Community-acquired Bacterial Meningitis Research Articles

Clinical Course and Outcome of Community-Acquired Bacterial Meningitis in Cancer Patients.

The aim of the study was to determine the course and outcome of bacterial meningitis (BM) in patients with cancer. We retrospectively reviewed files of patients with community-acquired BM, hospitalized in a single neuroinfection center between January 2010 and December 2017. There were 209 patients included in the analysis: 28 had cancer (9 women, 19 men; median age 76, IQR 67-80years) and 181 were cancer-free (76 women, 105 men; median age 52, IQR 33-65years) and constituted the control group. Cancer patients, compared with controls, were more likely to present with seizures (25% vs. 8%, p=0.019), scored higher on the Sequential Organ Failure Assessment, and had a higher mortality rate (32% vs. 13%, p=0.025). Further, cancer patients were less likely (64% vs. 83%, p=0.033) to present with two or more out of four clinical manifestations of BM (pyrexia, neck stiffness, altered mental status, and headache) and had a lower white blood cell (WBC) count than non-cancer controls. In multiple regression analysis, the presence of bacterial meningitis in cancer patients was independently associated only with older age (p=0.001) and lower WBC count (p=0.007), while mortality was associated with lower Glasgow Coma Score (p=0.003). In conclusion, bacterial meningitis in cancer patients is characterized by atypical symptoms and high mortality, which requires physicians' vigilance and a prompt investigation of cerebrospinal fluid in suspected cases. However, multiple regression analysis suggests that differences in clinical presentation and outcomes of bacterial meningitis between cancer and cancer-free patients may also be attributable to other factors, such as age differences.

57-Year-Old Woman With Fever and Confusion

57-Year-Old Woman With Fever and Confusion

324. Lack of Accuracy of the International Classification of Disease, Ninth (ICD-9) Codes in Identifying Patients With Encephalitis

BackgroundICD-9 codes have been widely used in studies utilizing large national databases that evaluate the clinical epidemiology of encephalitis in the United States. Many studies have showed that ICD-9 codes have poor accuracy in stroke, multiple sclerosis and pulmonary fibrosis but their utility in encephalitis is unknown.MethodsRetrospective study of all adults with a discharge diagnosis of encephalitis by an ICD-9 code. The study was performed in 17 hospitals from the Memorial Hermann Hospital and Harris Health Hospital system in the Greater Houston area from March 2010 until July 2015. Medical records were reviewed and a case was considered accurately classified as encephalitis if they met the definition established by the international encephalitis consortium.ResultsA total of 1,241 cases were identified by a discharge diagnosis of ICD-9 code as having encephalitis. The most common cause identified was not having a central nervous system infection in 580 (46.7%) patients. A total of 244 (19.6%) patients were correctly identified as having encephalitis. Other causes identified were nosocomial meningitis (11.9%), community-acquired bacterial meningitis (8.1%), aseptic meningitis (5.8%), fungal meningitis (5.4%), tuberculosis (2.0%), and parasitic meningitis (0.2%).ConclusionICD-9 codes have poor reliability in identifying patients with encephalitis questioning the accuracy of large nationwide studies that utilize them to identify patients.Table 1: Correct Clinical Diagnosis in 1,241 Patients with a Discharge Diagnosis of Encephalitis by ICD-9 Codes.DiagnosisNumber of Patients (%)Non-CNS infection580 (46.7)Encephalitis244 (19.6)Nosocomial meningitis148 (11.9)Bacterial meningitis101 (8.1)Aseptic meningitis72 (5.8)Fungal meningitis68 (5.4)Tuberculous meningitis25 (2.0)Parasitic meningitis3 (0.2)Abbreviation: ICD-9, an International Classification of Disease, Ninth; CNS, Central Nervous System.Disclosures All authors: No reported disclosures.

