Objective: To investigate the prevalence and poor prognosis of late-onset sepsis (LOS) in very low birth weight infant (VLBWI). Methods: This prospective, multicenter observational cohort study was conducted based on the data from Sina-Northern Neonatal Network (SNN). The general data, perinatal information and poor prognosis of 6 639 VLBWI, who were admitted to the 35 neonatal intensive care units from 2018 to 2021, were collected and analyzed. According to the occurrence of LOS during hospitalization, the VLBWI were assigned to the LOS group and non-LOS group. The LOS group was further divided into 3 subgroups according to the occurrence of neonatal necrotizing enterocolitis (NEC) and purulent meningitis. The Chi-square test or Fisher exact probability method, independent sample t test, Mann-Whitney U test and multivariate Logistic regression model were used to analyze the relationship between LOS and poor prognosis in VLBWI. Results: A total of 6 639 eligible VLBWI were enrolled, including 3 402 cases (51.2%) of males and 1 511 cases (22.8%) with LOS. The incidences of LOS in extremely low birth weight infants (ELBWI) and extremely preterm infants were 33.3% (392/1 176) and 34.2% (378/1 105), respectively. There were 157 cases (10.4%) who died in the LOS group and 48 cases (24.9%) in the subgroup of LOS complicated with NEC. Multivariate Logistic regression analysis showed that LOS complicated with NEC was associated with increased mortality and incidence of grade Ⅲ-Ⅳ intraventricular hemorrhage (IVH) or periventricular leukomalacia (PVL), moderate or severe bronchopulmonary dysplasia (BPD), and extrauterin growth retardation (EUGR) (OR_adjust=5.27, 2.59, 3.04, 2.04; 95%CI 3.60-7.73, 1.49-4.50, 2.11-4.37, 1.50-2.79; all P<0.01); LOS complicated with purulent meningitis was also associated with increased mortality and incidence of grade Ⅲ-Ⅳ IVH or PVL, and moderate or severe BPD (OR_adjust=2.22, 8.13, 3.69, 95%CI 1.30-3.37, 5.22-12.67, 2.49-5.48; all P<0.01); the infants without NEC or purulent meningitis in the LOS group was only associated with increased incidence of moderate or severe BPD (OR_adjust=2.20, 95%CI 1.83-2.65, P<0.001). After ruling out contaminated bacteria, a total of 456 cases showed positive blood culture, including 265 cases (58.1%) of Gram-negative bacteria, 126 cases (27.6%) of Gram-positive bacteria, and 65 cases (14.3%) of fungi. The most common pathogenic bacteria was Klebsiella pneumoniae (n=147, 32.2%), followed by coagulase-negative Staphylococcus (n=72, 15.8%) and subsequently Escherichia coli (n=39, 8.6%). Conclusions: The incidence of LOS is high in VLBWI. Klebsiella pneumoniae is the most common pathogenic bacteria, followed by coagulase-negative Staphylococcus and Escherichia coli. LOS is associated with a poor prognosis for moderate to severe BPD. The prognosis of LOS complicated with NEC is poor with the highest mortality, and the risk of brain damage is significantly increased when LOS complicated with purulent meningitis.
Infant ; Male ; Female ; Pregnancy ; Infant, Newborn ; Humans ; Prospective Studies ; Coagulase ; Infant, Extremely Low Birth Weight ; Sepsis/epidemiology* ; Bronchopulmonary Dysplasia ; Escherichia coli ; Infant, Extremely Premature ; Meningitis

