Reyin Lien

Successful Control of Methicillin-Resistant Staphylococcus aureus in Endemic Neonatal Intensive Care Units—A 7-Year Campaign

Background Methicillin-resistant Staphylococcus aureus (MRSA) is among the most important nosocomial pathogens in the intensive care unit (ICU) worldwide, including Taiwan. Since 1997, our neonatal ICUs (NICUs) had become endemic for MRSA. Methodology/Principal Findings To control MRSA spread in our NICUs, we implemented a series of infection control measures stepwise, including reinforcement of hand hygiene since January 2000, augmentation of aseptic care over the insertion site of central venous catheter since July 2001, introduction of alcohol-based handrubs since April 2003, surveillance culture for MRSA and cohort care for the colonized patients between March 2003 and February 2004, and surveillance culture with subsequent decolonization of MRSA between August 2005 and July 2006. After implementation of these measures, MRSA healthcare-associated infection (HAI) density reduced by 92%, from 5.47 episodes per 1000 patient-days in 1999 to 0.45 episodes per 1000 patient-days in 2006; MRSA bloodstream infection reduced from 40 cases in 1999 to only one case in 2006. Compared to those obtained during the period of surveillance culture without decolonization, both rates of MRSA colonization (8.6% vs. 41%, p<0.001) and infection (1.1% vs. 12%, p<0.001) decreased significantly during the period of surveillance and decolonization. Molecular analysis of the clinical isolates during the study period showed that the endemic clone, which dominated between 1998 and 2005, almost disappeared in 2006, while the community clones increased significantly in 2006–2007. Conclusion/Significance Through infection control measures, MRSA HAIs can be successfully controlled, even in areas with high levels of endemic MRSA infections such as our NICUs.

Catheter management in neonates with bloodstream infection and a percutaneously inserted central venous catheter in situ: Removal or not?

BACKGROUNDnThis study investigated whether removal of a percutaneously inserted central venous catheter (PICC) is compulsory in neonates with bloodstream infection (BSI), and also examined the risk factors for infectious complications when a PICC is retained in these patients.nnnMETHODSnThis was a cohort study of neonates with a PICC who developed a BSI between 2001 and 2007. BSI was defined according to Centers for Disease Control and Prevention criteria.nnnRESULTSnOf the 234 neonates in the cohort, 99 had early removal of PICC (ER-PICC, defined as removal within 3 days after the onset of clinical sepsis), and 135 had late removal of PICC (LR-PICC, defined as retention for more than 3 days after the onset of clinical sepsis). Resolution of clinical sepsis within 2 days was more frequent in the ER-PICC group compared with the LR-PICC group (80.8% vs 57.8%; P < .001). There was no significant difference between the 2 groups in terms of infectious complications and case fatalities, but the LR-PICC group had a significantly higher incidence of recurrence within 1 month after BSI (Pxa0= .002). Inappropriate initial antibiotic treatment was the only variable independently associated with infectious complications (odds ratio, 11.4; 95% confidence interval, 3.34∼39.2; P < .001).nnnCONCLUSIONSnPICCs should be removed in neonates with BSI, because retention of PICCs for more than 3 days is associated with delayed resolution of clinical sepsis and a higher incidence of recurrence within 1 month.

Effect of intravenous immunoglobulin for neonates with severe enteroviral infections with emphasis on the timing of administration

