| Objective By optimizing the diagnosis of neonatal septicemia and constructing predictive model to respond to the trend of the increasing morbidity and mortality of neonatal septicemia in recent years and the shortage of early diagnosis by clinicians.It can improve the early recognition ability of doctors at all levels and strengthen the clinical diagnosis and treatment ability of the specialty.Methods The first part: analysis of the clinical characteristics of neonatal septicemia.Through retrospective analysis of 707 cases of neonatal septicemia confirmed in the neonatology department of Tianjin Children’s Hospital from January 2016 to December 2018(The mother’s natural,social and humanistic information,Maternal and child epidemic history,the child’s clinical manifestations,inflammation related examination indicators,immune function test,etiology test,drug sensitivity test and other multi-dimensional information),the characteristics of the cases were summarized,and according to the conditions of early and late neonatal septicemia,preterm and non-preterm infants,and whether combined with neonatal purulent meningitis,the optimized diagnosis information was put forward.The second part: the research on the construction of the diagnosis and predictive model of neonatal septicemia.The clinical data of 228 newborns in the control group and 707 newborns in the case group were divided into training set and testing set according to the ratio of 7:3.The single factor Logistic regression analysis was carried out to screen the variables with statistical significance,through LASSO regression analysis to reduce the dimension of data,combined with literature review and clinical work characteristics,to determine the required variables.Logistic regression was used to construct the predictive model,model A and model B were established.The predictive variables of model A included nine variables,including mother’s living area,mother’s threatened abortion history,breastfeeding,mother’s prenatal antibiotic treatment,child’s body temperature,weak conscious,primitive reflex,child’s antibiotic treatment before consultation,child’s body weight and birth weight subtractive difference.All of this mainly involve two parts: the case history of the mother and the clinical manifestations of the child.On the basis of model A,the predictive variables of model B include the laboratory examination indexes that can be completed by all levels of medical institutions,i.e.abnormal peripheral blood leukocyte count and increased C-reactive protein.Finally,a nomogram is established,and the performance of the predictive model is evaluated by the discrimination and calibration.The third part: Study on the detection ability of culture bottle added β-lactamase to bacterial pathogens in simulated bacteremia samples containing antibiotics.After selecting common pathogenic bacteria and commonly used antibiotics in paediatrics,the bacterial solution,antibiotics(mid point and peak blood concentration),fresh sterile blood and β-lactamase were successively injected into each culture bottle,and then immediately put into the full-automatic bacterial culture instrument for culture.The positive rate and time to positivity(TTP)of each culture bottle within 120 hours were recorded for comparison.By comparing the culture bottles containing resin: BACTEC Beads Plus blood culture bottle(BD-F bottle),the culture bottles containing charcoal particles: BACT/ALERT PF blood culture bottle(BT-C bottle),the common culture bottles added β – lactamase: BACTEC FX blood culture bottle(BD-S bottle)and Bac T/ALERT SA blood culture bottle(BT-S bottle),the test efficiency of culture bottle containing β-lactamase was verified by the test ability of bacteria in simulated blood samples containing antimicrobial agents(positive rate and time to positivity).Results Part Ⅰ: 1.Important information of all the children with neonatal septicemia:(1)information of mother: the age of delivery was mainly under 35 years old(92.93%),and education level mainly includes junior college and undergraduate,junior high school(32.53%,31.97%);(2)Delivery areas: rural areas(53.61%)were more than urban areas(46.39%),and secondary hospitals(64.07%)were the main delivery hospitals;(3)Children’s condition: most of them were term infants(86.14%),the proportion of children with abnormal amniotic fluid and umbilical cord was high(19.52%,each),83.59% of children with 2500 g ≤ birth weight < 4000 g,62.09% of them were breastfed,26.17% of them had a clear contact history of infection,53.32% of them had a lower body weight than birth weight;(4)The clinical manifestations of admission: