Objective: To explore the value of metagenomic next-generation sequencing (mNGS) in the etiology diagnosis of bacterial meningitis in children. Methods: The etiological results of 189 children diagnosed with "bacterial meningitis" or "purulent meningitis" or "central nervous system infection" in the Children's Hospital of Fudan University from 1st January 2019 to 31st December 2020 were analyzed retrospectively. The cerebrospinal fluid (CFS) of the children with bacterial meningitis was detected by culture and mNGS respectively, and the difference of pathogen detection rate between the 2 methods was analyzed. According to the age at the time of visit, the children were divided into neonatal group (≤28 days of age) and non-neonatal group (>28 days of age), and χ² test was used to compare the positive rate between the 2 groups. Taking CFS culture as the gold standard, the sensitivity and specificity of mNGS in the diagnosing of bacterial meningitis in children were analyzed. Results: Among these 189 children with bacterial meningitis, 116 were males and 73 were females. A total of 76 strains of pathogens were detected in blood and (or) CSF cultures, of which 50 strains (65.8%) were Gram-positive bacteria; among those, 18 strains (23.7%) of Streptococcus agalactiae, 17 strains (19.7%) of Escherichia coli and 15 strains (19.7%) of Streptococcus pneumoniae were detected with higher detection rate. The infection rate of Gram-positive bacteria in the non-neonatal group was higher than that in the neonatal group (76.0% (38/50) vs. 50.0% (13/26), χ²=5.24, P=0.020).The same CSF samples of 48 cases were tested by mNGS and culture at the same time, and the detection rate of mNGS was higher than that of CSF culture (20 cases (41.7%) vs. 12 cases (25.0%), χ²=16.45, P<0.001). The consistency of mNGS and culture results was 79.2% (38/48), and the same pathogen was detected in 11 children with both positive mNGS and CSF culture. Taking the results of CSF culture as the gold standard, the sensitivity of mNGS in the diagnosing of bacterial meningitis was 91.7%, and the specificity was 75.0%. Conclusions: The mNGS technology can improve the pathogen detection rate of bacterial meningitis in children, and has a high consistency with CSF culture. In suspected cases where the pathogen cannot be identified by traditional methods, CSF mNGS should be considered timely.
Child ; Escherichia coli ; Fatigue Syndrome, Chronic ; Female ; Gram-Positive Bacteria ; High-Throughput Nucleotide Sequencing/methods* ; Humans ; Male ; Meningitis, Bacterial/microbiology* ; Metagenomics/methods* ; Retrospective Studies ; Sensitivity and Specificity

Infections by Cronobacter spp. are hazardous to infants since they can lead to neonatal meningitis, bacteremia, and necrotizing enterocolitis. Cronobacter spp. are frequently resistant to β-lactam derivatives, macrolides, and aminoglycosides. In addition, multi-resistant strains have also been detected. In China, the isolation rate of Cronobacter spp. from commercial powdered infant formula (PIF) or follow-up formula (FUF) is relatively high. Nevertheless, clinical cases of Cronobacter infection have been ignored to date. Here we describe two cases of Cronobacter infection detected at the Wuhan Women and Children Medical Care Center Hospital (Wuhan City, China). We provide the genomic analysis of the isolates and the antibiotic-resistance profiles of the two strains. The Cronobacter strains identified in this study were not susceptible to third-generation cephalosporins, aminoglycoside, and/or trimethoprim-sulfamethoxazole. Whole genome sequencing revealed various genes known to encode antibiotic resistance. Future studies are needed to determine whether the genes predicted in this study are functional. As with Enterobacter spp., the antibiotic resistance of Cronobacter is a serious issue that requires more attention.
Anti-Bacterial Agents ; pharmacology ; Cronobacter ; drug effects ; Drug Resistance, Multiple, Bacterial ; Fatal Outcome ; Female ; Gram-Negative Bacterial Infections ; microbiology ; Humans ; Infant ; Meningitis, Bacterial ; microbiology

No abstract available.
Aged ; Aneurysm/surgery ; Anti-Bacterial Agents/pharmacology ; Brain Diseases/surgery ; Craniotomy/adverse effects ; DNA, Bacterial/chemistry/genetics/metabolism ; Female ; Flavobacteriaceae Infections/etiology/microbiology ; Flavobacterium/classification/drug effects/*isolation & purification ; Humans ; Meningitis/*diagnosis/microbiology ; Microbial Sensitivity Tests ; Phylogeny ; Postoperative Complications ; Sequence Analysis, DNA

OBJECTIVETo 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.