BACKGROUNDnThe benefits of intravenous immunoglobulin (IVIG) therapy for severe neonatal enterovirus infections are still controversial.nnnOBJECTnTo evaluate whether timing of IVIG administration might affect clinical outcomes of neonates with severe enteroviral infections.nnnSTUDY DESIGNSnWe retrospectively analyzed 67 neonates with culture-confirmed severe enteroviral infection, defined as hepatitis with coagulopathy and thrombocytopenia. Clinical features, outcomes and the usage of IVIG therapy were collected and analyzed. IVIG administered within 3 days of illness onset was classified as early IVIG therapy.nnnRESULTSnOf the 67 cases, 38 (57%) were male, 27 (40%) were premature, 57 (85%) had disease onset within 7 days of life and all but 2 cases were caused by coxsackievirus B group. Ten infants (15%) had clinically evident myocarditis. 41 infants (61%) received IVIG therapy and 29 were early IVIG therapy. Fifteen infants (22%) eventually died, without IVIG therapy for 7 infants. The deceased had a significantly higher peak serum aspartate aminotransferase (AST) level than the survivors (3539 vs. 866 IU/L, p<0.01). The timing of IVIG therapy was highly correlated with the timing of peak AST level in patients with early IVIG therapy. Multiple logistic regression analysis showed that a higher nadir hemoglobin level (adjusted odds ratio 2.8, 95% confidence interval: 1.4-5.4), no concurrent myocarditis (42.6 [3.4-5289]) and early IVIG therapy (14.7 [1.3-163]) were independently associated with a favorable prognosis.nnnCONCLUSIONSnIn defined severe neonatal enterovirus infections, serum AST level correlated with the disease severity. Early IVIG therapy, if needed, may be beneficial for survival.

Serum Lactate, Brain Magnetic Resonance Imaging and Outcome of Neonatal Hypoxic Ischemic Encephalopathy after Therapeutic Hypothermia

BACKGROUNDnSerum lactate was used to predict the severity and outcome of neonatal hypoxic ischemic encephalopathy (HIE) before the era of therapeutic hypothermia (TH). There is no report on neurodevelopment (ND) outcome of neonates with HIE treated with TH in Taiwan.nnnMETHODSnBetween April 2011 and December 2012, newborn infants admitted to Chang Gung Memorial Hospital (CGMH), with gestational age > 35 weeks and birth weight ≥ 1800 g, who had acute perinatal events, evidence of significant fetal compromise, and ongoing clinical encephalopathy were prospectively enrolled for TH. Whole body cooling method was used to maintain the affected neonates esophageal temperature at 33.5 ± 0.5 °C for 72 hours. Demographic data were recorded and hemogram, biochemical parameters, serum lactate, and creatine kinase (CK) were measured as well. Brain magnetic resonance imaging (MRI) was performed between 7 and 14 days of life. ND outcome of infants was evaluated by Bayley Scales of Infant Development, third edition (BSID-III) at 24 months of corrected age. Poor ND (PND) outcome was defined as infants surviving with either disability or ND delay.nnnRESULTSnSeventeen patients were enrolled. Fifty-nine percent of babies (10/17) were born through cesarean section and 77% of babies (13/17) were transferred from outside hospitals. Six babies were moderate HIE and 11 babies were severe HIE. Among the 14 surviving patients, eight infants had PND outcome. There was no difference in demographic data between infants with and without PND. Serum level of lactate (mg/dL) after 72 hours of TH was higher (35.6 vs. 13.8, p = 0.042) in infants with PND. Neonates with abnormal brain MRI findings were also associated with PND (p = 0.01).nnnCONCLUSIONnThis is the first report on ND outcome of neonates with HIE treated with TH in Taiwan. Higher serum level of lactate following TH and abnormal results of brain MRI are associated with poor ND outcome.

Neurological Complications after Neonatal Bacteremia: The Clinical Characteristics, Risk Factors, and Outcomes

