Neonatal D-bifunctional protein deficiency: a report of two cases and literature review / 中华围产医学杂志

Objective:To summarize the clinical characteristics and genetic etiology of infants with D-bifunctional protein deficiency (DBPD).Methods:This study involved two DBPD newborns who were hospitalized in the Second Affiliated Hospital of Wenzhou Medical University in August 2020 and November 2020. Clinical data including manifestations, radiographic findings and genetic testing results were retrospectively analyzed. Relevant articles up to November 2022 were retrieved from various databases including CNKI, Wanfang, CQVIP, Online Mendelian Inheritance in Man and PubMed using the terms of "D-bifunctional protein deficiency" and " HSD17B4" in both Chinese and English. Clinical data of the cases diagnosed with DBPD by genetic testing within two years of age were collected. Clinical features and genetic etiology of the children with DBPD were summarized by descriptive statistical analysis. Results:Both neonates in this report presented with dyspnea, hypotonia, intractable epilepsy, poor response, absence of primitive reflexes, and craniofacial malformation. Whole-exome sequencing revealed that patient 1 carried heterozygous variations of c.972+1G>T and c.727T>A (p.W243R) in the HSD17B4 gene, which were inherited from his father and mother, respectively. A homozygous variation of c.1333+4A>G in the HSD17B4 gene was identified in patient 2. All these mutations were pathogenic. Thirteen papers (12 in English and one in Chinese) involving 19 patients from 16 pedigrees were retrieved. Altogether 21 patients (eight males and 13 females) were included, and among them, four from two pedigrees were born to consanguineous parents. There were 21 patients with hypotonia, 20 with epileptic seizures (17 presenting with epileptic seizures within 5 d after birth) and 12 with craniofacial deformities including high forehead, long philtrum and high palatine arches. Genetic tests showed that 13 patients carried compound heterozygous variations in the HSD17B4 gene and eight patients had homozygous variations. Twenty-six variations in the HSD17B4 gene were detected, including 16 missense mutations, seven splicing mutations, two nonsense mutations and one frameshift mutation. Conclusion:DBPD should be considered and genetic tests should be given when newborns have dystonia and intractable epilepsy complicated by appearance deformity.

Bacterial flora of biofilm in the endotracheal tube of mechanically ventilated neonates and its relationship with ventilator-associated pneumonia / 中华传染病杂志

Objective:To explore the relationship between endotracheal tube-bacterial biofilm (ETT-BF) in mechanically ventilated neonates and ventilator-associated pneumonia (VAP).Methods:A total of 30 mechanically ventilated neonates whose mechanical ventilation time were ≥48 h in the Department of Neonatology in The Second Affiliated Hospital of Wenzhou Medical University from January 2019 to January 2020 were included.According to the indwelling time of endotracheal tube, all cases were divided into three groups including group A(two to six days), group B(seven to 14 days) and group C (over 14 days). The morphological results of ETT-BF were scanned by scanning electron microscope (SEM). The incidence of VAP, the positive rates of strains isolated from endotracheal tube surface and lower respiratory tract secretion, the detection of strains and drug resistance were analyzed. Chi-squared test were used for statistical analysis.Results:The results of SEM showed that sheet matrix could be observed on the surface of the inner cavity of endotracheal tube in three days of tracheal catheter retention, and cocci adhered to it in four days. With prolonged indwelling time of endotracheal tube, the structure of bacterial biofilm (BF) had improved.The positive rate of strains isolated from the secretion of lower respiratory tract in 30 neonates was 23.3%(7/30) and all of them were Gram-negative bacteria. There was no patient developed VAP in group A, while there were two patients with VAP in group B, and five patients with VAP in group C. The incidences of VAP in the three groups were statistically significant ( χ2=10.82, P=0.004). There was no significant difference in the positive rate of strains isolated from the surface of endotracheal tube under different indwelling time in 30 cases ( χ2=1.03, P=0.598). Among of 13 neonates in group A, there were seven strains isolated from ETT-BF, mainly Gram-positive bacteria which turned out to be mainly Gram-negative bacteria with the prolongation of endotracheal tube indwelling time. Of the seven VAP cases, strains isolated from the lower respiratory tract secretion were consistent with the strains isolated from the surface of the corresponding endotracheal tube in five cases, which were Serratia liquefaciens, Klebsiella acidogenes, Serratia marcescens, Flavobacterium meningosepticum and Stenotrophomonas maltophilia, and the drug resistance was consistent. Conclusions:The colonization bacteria of early ETT-BF may come from the upper respiratory tract, with less migration which rarely causes VAP. With the prolongation of endotracheal tube indwelling time, the incidence of VAP in neonates increases. The same pathogen can be found in the ETT-BF and lower respiratory tract secretion. The source of pathogen needs further study.