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

Objective: To analyze the clinical epidemiological characteristics including composition of pathogens , clinical characteristics, and disease prognosis acute bacterial meningitis (ABM) in Chinese children. Methods: A retrospective analysis was performed on the clinical and laboratory data of 1 610 children <15 years of age with ABM in 33 tertiary hospitals in China from January 2019 to December 2020. Patients were divided into different groups according to age,<28 days group, 28 days to <3 months group, 3 months to <1 year group, 1-<5 years of age group, 5-<15 years of age group; etiology confirmed group and clinically diagnosed group according to etiology diagnosis. Non-numeric variables were analyzed with the Chi-square test or Fisher's exact test, while non-normal distrituction numeric variables were compared with nonparametric test. Results: Among 1 610 children with ABM, 955 were male and 650 were female (5 cases were not provided with gender information), and the age of onset was 1.5 (0.5, 5.5) months. There were 588 cases age from <28 days, 462 cases age from 28 days to <3 months, 302 cases age from 3 months to <1 year of age group, 156 cases in the 1-<5 years of age and 101 cases in the 5-<15 years of age. The detection rates were 38.8% (95/245) and 31.5% (70/222) of Escherichia coli and 27.8% (68/245) and 35.1% (78/222) of Streptococcus agalactiae in infants younger than 28 days of age and 28 days to 3 months of age; the detection rates of Streptococcus pneumonia, Escherichia coli, and Streptococcus agalactiae were 34.3% (61/178), 14.0% (25/178) and 13.5% (24/178) in the 3 months of age to <1 year of age group; the dominant pathogens were Streptococcus pneumoniae and the detection rate were 67.9% (74/109) and 44.4% (16/36) in the 1-<5 years of age and 5-<15 years of age . There were 9.7% (19/195) strains of Escherichia coli producing ultra-broad-spectrum β-lactamases. The positive rates of cerebrospinal fluid (CSF) culture and blood culture were 32.2% (515/1 598) and 25.0% (400/1 598), while 38.2% (126/330)and 25.3% (21/83) in CSF metagenomics next generation sequencing and Streptococcus pneumoniae antigen detection. There were 4.3% (32/790) cases of which CSF white blood cell counts were normal in etiology confirmed group. Among 1 610 children with ABM, main intracranial imaging complications were subdural effusion and (or) empyema in 349 cases (21.7%), hydrocephalus in 233 cases (14.5%), brain abscess in 178 cases (11.1%), and other cerebrovascular diseases, including encephalomalacia, cerebral infarction, and encephalatrophy, in 174 cases (10.8%). Among the 166 cases (10.3%) with unfavorable outcome, 32 cases (2.0%) died among whom 24 cases died before 1 year of age, and 37 cases (2.3%) had recurrence among whom 25 cases had recurrence within 3 weeks. The incidences of subdural effusion and (or) empyema, brain abscess and ependymitis in the etiology confirmed group were significantly higher than those in the clinically diagnosed group (26.2% (207/790) vs. 17.3% (142/820), 13.0% (103/790) vs. 9.1% (75/820), 4.6% (36/790) vs. 2.7% (22/820), χ²=18.71, 6.20, 4.07, all P<0.05), but there was no significant difference in the unfavorable outcomes, mortility, and recurrence between these 2 groups (all P>0.05). Conclusions: The onset age of ABM in children is usually within 1 year of age, especially <3 months. The common pathogens in infants <3 months of age are Escherichia coli and Streptococcus agalactiae, and the dominant pathogen in infant ≥3 months is Streptococcus pneumoniae. Subdural effusion and (or) empyema and hydrocephalus are common complications. ABM should not be excluded even if CSF white blood cell counts is within normal range. Standardized bacteriological examination should be paid more attention to increase the pathogenic detection rate. Non-culture CSF detection methods may facilitate the pathogenic diagnosis.
Adolescent ; Brain Abscess ; Child ; Child, Preschool ; Escherichia coli ; Female ; Humans ; Hydrocephalus ; Infant ; Infant, Newborn ; Male ; Meningitis, Bacterial/epidemiology* ; Retrospective Studies ; Streptococcus agalactiae ; Streptococcus pneumoniae ; Subdural Effusion ; beta-Lactamases

