Childhood Invasive Bacterial Disease in Kathmandu, Nepal (2005-2013).

BACKGROUND: Invasive bacterial disease (IBD; including pneumonia, meningitis, sepsis) is a major cause of morbidity and mortality in children in low-income countries. METHODS: We analyzed data from a surveillance study of suspected community-acquired IBD in children <15 years of age in Kathmandu, Nepal, from 2005 to 2013 before introduction of pneumococcal conjugate vaccines (PCV). We detailed the serotype-specific distribution of invasive pneumococcal disease (IPD) and incorporated antigen and PCR testing of cerebrospinal fluid (CSF) from children with meningitis. RESULTS: Enhanced surveillance of IBD was undertaken during 2005-2006 and 2010-2013. During enhanced surveillance, a total of 7956 children were recruited of whom 7754 had blood or CSF culture results available for analysis, and 342 (4%) had a pathogen isolated. From 2007 to 2009, all 376 positive culture results were available, with 259 pathogens isolated (and 117 contaminants). Salmonella enterica serovar Typhi was the most prevalent pathogen isolated (167 cases, 28% of pathogens), followed by Streptococcus pneumoniae (98 cases, 16% pathogens). Approximately, 73% and 78% of pneumococcal serotypes were contained in 10-valent and 13-valent PCV, respectively. Most cases of invasive pneumococcal disease (IPD) were among children ≥5 years of age from 2008 onward. Antigen and PCR testing of CSF for pneumococci, Haemophilus influenzae type b and meningococci increased the number of these pathogens identified from 33 (culture) to 68 (culture/antigen/PCR testing). CONCLUSIONS: S. enterica serovar Typhi and S. pneumoniae accounted for 44% of pathogens isolated. Most pneumococcal isolates were of serotypes contained in PCVs. Antigen and PCR testing of CSF improves sensitivity for IBD pathogens.

Increased cytokines/chemokines and hyponatremia as a possible cause of clinically mild encephalitis/encephalopathy with a reversible splenial lesion associated with acute focal bacterial nephritis.

OBJECTIVE: Clinically mild encephalitis/encephalopathy with a reversible splenial lesion (MERS), the second most common encephalopathy syndrome in Japan, is most often associated with viral infection. Bacterial MERS has been rarely reported but is mostly associated with acute focal bacterial nephritis (AFBN) for an unknown reason. We examined cytokines and chemokines in four MERS patients with AFBN to determine if they play an important role in the pathogenesis. METHODS: We examined the clinical charts and MRI results in four MERS patients with AFBN, and measured 10 cytokines and chemokines in serum and cerebrospinal fluid in the acute phase. These were analyzed using the Mann-Whitney U test, compared with the control group (cases with a non-inflammatory neurological disease). Longitudinal changes in the serum cytokine and chemokine levels were evaluated in two patients. RESULTS: Hyponatremia was observed in all four patients with MERS associated with AFBN (128-134 mEq/L). CSF analysis revealed increased cytokines/chemokines associated with Th1 (CXCL10, TNF-α, IFN-γ), T reg (IL-10), Th17 (IL-6), and neutrophil (IL-8 and CXCL1). In serum, upregulation was observed in those associated with Th1 (CXCL10, TNF-α, IFN-γ), Th17 (IL-6), and inflammasome (IL-1ß). The increased serum cytokines/chemokines in the acute stage normalized within 2 weeks in patients 1 and 2, so examined, in accordance with their clinical improvement. CONCLUSION: Increased cytokines/chemokines and hyponatremia may be factors that explain why AFBN is likely to cause MERS.

Metabolomic Characterization of Cerebrospinal Fluid from Intracranial Bacterial Infection Pediatric Patients: A Pilot Study.

