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    Update and advances in community acquired bacterial meningitis. Hasbun Rodrigo Current opinion in infectious diseases PURPOSE OF REVIEW:Community-acquired bacterial meningitis continues to occur and be associated with significant morbidity and mortality despite the availability of effective conjugate vaccines for the three most important meningeal pathogens. RECENT FINDINGS:Indications for cranial imaging in suspected bacterial meningitis varies significantly between guidelines. Cranial imaging is of no clinical utility in those patients without indications and fosters delays in performing a lumbar puncture. Delaying lumbar puncture is associated with increased costs in both adults and children with meningitis and previous antibiotic therapy impacts the yield of microbiological results. Delaying antibiotic therapy is associated with worse clinical outcomes. Adjunctive steroids have reduced the mortality of adults with pneumococcal meningitis but have been associated with increased adverse outcomes in Listeria monocytogenes and Cryptococcus neoformans. SUMMARY:Community-acquired bacterial meningitis remains a global health concern with high morbidity and mortality especially in low-income countries. Cranial imaging should be done only in patients with an indication with an attempt to do a prompt lumbar puncture and to initiate antibiotic therapy and adjunctive steroids as soon as possible to improve clinical outcomes. 10.1097/QCO.0000000000000543
    Predictive value of repeated cerebrospinal fluid parameters in the outcomes of bacterial meningitis in infants <90 days of age. Ting Joseph Y,Roberts Ashley,Khan Sarah,Bitnun Ari,Hawkes Michael,Barton Michelle,Bowes Jennifer,Brophy Jason,Ouchenir Lynda,Renaud Christian,Boisvert Andrée-Anne,McDonald Jane,Robinson Joan L PloS one BACKGROUND:There are variations in recommendations from different guidelines regarding the indications for repeat lumbar puncture (LP) in young infants with the diagnosis of bacterial meningitis. OBJECTIVE:To evaluate the frequency of repeat LPs and the characteristics of cerebrospinal fluid (CSF) parameters in repeated sampling and their predictive values for adverse outcomes in a national cohort. METHODS:This cohort study included infants born January 1, 2013 through December 31, 2014, who had proven or suspected bacterial meningitis within the first 90 days of life at seven paediatric tertiary care hospitals across Canada, and who underwent a repeat LP at the discretion of the treating physicians. RESULTS:Forty-nine of 111 infants (44%) underwent repeat LP at a median of 5 (IQR: 3, 13) days after the LP that led to the diagnosis of bacterial meningitis. Those who had meningitis caused by gram negative bacilli were more likely to have repeat LP than those with gram positive bacteria (77% versus 57%; p = 0.012). White blood cell (WBC) count on the second spinal tap yielded an area under the curve of 0.88 for predicting sequelae of meningitis at discharge from the hospital, with a cut-off value of 366 × 106/L, providing a sensitivity of 91% and specificity of 88%. CONCLUSION:In this multi-centre retrospective cohort study, infants with gram negative meningitis were more likely to have repeated LP. A high WBC on the second CSF sample was predictive of adverse outcome at the time of discharge from the hospital. 10.1371/journal.pone.0238056
    Epidemiology, clinical profile and role of rapid tests in the diagnosis of acute bacterial meningitis in children (aged 1-59 months). Chauhan Divya,Mokta Kiran,Kanga Anil,Grover Neelam Neurology India Objectives:To study the epidemiology, clinical profile, and the role of rapid tests in the diagnosis of acute bacterial meningitis (ABM) in children (1-59 months). Materials and Methods:A total of 250 cerebrospinal fluid (CSF) and 187 blood samples received from clinically suspected cases of ABM were processed based on standard microbiological protocols. CSF samples were also subjected to antigen and nucleic acid detection. Antibiotic susceptibility testing was done according to the Clinical Laboratory Standards Institute guidelines. Children were also evaluated for outcomes and were followed up until 6 months after discharge. Results:Eighty one cases were reported to be having clinically confirmed ABM, out of which group B Streptococcus was the most common pathogen detected in 49.3% (40) patients followed by Streptococcus pneumoniae, Staphylococcus aureus, Hemophilus influenzae type b, Escherichia coli, Klebsiella pneumoniae, and Neisseria meningitidis ACYW135 in 23.4% (19), 7.4% (6), 6.1% (5), 6.1% (5), 6.1% (5), and in 1.2% (1) patients, respectively. Complications were observed in 54.3% of the children. A follow-up of 6 months after discharge was possible in 39.5% (32) patients among whom sequelae were recorded in 93.7% (30) patients. Conclusion:ABM remains a major cause of neurological sequelae worldwide. Although culture is the gold standard test for its detection, the investigation takes a longer time and the results are influenced by prior antimicrobial therapy. In such cases, rapid tests aid in the early diagnosis of ABM for instituting appropriate management. 10.4103/0028-3886.236972
    [Analysis of current epidemiological and clinical characteristics for laboratory confirmed epidemic cerebrospinal meningitis cases in Shandong Province, 2007-2016]. Zhang Y,Song L Z,Liu G F,Li M S,Lin X J,Xu A Q Zhonghua yu fang yi xue za zhi [Chinese journal of preventive medicine] To analyze epidemiological and clinical characteristics of laboratory confirmed epidemic cerebrospinal meningitis cases. Epidemiological and clinical informations and cerebrospinal fluid (CSF) and blood specimens of AMES (acute meningitis/encephalitis syndrome) cases were collected in the six sentinel hospitals from 2007 to 2016. () species and serogroup identification were detected by the methods of real-time fluorescent quantitative polymerase chain reaction (Real-time PCR) and bacterial culture, and epidemiological and clinical characteristics of laboratory confirmed epidemic cerebrospinal meningitis cases were analyzed. 6 809 AMES cases were reported from 2007 to 2016. Total 4 422 cases were detected, and 90 cases were positive. Through the methods of Real-time PCR, bacterial blood culture and CSF culture, the numbers of positive cases were 90, 2 and 1 respectively. Twenty-two cases were identified from 2007 to 2011 (4 cases were ungrouped), which with the highest incidence in serogroup C cases (17/18), and one cases was ungroupable . laboratory confirmed cases (68 cases) were increased dramatically and mainly occurred in serogroup B cases (43/67, 64.2%) from 2012 to 2016, with serogroup C cases highly decreased (5/67, 7.5%) and ungroupable cases increased (13/67, 19.4%) meanwhile. Serogroup W135 and X cases were first detected at 2012 and 2014, and serogroup A remaining a low level which only detected one case at 2013. The morbidity of epidemic cerebrospinal meningitis was occured in the whole year, and mainly in winter and spring. The ratio of laboratory confirmed cases to AMES cases during November to May (3.5%, 67/1 920) was higher than that during June to October (0.9%, 23/2 502) (χ(2)=34.45, 0.001). Most cases were children, students and farmers, and account for 30.0% (27/90), 31.1% (28/90), 18.9% (17/90), respectively. The majority of cases were under 20 years old (60/90, 66.67%), and serogroup C cases (17/22, 77.3%) mainly occurred in over 12 years old population, while serogroup B (24/43, 55.8%) and ungroupable (6/14) cases mainly occurred in under 12 years old population. The main clinical symptoms of epidemic cerebrospinal meningitis cases were fever (78/90, 86.7%), headache (59/90, 65.6%) and vomiting (51/90, 56.7%). Misdiagnosis rate of admitting diagnosis was up to 87.8% (79/90) for the reason of atypical features in specific symptoms and blood or CSF positive index. The well-healed ratio in correct diagnosed group (7/11) was higher than that in misdiagnosed group (2.5%, 2/79) (χ(2)=40.61, 0.001). The clinical symptoms of epidemic cerebrospinal meningitis cases were atypical, and the diagnosed sensitivity and accuracy would be improved by enhanced molecular biology detection. The predominant epidemic serogroup of switched from serogroup C to B, and the key work was surveaylance of serogroup transition. 10.3760/cma.j.issn.0253-9624.2019.02.009
    A review of a 13-month period of FilmArray Meningitis/Encephalitis panel implementation as a first-line diagnosis tool at a university hospital. Boudet Agathe,Pantel Alix,Carles Marie-Josée,Boclé Hélène,Charachon Sylvie,Enault Cécilia,Stéphan Robin,Cadot Lucile,Lavigne Jean-Philippe,Marchandin Hélène PloS one Early diagnosis and treatment of meningitis and encephalitis is essential for reducing both their morbidity and mortality. The FilmArray® Meningitis/Encephalitis (FA-M/E) panel is a recently available molecular tool allowing the simultaneous detection of 14 pathogens in about one hour. We evaluated its routine use over a 13-month period at Nîmes University Hospital, France. Cerebrospinal fluid (CSF) specimens were prospectively analyzed, independently of cell count; results were retrospectively analyzed and positive results compared to clinical and microbiological data. Among the 708 patients included (734 CSF samples), 89 (12.6%) had a positive FA-M/E panel, 71 (80%) for a viral pathogen and 18 (20%) for a bacterial pathogen. Enterovirus and HHV-6 were the main detected pathogens. Mean time-to-results was 1h46mn. Four non-clinically relevant results were detected (3 HHV-6 and 1 Haemophilus influenzae) on the basis of inconsistent clinical and/or biological data, and/or after visualization of melting curves. No CSF pleocytosis was observed in 11% of the patients with a positive FA-M/E panel. For the 18 patients with a positive FA-M/E panel for a bacterial pathogen, five (28%) had CSF samples showing a positive Gram stain allowing an early diagnosis of bacterial infection and 67% had CSF displaying a positive culture. Altogether the panel detected 5 cases of bacterial M/E (29%) not diagnosed by culture. Despite undeniable advantages, mainly ease of use, quick result availability, and an extremely low rate of invalid results, measures should be implemented to limit false-positive results due to contamination and a careful interpretation based on the overall data for each patient is required. 10.1371/journal.pone.0223887