336. Characteristics of Acute Bacterial Meningitis and Predictors of Mortality

BackgroundAcute bacterial meningitis is a medical emergency associated with morbidity and mortality. The aim of the study was to describe clinical features, causative organisms and predictors of death among patients presented with community-acquired acute bacterial meningitis.MethodsThis retrospective study was conducted at Nakhonpathom Hospital, a 700-bed tertiary care hospital in Thailand during July 2013 and August 2017. The data on demography, clinical presentation, and outcome were collected. Factors associated with death were analysed.ResultsDuring study period, there were 55 patients. Median age was 45 (range 19 to 89) years and 38 (69%) were male. Median duration of symptom before hospitalization were 2 (range 1 to 6) days. The most common presenting symptoms were fever (98%), headache (94%), and decreased level of consciousness (75%). The classic triad of fever, headache, and neck stiffness was documented in 53%. Computed tomography scan of brain were abnormal among 57% of 35 patients. Bacteria was isolated in CSF or blood in 40 patients (73%). The most common isolates were S. agalactiae (17 cases), S. pneumoniae (4 cases) and Streptococcus group D (4 cases). All isolates of S. agalactiae and S. pneumoniae were penicillin sensitive. The in-hospital mortality was 20%. Factors associated with death were age more than 65 years (44% vs. 13%, P = 0.047), low CSF WBC (178 vs. 439 cells/mm3, P = 0.009), and the presence of hydrocephalus on imaging (67% vs. 9%, P = 0.047). The time interval between patients’ presentation and appropriate antibiotics administration differed significantly for patients who survive and die (22 vs. 0.5 hour, P = 0.016).ConclusionAcute bacterial meningitis remains associated with mortality. Age, CSF WBC, hydrocephalus, and delay antibiotics therapy were associated with outcome.Disclosures All authors: No reported disclosures.

Delayed Cerebral Injury in Adults With Bacterial Meningitis: A Novel Complication of Adjunctive Steroids?

To report the prevalence of delayed cerebral injury in adults with bacterial meningitis and explore its association with adjunctive steroids. Retrospective analysis of adults with bacterial meningitis between 2005 and 2016. Ten hospitals in the Greater Houston area. Consecutive subjects with culture proven community-acquired bacterial meningitis. Subjects were categorized as receiving or not adjunctive steroids within 4 hours. A total of 120 patients were identified who were admitted with community-acquired bacterial meningitis. Delayed cerebral injury was seen in five of 120 patients (4.1%); all five patients had fever and abnormal neurologic examinations. Adjunctive steroids within 4 hours were more likely given to those with delayed cerebral injury (5/5,100% vs 43/115, 37.5%; p = 0.01). Of the patients who developed delayed cerebral injury, three had Streptococcus pneumoniae, one had methicillin-resistant Staphylococcus aureus, and one had Listeria monocytogenes isolated. We observed an adverse clinical outcome as defined by the Glasgow Outcome Scale in four of the five patients (80%). Delayed cerebral injury occurred in 4.1% of adults with bacterial meningitis, and it was associated with the use of adjunctive steroids. Future studies should explore the etiology and prevention of this devastating complication.

Prognostic factors in critically ill patients with community-acquired acute bacterial meningitis and acute kidney injury

Prognostic factors in critically ill patients with community-acquired acute bacterial meningitis and acute kidney injury

Community-acquired meningitis in adults caused by Escherichia coli in Denmark and The Netherlands

ObjectivesWe aimed to examine risk factors, presenting characteristics and complications of Escherichia coli community-acquired bacterial meningitis in adults. MethodsObservational cohort study of adults > 16 years of age with cerebrospinal fluid culture-positive E. coli meningitis in Denmark and the Netherlands. Exclusion criteria were primary brain abscess, previous neurosurgery and nosocomial infections. We analysed baseline characteristics, concomitant infections and neurological complications. Outcome was assessed using the Glasgow Outcome Scale score (GOS) at discharge with GOS 1–4 categorised as unfavourable outcome. ResultsWe identified 36 patients with a median age of 69 years (interquartile range 61–83) of whom 15 (42%) were females. Immuno-compromise was present in 11 (31%) patients. Nineteen (53%) patients had concomitant infections consisting of urinary tract infections in 13 (36%), pneumonia in three (9%) and septic arthritis in two (6%). Bacteraemia with E. coli was found in 26 of 34 (76%) patients. Thirteen patients died (36%) and unfavourable outcome at discharge occurred in 23 (64%). Deaths were attributed to systemic complications in 12 (92%) patients. ConclusionCommunity-acquired E. coli meningitis in adults is a severe disease that primarily occurs in elderly patients with concomitant infections and an immunocompromised state. Outcome is often poor and mainly caused by systemic complications.