Background Neonates with bacteremia are at risk of neurologic complications. Relevant information warrants further elucidation. Study Design This was a retrospective cohort study of neonates with bacteremia-related neurologic complications (BNCs) in a tertiary-level neonatal intensive care unit (NICU). A systemic chart review was performed conducted to identify clinical characteristics and outcomes. A cohort of related conditions was constructed as the control group. Logistic regression analysis was used to identify independent risk factors for BNC. Results Of 1037 bacteremia episodes, 36 (3.5%) had BNCs. Twenty-four cases of BNCs were related to meningitis, five were presumed meningitis, and seven occurred after septic shock. The most common causative pathogens were Group B streptococcus (41.7%) and E. coli (16.7%). The major BNCs consisted of seizures (28), hydrocephalus (20), encephalomalacia (11), cerebral infarction (7), subdural empyema (6), ventriculitis (8), and abscess (4). Eight (22.8%) neonates died and six (16.7%) were discharged in critical condition when the family withdrew life-sustaining treatment. Among the 22 survivors, eight had neurologic sequelae upon discharge. After multivariate logistic regression analysis, neonates with meningitis caused by Group B streptococcus (adjusted odds ratio [OR]: 8.90, 95% confidence interval [CI]: 2.20–36.08; pu200a=u200a0.002) and combined meningitis and septic shock (OR, 5.94; 95% CI: 1.53–23.15; pu200a=u200a0.010) were independently associated with BNCs. Conclusions Neonates with bacteremia-related neurologic complications are associated with adverse outcomes or sequelae. Better strategies aimed at early detection and reducing the emergence of neurologic complications and aggressive treatment of Group B streptococcus sepsis are needed in neonates with meningitis and septic shock.

Hepatic failure in a newborn with maternal peripartum exposure to echovirus 6 and enterovirus 71

This case report describes a premature infant who developed jaundice, somnolence, and signs of disseminated intravascular coagulopathy soon after birth. Two siblings developed hand-foot and mouth disease 5 days before the patient’s delivery. Maternal fever and fetal distress prompted delivery by caesarean section. Echovirus 6 was recovered from blood and rectal swab cultures of the baby whereas his mother had adequate post-partum antibodies to enterovirus 71 and echovirus 6. Neonatal enterovirus (EV) infection may cause diverse clinical manifestations from a sepsis-like syndrome to subtle nonspecific febrile illness [1,2]. Disease severity and outcome of EV infection are affected by host defence and viral virulence. Maturity of the patient’s own immune system and the presence of maternally derived neutralising antibodies are pivotal to the neonatal host defence [6]. Within the EV family, both echovirus and coxsackie virus are known to cause neonatal hepatitis and severe disease. Since 1998, there has been an epidemic of EV71 infection among young children in Taiwan [5]. We report a case of acute hepatic failure in a premature newborn whose mother had peripartum exposure to echovirus 6 and EV71. The patient was a premature male infant who presented on the 5th post-natal day with jaundice, somnolence, and apnoea. He was born at 35 weeks gestation with a birth weight of 2460 g and his Apgar scores were 9 and 10 at 1 and 5 min after birth. Two siblings, aged 2 and 3 years respectively, developed hand-foot and mouth disease (HFMD) 5 days before our patient’s birth. Their mother also developed fever, and fetal distress in the baby prompted a caesarean section. The baby was lethargic from birth. Progressive jaundice and ecchymosis developed subsequently. On the 5th day of life, he was transferred to our hospital due to apnoea necessitating endotracheal intubation. Upon admission, the baby was semi-comatous with little spontaneous movement. His blood pressure and heart rate remained normal. An enlarged liver span and areas of ecchymosis were found. The baby was hypotonic without focal signs or seizures. Results of initial laboratory examination were: leukocyte count 5.1·10/l (segmented neutrophils 59%, band forms 8%, myelocytes 3%, lymphocytes 21%, monocytes 1%, eosinophils 3% and atypical lymphocytes 5%), NRBC 13%, haemoglobin 18.1 g/dl, platelet count 21·10/l, CRP 60.7 mg/l, aspartate aminotransferase (AST) 994 U/l, alanine aminotransferase (ALT) 126 U/l, total bilirubin 10.4 mg/dl and direct bilirubin 1.1 mg/dl. Both prothrombin time and activated partial thromboplastin time were prolonged. Due to the bleeding tendency, a lumbar puncture was not performed. Despite empirical antibiotic treatment, the patient went into a clinical state of septic shock with disseminated intravascular coagulopathy, progressive jaundice and worsening hepatic failure. Blood exchange transfusion was performed on the 13th and 25th hospital day because of hyperbilirubinaemia. Liver function parameters are shown in Fig. 1. On the 4th and 5th hospital day, the patient received two 1 g/kg doses of intravenous immunoglobulin (IVIG) infusion. Both blood and rectal swab cultures, obtained from the baby 1 day prior to IVIG administration, revealed echovirus 6. Throat swab and urine viral culture were negative (including cytomegalovirus). The baby’s serum antibody titres to EV71 were 1:32 and 1:16 on the 15th and 20th post-natal day, respectively; however, the antibody to echovirus 6 was not checked. Maternal rectal and throat swab cultures did not reveal any EV. Her serum antibody titre to EV71 was 1:256 and to echovirus 6 was 1:128 on the 15th post-partum day. Under aggressive support, this patient showed a slow but steady recovery. He came off ventilator support on Eur J Pediatr (2003) 162: 648–649 DOI 10.1007/s00431-003-1269-9