Intracranial bacterial infection remains a major cause of morbidity and mortality in neurosurgical cases. Metabolomic profiling of cerebrospinal fluid (CSF) holds great promise to gain insights into the pathogenesis of central neural system (CNS) bacterial infections. In this pilot study, we analyzed the metabolites in CSF of CNS infection patients and controls in a pseudo-targeted manner, aiming at elucidating the metabolic dysregulation in response to postoperative intracranial bacterial infection of pediatric cases. Untargeted analysis uncovered 597 metabolites, and screened out 206 differential metabolites in case of infection. Targeted verification and pathway analysis filtered out the glycolysis, amino acids metabolism and purine metabolism pathways as potential pathological pathways. These perturbed pathways are involved in the infection-induced oxidative stress and immune response. Characterization of the infection-induced metabolic changes can provide robust biomarkers of CNS bacterial infection for clinical diagnosis, novel pathways for pathological investigation, and new targets for treatment.

Impact of the Step-by-Step on febrile infants.

OBJECTIVE: To evaluate the impact of introducing the Step-by-Step approach on care quality in young febrile infants. DESIGN: Observational study including infants ≤90 days old with fever without source seen in a paediatric emergency department 5 years before (n=1222) and after (n=1151) its introduction. Quality of care was evaluated in terms of adherence to recommendations, resource use and safety. RESULTS: Adherence: percentages of infants undergoing both urine and blood tests and infants <15 days old receiving full sepsis evaluation increased (84.7% vs 91.0% and 23.9% vs 63.3%, respectively; p<0.01). Resource use: lumbar puncture and admission rates decreased (24.1% vs 18.7% and 43.6% vs 38.3%, respectively; p<0.01), while the rate of antibiotic therapy increased (30.2% vs 43.2%; p<0.01). SAFETY: the invasive bacterial infection rate among infants managed as outpatients was unchanged (0.7% vs 0.3%; p=0.24). CONCLUSION: The introduction of the Step-by-Step increased the quality of care provided to young febrile infants.

When a Root Is the Cause of Infection.

BACKGROUND: Sinorhizobium meliloti is a phytobacterium found in the root nodules of plants, where it is involved in fixing nitrogen for delivery to the roots in exchange for a photosynthate carbon source. There have been no reported cases of S. meliloti infection in humans. We conducted a retrospective review of clinical records and diagnostic tests. CASE DESCRIPTION: An 81-year-old woman who presented to the emergency department with a 1-day history of progressive decline in her level of consciousness following a head injury and deep scalp laceration. Her medical history was significant for a ventriculoperitoneal shunt due to normal pressure hydrocephalus. Imaging studies revealed hydrocephalus and a tear in the shunt catheter. Cerebrospinal fluid analysis was not suggestive for meningitis. Cerebrospinal fluid culture revealed an unfamiliar organism, identified as S. meliloti following sequencing of its entire genome, which was considered a contaminant. The patient subsequently developed peritonitis, and the same pathogen was detected in the peritoneal fluid, suggesting distal shunt infection. Symptoms resolved after shunt removal and antibiotic treatment. Thorough history taking revealed that the patient had fallen and struck her head against a flowerpot. CONCLUSIONS: S. meliloti is a phytopathogen that should not be easily disregarded as a contaminant when isolated from human sterile fluids or tissues. Aggressive management including removal of infected hardware, if present, is required to ensure resolution of infection. It emphasizes the importance of thorough history taking.

Neonates With Urinary Tract Infection: Is a Lumbar Puncture Always Indicated?

BACKGROUND: Our objectives were to determine the prevalence of and to identify risk factors for coexisting bacterial meningitis (BM) in neonates with urinary tract infection (UTI). METHODS: A cross-sectional study was conducted at pediatric emergency department of a tertiary teaching hospital from 2001 to 2017. Infants <29 days of age with UTI (≥10,000 colony-forming units/mL of a single pathogen from a catheterized specimen in association with positive urinalysis) were included. Definite BM was defined as growth of a single bacterial pathogen from a cerebrospinal fluid (CSF) sample and probable BM as (1) positive blood culture with CSF pleocytosis and treatment consistent with BM or (2) antibiotic pretreatment before lumbar puncture, CSF pleocytosis and treatment consistent with BM. Univariate testing was used to identify possible risk factors associated with BM. Receiver operating characteristics curves were constructed for the laboratory markers associated with BM. RESULTS: Three hundred seventy-one infants were included. Five [1.3%; 95% confidence interval (CI): 0.6%-3.1%] had BM: 4 definite BM and 1 probable BM. Risk factors detected for BM were classified as not being well-appearing and a procalcitonin value ≥0.35 ng/mL [sensitivity of 100% (95% CI: 56.6%-100%) and negative predictive value of 100% (95% CI: 96.1%-100%)]. CONCLUSIONS: Coexisting BM occurs uncommonly in neonates with UTI. Well-appearing neonates with UTI and procalcitonin value <0.35 ng/mL were at very low risk for BM; avoiding routine lumbar puncture in these patients should be considered.

