Status of fungal sepsis among preterm infants in 25 neonatal intensive care units of tertiary hospitals in China / 中华儿科杂志

Objective: To analyze the prevalence and the risk factors of fungal sepsis in 25 neonatal intensive care units (NICU) among preterm infants in China, and to provide a basis for preventive strategies of fungal sepsis. Methods: This was a second-analysis of the data from the "reduction of infection in neonatal intensive care units using the evidence-based practice for improving quality" study. The current status of fungal sepsis of the 24 731 preterm infants with the gestational age of <34+0 weeks, who were admitted to 25 participating NICU within 7 days of birth between May 2015 and April 2018 were retrospectively analyzed. These preterm infants were divided into the fungal sepsis group and the without fungal sepsis group according to whether they developed fungal sepsis to analyze the incidences and the microbiology of fungal sepsis. Chi-square test was used to compare the incidences of fungal sepsis in preterm infants with different gestational ages and birth weights and in different NICU. Multivariate Logistic regression analysis was used to study the outcomes of preterm infants with fungal sepsis, which were further compared with those of preterm infants without fungal sepsis. The 144 preterm infants in the fungal sepsis group were matched with 288 preterm infants in the non-fungal sepsis group by propensity score-matched method. Univariate and multivariate Logistic regression analysis were used to analyze the risk factors of fungal sepsis. Results: In all, 166 (0.7%) of the 24 731 preterm infants developed fungal sepsis, with the gestational age of (29.7±2.0) weeks and the birth weight of (1 300±293) g. The incidence of fungal sepsis increased with decreasing gestational age and birth weight (both P<0.001). The preterm infants with gestational age of <32 weeks accounted for 87.3% (145/166). The incidence of fungal sepsis was 1.0% (117/11 438) in very preterm infants and 2.0% (28/1 401) in extremely preterm infants, and was 1.3% (103/8 060) in very low birth weight infants and 1.7% (21/1 211) in extremely low birth weight infants, respectively. There was no fungal sepsis in 3 NICU, and the incidences in the other 22 NICU ranged from 0.7% (10/1 397) to 2.9% (21/724), with significant statistical difference (P<0.001). The pathogens were mainly Candida (150/166, 90.4%), including 59 cases of Candida albicans and 91 cases of non-Candida albicans, of which Candida parapsilosis was the most common (41 cases). Fungal sepsis was independently associated with increased risk of moderate to severe bronchopulmonary dysplasia (BPD) (adjusted OR 1.52, 95%CI 1.04-2.22, P=0.030) and severe retinopathy of prematurity (ROP) (adjusted OR 2.55, 95%CI 1.12-5.80, P=0.025). Previous broad spectrum antibiotics exposure (adjusted OR=2.50, 95%CI 1.50-4.17, P<0.001), prolonged use of central line (adjusted OR=1.05, 95%CI 1.03-1.08, P<0.001) and previous total parenteral nutrition (TPN) duration (adjusted OR=1.04, 95%CI 1.02-1.06, P<0.001) were all independently associated with increasing risk of fungal sepsis. Conclusions: Candida albicans and Candida parapsilosis are the main pathogens of fungal sepsis among preterm infants in Chinese NICU. Preterm infants with fungal sepsis are at increased risk of moderate to severe BPD and severe ROP. Previous broad spectrum antibiotics exposure, prolonged use of central line and prolonged duration of TPN will increase the risk of fungal sepsis. Ongoing initiatives are needed to reduce fungal sepsis based on these risk factors.

Value of metagenomic next-generation sequencing in children with severe infectious diseases / 中国当代儿科杂志