    [Therapeutic monitoring of cerebrospinal fluid vancomycin concentrations and analysis of their influencing factors in neurosurgical intensive care unit patients]. Yao Mingli,Li Jingchao,Shi Lei,Li Yan,Wang Lingyan,Guan Xiangdong,Ouyang Bin Zhonghua wei zhong bing ji jiu yi xue OBJECTIVE:To evaluate cerebrospinal fluid (CSF) vancomycin concentrations and identify factors influencing CSF vancomycin concentrations in critically ill neurosurgical patients. METHODS:A retrospective study was conducted. Adult patients who received vancomycin treatment and CSF vancomycin concentrations monitoring admitted to neurosurgical intensive care unit (ICU) of the First Affiliated Hospital of Sun Yat-sen University from January 2016 to June 2019 were enrolled. General information, vancomycin dosing regimens, CSF vancomycin concentrations, CSF drainage methods and volume of the previous day, and concurrent medications, etc. were collected for analysis. CSF vancomycin concentrations of patients with definite or indefinite central nervous system (CNS) infection, different vancomycin dosing regimens and their influencing factors were analyzed. RESULTS:A total of 22 patients were included. 168 CSF specimens were collected for culture, 20 specimens of which were culture positive, with a positive rate of 11.9%. Sixty cases of CSF vancomycin concentration were obtained. Among the 22 patients, 7 patients (31.8%) were diagnosed with proven CNS infection, 11 patients (50.0%) clinically diagnosed, 2 patients (9.1%) diagnosed with uncertain CNS infection, and 2 patients (9.1%) diagnosed without CNS infection. Intravenous (IV) administration of vancomycin alone was used in 15 cases (25.0%), intrathecal injection in 17 cases (28.3%), IV+intrathecal injection in 23 cases (38.3%), and IV+intraventricular administration in 5 cases (8.3%). The CSF vancomycin concentrations ranged from < 0.24 to > 100 mg/L, with an average level of 14.40 (4.79, 42.34) mg/L. (1) Administration methods of vancomycin affected CSF vancomycin concentrations. The CSF vancomycin concentration with intrathecal injection or intraventricular administration was higher than that of IV administration alone [mg/L: 25.91 (11.28, 58.17) vs. 2.71 (0.54, 5.33), U = 42.000, P < 0.01]. (2) When vancomycin was administered by IV treatment alone, CSF vancomycin concentrations were low in both groups with definite CNS infection (proven+probable) and indefinite CNS infection (possible+non-infection), the CSF vancomycin concentrations of which were 4.14 (1.40, 6.36) mg/L and 1.27 (0.24, 3.33) mg/L respectively, with no significant difference (U = 11.000, P = 0.086). (3) CSF vancomycin concentrations rose with the increased dose of vancomycin delivered by intrathecal injection or intraventricular administration. According to the dose of vancomycin administered locally on the day before therapeutic drug monitoring (TDM), cases were divided into the following groups: 0-15 mg group (n = 22), 20-35 mg group (n = 33), and 40-50 mg group (n = 5), the CSF vancomycin concentrations of which were 4.14 (1.09, 8.45), 30.52 (14.31, 59.61) and 59.43 (25.51, 92.45) mg/L respectively, with significant difference (H = 33.399, P < 0.01). Moreover, the cases of CSF vancomycin concentration of ≥ 10 mg/L accounted for 18.2%, 84.8% and 100% of these three groups, respectively. CSF vancomycin concentrations mostly reached target level when dose of vancomycin administered locally were 20 mg/L or more. CONCLUSIONS:It is difficult to reach target CSF vancomycin concentration for critically ill neurosurgical patients with or without CNS infection by IV treatment. Local administration is an effective treatment regimen to increase CSF vancomycin concentration. 10.3760/cma.j.issn.2095-4352.2019.10.014
    Factors associated with early complications in inpatients who were treated in our clinic between 1992 and 2011 with a diagnosis of acute bacterial meningitis. Bor Meltem,Çokuğraş Haluk Turk pediatri arsivi Aim:To evaluate factors associated with the development of early complications in acute bacterial meningitis. Material and Methods:In our study, 389 patients diagnosed with acute bacterial meningitis between January 1992 and January 2011 at Cerrahpaşa Medical Faculty were retrospectively analyzed to determine the risk factors for the development of early complications. Results:The causative agent was in 17% of cases, S. pneumoniae in 13.6%, and in 6.4%. In 55.5% of cases, the causative agent could not be identified. The mortality rate was found as 1% and the early complication rate was 27.8%. The complications observed included septic shock and disseminated intravascular coagulation (33.3%), hydrocephalus (23.1%), subdural effusion (19.4%), and epilepsy (12%). Risk factors for early complications included being aged below two years (p<0.010), restlessness (p<0.010), rash (p<0.010), leukocytosis in complete blood count (p<0.010), and a cerebrospinal fluid glucose level of <45 mg/dL (p<0.010). Three of the four patients who died were male. The incidence of hydrocephalus was higher in patients who used ampicillin-cefotaxime and who did not receive steroid therapy before treatment (p<0.050). Conclusion:When acute bacterial meningitis is treated properly and adequately, recovery without sequela is possible. Knowing the risk factors for early complications will guide in the monitoring of patients and decrease morbidity and mortality rates. 10.14744/TurkPediatriArs.2019.34445
    Pathogen Analysis of Central Nervous System Infections in a Chinese Teaching Hospital from 2012-2018: A Laboratory-based Retrospective Study. Tian Lei,Zhang Zhen,Sun Zi-Yong Current medical science Central nervous system (CNS) infections are associated with high mortality rates. The clinical presentation of many CNS infections by different pathogens is difficult to distinguish, but the definite diagnosis of the etiology is critical for effective therapy and prognosis. The aim of this study was to explore the etiology of CNS infections with definite diagnoses based on data from a clinical microbiology laboratory in Tongji Hospital, a teaching hospital in China, obtained over a six-year period. We conducted a retrospective study on all cerebrospinal fluid (CSF) specimens submitted to our clinical microbiology laboratory from September, 2012 to December, 2018. The etiology of CNS infections caused by Cryptococcus neoformans, Mycobacterium tuberculosis and common bacteria was analyzed. Antimicrobial susceptibility testing was conducted on all isolates. The results showed that 1972 cases of CNS infections were identified from 18 300 CSF specimens. Common bacterial meningitis (BM), cryptococcal meningitis (CM) and tuberculous meningitis (TM) accounted for 86.3% (677/785), 9.4% (74/785) and 4.3% (34/785) respectively of cases over the six-year period. BM was the most common among the different age groups, followed by CM. Of the TM cases, 44.1% (15/34) were distributed within the age group of 15-34 years, whereas for CM cases, 52.7% (39/74) occurred within the 35-54-year age group, and the age distribution of BM cases was fairly even. Among the bacterial pathogens isolated, Staphylococcus epidermidis was the most common, accounting for 12.5% (98/785), followed by Acinetobacter baumannii (ABA) and Staphylococcus aureus (SAU), accounting for 11.8% (93/785) and 7.6% (60/785) respectively. The resistance rates to antibiotics were >75%, with the exception of the resistance rate of ABA to tegafycline, which was <3%. More than 60% of SAU strains displayed resistance to penicillin, oxacillin, ampicillin/sulbactam, cefazolin, cefuroxime, gentamycin, tobramycin, erythromycin and levofloxacin, whereas more than 90% of SAU strains showed susceptibility to trimethoprim/sulfamethoxazole, tegafycline, vancomycin, teicoplanin and linezolid. For C. neoformans, the susceptibility rates to amphotericin B, 5-fluorocytosine, fluconazol and voriconazole were >95%. Analysis of samples from patients with CNS infection in a clinical microbiology laboratory at a teaching hospital in China over a six-year period indicated that the most common etiological agents were the bacteria ABA and SAU. The antibiotic resistance levels of ABA were found to be high and of concern, whereas isolates of C. neoformans were found to be sensitive to antifungal antibiotics. 10.1007/s11596-019-2058-7
    [Analysis of pathogenic bacteria and drug resistance in neonatal purulent meningitis]. Zhu Minli,Hu Qianhong,Mai Jingyun,Lin Zhenlang Zhonghua er ke za zhi = Chinese journal of pediatrics OBJECTIVE:To study the clinical characteristics, pathogenic bacteria, and antibiotics resistance of neonatal purulent meningitis in order to provide the guide for early diagnosis and appropriate treatment. METHOD:A retrospective review was performed and a total of 112 cases of neonatal purulent meningitis (male 64, female 58) were identified in the neonatal intensive care unit of Yuying Children's Hospital of Wenzhou Medical University seen from January 1, 2004 to December 31, 2013. The clinical information including pathogenic bacterial distribution, drug sensitivity, head imageology and therapeutic outcome were analyzed. Numeration data were shown in ratio and chi square test was applied for group comparison. RESULT:Among 112 cases, 46 were admitted from 2004 to 2008 and 66 from 2009 to 2013, 23 patients were preterm and 89 were term, 20 were early onset (occurring within 3 days of life) and 92 were late onset meningitis (occurring after 3 days of life). In 62 (55.4%) cases the pathogens were Gram-positive bacteria and in 50 (44.6%) were Gram-negative bacteria. The five most frequently isolated pathogens were Escherichia coli (32 cases, 28.6%), coagulase-negative staphylococcus (CNS, 20 cases, 17.9%), Streptococcus (18 cases, 16.1%, Streptococcus agalactiae 15 cases), Enterococci (13 cases, 11.6%), Staphylococcus aureus (9 cases, 8.0%). Comparison of pathogenic bacterial distribution between 2004-2008 and 2009-2013 showed that Gram-positive bacteria accounted for more than 50% in both period. Escherichia coli was the most common bacterium, followed by Streptococcus in last five years which was higher than the first five years (22.7% (15/66) vs. 6.5% (3/46), χ(2) = 5.278, P < 0.05). Klebsiella pneumoniae was more common isolate in preterm infants than in term infants (13.0% (3/23) vs. 1.1% (1/89), χ(2) = 7.540, P < 0.05). Streptococcus (most were Streptococcus agalactiae) was the most common bacteria in early onset meningitis and higher than those in late onset meningitis (35.0% (7/20) vs. 12.0% (11/92), χ(2) = 4.872, P < 0.05). Drug sensitivity tests showed that all the Gram-positive bacterial isolates were sensitive to linezolid. Staphylococci were resistant to penicillin, and most of them were resistant to erythromycin, oxacillin and cefazolin; 77.8%of CNS isolates were methicillin-resistant staphylococcus. No Streptococcus and Enterococcus faecalis was resistant to penicillin. None of enterococci was resistant to vancomycin. Among the Gram-negative bacterial isolates, more than 40% of Escherichia coli were resistant to commonly used cephalosporins such as cefuroxime, cefotaxime and ceftazidime, and all of them were sensitive to amikacin, cefoperazone sulbactam and imipenem. Isolates of Klebsiella pneumoniae were all resistant to ampicillin, cefuroxime, cefotaxime and ceftazidime, but none of them was resistant to piperacillin tazobactam and imipenem. Of the 112 patients, 69 were cured, 23 improved, 9 uncured and 11 died. There were 47 cases (42.0%) with poor prognosis, they had abnormal head imageology, severe complications and some cases died, 13 of 18 (72.2%) patients with meningitis caused by Streptococcus died. CONCLUSION:Escherichia coli, CNS and Streptococcus are the predominant pathogens responsible for neonatal purulent meningitis over the past ten years. There were increasing numbers of cases with Streptococcus meningitis which are more common in early onset meningitis with adverse outcome, therefore careful attention should be paid in clinic. Linezolid should be used as a new choice in intractable neonatal purulent meningitis cases caused by gram positive bacteria.