L-lactate in cerebrospinal fluid can be used as a biomarker of encephalitis in cattle.

Cerebrospinal fluid (CSF) changes are significant for antemortem diagnoses of some neurological diseases. The aim of this study was to evaluate if the concentration of L-lactate in CSF could be used to differentiate healthy from encephalitic cattle. Cerebrospinal fluid samples from healthy cattle (n = 10) and from those naturally affected by rabies (n = 15), bovine herpesvirus type 5 meningoencephalitis (n = 16), histophilosis (n = 6), or bacterial encephalitis (n = 4), including 1 case of listeriosis, were collected and analyzed. Physical, biochemical (i.e., protein and glucose), and cellular analyses were performed in fresh samples. L-lactate, electrolytes (sodium, potassium, and chloride), calcium, and magnesium concentrations were measured in CSF samples that were kept frozen. L-lactate concentrations were also measured in plasma. Analysis of variance was used for comparison between groups and receiver operating characteristic analysis was performed considering L-lactate in CSF of healthy versus encephalitic cattle. The CSF L-lactate concentration was significantly higher in cattle with bacterial encephalitis than in healthy cattle; however, it did not differ between viral and bacterial encephalitis. The calcium concentrations were lower in cattle with encephalitis. L-lactate concentration in CSF > 3.6 mmol/L can be accepted as a cut-off value to indicate encephalitis. Thus, L-lactate in CSF is important for the diagnosis of encephalitis in cattle. Despite the small number of cases of bacterial encephalitis, it is suggested that L-lactate was not important for the differentiation between viral and bacterial encephalitis. Additional studies with a greater number of observations are necessary to clarify this, specifically in cases of listeriosis.

Les modifications du liquide céphalorachidien (LCR) sont importantes pour le diagnostic antemortem de certaines maladies neurologiques. Le but de cette étude était d'évaluer si la concentration de L-lactate dans le LCR pouvait être utilisée pour différencier les bovins en bonne santé des bovins encéphalitiques. Des échantillons de LCR provenant de bovins en bonne santé (n = 10) et de sujets infectés naturellement par la rage (n = 15), de méningoencéphalite à BoHV-5 (n = 16), l'histophilose (n = 6), ou d'encéphalite bactérienne (n = 4), notamment un cas de listériose ont été collectés et analysés. Des analyses physiques, biochimiques (protéines et glucose), et cellulaires ont été effectuées dans des échantillons frais. Les concentrations de L-lactate, d'électrolytes (Na+, K+, et Cl−), de calcium (Ca), et de magnésium ont été mesurées dans des échantillons de LCR maintenus congelés. Les concentrations de L-lactate ont également été mesurées dans le plasma. Une analyse de variance a été utilisée pour la comparaison entre les groupes et une analyse ROC (Receiver Operating Characteristic) a été réalisée en considérant le L-lactate dans le LCR de bovins en bonne santé par rapport à des bovins encéphalitiques. La concentration de L-lactate dans le LCR était significativement plus élevée chez les bovins présentant une encéphalite bactérienne que chez les bovins en bonne santé. Cependant, elle ne différait pas entre les bovins présentant une encéphalite virale et bactérienne. Les concentrations de Ca étaient plus faibles chez les bovins atteints d'encéphalite. Une concentration de L-lactate dans le LCR > 3,6 mmol/L peut être acceptée comme valeur seuil indiquant une encéphalite. Ainsi, le L-lactate dans le LCR est important pour le diagnostic de l'encéphalite chez les bovins. Malgré le petit nombre de cas d'encéphalite bactérienne inclus, il a été suggéré que la concentration de L-lactate dans le LCR dans la présente étude n'était pas une méthode de diagnostic important dans la différenciation entre l'encéphalite virale et bactérienne chez les bovins. Des études supplémentaires comportant un plus grand nombre d'observations sont nécessaires pour clarifier cet aspect, en particulier dans les cas de listériose.(Traduit par les auteurs).