OBJECTIVES@#To study the application value of metagenomic next-generation sequencing (mNGS) in children with severe infectious diseases.@*METHODS@#An analysis was performed on the clinical data and laboratory test results of 29 children with severe infection who were admitted to the Second Affiliated Hospital of Wenzhou Medical University from June 2018 to December 2020. Conventional pathogen culture was performed for the 29 specimens (27 peripheral blood specimens and 2 pleural effusion specimens) from the 29 children, and mNGS pathogen detection was performed at the same time.@*RESULTS@#Among the 29 children, 2 tested positive by conventional pathogen culture with 2 strains of pathogen, and the detection rate was 7% (2/29); however, 20 children tested positive by mNGS with 38 strains of pathogen, and the detection rate was 69% (20/29). The pathogen detection rate of mNGS was significantly higher than that of conventional pathogen culture (P<0.05), and mNGS could detect the viruses, fungi, and other special pathogens that conventional pathogen culture failed to detect, such as Orientia tsutsugamushi. The univariate analysis showed that gender, routine blood test results, C-reactive protein, procalcitonin, D-dimer, radiological findings, and whether antibiotics were used before admission did not affect the results of mNGS (P>0.05).@*CONCLUSIONS@#Compared with conventional pathogen culture, mNGS is more sensitive for pathogen detection, with fewer interference factors. Therefore, it is a better pathogenic diagnosis method for severe infectious diseases in children.

Ellagic acid attenuates hypoxic-ischemic brain injury by alleviating autophagy / 中国病理生理杂志

AIM:To investigate whether ellagic acid (EA) attenuates hypoxic-ischemic encephalopathy (HIE) by down-regulating autophagy.METHODS:In vivo, Sprague-Dawley rats (n=17) were randomly divided into 3groups:5 rats for sham group, 6 rats for HIE group and 6 rats for HIE+EA pretreatment group.The rats in HIE+EA pretreatment group were treated with EA (10 mg/kg, 10 m L/kg, suspended in corn oil, ig).After 24 h of operation, the rats from each group were sacrificed and their brains were collected.TTC staining and HE staining were used to define the infarct areas and brain structure.The autophagy-related proteins beclin-1, P62, LC3-II/-I and Atg5 in the cortex in each group were compared by Western blot.In vitro, PC12 cells were divided into 3 groups:control group, Coand CoEA pretreatment group.Co800μmol/L was added to the PC12 cells to induce an anoxic environment.The PC12 cells were pretreated with EA at 8μmol/L and the cell viability was measured by CCK-8 assay.The production of reactive oxidative species (ROS) in the cells was detected by flow cytometry with DCFH-DA staining.MDC staining and TM-RE staining were applied to reflect the extent of autophagy and the state of apoptosis, respectively.The autophagy-related proteins in PC12 cells were also investigated.RESULTS:In HIE group, 7-day-old rats were given the operations and the their large infarct areas in the hemisphere were observed by TTC staining.HE staining displayed the injured hemispheres which contained few neurons, and exhibited edema status and serious structural damage.EA pretreatment decreased the infarct area and alleviated the damage to hemisphere with more visible neurons, compared with HIE group.Compared with sham group, the levels of autophagy-related proteins Atg5, beclin-1 and LC3-II/-I in the cortex were increased (P<0.01) , and P62 protein expression was decreased (P<0.01) in HIE group.Compared with HIE group, the protein expression of Atg5, beclin-1 and LC3-II/-I was decreased (P<0.01) and P62 protein expression was increased in HIE+EA pretreatment group (P<0.01).In vitro, compared with CoPC12 cells in CoEA pretreatment group showed a lower ROS level.Moreover, the cells in CoEA pretreatment group exhibited higher mitochondrial membrane potential than that in CoMDC staining in Coshowed high value of fluorescence and increased number of autophagosomes.EA pretreatment reduced the number of autophagosomes and the extent of autophagy to protect PC12cells.Furthermore, the protein levels of Atg5, beclin-1 and LC3-II/-I in Cowere higher (P<0.01) , and the protein expression of P62 was lower (P<0.01) than those in control group.In CoEA pretreatment group, the protein levels of Atg5, beclin-1 and LC3-II/-I were decreased (P<0.01) and the protein expression of P62 was increased as compared with Co (P<0.01).CONCLUSION:EA pretreatment attenuates autophagy to protect the neurons against HIE injury.