OBJECTIVE: This study was conducted to identify the characteristics of early infants with urinary tract infection (UTI) who visited the pediatric emergency department (PED) and to investigate the characteristics of patients with cerebrospinal fluid (CSF) pleocytosis and incidence of bacterial meningitis. METHODS: We retrospectively reviewed the records of UTI infants aged 31 to 90 days presenting at PED whom had lumbar puncture. From September 1, 2014 to August 31, 2017, a total of 225 infants were enrolled. RESULTS: Twenty three patients had CSF pleocytosis. Of these, two patients were positive for CSF enteroviral polymerase chain reaction, while none were positive for bacterial culture. We compared the characteristics of infants with CSF pleocystosis. There were not diffences in sex, vaccination before fever, general condition, peak body temperature, peripheral white blood cell, C-reactive protein, and procalcitonin between two groups. However, in patients with prematurity history, incidence of CSF pleocytosis was high. Four infants hot bacteremia, and organism of these patients was all Escherichia coli. All of them had negative CSF culture and normal CSF findings. CONCLUSION: No febrile early infants with UTI had bacterial meningitis. As a result, we must not do conventional test of CSF in patients with UTI.
Bacteremia ; Body Temperature ; C-Reactive Protein ; Cerebrospinal Fluid ; Emergencies ; Emergency Service, Hospital ; Escherichia coli ; Fever ; Humans ; Incidence ; Infant ; Leukocytes ; Leukocytosis ; Meningitis ; Meningitis, Bacterial ; Polymerase Chain Reaction ; Retrospective Studies ; Spinal Puncture ; Urinary Tract Infections ; Urinary Tract ; Vaccination

OBJECTIVE: This study examined the characteristics of febrile young infants with a serious bacterial infection (SBI) who visited emergency centers in Korea and validated the Philadelphia criteria and modified Philadelphia criteria to predict the risk of SBI. METHODS: This was a retrospective study conducted on 450 infants aged 31 days to 56 days who visited three emergency centers with fever from September 2014 to August 2017. The characteristics of the SBI patients were analyzed, and the validation of the Philadelphia and modified Philadelphia criteria sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and accuracy were checked. RESULTS: Of 450 patients, 165 patients (36.7%) had SBI, such as urinary tract infection (33.3%), bacteremia (4.0%), acute osteomyelitis (0.2%), and bacterial meningitis (BM) in two patients (0.4%). The most common pathogen of invasive bacterial infection was Escherichia coli. In the Philadelphia criteria, the sensitivity, specificity, PPV, NPV, and accuracy were 73.9%, 47.0%, 44.7%, 75.7%, and 56.9%, respectively. In the modified Philadelphia criteria that excluded lumbar puncture as a predictor, the sensitivity, specificity, PPV, NPV, and accuracy were 93.3%, 31.9%, 44.3%, 89.2%, and 54.4%, respectively. The most common failed low risk criteria was appearance (43.3%). Two patients with bacterial meningitis were excluded from low risk group by the modified Philadelphia criteria. Although one out of 2 patients met the failed low risk criteria due to their poor condition, this factor is not objective, so BM can be missed. CONCLUSION: Bacterial meningitis was too rare in this study. New criteria are needed to predict SBI. The Philadelphia and modified Philadelphia criteria were not useful for predicting SBI in this study. Other prediction models will be needed to predict SBI in the vaccination era.
Bacteremia ; Bacterial Infections ; Emergencies ; Emergency Service, Hospital ; Escherichia coli ; Fever ; Fibrinogen ; Humans ; Infant ; Korea ; Meningitis ; Meningitis, Bacterial ; Osteomyelitis ; Retrospective Studies ; Sensitivity and Specificity ; Spinal Puncture ; Urinary Tract Infections ; Vaccination

Strongyloides stercoralis is an intestinal nematode that often causes chronic diarrhea and may develop severe complicated form of hyperinfection or disseminated infection in immunocompromised patients. Here, we report a case of recurrent strongyloidiasis presenting with pulmonary and meningeal involvement. A 55-year-old male diagnosed with pancreatic cancer 4 months ago was admitted due to chronic diarrhea, abdominal pain, and weight loss for 2–3 months. He had been treated with albendazole for chronic recurrent strongyloidiasis 13 years ago and again 2 years ago. He developed sepsis of Klebsiella pneumoniae and Escherichia coli on Days 3 and 7, respectively, and then meningitis of E. coli on Day 42. Strongyloidiasis was diagnosed by detection of abundant filariform larvae in sputum specimens on Day 15. He was treated for disseminated strongyloidiasis with albendazole and ivermectin for five weeks until clearance of larvae was confirmed in sputum and stool specimens. Laboratory diagnosis is important to guide appropriate treatment and to prevent chronic and recurrent strongyloidiasis.
Abdominal Pain ; Albendazole ; Clinical Laboratory Techniques ; Diarrhea ; Escherichia coli ; Humans ; Immunocompromised Host ; Ivermectin ; Klebsiella pneumoniae ; Larva ; Male ; Meningitis ; Middle Aged ; Pancreatic Neoplasms ; Sepsis ; Sputum ; Strongyloides stercoralis ; Strongyloidiasis ; Weight Loss