Higher Procalcitonin Level in Cerebrospinal Fluid than in Serum Is a Feasible Indicator for Diagnosis of Intracranial Infection.

Objective: To explore the value of the difference in procalcitonin (PCT) levels in serum and cerebrospinal fluid (CSF) for diagnosing intracranial infection in post-neurosurgical patients. Methods: Patients who were treated at our hospital after craniotomy from January 2015 to January 2019 were enrolled in this study. Twenty patients eventually diagnosed with intracranial infection were included in a study group and 22 patients with no intracranial infection were included in a control group. A t-test was used to compare the differences between serum and CSF PCT levels of PCT, and the diagnostic value of PCT was evaluated by receiver operating characteristic (ROC) curve analysis. Results: The serum PCT levels in the study and control groups were 0. 10 ± 0. 03 ng/mL and 0. 09 ± 0. 03 ng/mL, respectively, and they were not substantially different between the groups. The CSF PCT level in the study group was substantially higher than that in the control group, with values of 0. 13 ± 0. 03 ng/mL and 0. 07 ± 0. 02 ng/mL, respectively. The CSF/serum PCT ratio in the study group was substantially higher than that in the control group, with values of 1. 31 ± 0. 19 and 0. 79 ± 0. 23, respectively. The areas under the ROC curve for serum PCT, CSF PCT and the CSF/serum PCT ratio were 0. 56, 0. 92, and 0. 95, respectively, resulting in a substantial difference among the three groups. Conclusion: CSF PCT may be a valuable marker for diagnosing intracranial infection in patients after neurosurgery; in particular, the specificity of CSF PCT is higher if the CSF PCT level is higher than the serum PCT level.

Risk factors for cerebrospinal fluid shunt infections during an outbreak: a case-control study.

BACKGROUND: There are few published reports of cerebrospinal fluid (CSF) shunt infection outbreaks. In 2017-2018, British Columbia Children's Hospital (BCCH) experienced an increase in CSF shunt infections co-incident with a move to new operating rooms and a change in shunt catheters used. AIMS: To describe how an outbreak was detected, investigations were undertaken to determine the cause, risk factors associated with CSF shunt infection during the outbreak, and changes implemented to attempt to control the outbreak. METHODS: Retrospective case-control study. Population included patients who underwent new shunt insertion or revision. Univariate logistic regression models were fitted for each of the variables. Associations with P-values <0.2 were considered of potential interest for further investigation. FINDINGS: There were six cases of CSF shunt infection and 19 controls. The causative organism was different in each case. The only risk factors that met the criteria for further investigation were being a neonate at the time of surgery [odds ratio (OR) 9.0, 95% confidence interval (CI) 0.7-125.3, P=0.10] and the presence of gastrointestinal disease (OR 3.8, 95% CI 0.5-26.2, P=0.18). No association was found with the operating room used or the surgical staff. In response to the outbreak, human traffic through the operating rooms was limited, rigid adherence to the wearing of surgical masks was enforced, and return to the previous CSF shunt catheters used was implemented. CONCLUSION: No modifiable risk factors were associated with CSF shunt infection. After implementation of surgical protocol changes, no further cases of CSF shunt infection linked to the outbreak were identified.

To LP or not to LP? Identifying the Etiology of Pediatric Meningitis.

Introduction of conjugate vaccines against Haemophilus influenzae type b, Streptococcus pneumoniae, and Neisseria meningitidis has led to a substantial reduction in cases of acute bacterial meningitis in countries with high routine childhood immunization coverage. The majority of children hospitalized with meningitis in high-income countries have viral or aseptic meningitis and do not require antibiotic treatment. Cerebrospinal fluid analysis is irreplaceable in appropriately diagnosing and treating bacterial meningitis and avoiding unnecessary antibiotics and prolonged hospitalizations in children with viral meningitis. New diagnostic tests have improved detection of bacterial and viral pathogens in cerebrospinal fluid, underscoring the importance of promptly performing lumbar puncture when meningitis is suspected. This article provides an overview of acute bacterial and viral meningitis in children, focusing on the changing epidemiology, the advantages and limitations of conventional and newer diagnostic methods, and considerations for clinical practice.