Case-control analysis of endemic Acinetobacter baumannii bacteremia in the neonatal intensive care unit

BACKGROUNDnWe aimed to characterize the clinical manifestations and outcomes of patients with Acinetobacter baumannii bacteremia in the neonatal intensive care unit (NICU).nnnMETHODSnAll patients with A baumannii bacteremia in our NICU from 2004 to 2010 were reviewed. A matched case-control study was performed by comparing each case of A baumannii to 2 uninfected controls and all cases of Escherichia coli and Klebsiella bacteremia, respectively.nnnRESULTSnThirty-seven cases with A baumannii bacteremia were identified. Multidrug-resistant isolate was noted in only 2 cases (5.4%), and the overall mortality rate was 8.1%. Compared with matched, uninfected controls, infants with A baumannii were more likely to have had a central vascular catheter (CVC) (Pxa0= .009), use of total parenteral nutrition (TPN) (Pxa0= .021), longer duration of ventilator use (Pxa0= .002), and hospitalization (Pxa0= .010). Compared with E coli or Klebsiella bacteremia, infants with A baumannii bacteremia had lower birth weight (median of 1,090 g vs 1,300 g, Pxa0= .044) and a higher rate of CVC and TPN use (both P < .001) at the time of infection.nnnCONCLUSIONnA baumannii bacteremia occurs endemically or sporadically in the NICU, primarily in low-birth-weight infants on TPN use and with CVC in situ. Although A baumannii does not often cause mortality, and multidrug-resistant A baumannii is uncommon, it contributes significantly to longer hospitalization.

Clinical consequences of twin-to-twin transfusion

Abstract. Twin-to-twin transfusion (TTT) is a complication of monochorionic twins that may result in high mortality and morbidity. To better understand pathophysiology in TTT and the consequences for affected fetuses and neonates, we describe the clinical features of 19 consecutive pregnancies complicated by TTT over 5xa0years. The diagnosis was made based on the findings of polyhydramnios–oligohydramnios sequence with weight discordance judged by obstetrical sonogram in monochorionic twins. Serial amnioreductions were performed as the sole modality of therapeutic intervention when indicated. The obstetrical diagnosis of TTT was first made at a median gestational age of 26xa0weeks (range 20–35xa0weeks). Median age of delivery was 30xa0weeks (range 26–36xa0weeks). Thirty-three babies of the 19 pairs of twins were born alive, but only 21 of them lived beyond 28xa0days of life. Fifteen pairs of twins with TTT had weight discordance greater than 20%, but only one pair showed initial hemoglobin difference greater than 5xa0g/dl. Newborn infants with TTT were at risk for development of renal insufficiency, periventricular leukomalacia, and necrotizing enterocolitis. Intrauterine fetal demise of one twin and severe anemia (hemoglobin <10xa0g/dl) at birth were poor prognostic factors. Recent advances in perinatal care improves pregnancy outcome of TTT; however, surviving neonates are still at risk for morbidities arising from hemodynamic aberrations.