temperature(anal temperature)abnormality and respiratory frequency abnormality were common,the proportion were 28.57% and 23.20% respectively,jaundice,umbilical stump exudation,muscle tension abnormality and primitive reflex abnormality were 47.95%,23.34%,21.08% and 19.66% respectively;(5)Laboratory characteristics: 31.68% of the children had abnormal leukocyte count.The proportion of children with neutrophils > 60%,IL-6 > 7pg / ml,C-reactive protein ≥ 8mg / L,procalcitonin ≥ 0.5mg/L were 31.54%,79.49%,49.93% and 21.48% respectively,The main pathogens were Gram-positive bacteria,accounting for 91.40% in blood samples.2.It was divided into different groups:(1)early-onset neonatal septicemia group 1(EOS1,≤72 hours)and late-onset neonatal septicemia group 1(LOS1,> 72 hours).The results showed that in LOS1 group,the age of mothers,the proportion of threatened abortion,living in the city and using antibiotics before delivery were higher than those in EOS1 group(P < 0.05;The proportion of fetal age,birth weight,and resuscitation in LOS1 group were lower than those in EOS1 group(P < 0.05).The proportion of cesarean section,at home before treatment,breast feeding,contact history of infection and antibiotics treatment before hospitalization in LOS1 group was higher than that in EOS1 group(P < 0.05).The proportion of hospitalized body weight ≥ birth weight,body temperature abnormality,heart rate abnormality,jaundice in LOS1 group was higher than that in EOS1 group(P < 0.05).The proportion of patients in LOS1 group with weak conscious,poor milk intake,abnormal muscle tone,and incomplete primitive reflex was lower than that in EOS1 group(P < 0.05).The proportion of patients with neutrophils>60% and IL-6>7pg/ml,blood lactate,Ig G,and the percentage of CD3 +,CD4 +,CD8 + lymphocytes in LOS1 group were lower than those of EOS1 group(P < 0.05).The proportion of neonatal purulent meningitis and mean platelet volume,hematocrit and mean platelet distribution width,prealbumin,CD19 + lymphocyte percentage,CD16 +,56 + lymphocyte percentage,Ig M,Ig A,Ig E,all of those in LOS1 group were higher than that in EOS1 group(P < 0.05).(2)early-onset neonatal septicemia group 2(EOS2,≤7 days)and late-onset neonatal septicemia group 2(LOS2,> 7 days).Compared with the first grouping method,the results showed that the comparison results were basically the same.There were differences between the two groups in the aspects of mother’s age,living in the city,multiple pregnancy,jaundice,respiratory infection,thrombocytopenia,C-reactive protein ≥ 8mg / L,etc.(3)Preterm group(< 37 weeks)and non-preterm group(≥ 37 weeks).The results showed that the age,age ≥ 35 years old ratio and pregnancy hypertension ratio of mothers in non-preterm group were lower than those in preterm group(P < 0.05),The proportion of multiple pregnancies,and resuscitation in the non-preterm group was lower than that in the preterm group,and the birth weight,the proportion at home before treatment in the non-preterm group were higher than those in the preterm group(P < 0.05),The proportion of abnormal body temperature,abnormal respiratory rate,abnormal heart rate,mental weakness,abnormal muscle tone and incomplete primitive reflex in non-preterm group was lower than that in preterm group(P < 0.05).The Ig G and the proportion of Gram-positive bacteria in blood culture in non-preterm group were higher than those in preterm group(P < 0.05).The percentage of neonatal purulent meningitis in non-preterm group were lower than those in preterm group(P < 0.05).(4)Non-purulent meningitis group and purulent meningitis group.The results showed that the proportion of the mothers using antibiotics before delivery in the purulent meningitis group was higher than that in the non-purulent meningitis group(P < 0.05),and the proportion of the fetus age and full-term infants in the purulent meningitis group was lower than that in the non-purulent meningitis group(P < 0.05).The proportion of patients in the purulent meningitis group treated with antibiotics before hospitalization was higher than that in the non-purulent meningitis group(P < 0.05);the proportion of children in the purulent meningitis group with abnormal temperature,heart rate,anterior fontanelle tension,convulsion and respiratory infection was higher than that in the non-purulent meningitis group(P < 0.05).Part II: The performance measurement results of the model are as follows: the sensitivity and specificity of model A on the training set are 0.725 and 0.768 respectively,and the sensitivity and specificity on the test set are 0.717 and 0.735 respectively.The sensitivity and specificity of model B on training set