Temporal trends in paediatric bacterial meningitis in a tropical Australian region: 1992-2014.

The epidemiology of community-acquired bacterial meningitis has changed following the introduction of routine immunisation against common causative organisms. Indigenous children living in the Northern Territory, Australia, have high rates of bacterial infections. This study describes changes in the epidemiology of childhood bacterial meningitis and the distribution of the burden of disease in the Top End. A retrospective review of cases derived from hospital medical records and laboratory data was performed. Inclusion criteria were children aged 3 months to 14 years of age, admitted to Royal Darwin Hospital between 1992 and 2014 and diagnosed with bacterial meningitis. Annual incidence of bacterial meningitis and the distribution of causative pathogens are described. Demographic data, investigations, treatment and outcomes were compared between Indigenous and non-Indigenous children. There were 137 cases of childhood bacterial meningitis identified over the 23-year period. The incidence reduced from 21 per 100 000 children per year for 1992-2002 to 11 per 100 000 per year for 2003-2014 (P = 0.0025). Haemophilus influenzae type b, Streptococcus pneumoniae and Neisseria meningitidis were the most common causative organisms, with a reduction in cases for each pathogen observed across the study period. Indigenous children were over-represented (104/137, 76%). Case fatality rate was 8% (11/137); 91% of fatal cases presented to a remote facility. The incidence of childhood bacterial meningitis has declined in the Northern Territory of Australia, but Indigenous children are disproportionately affected. Routine immunisation is beneficial for all, although further efforts to 'Close the Gap' between health outcomes in Indigenous and non-Indigenous Australians is required.

Variation in coagulation and fibrinolysis genes evaluated for their contribution to cerebrovascular complications in adults with bacterial meningitis in the Netherlands

To study whether genetic variation in coagulation and fibrinolysis genes contributes to cerebrovascular complications in bacterial meningitis. We performed a nationwide prospective genetic association study in adult community-acquired bacterial meningitis patients. The exons and flanking regions of 16 candidate genes involved in coagulation and fibrinolysis pathways were sequenced. We analyzed whether genetic variation in these genes resulted in a higher risk of cerebrovascular complications, unfavorable outcome and differences in thrombocyte count on admission. From 2006 to 2011, a total of 1101 bacterial meningitis patients were identified of whom 622 supplied DNA for genotyping and passed genetic quality control steps. In 139 patients (22%) the episode of bacterial meningitis was complicated by cerebral infarction, and 188 (30%) had an unfavorable outcome. We identified the functional variant rs494860 in the protein Z (PROZ) gene as our strongest association with occurrence of cerebral infarction (odds ratio (OR) 0.49 (95% confidence interval 0.33-0.73), p = 5.2 × 10-4). After Bonferroni correction for multiple testing no genetic variant was significantly associated (p-value threshold 2.7 × 10-4). Our study suggests a functional genetic variation in the PROZ gene, rs494860, may be of importance in bacterial meningitis pathogenesis and cerebral infarction risk. Replication of this finding in other cohort studies populations is needed.

Cranial Computed Tomography, Lumbar Puncture, and Clinical Deterioration in Bacterial Meningitis: A Nationwide Cohort Study.