METHODA 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.

RESULTAmong 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.

CONCLUSIONEscherichia 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.

Anti-Bacterial Agents ; pharmacology ; Cefotaxime ; Child ; Drug Resistance, Bacterial ; Female ; Gram-Negative Bacteria ; Gram-Positive Bacteria ; Humans ; Imipenem ; Infant ; Infant, Newborn ; Infant, Newborn, Diseases ; Intensive Care Units, Neonatal ; Male ; Meningitis, Bacterial ; diagnosis ; drug therapy ; microbiology ; Methicillin-Resistant Staphylococcus aureus ; Microbial Sensitivity Tests ; Penicillins ; Retrospective Studies ; Staphylococcus ; Staphylococcus aureus ; Streptococcal Infections ; Streptococcus ; Streptococcus agalactiae

OBJECTIVETo study the clinical features, treatment, and prognosis of purulent meningitis (PM) in children.

METHODSA retrospective analysis was performed on the clinical data of 317 children with PM aged from 1 month to 15 years.

RESULTSPM 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.

CONCLUSIONSPM 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.

Adolescent ; Child ; Child, Preschool ; Female ; Follow-Up Studies ; Humans ; Infant ; Male ; Meningitis, Bacterial ; complications ; drug therapy ; microbiology ; Suppuration ; microbiology

We describe a group of 3 cases of invasive meningococcal disease that occurred in a military training camp in April 2011. All three patients were hospitalized. Ultimately, two patients recovered and one died. One patient had meningitis, one patient had septicemia and meningitis, and the other had no definite septicemia or meningitis. Neisseria meningitidis serogroup W-135 was detected in the serum and cerebrospinal fluid (CSF) of all patients by real-time polymerase chain reaction. In the one case of mortality, two strains were isolated from the patient's blood and CSF. Using multilocus sequence typing analysis, these strains were identified as a novel sequence type, ST-8912. Special attention is required for the meningococcal disease in military camp because the military personnels are in high risk of contact transmission.
DNA, Bacterial/blood/cerebrospinal fluid ; Electrophoresis, Gel, Pulsed-Field ; Humans ; Male ; Meningitis/complications/*diagnosis/microbiology ; Military Personnel ; Multilocus Sequence Typing ; Neisseria meningitidis, Serogroup W-135/genetics/*isolation & purification ; Real-Time Polymerase Chain Reaction ; Sepsis/complications/*diagnosis/microbiology ; Young Adult

OBJECTIVETo investigate the inhibitory effect of Lactobacillus rhamnosus GG ( LGG) against Cronobacter-induced meningitis in neonatal rats.

METHODSThe cell adhesion and invasion capacities of Cronobacter were assayed in Caco-2 cells, and the optimal time length and concentration of the bacterium for infection were determined. The suppressive effects of LGG on the adhesion and invasion of Cronobacter in caco-2 cells were tested by competitive and exclusion experiments, and its inhibitory effect against Cronobacter-induced meningitis was evaluated in neonatal rats.

RESULTSCronobacter showed aggressive adhesion to caco-2 cells with an optimal infection time of 3 h. LGG produced a concentration-dependent inhibition of Cronobacter adhesion and invasion by competing with and excluding the latter for cell adhesion. In neonatal rats, LGG showed an obvious preventive effect and also a moderate therapeutic effect against Cronobacter-induced meningitis.

CONCLUSIONLGG can inhibit Cronobacter entry across the intestinal barrier to achieve preventive and therapeutic effects against Cronobacter-induced meningitis.