were 0.753 and 0.862 respectively,and on test set were 0.805 and 0.736 respectively.The area under ROC curve in training set and test set of model A is 0.817 and 0.764 respectively,and the area under ROC curve in training set and test set of model B is 0.884 and 0.824 respectively.Model calibration,the results of Hosmer-lemeshow test show that the p-values of training set and test set of model A are 0.1143 and 0.9024 respectively,and the good fitting degree of the model is good;the p-values of training set and test set of model B are 0.9602 and 0.4169 respectively.The results of calibration curves show that the calibration curves of model A and model B are good.Part III: In Staphylococcus aureus-penicillin sodium group and Escherichia coli-cefuroxime sodium group,the positive rates of BD-F bottle and BD-SE bottle(BD-S bottle added β-lactamase)were better than BD-S bottle(P < 0.05),When the peak blood concentration of antibiotics.Only when cefuroxime sodium was in peak blood concentration,the positive rates of BT-C and BT-SE bottles(BT-S bottles added β-lactamase)were higher than those of BT-S bottles(P < 0.05);When the concentration of antibiotics in the midpoint and peak blood,the positive rates of BD-F and BD-SE were the same(P > 0.05).The positive rate of BT-C bottle was higher than that of BT-SE bottle and there was no significant difference between the two groups(P > 0.05).When the concentration of antibiotics in the midpoint and peak blood,the TTP of BD-F bottle and BD-SE bottle was better than that of BD-S bottle(P < 0.001),the BT-C bottle and BT-SE bottle were better than that of BT-S bottle(P < 0.001).When the concentration of penicillin sodium in the blood of the midpoint,BD-SE bottle was better than BD-F bottle(P < 0.05);When the peak blood concentration of penicillin sodium,BD-F bottle was better than BD-SE bottle(P < 0.05).There was no significant difference in TTP between BD-F bottle and BD-SE bottle(P > 0.05)when cefuroxime sodium was used in the middle and peak blood concentrations.When the concentration of penicillin sodium in the midpoint and peak blood,the TTP of BT-C was better than that of BT-SE(P < 0.001).When the concentration of cefuroxime sodium in the mid point and peak blood concentration, there was no significant difference between the TTP of BT-C and BT-SE bottles(P > 0.05).Conclusions 1.Through the way of extensive and multi-dimensional sorting and grouping comparison of clinical case data of neonatal septicemia,it will help to optimize the diagnosis of neonatal septicemia,and improve the diagnosis and treatment ability of clinicians for neonatal septicemia,and also help to provide policy-making reference for the health administration department.The results of clinical characteristics comparison of early-onset and late-onset neonatal septicemia patients with 72 hours and 7 days as cut-off points were basically the same.Factors such as preterm birth,low weight and abnormal perinatal period should be paid more attention in clinical work.For suspected neonatal septicemia,especially those with neonatal purulent meningitis,it is advisable to be hospitalized as soon as possible or transferred to the neonatal special ward,conduct relevant examinations such as lumbar puncture cerebrospinal fluid test as appropriate,make a timely diagnosis,and give standardized and reasonable antibacterial treatment as soon as possible,so as to be effective reduce the mortality and disability rate of the disease.2.For the first time,a diagnosis and predictive model which can cover 0-28 days of neonatal septicemia was established,which is composed of the case history,clinical manifestations and laboratory indicators that can be easily obtained by the family members and primary clinicians.This model has the advantages of simple operation,strong operability,high sensitivity and specificity.It is easy to be popularized and applied in primary neonatal medical and health care institutions.3.For the first time,the method of added β-lactamase to eliminate the residue of antibacterial drugs in children’s blood culture samples was verified.It achieved the effect of shortening TTP and improving the positive detection rate.The test efficiency of culture bottle added β-lactamase was similar to that of culture bottle containing resin or charcoal particles.It optimizes the pathogenic diagnosis method of bacterial septicemia(including neonatal septicemia),and provides new ideas and options for medical staff in low-income countries,especially those who still take manual blood culture test to solve the problem of antibiotic residues in blood culture samples of children. |
PDF Full Text Request