It is unclear how often lumbar puncture (LP) is complicated by cerebral herniation in patients with bacterial meningitis and whether cranial computed tomography (CT) can be used to identify patients at risk for herniation. We performed a nationwide prospective cohort study of patients with community-acquired bacterial meningitis from 2006 to 2014 and identified patients with clinical deterioration possibly caused by LP. For systematic evaluation of contraindications for LP on cranial CT, these patients were matched to patients in the cohort without deterioration. Four experts, blinded for outcome, scored cranial CT results for contraindications for LP. A Fleiss' generalized κ for this assessment was determined. Of 1533 episodes, 47 (3.1%) had deterioration possibly caused by LP. Two patients deteriorated within 1 hour after LP (0.1%). In 43 of 47 patients with deterioration, cranial CT was performed prior to LP, so CT results were matched with 43 patients without deterioration. The interrater reliability of assessment of contraindications for LP on cranial CT was moderate (Fleiss' generalized κ = 0.47). A contraindication for LP was reported by all 4 raters in 6 patients with deterioration (14%) and in 5 without deterioration (11%). LP can be performed safely in the large majority of patients with bacterial meningitis, as it is only very rarely complicated by cerebral herniation. Cranial CT can be considered a screening method for contraindications for LP, but the interrater reliability of this assessment is moderate.

Cerebrospinal fluid lactate as a marker to differentiate between community-acquired acute bacterial meningitis and aseptic meningitis/encephalitis in adults: a Danish prospective observational cohort study

Background: The ability of cerebrospinal fluid (CSF) lactate to distinguish between acute bacterial meningitis (ABM) and aseptic meningitis/encephalitis (AME) is debated. We assessed the diagnostic value of CSF lactate to discriminate between ABM and AME.Methods: We included 176 patients from a prospective adult cohort with neuroinfections. In total, 51 ABM and 125 AME patients with clinically and/or microbiologically diagnosed acute meningitis were examined with CSF-lactate and traditional markers for infection. Receiver operating characteristic (ROC) curves were used to assess diagnostic performance.Results: In CSF, lactate, leukocytes, fraction of neutrophils, protein and glucose ratio, were significantly different between the ABM and AME groups. CSF lactate had the best diagnostic value, with an area under the curve (AUC) of 0.976 (95%CI 0.966–0.997) and using a cut-off of 3.5 mmol/L a sensitivity of 96% and specificity of 85%. Antibiotic treatment before lumbar puncture had no significant effect on the AUC of CSF lactate.Conclusions: Compared to traditional CSF-markers, CSF lactate is more accurate to distinguish between ABM and AME.

Osmotic therapies added to antibiotics for acute bacterial meningitis.

BackgroundEvery day children and adults die from acute community‐acquired bacterial meningitis, particularly in low‐income countries, and survivors risk deafness, epilepsy and neurological disabilities. Osmotic therapies may attract extra‐vascular fluid and reduce cerebral oedema, and thus reduce death and improve neurological outcomes.This is an update of a Cochrane Review first published in 2013.ObjectivesTo evaluate the effects of osmotic therapies added to antibiotics for acute bacterial meningitis in children and adults on mortality, deafness and neurological disability.Search methodsWe searched CENTRAL (2017, Issue 1), MEDLINE (1950 to 17 February 2017), Embase (1974 to 17 February 2017), CINAHL (1981 to 17 February 2017), LILACS (1982 to 17 February 2017) and registers of ongoing clinical trials (ClinicalTrials.com, WHO ICTRP) (21 February 2017). We also searched conference abstracts and contacted researchers in the field (up to 12 December 2015).Selection criteriaRandomised controlled trials testing any osmotic therapy in adults or children with acute bacterial meningitis.Data collection and analysisTwo review authors independently screened the search results and selected trials for inclusion. Results are presented using risk ratios (RR) and 95% confidence intervals (CI) and grouped according to whether the participants received steroids or not. We used the GRADE approach to assess the certainty of the evidence.Main resultsWe included five trials with 1451 participants. Four trials evaluated glycerol against placebo, and one evaluated glycerol against 50% dextrose; in addition three trials evaluated dexamethasone and one trial evaluated acetaminophen (paracetamol) in a factorial design. Stratified analysis shows no effect modification with steroids; we present aggregate effect estimates.Compared to placebo, glycerol probably has little or no effect on death in people with bacterial meningitis (RR 1.08, 95% CI 0.90 to 1.30; 5 studies, 1272 participants; moderate‐certainty evidence), but may reduce neurological disability (RR 0.73, 95% CI 0.53 to 1.00; 5 studies, 1270 participants; low‐certainty evidence).Glycerol may have little or no effect on seizures during treatment for meningitis (RR 1.08, 95% CI 0.90 to 1.30; 4 studies, 1090 participants; low‐certainty evidence).Glycerol may reduce the risk of subsequent deafness (RR 0.64, 95% CI 0.44 to 0.93; 5 studies, 922 participants; low to moderate‐certainty evidence).Glycerol probably has little or no effect on gastrointestinal bleeding (RR 0.93, 95% CI 0.39 to 2.19; 3 studies, 607 participants; moderate‐certainty evidence). The evidence on nausea, vomiting and diarrhoea is uncertain (RR 1.09, 95% CI 0.81 to 1.47; 2 studies, 851 participants; very low‐certainty evidence).Authors' conclusionsGlycerol was the only osmotic therapy evaluated, and data from trials to date have not demonstrated an effect on death. Glycerol may reduce neurological deficiency and deafness.