    [Clinical analysis of children with group B meningitis in 2013-2017 in a single center]. Zhang X X,Geng Z X,Zhu L,Li M H,Wang Y J,Qian S Y,Liu G Zhonghua er ke za zhi = Chinese journal of pediatrics To explore the clinical features, the risk factors of mortality and drug resistance of the isolates in patients with group B (GBS) meningitis. A retrospective analysis was performed in 96 children with GBS meningitis (46 males and 50 females) at Beijing Children's Hospital Affiliated to Capital Medical University from January 2013 to October 2017. The clinical characteristics, prognosis and drug resistance were reviewed and analyzed. According to the onset time, the patients were divided into early onset disease (EOD, 0-6 days), late onset disease (LOD, 7-89 days) and very late onset disease (VLOD, 90 days-16 years), the clinical features were compared. According to the results of cranial imaging examination, the patients were divided into two groups: those with neurological complications and those without neurological complications. The influencing factors of neurological complications were analyzed. According to the outcome of 28 days after discharge, patients were divided into death group and survival group. The risk factors of mortality were analyzed by multivariate Logistic regression analysis. Non-numeric variables were analyzed with χ(2) test or Fisher's exact test. Numeric variable between groups were compared with nonparametric test. A total of 96 patients were enrolled, including 18 (19%) EOD, 71 (74%) LOD and 7 (7%) VLOD cases. The median age of EOD cases was 2 days, with a range from 0 to 6 days. The median age of LOD cases was 31 days, with a range from 7 to 81 days. The median age of VLOD cases was 153 days, with a range from 95 to 214 days. Before the onset of the disease, the mother had mastitis in 6 cases and premature rupture of membranes in 6 cases. The common clinical manifestations of patients were fever (95%, 91/96), anorexia (65%, 62/96), seizure (56%, 54/96), and consciousness changes (36%, 35/96). The differences were statistically significant in gender (13/18 28/71 5/7, χ(2)=7.705, 0.024), the number of cases who was admitted to intensive care unit (ICU) (5/18 31/71 0, χ(2)=6.065, 0.042) and peripheral blood leukocyte (12(4, 18)×10(9)/L 6(3, 11)×10(9)/L 13(6, 17)×10(9)/L, =9.885, 0.007) in EOD group, LOD group and VLOD group. Cranial imaging was performed in 94 patients, 60 patients (64%) developed neurological complications, including subdural effusion (31/94, 33%), followed by intracranial hemorrhage (26/94, 28%), cerebral softening (19/94, 20%), cerebral atrophy (15/94, 16%), ependinitis (8/94, 9%) and hydrocephalus (4/94, 4%). By univariate χ(2) test analysis, seizure (63% (38/60) 41% (14/34), χ(2)=4.310, 0.038) was a risk factor of neurological complications. Within 28 days after discharge, 88 patients survived and 8 patients died, with a fatality rate of 8%. The independent risk factors for the death were septic shock (: 9.548, 95% 1.439-63.356, 0.019) and respiratory failure (: 7.053, 95% 1.160-42.888, 0.034). All of isolates were susceptible to penicillin (68/68), ceftriaxone (47/47), cefepime (50/50), vancomycin (60/60) and linezolid (54/54), while the rates of resistance to tetracycline, levofloxacin, clindamycin and erythromycin were 5/12, 17/45, 38/46 and 32/37, respectively. The main type of GBS meningitis is late onset cases. The incidence of neurological complications was high. The independent risk factors for death were septic shock and respiratory failure. The strains were severely resistant to clindamycin and erythromycin. 10.3760/cma.j.issn.0578-1310.2019.06.010
    Prevalence and antibiotic resistance profiles of cerebrospinal fluid pathogens in children with acute bacterial meningitis in Yunnan province, China, 2012-2015. Jiang Hongchao,Su Min,Kui Liyue,Huang Hailin,Qiu Lijuan,Li Li,Ma Jing,Du Tingyi,Fan Mao,Sun Qiangming,Liu Xiaomei PloS one Acute bacterial meningitis is still considered one of the most dangerous infectious diseases in children. To investigate the prevalence and antibiotic resistance profiles of cerebrospinal fluid (CSF) pathogens in children with acute bacterial meningitis in Southwest China, CSF samples from 179 meningitis patients (3 days to 12 years old) with positive culture results were collected from 2012 to 2015. Isolated pathogens were identified using the Vitek-32 system. Gram stain results were used to guide subcultures and susceptibility testing. The antimicrobial susceptibility of isolates was determined using the disc diffusion method. Of the isolates, 50.8% were Gram-positive bacteria, and 49.2% were Gram-negative bacteria. The most prevalent pathogens were E. coli (28.5%), Streptococcus pneumoniae (17.8%), Staphylococcus epidermidis (10.0%), Haemophilus influenzae type b (9.5%), and group B streptococcus (7.2%). In young infants aged ≤3 months, E. coli was the organism most frequently isolated from CSF (39/76; 51.3%), followed by group B streptococcus (13/76; 17.1%) and Streptococcus pneumoniae (8/76; 10.5%). However, in young infants aged >3 months, the most frequently isolated organism was Streptococcus pneumoniae (24/103; 23.3%), followed by Staphylococcus epidermidis (18/103; 17.5%) and Haemophilus influenzae type b (16/103; 15.5%). Antimicrobial susceptibility tests indicated that for E. coli isolates, the susceptibility rates to aminoglycosides ranged from 56.8% to 100.0%, among them, amikacin was identified as the most effective against E. coli. As for cephalosporins, the susceptibility rates ranged from 29.4% to 78.4%, and cefoxitin was identified as the most effective cephalosporin. In addition, the susceptibility rates of piperacillin/tazobactam and imipenem against E. coli were 86.3% and 100%. Meanwhile, the susceptibility rates of Streptococcus pneumoniae isolates to penicillin G, erythromycin, chloramphenicol, ceftriaxone and tetracycline were 68.8%, 0.0%, 87.5%, 81.3% and 0.0%, respectively. Gentamycin, ofloxacin, linezolid and vancomycin were identified as the most effective antibiotics for Streptococcus pneumoniae, each with susceptibility rates of 100%. It was notable that other emerging pathogens, such as Listeria monocytogenes and group D streptococcus, cannot be underestimated in meningitis. 10.1371/journal.pone.0180161
    Clinical and pathogenic analysis of 507 children with bacterial meningitis in Beijing, 2010-2014. Guo Ling-Yun,Zhang Zhi-Xiao,Wang Xi,Zhang Ping-Ping,Shi Wei,Yao Kai-Hu,Liu Lin-Lin,Liu Gang,Yang Yong-Hong International journal of infectious diseases : IJID : official publication of the International Society for Infectious Diseases OBJECTIVES:To explore the clinical characteristics and analyze the pathogens of bacterial meningitis in children. METHODS:Bacterial meningitis cases occurring from January 2010 through December 2014 at Beijing Children's Hospital were reviewed retrospectively. The records of all patients, including data on clinical features and laboratory information, were obtained and analyzed. RESULTS:In total, the cases of 507 pediatric patients seen over a 5-year period were analyzed; 220 of these cases were etiologically confirmed. These patients were classified into four age groups: 29 days to 1 year (n=373, 73.6%), 1-3 years (n=61, 12.0%), 3-6 years (n=41, 8.1%), and >6 years (n=32, 6.3%). The main pathogens identified in this study were Streptococcus pneumoniae (n=73, 33.2%), Escherichia coli (n=24, 10.9%), Enterococcus (n=22, 10.0%), and group B Streptococcus (n=18, 8.2%). All Gram-positive bacteria were sensitive to vancomycin and linezolid. All Gram-negative bacteria were sensitive to meropenem. The total non-susceptibility rate of S. pneumoniae to penicillin was 47.6% (20/42). The resistance rates to ceftriaxone, cefepime, and ceftazidime were 75% (9/12), 55.6% (5/9), and 40% (4/10), respectively. CONCLUSIONS:The main pathogen of bacterial meningitis in this study was S. pneumoniae. The antibiotic resistance rates among children with bacterial meningitis are of serious concern. 10.1016/j.ijid.2016.07.010
    Glycopeptide insensitive Staphylococcus aureus subdural empyema treated with linezolid and rifampicin. Gallagher R M,Pizer B,Ellison J A,Riordan F A I The Journal of infection A 4-year-old boy had surgical debulking of a cerebral astrocytoma followed by chemotherapy. He developed a subdural empyema with a teicoplanin and methicillin resistant Staphylococcus aureus. He was successfully treated with surgical drainage and 6 weeks of antibiotic therapy which included linezolid, rifampicin and metronidazole. Linezolid may be successful in treating other CNS infections caused by antibiotic resistant gram-positive organisms. 10.1016/j.jinf.2008.06.023
    Linezolid for treatment of subdural empyema due to Streptococcus: case reports. Lefebvre Laurent,Metellus Philippe,Dufour Henry,Bruder Nicolas Surgical neurology BACKGROUND:Recurring subdural empyema despite adequate surgical drainage and antibiotic treatment is still a life-threatening disease. This is mainly due to poor diffusion of the antibiotic into the subdural space. CASE DESCRIPTION:We report 2 cases of recurring subdural empyema due to Streptococcus, after repeat surgery and high-dose antibiotic treatment including beta-lactamines and vancomycin. Both patients showed marked clinical and radiologic improvement after introduction of linezolid. There was no drug-related adverse effect despite 36 and 90 days of treatment. CONCLUSION:Off-label use of linezolid for treatment of subdural empyema due to gram-positive bacteria should be considered after failure of conventional antibiotic treatment. 10.1016/j.surneu.2007.06.083
    Successful treatment with linezolid of meningitis complicated with subdural empyema in a 6-month-old boy. Dinleyici Ener Cagri,Yarar Coskun,Dinleyici Meltem,Yakut Ayten Journal of tropical pediatrics Recent findings have focused on the possible role of linezolid as a suitable candidate for the treatment of central nervous system infections. The linezolid treatment for meningitis was sporadically reported in adults but there was no report in children. Here, we present a 6-month-old boy with meningitis and subdural empyema which was unresponsive to more conventional agents but successfully treated with linezolid therapy. A previously healthy 6-month-old boy was referred to our clinic for deteriorating general condition with fever, vomiting and seizures. He had fever and tense-bulging anterior fontanelle. Based on his first cerebrospinal fluid (CSF) results, empirical antibiotic therapy for bacterial meningitis consisting of vancomycin and ceftriaxone was started. However, CSF culture yielded no micro-organisms but blood culture showed coagulase-negative Staphylococci. On the 7th day, he still had high fever and the erythrocyte sedimentation rate (ESR) and serum CRP levels had risen by 105 mm/h and 36.2 mg/dl, respectively. On 10th day, computerized cranial tomography showed bilateral frontoparietal subdural empyema. Purulent material was evacuated by burr hole, and gram stains of the material showed polymorphonuclear leukocytes and no microorganisms. Clinical and CSF findings of our case were, unresponsiveness to vancomycin, ceftriaxone and consecutive meropenem treatment while we still observed subdural empyema during these treatments. For this reason we started linezolid 10 mg/kg twice daily. Clinical signs improved dramatically, with both completely normal neurological findings and normalization of CSF and radiological findings. To the of our best knowledge, linezolid treatment of meningitis in children has not been reported previously. Clinical and CSF findings of our case were improved completely with linezolid treatment. Also, control cranial computerized tomography showed the total recovery of subdural empyema. Here we present the youngest case with meningitis which was successfully treated with linezolid treatment. 10.1093/tropej/fmm058
    Rapid diagnosis of pneumococcal meningitis: implications for treatment and measuring disease burden. Saha Samir K,Darmstadt Gary L,Yamanaka Noboru,Billal Dewan S,Nasreen Tania,Islam Maksuda,Hamer Davidson H The Pediatric infectious disease journal BACKGROUND:Streptococcus pneumoniae is the leading cause of childhood pneumonia and meningitis worldwide. Isolation of this organism, however, is uncommon in resource-poor countries, in part because of extensive use of prior antibiotics. A rapid, highly sensitive immunochromatographic test (ICT) for S. pneumoniae was evaluated for the diagnosis of meningitis. METHODS:Cerebrospinal fluid (CSF) from 450 children with suspected meningitis was tested with ICT, and results were compared with CSF culture, latex agglutination test (LAT) and/or polymerase chain reaction (PCR). Serial CSF specimens from 11 patients were also evaluated for duration of positive results during effective antimicrobial therapy. FINDINGS:All 122 cases of pyogenic pneumococcal meningitis positive either by culture (N = 87) or PCR (N = 35) were positive by ICT, yielding 100% (122 of 122) sensitivity. All purulent CSF specimens from patients with meningitis caused by other bacteria by culture (N = 149) or by LAT (N = 48) or those negative by culture, LAT and LytA and thus of unknown etiology (N = 20), and normal CSF specimens (N = 104) were negative by ICT. Thus the specificity of ICT also was 100% (321 of 321), although negativity of ICT was not confirmed by PCR, if it was positive for other organisms either by culture or LAT. Serotyping of S. pneumoniae strains revealed 28 different serotypes, indicating that outcome of ICT are independent of diverse capsular serotype of pneumococcus. Antigen was detected by ICT for at least 10 days after presentation, and 1 was still positive on day 20, which was longer than for either LAT or PCR. INTERPRETATION:ICT for pneumococcal antigen in CSF is 100% sensitive and specific in diagnosing pyogenic pneumococcal meningitis and can detect approximately 30% more pneumococcal meningitis cases than with culture alone. The simplicity of the test procedure and the longevity of CSF antigen detection suggest the potential utility of ICT to estimate the true burden of pneumococcal disease, as for Haemophilus influenzae type b using data from meningitis, and to guide selection of appropriate antibiotic treatment, especially in resource-poor countries with widespread prehospital antimicrobial use.