Etiology of Central Nervous System Infections in a Rural Area of Nepal Using Molecular Approaches.

The etiology of infections of the central nervous system (CNS) in Nepal often remains unrecognized because of underdeveloped laboratory facilities. The aim of this study was to investigate the etiology of CNS infections in a rural area of Nepal using molecular methods. From November 2014 to February 2016, cerebrospinal fluid (CSF) was collected from 176 consecutive patients presenting at United Mission Hospital in Tansen, Nepal, with symptoms of possible CNS infection. After the CSF samples were stored and transported frozen, polymerase chain reaction (PCR) was performed in Sweden, targeting a total of 26 pathogens using the FilmArray® ME panel (BioFire, bioMerieux, Salt Lake City, UT), the MeningoFinder® 2SMART (PathoFinder, Maastricht, The Netherlands), and an in-house PCR test for dengue virus (DENV), Japanese encephalitis virus (JEV), and Nipah virus (NiV). The etiology could be determined in 23%. The bacteria detected were Haemophilus influenzae (n = 5), Streptococcus pneumoniae (n = 4), and Neisseria meningitidis (n = 1). The most common virus was enterovirus detected in eight samples, all during the monsoon season. Other viruses detected were cytomegalovirus (n = 6), varicella zoster virus (n = 5), Epstein-Barr virus (n = 3), herpes simplex virus (HSV) type 1 (HSV-1) (n = 3), HSV-2 (n = 3), human herpes virus (HHV) type 6 (HHV-6) (n = 3), and HHV-7 (n = 2). Cryptococcus neoformans/gatti was found in four samples. None of the samples were positive for DENV, JEV, or NiV. Of the patients, 67% had been exposed to antibiotics before lumbar puncture. In conclusion, the etiology could not be found in 77% of the samples, indicating that the commercial PCR panels used are not suitable in this setting. Future studies on the etiology of CNS infections in Nepal could include metagenomic techniques.

Infectious causes and outcomes in patients presenting with cerebral spinal fluid pleocytosis.

To evaluate the infectious etiologies, clinical features, and outcomes of patients with CNS infections at a tertiary care center. Patients that present with a pleocytosis in the cerebral spinal fluid (CSF), defined as a CSF WBC count > 5 cells/mm3, from July 2015 to June 2016 at a tertiary care hospital were analyzed for this report. Data from patients with confirmed (n = 43) and presumed (n = 51) CNS infections were analyzed. CNS infection was the leading known cause of CSF pleocytosis (n = 43, 18% of all patients with a pleocytosis in the CSF), and HSV-2 was identified as the leading causative pathogen (n = 10) followed by varicella zoster virus (n = 5). Fifty-three percent of patients with a pleocytosis in the CSF did not receive a diagnosis. In the patients that did not receive a diagnosis, CNS infection was presumed to be the cause in 51 patients (21% of patients with CSF pleocytosis). The mean time to diagnosis for patients with confirmed CNS infection was 16 days, but time to diagnosis was highly variable depending on the causative pathogen. There was a significant overlap in CSF parameters and peripheral white blood cell counts in patients diagnosed with a viral, bacterial, or fungal infection. Neuroimaging changes were present in only 44% of CNS infections. The overall mortality was 7% for CNS infections, and 17% of patients with a CNS infection had a severe neurologic deficit at presentation while only 3% had a severe deficit at the last neurologic assessment. This study provides new insights into the infectious causes of disease in a cohort of patients with pleocytosis in the CSF. The study provides new insights into the time to diagnosis and outcomes in patients that present with pleocytosis in the CSF.

Cerebrospinal fluid CXLC13 indicates disease course in neuroinfection: an observational study.