Analysis of pathogenic bacteria and drug resistance in neonatal purulent meningitis / 中华儿科杂志

<p><b>OBJECTIVE</b>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.</p><p><b>METHOD</b>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.</p><p><b>RESULT</b>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.</p><p><b>CONCLUSION</b>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.</p>

Clinical analysis of nosocomial infection and risk factors of extremely premature infants / 中华儿科杂志

<p><b>OBJECTIVE</b>To investigate the incidence of nosocomial infections of extremely premature infants and to explore the risk factors and strategies for infection control.</p><p><b>METHOD</b>There were 118 extremely premature infants who were confirmed to have nosocomial infection in neonatal intensive care unit of the authors' hospital from January 2008 to December 2012. Their data of the infection rate, risk factors and clinical characteristics were retrospectively analyzed.</p><p><b>RESULT</b>During the study, nosocomial infection occurred in 78 extremely premature infants 129 times. The nosocomial infection rate was 66.10%. The rate of ventilator-associated pneumonia (VAP) was 1.43% (35/2 452). The catheter related blood stream infection (CRBSI) rate was 0.35% (16/4 613). There were 74 (57.36%) cases of pneumonia, which was the most common nosocomial infection of extremely premature infants. There were 35 cases of VAP, which accounted for 47.30% of pneumonia. The next was sepsis, 48 cases. Seventy-four (74/90, 82.22%) strains of isolates were Gram-negative bacteria, which accounted for the highest proportion, followed by Gram-positive (12 strains), fungus (4 strains); Klebsiella pneumonia is the most common pathogens of nosocomial infection in extremely premature infants. The isolation rates of Klebsiella pneumonia with positive extended-spectrum beta-lactamases (ESBL) were 90.91% (20/22) , universally resistant to cephalosporins. Single-factor analysis showed that the body weight, mechanical ventilation, umbilical vein catheterization, central venous catheter, parenteral nutrition and hospitalization time were risk factors for nosocomial infections in extremely preterm infants. Logistic regression analysis showed that length of hospitalization (OR = 1.024, P = 0.043) and central venous catheterization (OR = 6.170, P = 0.041) were independent risk factors of nosocomial infection.</p><p><b>CONCLUSION</b>Extremely preterm infants were at higher risk of nosocomial infection. It is important to identify the high risk factors for nosocomial infections in extremely premature infants. To shorten time for mechanical ventilation, central venous catheterization and hospitalization days would be conducive to reducing the morbidity of nosocomial infection.</p>

Comparative study on clinical manifestations and antibiotics resistance in neonates with the sepsis caused by Klebsiella pneumoniae and Escherichia coli / 中华围产医学杂志

Objective To compare the clinical characteristics and antibiotics resistance of neonatal sepsis caused by Klebsiella pneumoniae and Escherichia coli in order to provide guidance for early diagnosis and appropriate treatment. Methods Forty-two newborns with Klebsiella pneumoniae sepsis and 50 newborns with Escherichia coli sepsis in the neonatal intensive care unit of Yuying Children's Hospital of Wenzhou Medical College from January 2000 to October 2009 were enrolled into this study. The clinical data, laboratory examinations and prognosis of these newborns were retrospectively analyzed and compared. The antibiotic resistance data of different onset age of the two diseases were compared. Early-onset sepsis was defined as the age at the onset ≤3 days, and late-onset sepsis was defined as the age at the onset ＞3 days. Results (1) Comparison of clinical characteristics: Klebsiella pneumoniae sepsis caused higher incidence of apnea or gasp compared with Escherichia coli sepsis (61.9% vs 6.0% ,x2= 17. 34, P＜0. 05); the time of developing to multiple organ dysfunction syndrome or disseminated intravascular coagulation of the newborns with Klebsiella pneumoniae sepsis [(40±28) h] was shorter than that of the newborns with Escherichia coli sepsis [(89±26) h] (t= -3.17, P＜0.05); while the incidence of purulent meningitis of Klebsiella pneumoniae sepsis was lower ( 4. 8% vs 30. 0 %, x2 = 9.65, P ＜ 0. 05 ). ( 2 ) Comparison of non-specific laboratory examinations: compared with Escherichia coli sepsis, Klebsiella pneumoniae sepsis caused higher incidence of the leucocyte count ＞ 25 × 109/L (42. 9% vs 22.0%, x2 = 4. 60,P＜0. 05), platelet count ＜ 100 × 109/L (52.4% vs 18.0%, x2 = 12.07, P＜0. 05) and C-reaction protein ＞8 mg/L (95.2% vs 76.0% ,x2 =6. 55, P＜0. 05). (3) Comparison of results of antibiotic resistance: the resistance rate of Klebsiella pneumoniae (81.8%00-100. 0%) to Cephalosporins was higher than that of Escherichia coli (17. 2%-63. 2%) (x2 =6.97-11.92, P＜0. 05); the resistance rates of late-onset sepsis of Klebsiella pneumoniae to Amoxicillin/clavulanic-acid and Cefoperazone/sulbactam were higher than those of Escherichia coli (75.0% vs 0.0%, x2 =26.67, P＜0. 05;83. 3%vs 0. 0%, x2 = 12.53, P＜0. 05 respectively); no resistance to Imipenem were found. The percentages of extended spectrum β-lactamases (ESBLs) positive Escherichia coli and Klebsiella pneumoniae were obviously higher in neonates with late-onset sepsis than those early-onset ones (65.0% vs 17. 8%,x2 = 11.06, P＜0. 05; 100. 0 % vs 30. 0 %, x2 = 20. 22, P＜0. 05 respectively); and positive ESBLs rate of the late-onset Klebsiella pneumoniae sepsis was higher than that of Escherichia coli sepsis (100. 0% vs 65.0%, x2 =9.16, P＜0. 05). (4) Comparison of mortality rate: the mortality rate of Klebsiella pneumoniae sepsis was higher than that of Escherichia coli sepsis (21.4% vs 4. 0%,x2=6.59, P ＜ 0. 05 ) . Conclusions Compared with Escherichia coli septicemia, Klebsiella pneumoniae septicemia has more severe symptoms, developed to multiple organ dysfunction syndrome or disseminated intravascular coagulation quicker, and has higher mortality rate. The percentage of ESBLs positive Escherichia coli and Klebsiella pneumoniae increased rapidly. The clinical use of antibiotics should be rationale.