    [Significance of soluble DLL1 in diagnosis of intracranial infectious diseases in children]. Li Jin-Yi,Jia Yan-Jie,Jia Yong-Lin,Lu Jing-Jing,Jing Li-Jun,Peng Tao,Li Jing-Hong Zhongguo dang dai er ke za zhi = Chinese journal of contemporary pediatrics OBJECTIVE:To investigate the significance of soluble DLL1 (Delta-like-1) levels of cerebrospinal fluid (CSF) and serum in the diagnosis of intracranial infection in children. METHODS:Fifty children with intracranial infection, including 20 cases of tuberculous meningitis (TM), 20 cases of viral meningitis (VM) and 10 cases of purulent meningitis (PM), and 20 children without intracranial infection (control group) were enrolled. The levels of soluble DLL1 in CSF and serum were measured using ELISA. RESULTS:The level of CSF soluble DLL1 in the TM group was significantly higher than that in the VM, PM and control groups (2.89 ± 1.72 ng/mL vs 0.14 ± 0.14 ng/mL, 0.27 ± 0.21 ng/mL, 0.13 ± 0.12 ng/mL; P<0.01). The level of serum soluble DLL1 in the TM group was also significantly higher than that in the VM, PM and control groups (12.61 ± 6.45 ng/mL vs 2.28 ± 2.27 ng/mL, 2.38 ± 1.79 ng/mL, 2.26 ± 2.10 ng/mL; P<0.01). The levels of soluble DLL1 in the CSF and serum in the VM and PM groups were not significantly different from those in the control group. CONCLUSIONS:Soluble DLL1 as a novel indicator might have potentially important value in the diagnosis of TM.
    Subdural empyema in children. Muzumdar Dattatraya,Biyani Naresh,Deopujari Chandrashekhar Child's nervous system : ChNS : official journal of the International Society for Pediatric Neurosurgery BACKGROUND:Subdural empyema denotes the collection of purulent material in the subdural spaceand is commonly seen in infants and older children. In infants, the most common cause is bacterialmeningitis. In older children, sinusitis and otitis media are usually the source for subdural empyema. Theclinical symptomatology is varied and has a wide range including prolonged or recurrent fever, seizures,meningeal irritation, and raised intracranial pressure. It can mimic as well as complicate meningitis and aheightened clinical awareness is therefore paramount. AIMS AND OBJECTIVES:The clinical profile, etiopathogenesis, imaging features and management of subdural empyema in children is discussed and the relevant literature is reviewed. CONCLUSION:Subdural empyema is a neurosurgical emergency and rapid recognition and treatment canavoid life-threatening complications. In most cases, surgical decompression through burr hole or craniotomyis warranted. Near complete evacuation of the purulent material and appropriate long-term intravenous antibiotics are necessary for a gratifying outcome. 10.1007/s00381-018-3907-6
    Evaluation of brainstem auditory evoked response audiometry findings in children with tuberculous meningitis at admission. Topcu Ismail,Cüreoğlu Sebahattin,Yaramiş Ahmet,Tekin Muhammet,Oktay Faruk,Osma Ustün,Meric Faruk,Katar Selahattin Auris, nasus, larynx OBJECTIVE:To determine the characteristics of Brainstem auditory evoked response (BAER) findings in children with tuberculous meningitis (TBM) at admission. METHODS:Twenty-seven children with highly probable TBM were admitted to the University Hospital. The control group was 23 healthy, age and sex matched subjects. Brainstem response audiometry recording was performed in all patients and controls. Ninety dB sound pressure level (SPL) was used for comparisons. The main BAER measurements analysed were the I-III, III-V, I-V interpeak intervals. In statistical analysis, t-test for independent groups were performed. At the same time, for interpeak intervals, values exceeding 2.5 standard deviations (S.D.) above the means of the normal controls were considered abnormal. To the result of BAER findings, HL was classified as mild (until 40 dBHL), severe (until 80 dBHL) and total HL (no hearing was detected). RESULTS:The latencies of interpeak intervals (except III-V latency at 10 per s) have significantly prolonged in comparison with controls. Mild HL was detected in four ears. In eight ears, any wave form could not be obtained at 110 dBSPL. Abnormal BAER result was seen in 13 of 54 ears (24%) at the click of 10 per s and five ears (12%) at the click of 50 per s. CONCLUSION:Abnormal BAER result was seen in 24% of patients with TBM before treatment. Depending on these findings, it can be inferred that hearing impairments must be lower than those values which was detected by BAER during the acute phase of TBM, since the abnormal BAER may be reversible following the illness, returning to normal with recovery.
    Outcome of brain stem auditory electrophysiology in children who survive purulent meningitis. Jiang Z D The Annals of otology, rhinology, and laryngology Brain stem auditory electrophysiology was assessed in children long after purulent meningitis by examining the central components of brain stem auditory evoked response (BAER) at different presentation rates of clicks. Children with peripheral hearing loss were excluded from this study to avoid any possible influence of the loss on the measurements of BAER central components. Of the 70 children who had recovered from meningitis 2 to 8 years earlier, 9 (12.9%) showed abnormalities in BAER central components--mainly a slight reduction of wave V amplitude, at the click presentation rate of 10/s. Of the remaining 61 children who did not show any obvious abnormalities in the BAER at 10/s, an abnormally prolonged I-V interval and a reduced amplitude of wave V were seen in 5 children (8.2%) at the click rate of 90/s. The total BAER abnormality rate was therefore 20.0% (14/70 cases). The results suggest that most children who survive purulent meningitis have a favorable outcome for the brain stem auditory pathway, with about 1 in 5 having mild dysfunction or a suboptimal outcome in the pathway. 10.1177/000348949910800502
    [Complications of purulent meningoencephalitis in children]. Rubin A N,Shcherbuk Yu A,Lyapin A P Vestnik khirurgii imeni I. I. Grekova An analysis of 19 cases of meningoencephalitis was made in infants aged under one year old. The disease was complicated by chronic subdural hematomas in 11 patients and by hydrocephalus in 8 patients. The article presents the strategy, treatment results and diagnostic procedures volume. Based on their work, the authors made a conclusion that meningoencephalitis required an emergency neurosurgical interference in order to avoid complications in convalescence period.
    Anti-interleukin-8 auto-antibodies in cerebrospinal fluid of children with purulent meningitis. Takasaki J,Ogawa Y Pediatrics international : official journal of the Japan Pediatric Society BACKGROUND:Cerebrospinal fluid (CSF) of patients with purulent meningitis contains a high concentration of interleukin (IL)-8. Recently, the presence of anti-IL-8 auto-antibodies was noted in blood and alveolar fluid. Therefore, measurement of the concentration of anti-IL-8 auto-antibodies was attempted in CSF of children with and without meningitis. METHODS AND RESULTS:We measured the concentration of anti-IL-8 auto-antibodies in CSF of children with purulent or aseptic meningitis and those without meningitis. The CSF obtained on admission showed a significantly higher concentration of anti-IL-8 IgG and IgM auto-antibodies in children with purulent meningitis, compared with those with aseptic meningitis or without meningitis. Among the three groups of children, the concentration of IL-8 was also significantly higher in CSF of children with purulent meningitis. CONCLUSION:Because the anti-IL-8 IgG auto-antibody binds to IL-8 and inhibits IL-8 interaction with specific receptors on neutrophils, the presence of anti-IL-8 auto-antibodies seems to provide a mechanism that limits the bioavailability of free IL-8 in CSF. 10.1046/j.1442-200x.2000.01198.x
    Characteristics of brain stem auditory evoked potentials in children with hearing impairment due to infectious diseases. Ječmenica Jovana Radovan,Opančina Aleksandra Aleksandar Bajec Journal of child neurology Among objective audiologic tests, the most important were tests of brain stem auditory evoked potentials. The objective of the study was to test the configuration, degree of hearing loss, and response characteristics of auditory brain stem evoked potentials in children with hearing loss occurred due to infectious disease. A case control study design was used. The study group consisted of 54 patients referred for a hearing test because of infectious diseases caused by other agents or that occurred as congenital infection. Infectious agents have led to the emergence of various forms of sensorineural hearing loss. We have found deviations from the normal values of absolute and interwave latencies in some children in our group. We found that in the group of children who had the diseases such as purulent meningitis, or were born with rubella virus and cytomegalovirus infection, a retrocochlear damage was present in children with and without cochlear damage. 10.1177/0883073814536467
    [First experience with detecting bacterial DNA in the cerebrospinal fluid of patients with purulent meningitis using broad spectrum multiplex nested PCR]. Moravcová Lenka,Pícha Dusan,Zdárský Emanuel,Holecková Daniela,Dzupová Olga,Lásiková Sárka Klinicka mikrobiologie a infekcni lekarstvi OBJECTIVES:To propose and verify a PCR assay for detecting Escherichia coli, Haemophilus influenzae, Listeria monocytogenes, Staphylococcus species, Streptococcus pneumoniae and Neisseria meningitidis serogroups B and C in a single sample of the cerebrospinal fluid of patients with purulent meningitis. MATERIAL AND METHODS:DNA from the cerebrospinal fluid was isolated using the QIAamp DNA Mini Kit. PCR was performed as two-step amplification (nested PCR). For E. coli, H. influenzae, L. monocytogenes, S. species and S. pneumoniae, universal and species-specific primers encoding bacterial 16S rDNA were used in the first and second reaction, respectively. For N. meningitidis serogroups B and C, an amplification system with primers for the SiaD gene was utilized. RESULTS:Of 25 patients examined at the beginning of their treatment, bacterial DNA was detected in the cerebrospinal fluid of 17 (68 %) of them. Those were six cases of N. meningitidis serogroup B, four of N. meningitidis serogroup C, five of S. pneumoniae, one of H. influenzae and one of L. monocytogenes. Of 7 patients in whom antibiotic therapy was initiated prior to diagnostic lumbar puncture, PCR was positive in four cases. CONCLUSIONS:The proposed nested PCR approach is faster than traditional culture methods and suitable for early laboratory diagnosis of infectious agents. When compared to culture methods, the technique offers slightly higher positivity (by 16 %). This is similar in samples analyzed after the initiation of antibiotic therapy. The PCR method never detected other bacteria than the cultured ones.