Animals ; Animals, Newborn ; Bacterial Adhesion ; Caco-2 Cells ; Cronobacter ; pathogenicity ; Enterobacteriaceae Infections ; therapy ; Humans ; Intestines ; microbiology ; Lactobacillus rhamnosus ; Meningitis, Bacterial ; therapy ; Probiotics ; Rats

BACKGROUND: Streptococcus pneumoniae causes life-threatening infections such as meningitis, pneumonia, and febrile bacteremia, particularly in young children. The increasing number of drug-resistant isolates has highlighted the necessity for intervening and controlling disease. To achieve this, information is needed on serotype distribution and patterns of antibiotic resistance in children. METHODS: All cases of invasive pneumococcal disease (IPD) in children aged less than 15 yr recorded at King Khalid University Hospital, King Saud University, Riyadh, Saudi Arabia, were reviewed for serotyping and antibiotic susceptibility. Isolates were collected from 78 consecutive patients with IPD between 2009 and 2012. All collected isolates were subjected to serotyping by co-agglutination, sequential multiplex PCR, and single PCR sequetyping as previously described. RESULTS: The most frequently isolated IPD serotypes were 23F, 6B, 19F, 18C, 4, 14, and 19A, which are listed in decreasing order and cover 77% of total isolates. The serotype coverage for the pneumococcal conjugate vaccine (PCV)7, PCV10, and PCV13 was 77%, 81%, and 90%, respectively. Results from sequential multiplex PCR agreed with co-agglutination results. All serotypes could not be correctly identified using single PCR sequetyping. Minimum inhibitory concentration showed that 50 (64%) isolates were susceptible to penicillin, whereas 70 (90%) isolates were susceptible to cefotaxime. CONCLUSIONS: The most common pneumococcal serotypes occur with frequencies similar to those found in countries where the PCV has been introduced. The most common serotypes in this study are included in the PCVs. Addition of 23A and 15 to the vaccine would improve the PCV performance in IPD prevention.
Adolescent ; Anti-Bacterial Agents/*pharmacology ; Bacterial Proteins/genetics ; Cefotaxime/pharmacology ; Child ; Child, Preschool ; DNA, Bacterial/analysis ; Humans ; Infant ; Meningitis/*diagnosis/microbiology ; Microbial Sensitivity Tests ; Multiplex Polymerase Chain Reaction ; Penicillins/pharmacology ; Pneumococcal Vaccines/immunology ; Pneumonia/*diagnosis/microbiology ; Protein Tyrosine Phosphatases/genetics ; Retrospective Studies ; Saudi Arabia ; Serotyping ; Streptococcus pneumoniae/*drug effects/genetics

OBJECTIVETo evaluate the safety of meningococcal group AC bivalent polysaccharide conjugate vaccine among children aged 5-24 months old.

METHODSFrom July 2011 to June 2012, a total of 34 411 children aged 5-24 month-old who voluntarily vaccinated meningococcal group AC bivalent polysaccharide conjugate vaccine in Zhongshan city were included. The adverse effects within 72 hours were recorded and analyzed.