BACKGROUND: The chemokine CXCL13 is an intensively investigated biomarker in Lyme neuroborreliosis (LNB). Its role in other neuroinfections is increasingly recognized but less clear. OBJECTIVE: To determine the significance of CXCL13 in established central nervous system (CNS) infections other than LNB by matching cerebrospinal fluid (CSF) CXCL13 elevations with severity of the disease course. METHODS: We investigated 26 patients with bacterial (n = 10) and viral (n = 16; tick-borne encephalitis, n = 6; varicella zoster infection, n = 10) neuroinfections of whom CSF CXCL13 levels were available twice, from lumbar punctures (LP) performed at admission and follow-up. As outcome classification, we dichotomized disease courses into "uncomplicated" (meningitis, monoradiculitis) and "complicated" (signs of CNS parenchymal involvement such as encephalitis, myelitis, abscesses, or vasculitis). CXCL13 elevations above 250 pg/ml were classified as highly elevated. RESULTS: Eight of 26 patients (31%) with both bacterial (n = 4) and viral (n = 4) neuroinfections had a complicated disease course. All of them but only 3/18 patients (17%) with an uncomplicated disease course had CSF CXCL13 elevations > 250 pg/ml at the follow-up LP (p < 0.001). At admission, 4/8 patients (50%) with a complicated disease course and 3/18 patients (17%) with an uncomplicated disease course showed CXCL13 elevations > 250 pg/ml. All four patients with a complicated disease course but only one with an uncomplicated disease course had sustained CXCL13 elevations at follow-up. Patient groups did not differ with regard to age, time since symptom onset, LP intervals, type of infections, and anti-pathogen treatments. CONCLUSION: Our study revealed pronounced CXCL13 elevations in CSF of patients with severe disease courses of bacterial and viral neuroinfections. This observation indicates a role of CXCL13 in the CNS immune defense and points at an additional diagnostic value as biomarker for unresolved immune processes leading to or associated with complications.

Patient and Treatment Characteristics by Infecting Organism in Cerebrospinal Fluid Shunt Infection.

BACKGROUND: Previous studies of cerebrospinal fluid (CSF) shunt infection treatment have been limited in size and unable to compare patient and treatment characteristics by infecting organism. Our objective was to describe variation in patient and treatment characteristics for children with first CSF shunt infection, stratified by infecting organism subgroups outlined in the 2017 Infectious Disease Society of America's (IDSA) guidelines. METHODS: We studied a prospective cohort of children <18 years of age undergoing treatment for first CSF shunt infection at one of 7 Hydrocephalus Clinical Research Network hospitals from April 2008 to December 2012. Differences between infecting organism subgroups were described using univariate analyses and Fisher's exact tests. RESULTS: There were 145 children whose infections were diagnosed by CSF culture and addressed by IDSA guidelines, including 47 with Staphylococcus aureus, 52 with coagulase-negative Staphylococcus, 37 with Gram-negative bacilli, and 9 with Propionibacterium acnes. No differences in many patient and treatment characteristics were seen between infecting organism subgroups, including age at initial shunt, gender, race, insurance, indication for shunt, gastrostomy, tracheostomy, ultrasound, and/or endoscope use at all surgeries before infection, or numbers of revisions before infection. A larger proportion of infections were caused by Gram-negative bacilli when antibiotic-impregnated catheters were used at initial shunt placement (12 of 23, 52%) and/or subsequent revisions (11 of 23, 48%) compared with all other infections (9 of 68 [13%] and 13 of 68 [19%], respectively). No differences in reinfection were observed between infecting organism subgroups. CONCLUSIONS: The organism profile encountered at infection differs when antibiotic-impregnated catheters are used, with a higher proportion of Gram-negative bacilli. This warrants further investigation given increasing adoption of antibiotic-impregnated catheters.

Rapid identification of nonblood sterile site broth cultures using the FilmArray blood culture identification panel.

The FilmArray Blood Culture Identification Panel was validated for nonblood sterile site specimens with clinical impact of rapid identification compared to conventional diagnostics. The panel accurately identified target organisms from 98% of positive broth cultures a median 1.1 day faster than conventional techniques (P < 0.0001) with potential clinical impact in 22% of cases.