Mortality and Morbidity of Extremely Low Birth Weight Infants in the Mainland of China: A Multi-center Study / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>With the progress of perinatal medicine and neonatal technology, more and more extremely low birth weight (ELBW) survived all over the world. This study was designed to investigate the short-term outcomes of ELBW infants during their Neonatal Intensive Care Unit (NICU) stay in the mainland of China.</p><p><b>METHODS</b>All infants admitted to 26 NICUs with a birth weight (BW) < l000 g were included between January l, 2011 and December 31, 2011. All the data were collected retrospectively from clinical records by a prospectively designed questionnaire. The data collected from each NICU transmitted to the main institution where the results were aggregated and analyzed. Categorical variables were performed with Pearson Chi-square test. Binary Logistic regression analysis was used to detect risk factors.</p><p><b>RESULTS</b>A total of 258 ELBW infants were admitted to 26 NICUs, of whom the mean gestational age (GA) was 28.1 ± 2.2 weeks, and the mean BW was 868 ± 97 g. The overall survival rate at discharge was 50.0%. Despite aggressive treatment 60 infants (23.3%) died and another 69 infants (26.7%) died after medical care withdrawal. Furthermore, the survival rate was significantly higher in coastal areas than inland areas (53.6% vs. 35.3%, P = 0.019). BW < 750 g and GA < 28 weeks were the largest risk factors, and being small for gestational age was a protective factor related to mortality. Respiratory distress syndrome was the most common complication. The incidence of patent ductus arteriosus, intraventricular hemorrhage, periventricular leukomalacia, bronchopulmonary dysplasia, retinopathy of prematurity was 26.2%, 33.7%, 6.7%, 48.1%, and 41.4%, respectively. Ventilator associated pneumonia was the most common hospital acquired infection during hospitalization.</p><p><b>CONCLUSIONS</b>Our study was the first survey that revealed the present status of ELBW infants in the mainland of China. The mortality and morbidity of ELBW infants remained high as compared to other developed countries.</p>

Clinical analysis of 101 cases of neonatal intestinal perforation / 中国当代儿科杂志

<p><b>OBJECTIVE</b>To analyze the clinical characteristics of neonatal intestinal perforation and to provide a theoretical basis for improving the prognosis of this disease.</p><p><b>METHODS</b>The clinical data of 101 patients with neonatal intestinal perforation who were hospitalized in the Neonatal Intensive Care Unit between January 2000 and June 2014 were retrospectively reviewed.</p><p><b>RESULTS</b>The main causes of neonatal intestinal perforation were neonatal necrotizing enterocolitis (NEC, 41 cases, 40.6%), idiopathic intestinal perforation (17 cases, 16.8%), and congenital megacolon (10 cases, 9.9%). The average birth weight and average gestational age of the idiopathic intestinal perforation group were significantly higher than those of the NEC group (P<0.05). The main pathogen of the NEC group was enterococci, which accounted for 57% (13/23), while in the idiopathic intestinal perforation group Gram-negative bacteria became the major pathogen; the distribution of pathogens were significantly different between the two groups (P<0.05). Multiple logistic regression analysis found that acidosis, multi-site intestinal perforation, and prolonged perforation-operation interval were independent risk factors for death due to neonatal intestinal perforation.</p><p><b>CONCLUSIONS</b>Multiple causes contribute to neonatal intestinal perforation, and NEC is the major one. Neonatal intestinal perforation caused by NEC has different pathogens compared with idiopathic intestinal perforation, and the two diseases may be mutually independent. Early diagnosis and timely operation is the main measure to rescue the lives of patients with neonatal intestinal perforation.</p>

What is the optimal oxygen saturation for extremely premature infants? A Meta analysis / 中国当代儿科杂志