    Cranial computed tomography in purulent meningitis of childhood. Tuncer Oguz,Caksen Hüseyin,Arslan Sükrü,Atas Bülent,Uner Abdurrahman,Oner Ahmet Faik,Odabas Dursun The International journal of neuroscience The cranial computed tomography (CT) findings of 48 children with purulent meningitis were examined, prospectively, to determine the importance of cranial CT findings on the prognosis of childhood meningitis, in a developing country. The age of children ranged from 2 months to 13 years. Of 48 patients, 29 (60.5%) survived without sequelae, 13 (27%) survived with sequelae, and six (12.5%) died. Cranial CT was normal in 21 (43%) patients of 48 children with meningitis at admission. Abnormal CT findings were detected in 10, 11, and 6 children in the groups of survived without sequelae, survived with sequelae, and deaths, respectively, at admission (p <.05) We found that CT scan results were correlated with neurological signs (p <.05). At least one or more cranial CTs were was re-taken in children in whom the first CT revealed abnormal findings; we did not find a statistically significant difference for the follow-up CT findings between the groups (p >.05). Hydrocephalus and subdural effusion were the commonest abnormal CT findings. In conclusion, our findings showed that cranial CT may safely be used to detect intracranial complications of meningitis in childhood and the ratio of sequelae and death were more common in children with abnormal cranial CT than those of normal cranial CT findings. Additionally, there was a positive correlation between CT scan results and neurological signs. 10.1080/00207450490269435
    Soluble urokinase receptor is elevated in cerebrospinal fluid from patients with purulent meningitis and is associated with fatal outcome. Ostergaard Christian,Benfield Thomas,Lundgren Jens D,Eugen-Olsen Jesper Scandinavian journal of infectious diseases The urokinase-type plasminogen activator system has been suggested to play a pathophysiological role in brain damage. The aim of this study was to evaluate CSF levels of suPAR in 183 patients clinically suspected of having meningitis on admission. Of these, 54 patients were found to have purulent meningitis, 63 had lymphocytic meningitis, 12 had encephalitis, and 54 patients were suspected of, but had no evidence of, meningitis. There was a significant difference in suPAR levels among patient groups (Kruskal Wallis test, p < 0.0001) with significantly higher CSF suPAR levels in patients with CNS infection (purulent meningitis: median suPAR 2.41 microg/l (range 0.12-35), lymphocytic meningitis: 1.10 microg/l (0.15-5.31), and encephalitis (1.77 microg/l (0.17-11.7)) than in patients without meningitis (0.64 microg/l (0-5.34) (Dunn's multiple comparison test, p < 0.05). Also, patients with purulent meningitis had significantly higher CSF suPAR levels than patients with lymphocytic meningitis (p < 0.001). Patients with purulent meningitis who died (n = 8, 4.9 microg/l (1.3-35) had significantly higher CSF levels of suPAR than patients who survived (n = 46, 2.1 microg/l (0.1-24), Mann Whitney, p = 0.046). Employing a cut-off point of 3.1 and above, the OR (95%CI) for fatal outcome was 11.9 (1.4-106), univariate logistic regression analysis, p = 0.026. In conclusion, CSF suPAR levels may be an important predictor for fatal outcome in purulent meningitis.
    [An analysis of 181 cases with blood stream infection caused by Streptococcus agalactiae in children from 2011 to 2015: a multi-center retrospective study]. Hua C Z,Yu H,Zhuang J Q,Li X L,Xu H M,Luo Q E,Lu H P,Yu H M,Cao Y,Chen Y P,Zhang T,Jing C M,Du L Z,Wang C Q,Lin Z L,Zhang H,Chen X J,Hua Z Y Zhonghua er ke za zhi = Chinese journal of pediatrics OBJECTIVE:To analyze the clinical characteristics of blood stream infection caused by Streptococcus agalactiae in children and the drug-resistance of the isolates. METHOD:All cases with Streptococcus agalactiae growth in blood or cerebrospinal fluid cultures from January 1, 2011 to December 31, 2015 were enrolled by checking the laboratory information system (LIS) from 7 Class 3 Grade A hospitals (4 in Zhejiang, 2 in Shanghai and 1 in Chongqing). Clinical data were collected for analysis. χ(2) test, t test and non parametric test were used in the study. RESULT:One hundred and eighty-one pediatric cases of blood stream infection caused by Streptococcus agalactiae were included in current study. Eighty-six cases (47.5%) were male, and with age range from one day to 9 years (media 13 days). Thirty cases (16.6%) were premature infants and 127 cases (70.2%) were born via vaginal delivery. Seventy-one cases (39.2%) had early onset (<7 d) infections, and 106 cases (58.6%) had late onset (7-89 d) infections. Seventy-eight cases (43.1%) were complicated with purulent meningitis. Incidences of vaginal delivery(81.7%(58/71) vs. 62.3%(66/106)), shortness of breath moaning (43.7%(31/71) vs. 15.1%(16/106)) and preterm premature rupture of membranes (25.4%(18/71) vs. 3.8%(4/106)) were higher in the early onset infection group compared with the late onset group(P all<0.05). However, the number of cases who had fever(25.4%(18/71)vs.85.8%(91/106)) and complicated with purulent meningitis (29.6%(21/71) vs. 53.8%(57/106)) in early onset infections group was less than that in the late onset group(P both<0.05). The blood cultures of most patients (87.8%) were performed before the use of antibiotics. Drug-resistant tests showed that the sensitive rates to penicillin G, ceftriaxone and cefotaxime were 98.9%, 99.0% and 99.0% respectively. All strains were sensitive to vancomucine. The rates of resistance to clindamycin and erythromycin were 68.0% and 34.0%, respectively. Only 39 cases (22.0%) were treated with single antibiotics of either penicillins or cephalosporins, 80 cases (45.2%) were treated with antibiotics containing β lactamase inhibitor, 61 cases (34.5%) were treated with either meropenem or cefoperazone-sulbactam. One hundred and fifty-four cases were cured, while 19 died (including 13 complicated with purulent meningitis) and 8 lost to follow up after giving up of treatment. CONCLUSION:The incidence and mortality of blood stream infection caused by Streptococcus agalactiae complicated with purulent meningitis are high in children. Penicillin is the first choice in treatment. Antibiotics should be selected accorrding to the drug-resistance test. 10.3760/cma.j.issn.0578-1310.2016.08.004
    Diagnostic Yield of Pneumococcal Antigen Detection in Cerebrospinal Fluid for Diagnosis of Pneumococcal Meningitis Among Children in China. Xie Yong-Ping,Hua Chun-Zhen,Wang Hong-Jiao,Sun An-Na,Shen Jue Indian pediatrics OBJECTIVE:To determine the diagnostic accuracy of pneumococcal antigen detection in diagnosis of pneumococcal meningitis in children. METHODS:Purulent meningitis was diagnosed according to European Society for Clinical Microbiology and Infectious Diseases (ESCMID) guideline between July 2014 and June 2016. Along with a cerebrospinal fluid (CSF) culture, pneumococcal antigen detection in cerebrospinal fluid (CSF) was performed, and further identification of pathogens was done with 16S rDNA-PCR and high-throughput sequencing. RESULTS:CSF samples collected from 184 children (median age of 1.92 mo). CSF culture was used as the gold standard. 46 (25%) had positive results for culture and 10 (5.4%) were pneumococci; 34 (18.5%) were pneumococcal antigen positive. The sensitivity and specificity of pneumococcal antigen detection were 100% (95% CI: 89.4%-100%) and 86.2% (95% CI: 96.4%-99.9%), respectively. 92.3% (12/13) were confirmed by nucleic acid detection to be pneumococci. CONCLUSIONS:Pneumococcal antigen detection in CSF has adequate sensitivity and specificity in diagnosing pneumococcal meningitis.
    [Analysis by questionnaire survey concerning example such as purulent meningitis and severe infectious diseases--relation among patient background factor, sequelae, and infecting organism]. Sunakawa Keisuke The Japanese journal of antibiotics Concerning major causative organisms of purulent meningitis, i. e., Haemophilus influenzae and Streptococcus pneumoniae, a questionnaire was sent to medical institutions all over Japan with the aim of investigating the patient background factors, sequelae and causal relationship with the causative organisms. Responses from 84 institutions in various parts of Japan were summarized and the following conclusions were drawn. 1. The diagnostic names of 227 patients for whom the questionnaire could be recollected were as follows: Purulent meningitis 138 cases (patient under 15 years old; 134 cases); purulent meningitis and sepsis, 58 cases; sepsis, 28 cases; and others, 3 cases. The causative organisms for the patients with meningitis and meningitis + sepsis were as follows: Haemophilus influenzae, 132 patients; and Streptococcus pneumoniae, 44 patients. 2. With respect to age distribution among the patients with meningitis and those with meningitis + sepsis, the number of the patients of the age younger than 1 year old was more than twice larger than that of one-year-old patients. The percentage of the cases in which sequelae remained was 35.9% among the cases caused by Streptococcus pneumoniae and 13.4% among the cases caused by Haemophilus influenzae. A significant difference was observed between the bacterial strains (p=0.0025). 3. The major initial symptoms observed were high fever, vomiting, consciousness disorder, drowsiness and poor sucking. The percentage of the patients with remaining sequelae was significantly high among the patients who exhibited convulsion in the early stage after the onset. 4. As to the relationship with administration of dexamethasone, sequelae remained in 40.0% (10/25) of the patients who did not receive dexamethasone, and 17.3% (23/133) of the patients who received the drug. The percentage of the patients with remaining sequelae was significantly low among the patients who received dexamethasone (p=0.0043).