Characteristics of neonates with culture-proven bloodstream infection who have low levels of C-reactive protein (≦10 mg/L)

BackgroundElevated C-reactive protein (CRP) level is widely used in clinical practice as a marker to distinguish between neonates with or without sepsis. However, some neonates with bacteremia have a CRP level within the normal range and they are not well characterized.MethodsAll episodes of neonatal culture-proven bloodstream infections (BSIs) between July 2004 and June 2012 were enrolled. Patients characteristics were compared for three CRP groups (low, ≤ 10xa0mg/L; intermediate, 11–100xa0mg/L; and high, > 100xa0mg/L) using the Chi-square test and one-way ANOVA. The sepsis-attributable mortality rates were compared using logistic regression analyses.ResultsOf 986 episodes of neonatal BSI, 247 (25.1xa0%) had CRP ≤10xa0mg/L at the onset of clinical sepsis. In the low CRP group, patients had lower gestational age and birth weight, and an earlier occurrence of BSI. Patients with underlying gastrointestinal pathology, renal disorders, cholestasis, and pulmonary hypertension had a non-significant elevated CRP level at the onset of sepsis. In the blood culture of the low CRP group, coagulase-negative staphylococci (CoNS) were relatively more common (55.9xa0%, pu2009<u20090.001) than the other two groups, although one-fourth were infected with gram-negative bacilli (19.0xa0%), fungi (2.8xa0%), or polymicrobial pathogens (3.6xa0%). Of the BSIs with initial low CRP, 29.1xa0% were treated with inadequate antibiotics, 13.0xa0% progressed to septic shock, and 5.3xa0% had infectious complications. The sepsis-attributable mortality rate was lower in the low CRP group (4.9xa0%) than in the high CRP group (13.6xa0%).ConclusionsA considerable proportion of neonatal BSIs had a normal or low initial CRP level (≤10xa0mg/L), which was more likely to occur in low birth weight or extremely preterm infants, those with earlier onset of sepsis, and those infected with CoNS. Plasma CRP level should not be used to rule out severe culture-proven sepsis or guide the empirical choice of antibiotics.

Polymicrobial Bloodstream Infection in Neonates: Microbiology, Clinical Characteristics, and Risk Factors

Background Polymicrobial bloodstream infections (PBSIs) have been associated with complex underlying medical conditions and a high incidence of specific microorganisms in several settings, but the relevant data are scarce in neonates. Methods Positive blood cultures from January 2004 to December 2011 in the neonatal intensive care unit (NICU) of Chang Gung Memorial Hospital (CGMH) were reviewed. Each neonate with PBSI (case episode) was matched to two episodes of monomicrobial BSI (control episode) by birth weight, gestational age and gender. Records were reviewed to compare their underlying medical conditions, organisms isolated, adequacy of therapy, clinical characteristics and outcomes. Results Forty-five episodes of PBSI (4.4% of all neonatal BSIs) were identified in 43 neonates. Gram-negative organisms constituted 59.8% of all PBSI pathogens, and 33 (73.3%) of PBSIs were caused by at least one Gram-negative organism. PBSIs were significantly more likely to be the recurrent episode and have endotracheal tube in place. No significant difference was found between PBSIs and controls in terms of demographics and most chronic conditions. PBSIs were significantly associated with a higher severity of illness, a longer duration of septic symptoms, and a higher rate of modification of antimicrobial regimens than monomicrobial BSIs. However, the sepsis-attributable mortality rates were comparable between these two groups. Conclusions In the NICU, PBSIs were more often caused by Gram-negative bacilli, and often occurred in neonates without any chronic conditions. The clinical significance of PBSIs included a more severe illness, longer duration of septic symptoms and a higher rate of modification of antimicrobial regimens.