<p><b>OBJECTIVE</b>To explore an optimal oxygen saturation for extremely preterm infants based on a systemic review of the published studies.</p><p><b>METHODS</b>A Meta analysis of the published studies by the NeOProM Group which compared the outcomes of extremely preterm infants (gestational age <28 weeks) maintained in either a low (85%-89%) or high (91%-95%) oxygen saturation (SpO2) by using the STATA 12.0. The outcomes measured included the mortality and the incidences of retinopathy of prematurity (ROP), necrotizing enterocolitis of newborn (NEC), broncho-pulmonary dysplasia (BPD), intraventricular hemorrhage (IVH) and patent ductus arteriosus (PDA).</p><p><b>RESULTS</b>Three studies were included, in which 2 460 infants were assigned into the low SpO2 group and 2 459 infants in the high SpO2 group. The Meta analysis demonstrated that the risk of mortality before discharge or at the age of 18 months increased in the low SpO2 group compared with the high SpO2 group (RR: 1.19; 95%CI: 1.05-1.35); the risk of ROP decreased in the low SpO2 group (RR: 0.73; 95%CI: 0.53-1.00); the risk of NEC increased in the low SpO2 group (RR: 1.26; 95%CI: 1.06-1.49). There was no significance in the incidences of BPD, IVH and PDA between the two groups.</p><p><b>CONCLUSIONS</b>Maintaining SpO2 at 85%-89% may decrease the incidence of ROP, but increase the mortality rate and the incidence of NEC in extremely premature infants.</p>

Clinical analysis of 31 cases of neonatal purulent meningitis caused by Escherichia coli / 中国当代儿科杂志

<p><b>OBJECTIVE</b>Neonatal purulent meningitis is a severe infection responsible for high mortality and disabling sequelae. Escherichia coli is the main pathogen of neonatal purulent meningitis. This study explored the clinical characteristics and antibiotic resistance of Escherichia coli-induced neonatal meningitis.</p><p><b>METHODS</b>A retrospective chart review was performed. A total of 31 cases of neonatal purulent meningitis caused by Escherichia coli were identified in the neonatal intensive care unit between January 1, 2001 and December 31, 2011. The clinical characteristics and antibiotic sensitivity test results were analyzed.</p><p><b>RESULTS</b>Fever, poor feeding, lethargy and seizure were common clinical signs of neonatal purulent meningitis caused by Escherichia coli. Acute complications mainly included hyponatremia (17 cases), hydrocephalus (8 cases), subdural collection (2 cases), ventriculitis (2 cases) and cerebral infarction (1 case). Thirty neonates (97%) had increased CRP levels. Of the 31 patients, 14 cases were cured and 12 had adverse outcomes (5 patients died during hospitalization). Escherichia coli strains were resistant (>50%) to commonly used penicillins and cephalosporins between 2007 and 2011, presenting significantly higher resistance rates than between 2001 and 2006. The detection rate of extended spectrum β-lactamases (ESBLs)-producing strains between 2007 and 2011 increased significantly compared with between 2001 and 2006 (57% vs 0).</p><p><b>CONCLUSIONS</b>The clinical manifestations of neonatal purulent meningitis caused by Escherichia coli are non specific. The outcome is poor. Monitoring of CRP levels is valuable for the early diagnosis of neonatal purulent meningitis. The antimicrobial resistance rates of Escherichia coli are increasing, especially to cephalosporins. The percentage of ESBLs-producing strains is increasing over the years.</p>