Editorial introductions

Editorial introductions

Prognostic factors among critically ill patients with community-acquired acute bacterial meningitis and acute kidney injury.

ObjectiveTo investigate prognostic factors among critically ill patients with community-acquired bacterial meningitis and acute kidney injury.MethodsA retrospective study including patients admitted to a tertiary infectious disease hospital in Fortaleza, Brazil diagnosed with community-acquired bacterial meningitis complicated with acute kidney injury. Factors associated with death, mechanical ventilation and use of vasopressors were investigated.ResultsForty-one patients were included, with a mean age of 41.6 ± 15.5 years; 56% were males. Mean time between intensive care unit admission and acute kidney injury diagnosis was 5.8 ± 10.6 days. Overall mortality was 53.7%. According to KDIGO criteria, 10 patients were classified as stage 1 (24.4%), 18 as stage 2 (43.9%) and 13 as stage 3 (31.7%). KDIGO 3 significantly increased mortality (OR = 6.67; 95%CI = 1.23 - 36.23; p = 0.028). Thrombocytopenia was not associated with higher mortality, but it was a risk factor for KDIGO 3 (OR = 5.67; 95%CI = 1.25 - 25.61; p = 0.024) and for mechanical ventilation (OR = 6.25; 95%CI = 1.33 - 29.37; p = 0.02). Patients who needed mechanical ventilation by 48 hours from acute kidney injury diagnosis had higher urea (44.6 versus 74mg/dL, p = 0.039) and sodium (138.6 versus 144.1mEq/L; p = 0.036).ConclusionMortality among critically ill patients with community-acquired bacterial meningitis and acute kidney injury is high. Acute kidney injury severity was associated with even higher mortality. Thrombocytopenia was associated with severer acute kidney injury. Higher urea was an earlier predictor of severer acute kidney injury than was creatinine.

Outbreak of cerebrospinal meningitis in Kebbi State, Nigeria, April 2017

Introduction: community-acquired bacterial meningitis continues to exact a heavy toll, even in developed countries, despite the implementation of childhood vaccination programs and effective antimicrobial agents. Nigeria experienced an outbreak of cerebrospinal meningitis (CSM), majorly affecting five states (Zamfara, Sokoto, Kebbi, Niger, and Katsina). We investigated the outbreak in Kebbi State to determine the magnitude, characterize the outbreak in person, place and time, and strengthen case management.