    5 versus 10 days of treatment with ceftriaxone for bacterial meningitis in children: a double-blind randomised equivalence study. Molyneux Elizabeth,Nizami Shaikh Qamaruddin,Saha Samir,Huu Khanh Truong,Azam Matloob,Bhutta Zulfiqar Ahmad,Zaki Ramadan,Weber Martin Willi,Qazi Shamim Ahmad, Lancet (London, England) BACKGROUND:Bacterial meningitis is an important cause of morbidity and mortality in developing countries, but the duration of treatment is not well established. We aimed to compare the efficacy of 5 and 10 days of parenteral ceftriaxone for the treatment of bacterial meningitis in children. METHODS:We did a multicountry, double-blind, placebo-controlled, randomised equivalence study of 5 versus 10 days of treatment with ceftriaxone in children aged 2 months to 12 years with purulent meningitis caused by Streptococcus pneumoniae, Haemophilus influenzae type B, or Neisseria meningitidis. Our study was done in ten paediatric referral hospitals in Bangladesh, Egypt, Malawi, Pakistan, and Vietnam. We randomly assigned children who were stable after 5 days of treatment, through site-balanced computer-generated allocation lists, to receive a further 5 days of ceftriaxone or placebo. Patients, their guardians, and staff were masked to study-group allocation. Our primary outcomes were bacteriological failure or relapse. Our analysis was per protocol. This study is registered with the International Standard Randomised Controlled Trial Number Register, number ISRCTN38717320. FINDINGS:We included 1004 of 1027 children randomly assigned to study groups in our analyses; 496 received treatment with ceftriaxone for 5 days, and 508 for 10 days. In the 5-day treatment group, two children (one infected with HIV) had a relapse; there were no relapses in the 10-day treatment group and there were no bacteriological failures in either study group. Side-effects of antibiotic treatment were minor and similar in both groups. INTERPRETATION:In children beyond the neonatal age-group with purulent meningitis caused by S pneumoniae, H influenzae type b, or N meningitidis who are stable by day 5 of ceftriaxone treatment, the antibiotic can be safely discontinued. FUNDING:United States Agency for International Development. 10.1016/S0140-6736(11)60580-1
    High-throughput sequencing of 16S rDNA amplicons characterizes bacterial composition in cerebrospinal fluid samples from patients with purulent meningitis. Liu Aicui,Wang Chao,Liang Zhijuan,Zhou Zhi-Wei,Wang Lin,Ma Qiaoli,Wang Guowei,Zhou Shu-Feng,Wang Zhenhai Drug design, development and therapy Purulent meningitis (PM) is a severe infectious disease that is associated with high rates of morbidity and mortality. It has been recognized that bacterial infection is a major contributing factor to the pathogenesis of PM. However, there is a lack of information on the bacterial composition in PM, due to the low positive rate of cerebrospinal fluid bacterial culture. Herein, we aimed to discriminate and identify the main pathogens and bacterial composition in cerebrospinal fluid sample from PM patients using high-throughput sequencing approach. The cerebrospinal fluid samples were collected from 26 PM patients, and were determined as culture-negative samples. The polymerase chain reaction products of the hypervariable regions of 16S rDNA gene in these 26 samples of PM were sequenced using the 454 GS FLX system. The results showed that there were 71,440 pyrosequencing reads, of which, the predominant phyla were Proteobacteria and Firmicutes; and the predominant genera were Streptococcus, Acinetobacter, Pseudomonas, and Neisseria. The bacterial species in the cerebrospinal fluid were complex, with 61.5% of the samples presenting with mixed pathogens. A significant number of bacteria belonging to a known pathogenic potential was observed. The number of operational taxonomic units for individual samples ranged from six to 75 and there was a comparable difference in the species diversity that was calculated through alpha and beta diversity analysis. Collectively, the data show that high-throughput sequencing approach facilitates the characterization of the pathogens in cerebrospinal fluid and determine the abundance and the composition of bacteria in the cerebrospinal fluid samples of the PM patients, which may provide a better understanding of pathogens in PM and assist clinicians to make rational and effective therapeutic decisions. 10.2147/DDDT.S82728
    Ameliorative effects of ceftriaxone sodium combined with dexamethasone on infantile purulent meningitis and associated effects on brain-derived neurotrophic factor levels. Zeng Yiwen,Zhang Wei Experimental and therapeutic medicine The aim of the present study was to evaluate the role of ceftriaxone sodium combined with dexamethasone on the treatment of infant purulent meningitis (PM) and to measure brain-derived neurotrophic factor (BDNF) levels in children with PM. Of the 177 patients enrolled into the present study, 92 patients received ceftriaxone sodium+dexamethasone (combination group) and 85 patients received ceftriaxone sodium alone (monotherapy group). The time taken for the body temperature, peripheral blood (PB) and cerebrospinal fluid (CSF) white blood cell (WBC) counts to recover back to normal levels were compared between the two groups. In addition, changes in the CSF WBC counts, CSF protein and sugar concentrations, BDNF levels, effective treatment rates and incidence of adverse reactions three days before treatment (T1), after one week of treatment (T2) and after two weeks of treatment (T3) were compared between the two groups. In the combination group, the recovery time of body temperature, WBC counts in both PB and CSF were significantly lower compared with those in the monotherapy group. The combination group also exhibited lower CSF protein concentrations and higher CSF sugar concentrations at T2 and T3 compared with those in the monotherapy group (P<0.05). The effective treatment rate of the combination group was significantly higher compared with that of the monotherapy group (P=0.006). CSF protein at T1, T2 T3, and CSF sugar concentrations and BDNF levels at T1 were significantly lower in the combination group than in the monotherapy group (P<0.05) while the CSF sugar concentrations at T2, T3 were higher in the combination group than in the monotherapy group (P<0.05). Taken together, these observations suggest that ceftriaxone combined with dexamethasone was superior compared with that of ceftriaxone alone for the treatment of infantile PM, and that this combination therapy may improve the effective treatment rate and accelerate patient rehabilitation. 10.3892/etm.2020.8769
    [A multicentric clinical study on clinical characteristics and drug sensitivity of children with meningitis in China]. Wang C Y,Xu H M,Deng J K,Yu H,Chen Y P,Lin A W,Cao Q,Hao J H,Zhang T,Deng H L,Chen Y H Zhonghua er ke za zhi = Chinese journal of pediatrics To understand clinical characteristics of children with meningitis (PM) in China and to analyze the drug sensitivity of isolates and associated impacts on death and sequelae. The clinical data, follow-up results and antimicrobial sensitivity of isolated strains of 155 children (including 98 males and 57 females, age ranged from 2 months to 15 years) with PM in 10 tertiary-grade A class hospitals of Infectious Diseases Surveillance of Pediatrics (ISPED) from 2013 to 2017 were collected and analyzed retrospectively. Patients were divided into different groups according to the following standards: ≤1 year old group,>1-3 years old group and >3 years old group according to age; death group and non-death group according to the death within 30 days after PM diagnosis; complication group and non-complication group according to the abnormal cranial imaging diagnosis; sequelae group and no-sequelae group according to the follow-up results. Bonfereoni chi-square segmentation and Kruskal-Wallis test were used for statistical analysis. There were 64 cases (41.3%) in the ≤1 year old group, 39 cases in the >1-3 years old group (25.2%), and 52 cases (33.5%) in the >3 years old group. The most common clinical manifestation was fever (151 cases, 97.4%). The mortality was 16.8% (26/155) during hospitalization. The neurological complication rate was 49.7% (77/155) during hospitalization, including the most common complication, subdural effusion and (or) empyema in 50 cases (32.3%) and hearing impairment in 6 cases. During follow-up after discharge, no death was found and focal neurological deficits were found in 47 cases (30.3%), including the frequent neurological sequelae: cognitive and mental retardation of different degree in 22 cases and hearing impairment in 14 cases (9.0%). The rate of cure and improvement on discharge was 74.8% (116/155) and the lost to follow-up rate was 8.4% (13/155). The proportions of died cases, neurological complications during hospitalization and proportions of peripheral white blood cell count 12 × 10(9)/L before admission in ≤1 year old group were significantly higher than those in 3 years old group (25.0% (16/64) . 5.8% (3/52), 75.0% (48/64) . 25.0% (13/52), 48.4% (31/64) . 15.4% (8/52), χ(2)=7.747, 28.767, 14.044; 0.005, 0.000, 0.000). The proportions of headache, vomiting, neck resistance and high risk factors of purulent meningitis in 3 years old group were significantly higher than those in ≤ 1 year old group (67.3%(35/52) . 1.6%(1/64), 80.8% (42/52) . 48.4% (31/64), 69.2% (36/52) . 37.5% (24/64), 55.8% (29/52) . 14.1%(9/64), χ(2)=57.940, 12.856, 11.568, 22.656; 0.000, 0.000, 0.001, 0.000). isolates were completely sensitive to vancomycin (100.0%, 152/152), linezolid (100.0%, 126/126), moxifloxacin (100.0%, 93/93) and ofloxacin (100.0%,41/41); highly sensitive to levofloxacin (99.3%, 142/143) and ertapenem (84.6%, 66/78); moderately sensitive to ceftriaxone (48.4%, 45/93), cefotaxime (40.0%, 44/110) and meropenem (38.0%, 38/100); less sensitive to penicillin (19.6%, 27/138) and erythromycin (4.2%, 5/120). The proportions of non-sensitive strains of penicillin (21/21) and meropenem (17/18) in the death group were significantly higher than those (90/117, 45/82) in the survived group(χ(2)=4.648 and 9.808, 0.031 and 0.002). The children's PM is mainly found in infants under 3 years old in China. Death and neurological complications are more common in PM children under 1 year old. The clinical manifestations and peripheral blood inflammatory markers of PM patients under 1 year old are not typical. Fever is the most common clinical manifestation and subdural effusion and (or) empyema is the most common complication. Long-term hearing impairment is common in PM and the follow-up time must be prolonged. The dead PM cases had high in sensitive rates to penicillin and meropenem. 10.3760/cma.j.issn.0578-1310.2019.05.008
    [Risk factors associated with the development of early neurological complications in purulent meningitis in a pediatric population]. Espinoza-Oliva Martha Marcela,Rizo-Santos Dalia Berenice,Díaz-Peña Rafael,Ortega-Cortés Rosa,Barrera de León Juan Carlos Gaceta medica de Mexico OBJECTIVE:To determine the risk factors associated with the development of early neurological complications in purulent meningitis in a pediatric population. METHODS:This was a case-control study including 78 children aged one month to 16 years with purulent meningitis divided into two groups: cases, with early neurological complications (defined as those presenting < 72 hours from initiation of clinical manifestation), and controls, without early neurological complications. Clinical, serum laboratory, and cerebrospinal fluid (CSF). RESULTS:Seventy-eight patients were included: cases, n = 33, and controls, n = 45. Masculine gender, 19 (57%) vs. feminine gender, 28 (62%) (p = 0.679). Median age in months, 36 months (range, 1-180) vs. 12 months (range, 1-168) (p = 0.377). Factors associated with neurological complications: convulsive crises on admission, p = 0.038, OR, 2.65 (range, 1.04-6.74); meningeal signs, p = 0.032, OR, 2.73 (range, 1.07-6.96); alteration of the alert state, p = 0.003, OR, 13.0 (range, 1.64-105.3); orotracheal intubation, p = 0.000, OR, 14.47 (range, 4.76-44.01); neurological deterioration, p = 0.000, OR, 9.60 (range, 3.02-30.46); turbid CSF, p = 0.003, OR, 4.20 (range, 1.57-11.20); hypoglycorrhachia, < 30 mg/dl, p = 0.001, OR, 9.2 (range, 3.24-26.06); and positive CSF culture, p = 0.001, OR, 16.5 (range, 1.97-138.1). CONCLUSIONS:The factors associated with early neurological complications included convulsive crises on admission, meningeal signs, alteration of the alert state, need for orotracheal intubation, turbid CSF, hypoglycorrhachia, and positive CSF culture.