BACKGROUND: Invasive bacterial infections in apparently immunocompetent children were retrospectively analyzed to figure causative bacterial organisms in Korea. METHODS: A total of 947 cases from 25 university hospitals were identified from 2006 to 2010 as a continuance of a previous 10-year period study from 1996 to 2005. RESULTS: Escherichia coli (41.3%), Streptococcus agalactiae (27.7%), and Staphylococcus aureus (27.1%) were the most common pathogens in infants < 3 months of age. S. agalactiae was the most prevalent cause of meningitis and pneumonia and E. coli was the major cause of bacteremia without localizing signs in this group. In children 3 to 59 months of age, Streptococcus pneumoniae (54.2%), S. aureus (20.5%), and Salmonella spp. (14.4%) were the most common pathogens. S. pneumoniae was the leading cause of pneumonia (86.0%), meningitis (65.0%), and bacteremia without localizing signs (49.0%) in this group. In children ≥ 5 years of age, S. aureus (62.8%) was the predominant pathogen, followed by Salmonella species (12.4%) and S. pneumoniae (11.5%). Salmonella species (43.0%) was the most common cause of bacteremia without localizing signs in this group. The relative proportion of S. aureus increased significantly over the 15-year period (1996–2010) in children ≥ 3 months of age (P < 0.001), while that of Haemophilus influenzae decreased significantly in both < 3 months of age group (P = 0.036) and ≥ 3 months of age groups (P < 0.001). CONCLUSION: S. agalactiae, E. coli, S. pneumoniae, and S. aureus are common etiologic agents of invasive bacterial infections in Korean children.
Bacteremia ; Bacterial Infections ; Child ; Epidemiology ; Escherichia coli ; Haemophilus influenzae ; Hospitals, University ; Humans ; Infant ; Korea ; Meningitis ; Pneumonia ; Retrospective Studies ; Salmonella ; Staphylococcus aureus ; Streptococcus agalactiae ; Streptococcus pneumoniae

BACKGROUND: Meningitis is a clinically important disease because of its high mortality and morbidity. The epidemiology of this disease has changed remarkably due to the introduction of pneumococcal vaccines and Haemophilus influenzae type b (Hib) conjugate vaccine. Therefore, it is required to continuously monitor and research the organisms isolated from cerebrospinal fluid (CSF) cultures. METHODS: We analyzed trends of bacteria and fungi isolates obtained from CSF cultures between 1997 and 2016 in a tertiary care hospital according to year, month, gender, and age. RESULTS: Out of a total of 38,450 samples, we identified 504 (1.3%) isolates. The isolation rate in the first tested decade (1997–2006) ranged from 1.3% to 3.1%, while that in the second decade (2007–2016) ranged from 0.4% to 1.5%. The most common organisms was coagulase-negative staphylococci (CoNS) (31.9%), followed by Staphylococcus aureus (9.5%), Streptococcus pneumoniae (7.5%), Acinetobacter baumannii (5.8%), and Mycobacterium tuberculosis (5.8%). Monthly isolation rates were highest in May and July and lowest in February and December. Male to female ratio was 1.5:1. The isolation rates of S. pneumoniae, Enterococcus faecium, and Escherichia coli were similar in children and adults, but those of S. aureus, E. faecalis, A. baumannii, Pseudomonas aeruginosa, M. tuberculosis, and Cryptococcus neoformans were higher in adults than in children. CONCLUSION: During the last two decades, the isolation rate of CSF culture per year has decreased, with monthly isolation rates being highest in May and July. CoNS, S. aureus, and S. pneumoniae were most common in males, whereas CoNS, S. pneumoniae, and M. tuberculosis were most common in females. While Group B Streptococcus was most common in infants younger than 1 year, S. aureus and C. neoformans were more common in adults.
Acinetobacter baumannii ; Adult ; Bacteria* ; Cerebrospinal Fluid* ; Child ; Cryptococcus neoformans ; Enterococcus faecium ; Epidemiology ; Escherichia coli ; Female ; Fungi* ; Haemophilus influenzae type b ; Humans ; Infant ; Male ; Meningitis ; Mortality ; Mycobacterium tuberculosis ; Pneumococcal Vaccines ; Pneumonia ; Pseudomonas aeruginosa ; Staphylococcus aureus ; Streptococcus ; Streptococcus pneumoniae ; Tertiary Healthcare* ; Tuberculosis