Investigation and analysis of nosocomial infection in neonates / 中华儿科杂志

<p><b>OBJECTIVE</b>To investigate the incidence of nosocomial infections of newborn infants in neonates and to explore the risk factors and strategies of infection control.</p><p><b>METHODS</b>There were 433 confirmed cases of nosocomial infection in the neonatal ward of the authors' hospital from January 2007 to December 2009. Their data of epidemiological and clinical characteristics, results of etiological examinations and antibiotic resistance were retrospectively analyzed.</p><p><b>RESULTS</b>During the study, the number of hospitalizations were 6437. Nosocomial infection occurred in 433 patients 513 times. The overall nosocomial infection rate was 6.82%. The overall hospitalization days were 73 663 and nosocomial infection patient-day rates were 6.96‰. The VAP infection rate was 28.7‰. The CRBSI rate was 3.5‰. Gestational age (OR = 1.049), mechanical ventilation (OR = 1.810), umbilical vein catheter (OR = 1.106), hospitalization days (OR = 1.081), premature rupture of membrane (OR = 1.433) were the risk factors for the development of nosocomial infection. There were 197 (38.4%) cases of pneumonia, which was the most common nosocomial infection in Neonatal Ward. There were 129 cases of ventilator-associated pneumonia (VAP), which accounts for 65.5% of pneumonia and 24.4% of cases treated with ventilator. The next was sepsis, 124 cases (24.2%) and 64 cases of diarrheal disease (12.7%). One hundred and eighty two (54.4%) strains of isolates were Gram-negative bacteria, which accounted for the highest proportion. The predominant pathogens of Gram-negative bacteria were Klebsiella pneumoniae (19.6%), followed by Acinetobacter baumannii (8.1%), Pseudomonas aeruginosa (7.2%), Stenotrophomonas maltophilia (4.8%) and Escherichia coli (4.8%). The isolation rates of Klebsiella pneumoniae and Escherichia coli with positive extended-spectrum beta-lactamases (ESBLs) were 91.4% and 75%, respectively. Those two bacteria were universally resistant to cephalosporins. The rate of resistance to imipenem of Klebsiella pneumoniae, Acinetobacter baumannii and Pseudomonas aeruginosa were 1.5%, 11.1% and 41.7%. The isolation rates of methicillin-resistant Staphylococcus aureus and methicillin-resistant coagulase-negative Staphylococcus were 28.6% and 95.5%.</p><p><b>CONCLUSION</b>It is important to identify the high risk factors for nosocomial infections in newborn infants. To shorten time for mechanical ventilation and hospitalization days, removal of the central venous catheter as early as possible would be conducive to reducing the morbidity of nosocomial infection. The main pathogens were Gram-negative bacteria. The multidrug resistance of Enterobacteriaceae and Non-fermenters is serious.</p>

Clinical characteristics of neonatal Klebsiella pneumoniae sepsis and the antibiotic sensitivity pattern of strains / 中国当代儿科杂志

<p><b>OBJECTIVE</b>To study the clinical characteristics of neonatal sepsis caused by Klebsiella pneumoniae and the antibiotic sensitivity pattern of Klebsiella pneumoniae strains.</p><p><b>METHODS</b>The clinical data of 42 cases of neonatal sepsis caused by Klebsiella pneumoniae from January, 2000 to August, 2009 were retrospectively studied.</p><p><b>RESULTS</b>The clinical presentations were non-specific, including fever or hypothermia, tachypnea, apnea and feeding intolerance. C-reactive protein (CRP) level increased in 95% of the cases. The mortality was 21%. In neonates with early onset sepsis, Klebsiella pneumoniae strains were sensitive to amoxicillin/clavulanic-acid, piperacillin/tazobactam, cefoxitin, imipenem, cefoperazone/and sulbactam. In neonates with late onset sepsis, the sensitive antibiotics of Klebsiella pneumoniae strains were less, including cefoxitin, piperacillin/tazobactam and imipenem. Klebsiella pneumoniae strains were not sensitive to penicillins and cephalosporins in either neonates with early onset sepsis or late onset sepsis. The extended spectrum β-lactamases (ESBLs)-producing strains were found in 92% of the cases. The neonates with late onset sepsis presented a higher prevalence of ESBLs-producing strains than those with early onset sepsis (100% vs 70%; P<0.05).</p><p><b>CONCLUSIONS</b>The clinical manifestations of neonatal sepsis caused by Klebsiella pneumoniae are usually non-specific. CRP detection is valuable for early diagnosis of sepsis. There are differences in the antibiotic sensitivity of strains between the neonates with early onset and late onset Klebsiella pneumoniae sepsis.</p>

Risk factors for ventilator-associated pneumonia in neonates and the changes of isolated pathogens / 中国当代儿科杂志