    Accuracy of cerebrospinal fluid ferritin for purulent meningitis. Garcia Pedro Celiny Ramos,Barcelos Andrea Lucia Machado,Tonial Cristian Tedesco,Fiori Humberto Holmer,Einloft Paulo Roberto,Costa Caroline Abud Drumond,Portela Janete L,Bruno Francisco,Branco Ricardo Garcia Archives of disease in childhood OBJECTIVE:To evaluate the use of cerebrospinal fluid (CSF) ferritin levels in the diagnosis of purulent meningitis (PM). METHOD:We studied 81 children between 28 days and 12 years of age who presented with clinical suspicion of meningitis to the emergency department. CSF ferritin levels were measured and compared between diagnostic groups (PM, aseptic meningitis (AM) and no meningitis). RESULTS:The median age was 24 (IQR 8-69) months. There were 32 patients with AM (39%), 23 with PM (28%) and 26 with no meningitis (32%). Median CSF ferritin was 4.2 ng/mL (IQR 3.0-6.5), 52.9 ng/mL (IQR 30.7-103 ng/mL) and 2.4 ng/mL (IQR 2-4), respectively. CSF ferritin was higher in children with PM compared with AM (p<0.001) or no meningitis (p<0.001). There was no difference between AM and no meningitis. CONCLUSION:CSF ferritin may be a useful biomarker to discriminate PM in children with clinical symptoms of this disease. 10.1136/archdischild-2019-317960
    [Clinical features of childhood purulent meningitis caused by Escherichia coli and Streptococcus pneumoniae: a comparative analysis]. Han Wei,Jiang Li,Ma Jian-Nan,Song Xiao-Jie,He Rong Zhongguo dang dai er ke za zhi = Chinese journal of contemporary pediatrics OBJECTIVE:To investigate the differences in clinical features of childhood purulent meningitis (PM) caused by Escherichia coli and Streptococcus pneumoniae, and to provide help for the selection of antibiotics for PM children with unknown etiology. METHODS:A retrospective analysis was performed for the clinical data of children with PM caused by Escherichia coli (12 children) or Streptococcus pneumoniae (15 children). RESULTS:Compared with the Streptococcus pneumoniae infection group, the Escherichia coli infection group had a significantly higher proportion of children with an age of onset of <3 months and a significantly higher incidence rate of convulsion, but significantly lower incidence rates of severe fever (>39°C) and disturbance of consciousness and a significantly lower proportion of children with an increased leukocyte count at diagnosis (>12×10(9)/L). The results of routine cerebrospinal fluid test and biochemical examinations showed no significant differences between the two groups. Escherichia coli and Streptococcus pneumoniae were resistant to cephalosporins and had a sensitivity to chloramphenicol more than 90%. Escherichia coli was fully sensitive to meropenem and Streptococcus pneumoniae was fully sensitive to vancomycin. CONCLUSIONS:PM caused by Escherichia coli and Streptococcus pneumoniae has different clinical features. As for PM children with severe fever, disturbance of consciousness, and an increased leukocyte count, the probability of Streptococcus pneumoniae infection should be considered. For PM children with an age of onset of <3 months, medium- and low-grade fever, frequent convulsions, and a leukocyte count of <12×10(9)/L, the probability of Escherichia coli infection should be considered.
    Correlation between CD64 and PCT levels in cerebrospinal fluid and degree of hearing impairment sequelae in neonates with purulent meningitis. Liu Cui,Zhao Dongchi Experimental and therapeutic medicine This study investigated the possible correlation between the degree of hearing impairment caused by neonatal purulent meningitis and the levels of CD64 and PCT in cerebrospinal fluid of patients, and assessed the prognostic value of such levels. We recorded data from 156 cases of neonatal purulent meningitis retrospectively. All the patients received brainstem response audiometry, and cerebrospinal fluid samples were collected within the first day after admission through lumbar puncture. Flow cytometry was used to detect CD64 levels and enzyme-linked fluorescent assay was used to detect PCT levels. The children with hearing impairment were followed up for 1 year and brainstem response audiometry was performed again in them. We found that 43.59% of the children showed different degrees of hearing impairment, and 55% of them did not fully recover. The levels of PCT and CD64 in cerebrospinal fluid of children with hearing impairment were significantly higher than those of children with normal hearing (P<0.01). The levels of PCT and CD64 in mild, moderate and severe hearing impaired children increased gradually with higher degrees of impairment, and the differences between groups were significant (P<0.01). During the follow-up, it was found that the levels of PCT and CD64 in children correlated well with the degree of hearing recovery, and the differences between groups were significant (P<0.01). In our study, approximately 1/4 children with purulent meningitis showed long-term hearing impairment. Based on our analyses, the levels of CD64 and PCT in cerebrospinal fluid can be used to predict the degree and long-term prognosis of hearing impairment caused by purulent meningitis in children. 10.3892/etm.2017.5273
    Differential fatty acid analysis of cerebrospinal fluid in infants and young children with suspected meningitis. Ekhtiyari Elham,Barzegar Mohammad,Mehdizadeh Amir,Shaaker Maghsood,Ghodoosifar Sepideh,Abhari Alireza,Darabi Masoud Child's nervous system : ChNS : official journal of the International Society for Pediatric Neurosurgery PURPOSE:Meningitis is relatively common in infants and young children and can cause permanent brain damage. The aim of this study was to determine whether meningitis is associated with fatty acids in cerebrospinal fluid (CSF). METHODS:CSF samples from children between 3 months and 6 years of age admitted to the Tabriz public hospitals who met clinical criteria of meningitis were collected at enrollment. A total of 81 samples were analyzed for fatty acid profile by gas-liquid chromatography. RESULTS:Children with a purulent meningitis demonstrated a higher percentage of oleic acid (p < 0.05, >10 %) and lower percentages of omega-3 polyunsaturated fatty acids (p < 0.001, <-40 %) than aseptic meningitis and nonmeningitis groups did. There was an inverse relationship between CSF long-chain omega-3 fatty acids and the total number of leukocytes and differential counts of neutrophils and lymphocytes in the purulent meningitis group. Moreover, significantly lower omega-3 fatty acids (p = 0.001, -37 %) and higher ratio of n-6/n-3 (p = 0.02, -29 %) were found in patients with purulent meningitis with sepsis than in those with meningitis and no sepsis. CONCLUSIONS:This study provides evidence that purulent meningitis and its complication with sepsis are associated with important disturbances in CSF fatty acids, mainly deficiency in long-chain omega-3 polyunsaturated fatty acids. 10.1007/s00381-016-3232-x
    [Clinical analysis of purulent meningitis in 317 children]. Xu Qing-Qing,Li Mei Zhongguo dang dai er ke za zhi = Chinese journal of contemporary pediatrics OBJECTIVE:To study the clinical features, treatment, and prognosis of purulent meningitis (PM) in children. METHODS:A retrospective analysis was performed on the clinical data of 317 children with PM aged from 1 month to 15 years. RESULTS:PM was commonly seen in infants (198 cases, 62.6%). Most children with PM had preceding respiratory infection (171 cases, 53.9%). The major clinical manifestations of PM were fever, convulsions, and intracranial hypertension, and convulsions were more commonly seen in infants (152 cases, 93.6%). The major complication was subdural effusion (95 cases, 29.9%). Of the 95 cases of subdural effusion, 22 cases were diagnosed by subdural puncture; 68 cases underwent subdural puncture and 62 cases restored to normal temperature 3-5 days after puncture. Risk factors associated with complications and sequelae were young age and protein≥1 g/L in cerebrospinal fluid (CSF) (OR=0.518, 1.524 respectively; P<0.05). The third-generation cephalosporins were the first choice for PM, and vancomycin or carbapenems were replacement therapy. Thirteen (14.4%) out of 90 children had delayed cerebral vasculitis during a follow-up visit within 3 months after discharge. CONCLUSIONS:PM is more commonly seen in infants, and the infants have a high incidence of convulsions. Young age and protein≥1 g/L in CSF may increase the risk of complications and sequelae. Subdural puncture is not only a diagnostic method but also a therapy for subdural effusion. Some children have delayed cerebral vasculitis during a follow-up visit within 3 months after discharge, so follow-up visits should be performed within 3 months after discharge.