Use of Adjunctive Steroids and Incidence of Delayed Cerebral Venous Thrombosis in Adults with Bacterial Meningitis

BackgroundBacterial meningitis is associated with significant morbidity and mortality. Adjunctive steroids decrease mortality in adults with meningitis due to Streptococcus pneumoniaebut its use has been recently linked to the development of delayed cerebral thrombosis (DCT). The purpose of our study was to determine the utilization of adjunctive steroids and its incidence.MethodsA retrospective multicenter study involving 10 Houston area hospitals from 2008 to 2016. Data was gathered from 120 adults with culture proven community-acquired bacterial meningitis. An adverse clinical outcome was defined as a Glasgow outcome score of 1–4.ResultsThere was a total of 120 patients enrolled; of which, 55% were male. Adjunctive intravenous steroids were administered in 82 (68%) patients with bacterial meningitis. The steroid median duration was 3.8 days. The average age of patients was 55.3 years (range 20–92). There was no difference in Charlson comorbidity score, immunosuppression, presence of sinusitis or otitis, fever, meningeal signs or symptoms, abnormal neurological findings, Gram stain or severity of illness, based on Aronin score (P > 0.05), between patients who received steroids and those that did not. Older patients, age >65, were less likely to receive adjunctive steroids (P = 0.028). The most common organism isolated was Streptococcus pneumoniae, which occurred in 46 (38%) patients. An adverse clinical outcome was seen in 46 (38%) patients with no difference between groups (P = 0.819). Delayed cerebral thrombosis was seen in a total of 9 (7.5%) patients with bacterial meningitis. Of these, 1 patient (2.6%) did not receive steroids and the remaining 8 (10.9%) patients received steroids (P = 0.158). Five cases of meningitis that were complicated by DCT were caused by Streptococcus pneumoniae, 1 by Listeria monocytogenes, and 2 with Staphylococcus aureus.ConclusionAdjunctive steroids are being used in the majority of adults with bacterial meningitis but it is possibly associated with DCT, a devastating complicationDisclosures All authors: No reported disclosures.

Streptococcus pneumoniae and lytic antibiotic therapy: are we adding insult to injury during invasive pneumococcal disease and sepsis?

Streptococcus pneumoniae (S. pneumoniae), otherwise known as 'the pneumococcus', is a fascinating microbe that continues to pose a significant problem to public health. Currently there are no specific National Institute for Clinical Excellence (NICE) or British Thoracic Society (BTS) clinical guidelines referring to the treatment of invasive pneumococcal infection. NICE clinical guidelines suggest the use of lytic β-lactam antibiotic regimens for the management of community-acquired pneumonia and bacterial meningitis; infections for which S. pneumoniae is a likely causative organism. Lytic antibiotics have been shown to increase the release of pneumolysin (the highly inflammatory and damaging toxin of the pneumococcus), thus theoretically increasing host damage, which may lead to a decline of clinical outcomes in vulnerable patients. In light of this information, should the use of non-lytic antibiotics, such as quinolones, rifamycins and macrolides, be considered for the treatment of invasive pneumococcal disease?

Early versus late diagnosis in community-acquired bacterial meningitis: a retrospective cohort study

ObjectivesTo examine clinical characteristics and outcome of patients with late diagnosis of community-acquired bacterial meningitis (CABM). MethodsWe conducted a chart review of all adults with proven CABM in three centres in Denmark from 1998 through to 2014. Patients were categorized as early diagnosis of CABM immediately on admission, or late diagnosis if CABM was not listed in referral or admission records and neither lumbar puncture nor antibiotic therapy for meningitis was considered immediately on admission. We used modified Poisson regression analysis to compute adjusted relative risks with 95% CIs for predictors of late diagnosis and in-hospital mortality. ResultsA total of 113/358 (32%) patients were categorized as late diagnosis demonstrating a variety of tentative diagnoses of which 81/113 (72%) were non-infectious. We observed several statistically significant baseline differences (p <0.05) in patients with late versus early diagnosis including age >65 years (56/113, 50% versus 67/245, 27%), neck stiffness (35/97, 36% versus 183/234, 78%), concomitant pneumonia (26/113, 23% versus 26/245, 11%), and meningococcal meningitis (6/113, 5% versus 52/245, 21%). These variables remained statistically significant in multivariate analysis. Moreover, late diagnosis was associated with increased in-hospital mortality (41/113, 36% versus 43/245, 18%; adjusted relative risk 1.7, 95% CI 1.2–2.5). ConclusionsLate diagnosis of CABM was common and patients were admitted with mostly non-infectious diagnoses. Absence of neck stiffness did not rule out CABM and special attention should be given to patients with pneumonia and the elderly. Late diagnosis was associated with incorrect patient management and increased mortality.

