gram stain, and these patients were proven to have BM. The clinical features of the four BM patients are shown in Table 3. These patients not only had high BMS scores, but also had histories of seizure with the illness.

Performance of the BMS
The BMS of all patients are analyzed in Table 4. Scores included a BMS of 0 in 635 patients, and a BMS of 1 in 405. Thus, 98% of the patients scored 1 point or lower and were diagnosed with AM. Twenty-three patients (2%) scored 2 points or higher with BMS, and had risk of BM. Among the BM patients, one patient scored 4 points, while the three others had a BMS of 6.
We found that all four BM patients in our study had a BMS >0, suggesting that 'BMS >0' distinguishes BM from AM with 100% sensitivity. The patients who had a BMS of 0 were all diagnosed with AM. Thus, the NPV of BMS of 0 to predict AM is also 100% (635 out of 635 patients).
In the first study on 1,063 South Korean patients, we found that BMS has 100% sensitivity and 100% NPV in ruling out BM. There was no misdiagnosis of BM as AM. Therefore, BMS is expected to be a good CPR. However, it should be used as an adjunct to one's clinical reasoning, not purely as a clinical decision making tool. The BMS should not be applied to ill-appearing children, infants younger than two months of age (who have increased risk of BM and/or invasive bacterial infections), and patients whose clinical features are suggestive of other forms of CNS infection (such as herpes simplex virus, tuberculous meningitis, or viral encephalitis) 1,4) . Therefore BMS as a CPR should be used in concert with careful clinical assessment of the patient.
As seen in Table 4, twenty-three patients (2%) were scored 2 points or higher with BMS, and had risk of BM. One point was given for an increased peripheral blood ANC. Thus it is hard to tell increased peripheral blood ANC contribute to discriminating BM as criteria of BMS in this study.
Out of 1,063 patients, 99.6% of patients had AM and 0.4% had BM. There are several possible explanations for the much lower rate of BM as compared to AM in this study. The rate of conjugate vaccination in South Korea is higher than it was previously. Vaccinations against S. pneumoniae and H. influenzae had increased from 40% to 74% and from 82% to 88% between 2005 and 2010, respectively 34) . Thus, in the era of widespread conjugate vaccines, the incidence of BM is expected to decrease. Another reason for the lower rate of BM is the possibility that patients had taken oral antibiotics before lumbar puncture 35) . The laboratory findings and markers of CNS inflammation in BM patients were consistently different from those of AM patients. However, given that there were only four patients with BM, this study cannot fully represent