<p><b>OBJECTIVE</b>To study the risk factors for neonatal ventilator-associated pneumonia (VAP) and the changes of isolated pathogens in the last eight years.</p><p><b>METHODS</b>The clinical data of 230 neonates who were admitted into the neonatal intensive care unit (NICU) and received mechanical ventilation for equal to or longer than 48 hrs in 2008 were retrospectively reviewed. The isolated pathogens were compared with those of eight years ago.</p><p><b>RESULTS</b>The incidence of VAP (25.2%) in the year 2008 was lower than that of eight years ago (36.1%; P<0.05). The development of VAP was negatively correlated with the gestational age and the birth weight, but positively correlated with the duration of mechanical ventilation, intubation times, duration of hospitalization, presence of gastrointestinal bleeding and need for blood products transfusion. The main isolated pathogens were opportunistic antibiotics resistant bacteria, and the majority was gram negative bacilli (77%). The most frequently detected gram negative bacilli were Klebsiella (20%), Stenotrophomonas maltophilia (18%) and Acinetobacter (13%). Streptococcus mitis was the most frequently detected gram positive bacilli (14%). The distribution pattern of pathogens isolated in the same NICU eight years ago was somewhat different: Klebsiella (23%), Pseudomonas aeruginosa (17%), Acinetobacter (16%), Streptococcus mitis (11%), Fungi (1%) and Candida albicans (1%).</p><p><b>CONCLUSIONS</b>The incidence of VAP is correlated with gestational age, birth weight, duration of mechanical ventilation and hospitalization, intubation times, presence of gastrointestinal bleeding and need for blood products transfusion. The main isolated pathogens are usually antibiotic resistant opportunistic bacteria. The detection rate of Stenotrophomonas maltophilia increased and that of Pseudomonas aeruginosa decreased when compared with eight years ago.</p>

Role of Ommaya reservoir in the management of neonates with post-hemorrhagic hydrocephalus / 中华儿科杂志

<p><b>OBJECTIVE</b>Intra-ventricular hemorrhage (IVH) is one of the most serious complications of preterm infants. Significant numbers of the surviving infants with severe IVH go on to develop post-hemorrhagic hydrocephalus (PHH). The management of PHH remains a very challenging problem for both neonatologists and pediatric neurosurgeons. This study aimed to evaluate the efficacy and safety of the use of Ommaya reservoirs and serial cerebrospinal fluid (CSF) drainage in the management of a series of neonates with PHH.</p><p><b>METHOD</b>Between January 1, 2003 and December 30, 2005, 15 consecutive newborn infants with IVH grades III to IV, complicated with progressive ventricular dilatation, underwent placement of an Ommaya reservoir. CSF was intermittently aspirated percutaneously from the reservoir. The amount and frequency of CSF aspiration were based on the clinical presentation and the follow-up results of serial cranial ultrasonograms or CT scans. The changes of CSF cell counts and chemistries were also followed. Patients whose progressive ventricular dilatation persisted despite serial CSF aspiration through Ommaya reservoir eventually had ventriculo-peritoneal shunts (V-P shunt) placed. All the patients were followed up in the outpatient clinic after discharge from the hospital and the neurodevelopmental outcomes were evaluated through 18-36 months of age.</p><p><b>RESULT</b>A total of 15 infants were included in this series. Of them, 11 were preterm infants who were at gestational ages of 29 to 34 weeks and 4 infants were full-term. All of the 4 full term infants presented with progressive ventricular dilatation after suffering from the intra-cranial hemorrhage (3 infants were due to vitamin K deficiency and 1 was due to birth trauma). Thirteen infants had grade III IVH, and 2 had grade IV IVH based on initial cranial ultrasonographic and CT scans. The mean age when IVH was diagnosed was (9 +/- 1) days in preterm infants and (22 +/- 7) days in full-term infants; the mean age when Ommaya reservoir was placed was (18 +/- 11) days in preterm infants and (31 +/- 7) days in full-term infants. All the infants tolerated the surgical procedure well. The Ommaya reservoir was tapped for an average of (21.5 +/- 4.6) times per patient. The mean CSF volume per tap was (10.2 +/- 1.3) ml/kg. The values of CSF protein, glucose and cell counts slowly reached normal levels at approximately 3 - 5 weeks after the placement of the reservoir. The velocity of head circumference increase per week was less than 1 cm in 13 patients in 1 - 4 weeks after the placement of the reservoir and the size of ventricles decreased gradually. By 12 - 18 months, 12 infants had normal size ventricles, and 1 patient still had mild ventricular dilation at 36 months. Two infants developed progressive hydrocephalus after serial CSF aspiration through Ommaya reservoir. One infant had a V-P shunt placed at 2 months of age and another infant died at 3 months of age at home after parents refused further therapy. Complications consisted of reservoir leaking and CSF infection at 16th day of placement in one patient after repeated tapping. By the end of 18 - 36 months of follow-up, 11 of 14 infants were considered normal, two patients had mild impairment in neurodevelopmental outcome (both had spastic bilateral lower limbs paresis, and one of whom also had amblyopia) and the other had seizure disorder.</p><p><b>CONCLUSION</b>The results from this series indicate that the placement of an Ommaya reservoir is relatively safe in newborn infants and is useful in the initial management of neonates with PHH and may be beneficial in improving their neurodevelopmental outcomes. A multicenter randomized trial may be needed to further validate the results of this report.</p>