RESULTS34 411 children were recruited, including 18 708 boys (54.36%), whose mean age were ( 11.4 ± 3.9 ) months old.Within 72 hours, the incidence rates of local adverse effects were 0.76% (261/34 411) for erythema,0.57% (197/34 411) for sclerosis,0.56% (191/34 411) for swelling,0.42% (143/34 411) for pain,0.15% (53/34 411) for pruritus, and 0.15% (50/34 411) for rash on the injection site. The overall incidence rate of local adverse effects was 1.61% (554/34 411; 95%CI:1.48%-1.74%). The incidence rates of systemic adverse effects were 0.98% (312/34 411) for fever,0.48% (164/34 411) for anorexia,0.31% (108/34 411) for diarrhea,0.29% (100/34 411) for malaise,0.20% (70/34 411) for nausea and vomiting, and 0.08% (26/34 411) for headache. The overall incidence rate of systemic adverse effects was 1.64% (565/34 411; 95%CI:1.51%-1.78%).25 children (0.07%) had hyperpyrexia ( > 39°C), and the time of duration lasted less than 48 hours.16 children (0.05%) had symptoms of cold, such as cough and catarrh.No accident and other serious events were reported. The incidence rate of systemic adverse effects among boys was 1.79% (334/18 708), which was higher than that of girls (1.47%, 231/15 703), the difference showed statistical significance (χ(2) = 5.22, P < 0.01). The incidence rate of systemic adverse effects among children aged 5-12 month-old was 1.78% (411/23 113), which was higher than that among children aged 13-24 month-old (1.36%, 154/11 298), the difference showed statistical significance (χ(2) = 8.10, P < 0.01). The incidence rate of local adverse effects in children vaccinated the first dose was 1.72% (536/31 129), which was higher than that in children vaccinated the second or third dose (0.55%, 18/3282), the difference showed statistical significance (χ(2) = 25.81, P < 0.01). The incidence rate of systemic adverse effects in children vaccinated the first dose was 1.73% (539/31 129), which was higher than that in children vaccinated the second or third dose (0.79%, 26/5282), whose difference also showed statistical significance (χ(2) = 16.22, P < 0.01).

CONCLUSIONThe safety of meningococcal group AC bivalent polysaccharide conjugate vaccine among children aged 5-24 months old is relative good.

Female ; Humans ; Infant ; Male ; Meningitis, Meningococcal ; microbiology ; prevention & control ; Meningococcal Vaccines ; administration & dosage ; adverse effects ; immunology ; Neisseria meningitidis, Serogroup A ; Neisseria meningitidis, Serogroup C ; Polysaccharides, Bacterial ; immunology ; Vaccines, Conjugate ; administration & dosage ; adverse effects ; immunology

OBJECTIVETo determine the frequency distribution and antibiotic resistance of pathogens isolated from the cerebrospinal fluid samples of children with bacterial meningitis (BM) and to provide a basis for the timely and effective treatment of childhood BM.

METHODSRetrospective analysis was performed on pathogens isolated from 5097 cerebrospinal fluid samples collected from children in Kunming Children's Hospital between January 2008 and June 2012, as well as drug sensitivity test results. Kirby-Bauer antibiotic testing was used to analyze the sensitivity of these pathogens to commonly used antibiotics.

RESULTSA total of 116 pathogen strains were detected from the 5097 cerebrospinal fluid samples, including 77 (66.4%) Gram-positive strains, 30 (25.9%) Gram-negative strains, and 9 (7.8%) fungal strains, with a positive rate of 2.28%. The six most frequently isolated pathogens were Staphylococcus epidermidis (32 strains, 27.6%), Streptococcus pneumoniae (15 strains, 12.9%), Escherichia coli (15 strains, 12.9%), Staphylococcus haemolyticus (9 strains, 7.8%), Cryptococcus neoformans (8 strains, 6.9%) and Staphylococcus aureus (6 strains, 5.2%). Coagulase-negative staphylococci was the predominant pathogen in neonates and young infants with BM, and its sensitivity rates to penicillin, erythromycin and clindamycin were lower than 40%. Streptococcus pneumoniae had a penicillin sensitivity rate of 13.4%, while sensitivity rates to erythromycin and clindamycin reached 60.0%. No Staphylococcus and Streptococcus pneumoniae pathogens resistant to vancomycin were found. Gram-negative bacilli had relatively high sensitivity rates to imipenem, meropenem, cefoperazone/sulbactam and cefepime.

CONCLUSIONSGram-positive cocci are the predominant pathogens for childhood BM over the past five years. The detected pathogens develop high resistance to commonly used antibiotics. To prevent misdiagnosis, careful attention should be paid to BM caused by Cryptococcus neoformans.

Child ; Child, Preschool ; Drug Resistance, Bacterial ; Female ; Gram-Negative Bacteria ; drug effects ; isolation & purification ; Gram-Positive Cocci ; drug effects ; isolation & purification ; Humans ; Infant ; Infant, Newborn ; Male ; Meningitis, Bacterial ; cerebrospinal fluid ; drug therapy ; microbiology ; Retrospective Studies