Prevalence and antibiotic resistance of bacteria isolated from the cerebrospinal fluid of neurosurgical patients at Peking Union Medical College Hospital.

Background: Postoperative central nervous system infections (PCNSIs) represent a serious complication, and the timely use of antibiotics guided by the identification of the causative pathogens and their antibiotic sensitivities is essential for treatment. However, there are little data regarding the prevalence of PCNSI pathogens in China. The aim of this study is to investigate the features of pathogens in patients with PCNSIs, which could help clinicians to choose the appropriate empirical antibiotic therapy. Methods: We retrospectively examined the positive CSF cultures in patients who underwent craniotomy between January 2010 and December 2015. We collected data, including demographic characteristics, type of neurosurgery, laboratory data, causative organisms and antimicrobial susceptibility testing results. Results: A total of 62 patients with 90 isolates out of 818 patients with 2433 CSF culture samples were available for data analysis. The estimated incidence and culture-positive rate of PCNSIs were approximately 0.9 and 7.5%, respectively. The predominant organism was coagulase-negative staphylococci, of which most were methicillin-resistant coagulase-negative staphylococci (MRCoNS). All were susceptible to vancomycin, linezolid, rifampicin and amoxicillin-clavulanate. Acinetobacter baumannii was the most frequent causative Gram-negative agent and was resistant to 12 out of 18 antimicrobials tested. The sensitivity rates for tigecycline and minocycline were only 40 and 33%, respectively. Conclusion: PCNSIs could lead to high mortality. Although the MRCoNS were the predominant organism, the management of Acinetobacter baumannii was a major clinical challenge with few effective antimicrobials in PCNSIs.

Evaluation of a Commercial Multiplex Molecular Panel for Diagnosis of Infectious Meningitis and Encephalitis.

Rapid and accurate laboratory tests are important for the timely diagnosis and treatment of central nervous system infections. The FilmArray meningitis/encephalitis (ME) panel (BioFire Diagnostics, Salt Lake City, UT) is an FDA-cleared, multiplex molecular panel that allows the detection of 14 pathogens (bacterial [n = 6], viral [n = 7], and fungal [n = 1] pathogens) from cerebrospinal fluid (CSF). In this study, we evaluated the performance characteristics of the FilmArray ME panel using clinical, residual CSF samples (n = 291) that tested positive by a routine method(s) (e.g., bacterial culture, individual real-time PCR assay) for a pathogen represented on the ME panel. Of note, a subset (n = 76) of the CSF specimens was collected during the prevaccine era and had been characterized as positive for a bacterial pathogen. The FilmArray ME panel demonstrated an overall percent positive agreement (PPA) of 97.5% (78/80) for bacterial pathogens, 90.1% (145/161) for viruses, and 52% (26/50) for Cryptococcusneoformans/C. gattii Despite the low overall agreement (52%) between the ME panel and antigen testing for detection of C. neoformans/C. gattii, the percent positive agreement of the FilmArray assay for C. neoformans/C. gattii was 92.3% (12/13) when the results were compared directly to the results of routine fungal smear or culture. The FilmArray ME panel offers a rapid (∼60-min), syndrome-based approach for the detection of select meningitis and encephalitis pathogens.

Factors Influencing Norvancomycin Concentration in Plasma and Cerebrospinal Fluid in Patients After Craniotomy and Dosing Guideline: A Population Approach.