OBJECTIVETo analyze risk factors, clinical features, outcomes and antibiotic resistance of Escherichia coli(E.coli) causing bloodstream infections in children.

METHODAll inpatients with E. coli positive blood culture in Beijing Children's Hospital from January 2012 to May 2014 were enrolled; 112 cases were included, 66 cases (58.9%) were male, and 46 cases(41.1%) were female. Age range was 2 days to 16 years. Among them, 43 cases (38.4%) were neonates, 19 cases (17.0%) aged from 1 month to 1 year, 14 cases (12.5%) were 1-3 years old, and 36 cases (32.1%) were over three years old. We analyzed the divisions to which the patients were admitted, source of infection, underlying diseases, clinical characteristics, antibiotic resistance, and treatment outcomes, etc.

RESULTForty-six cases (41.1%) were treated in division of hematology, 42 (37.5%) in neonatology, 9 (8.0%) in internal medicine, 8 (7.1%) in surgery, and 7 (6.3%) in pediatric intensive care unit. Sixty-five cases(58.0%) had underlying diseases. Fever was the most frequently presented symptom, as it was seen in 91 cases (81.3%); 52 cases(46.4%) had respiratory symptoms. Among these, 43 cases had pneumonia, 3 cases had respiratory failure, 3 cases were diagnosed as upper respiratory tract infection, 2 had pulmonary hemorrhage and 1 case had bronchitis. Twenty-six cases (23.2%)were diagnosed as severe sepsis and purulent meningitis separately, 14 cases(12.5%) had urinary tract infection. There were 73 (65.2%) strains inducing extended spectrum β-lactamases (ESBLs), of which 6 (8.2%) and 10 (13.7%) strains were resistant to amikacin and carbapenems respectively. Resistance rate against other antimicrobial agents varied from 64.6% to 100%.

OUTCOMES92 (82.1%) cases were cured or had improvement while 20 patients (17.9%) died or could not be cured at the end of treatment. Positive ESBLs (χ(2) = 6.609, P = 0.010), being complicated with severe sepsis (χ(2) = 40.253, P = 0.000) and requiring mechanical ventilation (χ(2) = 34.441, P = 0.000) indicate poor prognosis.

CONCLUSIONPatients with underlying diseases and newborns are susceptible to E. coli bloodstream infection. ESBLs infection, severe sepsis and mechanical ventilation indicate poor prognosis in E. coli blood stream infection. Clinicians may use carbapenems as empirical treatment for ESBLs infection. There may be carbapenem-resistant enterobacteriaceae strains infection if patients receiving treatment with carbapenems have no response.

Adolescent ; Bacteremia ; Carbapenems ; therapeutic use ; Child ; Child, Preschool ; Drug Resistance, Bacterial ; Escherichia coli ; drug effects ; Escherichia coli Infections ; blood ; drug therapy ; Female ; Humans ; Infant ; Infant, Newborn ; Male ; Meningitis, Bacterial ; Microbial Sensitivity Tests ; Pneumonia ; Urinary Tract Infections ; beta-Lactamases

OBJECTIVETo 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.

METHODSA retrospective analysis was performed for the clinical data of children with PM caused by Escherichia coli (12 children) or Streptococcus pneumoniae (15 children).

RESULTSCompared 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.

CONCLUSIONSPM 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.

Adolescent ; Child ; Child, Preschool ; Female ; Humans ; Infant ; Infant, Newborn ; Male ; Meningitis, Escherichia coli ; diagnosis ; drug therapy ; Meningitis, Pneumococcal ; diagnosis ; drug therapy ; Microbial Sensitivity Tests ; Retrospective Studies ; Suppuration