Comparative analysis of the pathogens responsible for hospital acquired and community acquired late onset neonatal septicemia / 中华儿科杂志

<p><b>OBJECTIVE</b>Late onset neonatal septicemia (systemic infection after 72 hours of life) remains a major cause of neonatal morbidity and mortality. Early treatment with appropriate antibiotics is critical since infected infants can deteriorate rapidly. The aim of this study was to review the pathogens responsible for late onset neonatal septicemia (LONS) and their antimicrobial susceptibilities in order to guide the initial selection of appropriate antibiotics for infants with suspected LONS.</p><p><b>METHODS</b>A retrospective chart review of all cases with LONS seen in the neonatal intensive care unit (NICU) of Yuying Children's Hospital of Wenzhou Medical College from January 1, 2002 to December 31, 2005 was conducted. All cases were selected based on the clinical presentation and at least one positive result of blood culture. The basic clinical characteristics and the results of blood culture and antimicrobial susceptibilities were analyzed.</p><p><b>RESULTS</b>A total of 102 cases with LONS were identified. Among those 102 cases, 80 were community acquired (infants admitted from home and the blood culture was done on admission) and 22 were hospital acquired (infants became sick while in the NICU and the blood culture was done prior to use of antibiotics). The clinical presentations were non-specific. Compared to the infants with community acquired LONS, infants with hospital acquired LONS were usually born more prematurely (mean gestational age 33 +/- 3 vs 39 +/- 2 wks, t = 2.255, P < 0.01), with lower weight (mean weight 1.79 +/- 0.70 vs 3.23 +/- 0.67 kg, t = 8.818, P < 0.01) and with younger age (mean age 12 +/- 6 vs 16 +/- 7 days, t = 7.581, P < 0.05). Of the 102 cases, a total of 103 strains of bacteria were isolated. Among the pathogenic bacteria isolated, the most common were coagulase-negative Staphylococcus (CoNS) (50/103, 48.5%), followed by Klebsiella pneumoniae (16/103, 15.5%). The main pathogens for community acquired LONS were Staphylococcus species and Escherichia coli. The most important pathogen responsible for hospital acquired LONS was Klebsiella pneumoniae. Most (> 80%) of the Staphylococcus especially CoNS were resistant to common antibiotics such as penicillin, erythromycin and cefazolin. Significant numbers (6/9) of Staphylococcus aureus isolated were methicillin-resistant Staphylococcus aureus (MRSA). However, all of the Staphyloccus isolates were sensitive to vancomycin. Almost all (15/16) of the Klebsiella pneumoniae isolated were multi-drug resistant due to production of extended-spectrum beta-lactamases (ESBLs). They were sensitive only to a few antibiotics such as carbapenems, aminoglycosides and quinolones. There was also one strain of vancomycin-resistant Enterococcus (VRE). Furthermore, there was no a single case of late onset neonatal sepsis due to infection with group B Streptococcus (GBS).</p><p><b>CONCLUSIONS</b>The clinical manifestations of late onset neonatal sepsis are usually non-specific. GBS is not a significant pathogen responsible for community acquired LONS in the Wenzhou area. There are increasing numbers of multi-drug resistant bacterial species isolated from the newborn infants with late onset neonatal septicemia, which is most likely due the non-restricted use of antibiotics in the hospitals as well as in the communities. A routine blood culture should be taken from any newborn infant who is suspected of LONS and empirical use of appropriate antibiotics should be initiated as soon as the blood specimen for culture has been drawn. To reduce the occurrence of multi-drug resistant bacteria, the use of antibiotics especially the third generation cephalosporins in neonates should be restricted as much as possible.</p>