The use of matrix-assisted laser desorption/ionization time-of-flight mass spectrometry for rapid bacterial identification in patients with smear-positive bacterial meningitis

ObjectivesTo assess the potential of matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF-MS) in rapid identification of bacteria from smear-positive cerebrospinal fluid (CSF) in a cohort of patients with meningitis. MethodsSingle-centre observational study, including adults and children with community-acquired or postneurosurgical bacterial meningitis. Meningitis was defined using established criteria. Samples of CSF that had a positive CSF Gram stain were directly examined by MALDI-TOF-MS. Identification was considered accurate when identical to the CSF culture or PCR results (species and genus level). Laboratory workers performing the MALDI-TOF-MS and interpreting its results were blinded to the direct smear results, except for the fact that it was positive. MALDI-TOF-MS results were not conveyed to clinicians. ResultsMALDI-TOF-MS was tested on 44 CSF samples; ten samples were obtained from patients with community-acquired meningitis, and 34 samples were from patients with postneurosurgical meningitis. The assay identified bacteria correctly in 17/21 of the samples with Gram-negative rods observed on the direct smear, all obtained from patients who had undergone neurosurgery, (sensitivity 81%, 95% CI 64.2%–97.7%). In the postneurosurgical group, Gram-positive cocci were identified correctly in only 1/11 (9.1%) of the samples, and Candida species were not identified in two samples. Among patients with community-acquired meningitis, the assay did not identify Streptococcus pneumoniae in eight of eight samples, Neisseria meningitidis in one sample (1/1), and Streptococcus agalactiae in one sample (1/1). ConclusionsWe found MALDI-TOF-MS to be useful in the rapid identification of Gram-negative rods directly from smear-positive CSF samples, but not of Gram-positive bacteria.

Diagnostic accuracy of two multiplex real-time polymerase chain reaction assays for the diagnosis of meningitis in children in a resource-limited setting.

IntroductionAccurate etiological diagnosis of meningitis is important, but difficult in resource-limited settings due to prior administration of antibiotics and lack of viral diagnostics. We aimed to develop and validate 2 real-time multiplex PCR (RT-PCR) assays for the detection of common causes of community-acquired bacterial and viral meningitis in South African children.MethodsWe developed 2 multiplex RT- PCRs for detection of S. pneumoniae, N. meningitidis, H. influenzae, enteroviruses, mumps virus and herpes simplex virus. We tested residual CSF samples from children presenting to a local paediatric hospital over a one-year period, whose CSF showed an abnormal cell count. Results were compared with routine diagnostic tests and the final discharge diagnosis. We calculated accuracy of the bacterial RT-PCR assay compared to CSF culture and using World Health Organisation definitions of laboratory-confirmed bacterial meningitis.ResultsFrom 292 samples, bacterial DNA was detected in 12 (4.1%) and viral nucleic acids in 94 (32%). Compared to CSF culture, the sensitivity and specificity of the bacterial RT-PCR was 100% and 97.2% with complete agreement in organism identification. None of the cases positive by viral RT-PCR had a bacterial cause confirmed on CSF culture. Only 9/90 (10%) of patients diagnosed clinically as bacterial meningitis or partially treated bacterial meningitis tested positive with the bacterial RT-PCR.DiscussionIn this population the use of 2 multiplex RT-PCRs targeting 6 common pathogens gave promising results. If introduced into routine diagnostic testing, these multiplex RT-PCR assays would supplement other diagnostic tests, and have the potential to limit unnecessary antibiotic therapy and hospitalisation.