PURPOSE: Antibacterial spectrum and activity of norvancomycin are comparable with vancomycin, and it has been widely used in China. Norvancomycin can penetrate into the cerebrospinal fluid (CSF) through the damaged blood-brain barrier in patients after craniotomy. Because higher inter-individual variability was observed, we aimed to identify factors related to drug concentration to guide clinicians with norvancomycin dosing. METHODS: After craniotomy, patients with an indwelling catheter in the operational area/ventricle were intravenously administered norvancomycin. Venous blood and CSF specimens were collected at a scheduled time for measuring drug concentrations. Blood and CSF data were fitted simultaneously with the use of the nonlinear fixed-effects modeling method to develop the population pharmacokinetic model. Covariate analysis was applied to select candidate factors associated with pharmacokinetic parameters. A model-based simulation was performed to find optimized regimens for different subgroups of patients. FINDINGS: A 3-compartmental model (central, peripheral, and CSF compartments) with 2 elimination pathways (drug elimination from the kidney and CSF outflow) was developed to characterize the in vivo process of norvancomycin. The covariate analysis identified that weight and drainage amount were strongly associated with the central volume and the drug clearance from CSF, respectively. Goodness-of-fit and model validation suggested that the proposed model was acceptable. A dosage regimen table was created for specific patient populations with different weights and drainage amounts to facilitate clinical application. IMPLICATIONS: We identified 2 clinical markers associated with plasma and CSF concentrations. The proposed simulation may be useful to clinicians for norvancomycin dosing in this specific population with normal kidney function.

Analysis of microbial community composition and diversity in postoperative intracranial infection using high­throughput sequencing.

Intracranial infection is one of the most serious complications following neurosurgery. It is well acknowledged that bacteria and fungi are the main pathogens responsible for postoperative intracranial infection. However, the microbial community structure, including composition, abundance and diversity, in postoperative intracranial infection is not fully understood, which greatly compromises our understanding of the necessity and effectiveness of postoperative antibiotic treatment. The present study collected eight cerebrospinal fluid (CSF) samples from patients with intracranial infection following neurosurgical procedures. High­throughput amplicon sequencing for 16S rDNA and internal transcribed spacer (ITS) was performed using the Illumina MiSeq platform to investigate the microbial community composition and diversity between treated and untreated patients. Bioinformatics analysis revealed that the microbial composition and diversity in each patient group (that is, with or without antibiotic treatment) was similar; however, the group receiving antibiotic treatment had a comparatively lower species abundance and diversity compared with untreated patients. At the genus level, Acinetobacter and Staphylococcus were widely distributed in CSF samples from patients with postoperative intracranial infection; in particular, Acinetobacter was detected in all CSF samples. In addition, five ITS fungal libraries were constructed, and Candida was detected in three out of four patients not receiving antibiotic treatment, indicating that the fungal infection should be given more attention. In summary, 16S and ITS high­throughput amplicon sequencing were practical methods to identify pathogens in the different periods of treatment in patients with postoperative intracranial infection. There was a notable difference in microbial composition and diversity between the treated and untreated patients. Alterations in the microbial community structure may provide a signal whether antibiotic treatment worked in postoperative intracranial infection and may assist surgeons to better control the progression of infection.

Moving the goalposts: A comparison of different definitions for primary external ventricular drain infection and its risk factors: A multi-center study of 2575 patients.

External ventricular drainage is the most common procedure performed in daily neurosurgical practice. One devastating complication is ventriculostomy-associated infection, but the establishment of evidence-based management guidelines has been hindered by the lack of an universal definition. There is also limited data with regard to the utility of comorbidity health indices and surgery-related factors in predicting infection. This study aims to compare the incidence of infection according to five commonly used definitions and to identify risk factors for this complication. 2575 patients from seven neurosurgical centers in Hong Kong underwent primary external ventricular drainage. The frequency of infection according to Gozal was 2.2% (n=57), 4.7% (Chi), 0.6% (Lozier), 0.8% (Lyke) and 2.8% (Scheithauer). The commonest pathogen was coagulase negative staphylococcus (39%) and 49% of all microbial isolates were multiple-drug resistant. The mean Charlson comorbidity index was 0.5±1.1. Using Gozal's definition as the primary endpoint, the index was not predictive of infection and no surgical risk factors were identified. The only significant risk factor was the performance of two or more additional neurosurgical procedures within 30days of catheterization (OR: 2.1, 95% CI 1.1-4.5). The rate of infection is relatively low, but considerable disparity exists depending on the definition used. Our data implies that patient factors, in particular the Charlson comorbidity index, and variations in surgical practice are less influential than the strict observance of infection control measures. The high incidence of antibiotic-resistant bacteria is concerning and the routine of exchange of catheters within 30days should be discouraged.