    Development of a TaqMan Array card to target 21 purulent meningitis-related pathogens. Zhao Chengna,Wang Xi,Zhang Chao,Liu Bing,Jing Hongbo,Ming Lihua,Jiang Hua,Zheng Yuling,Liu Peng,Liu Gang,Jiang Yongqiang BMC infectious diseases BACKGROUND:Purulent meningitis (PM) is a serious life-threatening infection of the central nervous system (CNS) by bacteria or fungi and associated with high mortality and high incidence of CNS sequelae in children. However, the conventional cerebrospinal fluid (CSF) culture method is time-consuming and has a low sensitivity. METHODS:Our study developed a real-time PCR-based purulent meningitis-TaqMan array card (PM-TAC) that targeted 21 PM-related pathogens and could produce results within 3 h. Primers and probes were adapted from published sources possibly. The performance of them were evaluated and optimized and then they were spotted on TAC. RESULTS:The PM-TAC showed a sensitivity and specificity of 95 and 96%, respectively. For all of the 21 targeted pathogens, the PM-TAC assay had a LOD ranging from 5 copies/reaction to 100 copies/reaction, an intra-assay variation of 0.07-4.45%, and an inter-assay variation of 0.11-6.81%. Of the 15 CSF samples collected from patients with PM after empiric antibiotic therapies, the positive rate was 53.3% (8/15) for our PM-TAC assay but was only 13.3% (2/15) for the CSF culture method. Of the 17 CSF samples showing negative CSF culture, the PM-TAC assay identified a case of Neisseria meningitidis infection. Furthermore, all of the 10 CSF samples from patients without CNS infection showed negative for the PM-TAC assay. CONCLUSIONS:Our PM-TAC assay also demonstrated that the pathogen loads in the CSF samples correlated with the severity of PM. Thus, the PM-TAC may be helpful to improve the prognosis of PM and clinical outcomes from antibiotic therapies. 10.1186/s12879-019-3856-z
    Rapid pathogen identification using a novel microarray-based assay with purulent meningitis in cerebrospinal fluid. Hou Yuting,Zhang Xu,Hou Xiaolin,Wu Ruofen,Wang Yanbai,He Xuexian,Wang Libin,Wang Zhenhai Scientific reports In order to improve the diagnosis of pathogenic bacteria in cerebrospinal fluid (CSF) with purulent meningitis, we developed a DNA microarray technique for simultaneous detection and identification of seven target bacterium. DNA were extracted from 24 CSF samples with purulent meningitis (or suspected purulent meningitis). The specific genes of each pathogen were chosen as the amplification target, performed the polymerase chain reaction (PCR), labeled with a fluorescence dye, and hybridized to the oligonucleotide probes on the microarray. There is no significant cross-hybridization fluorescent signal occurred in untargeted bacteria. There were 87.5% (21/24) positive results in DNA microarray compared with the 58.3% (14/24) of the CSF culture test. Of which 58.3% (14/24) of the patients with culture-confirmed purulent meningitis, 37.5% (9/24) patients who were not confirmed by culture test but were demonstrated by the clinical diagnosis and DNA microarray. Multiple bacterial infections were detected in 5 cases by the microarray. In addition, the number of gene copies was carried out to determine the sensitivity of this technique, which was shown to be 3.5 × 10 copies/μL. The results revealed that the microarray technique which target pathogens of the CSF specimen is better specificity, accuracy, and sensitivity than traditional culture method. The microarray method is an effective tool for rapidly detecting more target pathogens and identifying the subtypes of strains which can eliminate the impact of the different individuals with purulent meningitis for prompt diagnosis and treatment. 10.1038/s41598-018-34051-0
    Bacterial meningitis in Sudanese children; critical evaluation of the clinical decision using clinical prediction rules. Abdelrahim Nada Abdelghani,Fadl-Elmula Imad Mohammed,Ali Hassan Mohammed BMC pediatrics BACKGROUND:Sudan falls in the meningitis belt where most global cases of bacterial meningitis are reported. Highly accurate decision support tools have been developed by international specialized societies to guide the diagnosis and limit unnecessary hospital admissions and prolonged antibiotic use that have been frequently reported from countries around the world. The goals of this study are to critically evaluate the clinical decision of bacterial meningitis in children in Sudan using clinical prediction rules and to identify the current bacterial aetiology. METHODS:This cross-sectional hospital-based study was conducted in October to July of 2010 in a major referral pediatric hospital in Khartoum, Sudan. Febrile children age 1 day to 15 years who were provisionally diagnosed as having meningitis on admission were included (n = 503). Cerebrospinal fluid (CSF) specimens were obtained from all patients while clinical and demographic data were available for only 404. Conventional laboratory investigations were performed. The clinical decision was evaluated by the International Classification of Diseases-Clinical Modification code 320.9 and the Bacterial Meningitis Score. Ethical clearance and permissions were obtained. RESULTS:Out of 503 provisionally diagnosed bacterial meningitis patients, the final clinical confirmation was assigned to 55.9%. When codes were applied; 5.7% (23/404) with CSF pleocytosis were re-classified as High Risk for bacterial meningitis and 1.5% (6/404) with confirmed bacterial aetiology as Proven Bacterial Meningitis. Neisseria meningitidis was identified in 0.7% (3/404) and Streptococcus pneumoniae in another 0.7%. Typical laboratory findings (i.e. CSF pleocytosis and/or low glucose and high protein concentrations, Gram positive or Gram negative diplococcic, positive bacterial culture) were seen in 5 (83%). Clinically, patients showed fever, seizures, chills, headache, vomiting, stiff neck and bulging fontanelle. All confirmed cases were less than 5 years old and were admitted in summer. All patients were prescribed with antibiotics; they were all recovered and discharged. CONCLUSIONS:Bacterial meningitis is over-diagnosed in hospitals in Khartoum therefore clinical prediction rules must be adopted and applied to guide the clinical decision. The sole bacterial aetiology in this selected group of Sudanese children remain N. meningitidis and S. pneumoniae, but with significant decrease in prevalence. Some cases showed atypical clinical and laboratory findings. 10.1186/s12887-019-1684-3
    How many single-nucleotide polymorphisms (SNPs) must be tested in order to prove susceptibility to bacterial meningitis in children? Analysis of 11 SNPs in seven genes involved in the immune response and their effect on the susceptibility to bacterial meningitis in children. Gowin Ewelina,Świątek-Kościelna Bogna,Kałużna Ewelina,Strauss Ewa,Wysocki Jacek,Nowak Jerzy,Michalak Michał,Januszkiewicz-Lewandowska Danuta Innate immunity The aim of this study is to describe the prevalence of single single-nucleotide polymorphisms (SNPs) as well as their combinations in genes encoding proteins involved in the immune response in children with bacterial meningitis. The prospective study group consisted of 39 children with bacterial meningitis and 49 family members surveyed between 2012 and 2016. Eleven SNPs in seven genes involved in immune response were analysed. The mean number of minor frequency alleles (MAF) of studied SNPs was lowest in the control group and highest in patients with pneumococcal meningitis. We found that carrying ≥6 MAF of studied SNPs was associated with an increased risk of pneumococcal meningitis. The prevalence of risky variants was noted to be higher in patients with pneumococcal meningitis as compared to the control group. In conclusion, genetic factors are a relevant factor in determining the susceptibility to bacterial meningitis. A statistically significant cumulative effect of mutated variants on increasing the risk of bacterial meningitis was detected. Combining all three SNPs in MBL2 improves the prediction of susceptibility to pneumococcal meningitis. Analysis of risky alleles can help indicate people prone to the disease who are 'gene-immunocompromised'. 10.1177/1753425918762038
    Etiology of Bacterial Meningitis Among Children <5 Years Old in Côte d'Ivoire: Findings of Hospital-based Surveillance Before and After Pneumococcal Conjugate Vaccine Introduction. Boni-Cisse Catherine,Jarju Sheikh,Bancroft Rowan E,Lepri Nicaise A,Kone Hamidou,Kofi N'zue,Britoh-Mlan Alice,Zaba Flore Sandrine,Usuf Effua,Ndow Peter Sylvanus,Worwui Archibald,Mwenda Jason M,Biey Joseph N,Ntsama Bernard,Kwambana-Adams Brenda A,Antonio Martin Clinical infectious diseases : an official publication of the Infectious Diseases Society of America BACKGROUND:Bacterial meningitis remains a major disease affecting children in Côte d'Ivoire. Thus, with support from the World Health Organization (WHO), Côte d'Ivoire has implemented pediatric bacterial meningitis (PBM) surveillance at 2 sentinel hospitals in Abidjan, targeting the main causes of PBM: Streptococcus pneumoniae (pneumococcus), Haemophilus influenzae, and Neisseria meningitidis (meningococcus). Herein we describe the epidemiological characteristics of PBM observed in Côte d'Ivoire during 2010-2016. METHODS:Cerebrospinal fluid (CSF) was collected from children aged <5 years admitted to the Abobo General Hospital or University Hospital Center Yopougon with suspected meningitis. Microbiology and polymerase chain reaction (PCR) techniques were used to detect the presence of pathogens in CSF. Where possible, serotyping/grouping was performed to determine the specific causative agents. RESULTS:Overall, 2762 cases of suspected meningitis were reported, with CSF from 39.2% (1083/2762) of patients analyzed at the WHO regional reference laboratory in The Gambia. In total, 82 (3.0% [82/2762]) CSF samples were positive for bacterial meningitis. Pneumococcus was the main pathogen responsible for PBM, accounting for 69.5% (52/82) of positive cases. Pneumococcal conjugate vaccine serotypes 5, 18C, 19F, and 6A/B were identified post-vaccine introduction. Emergence of H. influenzae nontypeable meningitis was observed after H. influenzae type b vaccine introduction. CONCLUSIONS:Despite widespread use and high coverage of conjugate vaccines, pneumococcal vaccine serotypes and H. influenzae type b remain associated with bacterial meningitis among children aged <5 years in Côte d'Ivoire. This reinforces the need for enhanced surveillance for vaccine-preventable diseases to determine the prevalence of bacterial meningitis and vaccine impact across the country. 10.1093/cid/ciz475
    Vitamin D was not associated with survival or cerebrospinal fluid cathelicidin levels in children with bacterial meningitis. Savonius Okko,Pelkonen Tuula,Roine Irmeli,Viljakainen Heli,Andersson Sture,Fernandez Josefina,Peltola Heikki,Helve Otto Acta paediatrica (Oslo, Norway : 1992) AIM:Vitamin D deficiency impairs the immunological system and has been associated with worse outcomes of infectious diseases, but its role in bacterial meningitis remains unknown. We investigated whether serum 25-hydroxyvitamin D concentrations related to disease outcomes and to cerebrospinal fluid (CSF) cathelicidin concentrations in childhood bacterial meningitis. METHODS:All consecutively enrolled patients in a clinical trial on childhood bacterial meningitis in Latin America in 1996-2003 were considered, and 142 children, with a median age of seven months who had a confirmed bacterial aetiology and frozen serum available for further analyses, were included in this study. Serum 25-hydroxyvitamin D concentrations were determined with a chemiluminescence immunoassay analyser, while CSF cathelicidin was measured by enzyme-linked immunosorbent assay. RESULTS:The median serum 25-hydroxyvitamin D concentration was 96 (range 19-251) nmol/L. No relationship was found with patient survival, but children with any neurological sequelae had lower serum 25-hydroxyvitamin D levels than children without sequelae. Serum 25-hydroxyvitamin D was unrelated to cathelicidin concentrations in CSF. CONCLUSION:Although serum 25-hydroxyvitamin D in children with bacterial meningitis was not associated with survival or CSF cathelicidin concentrations, its relationship with more detailed disease outcomes warrants further study. 10.1111/apa.14393
    Etiology of Pediatric Bacterial Meningitis Pre- and Post-PCV13 Introduction Among Children Under 5 Years Old in Lomé, Togo. Tsolenyanu Enyonam,Bancroft Rowan E,Sesay Abdul K,Senghore Madikay,Fiawoo Mawouto,Akolly Djatougbe,Godonou Mawussi A,Tsogbale Novissi,Tigossou Segla D,Tientcheu Leopold,Dagnra Anoumou,Atakouma Yawo,Sylvanus Ndow Peter,Worwui Archibald,Landoh Dadja E,Mwenda Jason M,Biey Joseph N,Ntsama Bernard,Kwambana-Adams Brenda A,Antonio Martin Clinical infectious diseases : an official publication of the Infectious Diseases Society of America BACKGROUND:Pediatric bacterial meningitis (PBM) causes severe morbidity and mortality within Togo. Thus, as a member of the World Health Organization coordinated Invasive Bacterial Vaccine Preventable Diseases network, Togo conducts surveillance targeting Streptococcus pneumoniae (pneumococcus), Neisseria meningitidis (meningococcus), and Haemophilus influenzae, at a sentinel hospital within the capital city, Lomé, in the southernmost Maritime region. METHODS:Cerebrospinal fluid was collected from children <5 years with suspected PBM admitted to the Sylvanus Olympio Teaching Hospital. Phenotypic detection of pneumococcus, meningococcus, and H. influenzae was confirmed through microbiological techniques. Samples were shipped to the Regional Reference Laboratory to corroborate results by species-specific polymerase chain reaction. RESULTS:Overall, 3644 suspected PBM cases were reported, and 98 cases (2.7%: 98/3644) were confirmed bacterial meningitis. Pneumococcus was responsible for most infections (67.3%: 66/98), followed by H. influenzae (23.5%: 23/98) and meningococcus (9.2%: 9/98). The number of pneumococcal meningitis cases decreased by 88.1% (52/59) postvaccine introduction with 59 cases from July 2010 to June 2014 and 7 cases from July 2014 to June 2016. However, 5 cases caused by nonvaccine serotypes were observed. Fewer PBM cases caused by vaccine serotypes were observed in infants <1 year compared to children 2-5 years. CONCLUSIONS:Routine surveillance showed that PCV13 vaccination is effective in preventing pneumococcal meningitis among children <5 years of age in the Maritime region. This complements the MenAfriVac vaccination against meningococcal serogroup A to prevent meningitis outbreaks in the northern region of Togo. Continued surveillance is vital for estimating the prevalence of PBM, determining vaccine impact, and anticipating epidemics in Togo. 10.1093/cid/ciz473