Ofra Peleg

Cluster of Neonatal Infections in Jerusalem due to Unusual Biochemical Variant of Enterobacter sakazakii

Abstract.Reported here is a cluster of infections due to a nitrate-negative variant of Enterobacter sakazakii, which occurred among premature neonates at the Hadassah Hospital, Mount Scopus, Jerusalem, in December 1999–January 2000. Pulsed-field gel electrophoresis showed cluster isolates to be identical but unrelated to previous systemic isolates recovered in 1993 and 1998. The organism was not isolated from infant formula powder, but it was recovered from prepared formula and from a kitchen blender. Elimination of the environmental focus, a change to factory-prepared infant formula, and isolation of affected infants terminated the event. Faecal carriage of Enterobacter sakazakii was observed for up to 18 weeks, emphasising the potential for cross-infection.

Idiopathic gastrointestinal perforation in the neonate

Spontaneous localized perforation of the gastrointestinal tract, unrelated to mechanical intestinal obstruction and with no evidence of necrotizing entrocolitis (NEC), occurred in 20 neonates. Three perforations were located in the stomach, 11 in the small intestine, and six in the colon. Maternal obstetric complications as well as prematurity and postnatal distress were common in these patients. The overall survival rate was 80%. There was no late gastrointestinal symptoms in the survivors. Whether idiopathic perforation of the gastrointestinal tract results from a localized form of NEC or from a distinct lesion of unknown etiology has not yet been ascertained. Some ideas concerning the etiology of this entity, as well as some diagnostic aspects are discussed.

Continuous surveillance to reduce extended-spectrum β-lactamase Klebsiella pneumoniae colonization in the neonatal intensive care unit.

Background: Clinical illness caused by resistant bacteria usually represents a wider problem of asymptomatic colonization. Active surveillance with appropriate institution of isolation precautions represents a potential mechanism to control colonization and reduce infection. The neonatal intensive care unit (NICU) is an environment particularly appropriate for such interventions. Neonates are rarely colonized by resistant bacteria on admission and staff enthusiasm for infection control is high. Objective: To reduce extended-spectrum β-lactamase-producing Klebsiella pneumoniae (ESBL-KP) acquisition amongst neonates through a continuous active surveillance intervention. Methods: Fecal ESBL-KP cultures were performed weekly on all neonates over 4 years. Neonates with positive cultures were managed with contact precautions by dedicated nurses separately from other neonates. ESBL-KP acquisition amongst neonates staying >7 days was compared for the consecutive years. A subset of ESBL-KP isolates was typed with pulsed-field gel electrophoresis (PFGE). Results: Surveillance cultures were obtained from 1,482/1,763 (84%) neonates over 4 years. ESBL-KP acquisition decreased continuously from 94/397 (24%) neonates in 2006 to 33/304 (11%) in 2009 (p < 0.001, hazard ratio 0.75, 95% confidence interval 0.66–0.85, p < 0.001 for comparison of years). Hospital-wide ESBL-KP acquisition did not decrease outside the NICU. PFGE identified identical ESBL-KP strains from multiple neonates on six occasions and different strains from single neonates on seven occasions. Conclusions: ESBL-KP is probably both imported into and spread within the NICU. Continuous long-term surveillance with cohorting was associated with a decrease in ESBL-KP acquisition within the NICU. This low-risk intervention should be considered as a means to decrease neonatal acquisition of resistant bacteria.

Neonatal bacteremia: Patterns of antibiotic resistance

OBJECTIVE To determine the incidence and evaluate the antimicrobial-susceptibility patterns of bacterial infections in our neonatal units. DESIGN Retrospective surveillance study. SETTING The neonatal units of the Hadassah University Hospitals, Jerusalem, Israel. PATIENTS All newborns admitted from January 1994 through February 1999. METHODS The records of all patients with positive blood and cerebrospinal fluid cultures were reviewed. Bacteremia was considered early-onset (vertical) when occurring within the first 72 hours of life and late-onset (nosocomial) when occurring later. The prevalence and antibiotic-resistance patterns of vertically transmitted and nosocomially acquired strains were compared and studied over time. RESULTS 219 of 35,691 newborn infants had at least one episode of bacteremia (6.13/1,000 live births). There were 305 identified organisms, of which 21% (1.29/1,000 live births) were considered vertically transmitted and 79% nosocomially acquired. The most common organism causing early-onset disease (29.2%) was group B streptococcus (0.38/1,000 live births), whereas coagulase-negative staphylococci (51%) were the most prevalent in late-onset disease. All gram-positive bacteria were susceptible to vancomycin. Most gram-positive organisms other than staphylococci were susceptible to ampicillin. Gram-negative organisms represented 31% of all isolates. Generally, there was a trend of increasing resistance to commonly used antibiotics among nosocomially acquired gram-negative organisms, compared to those vertically transmitted, with statistically significant differences for ampicillin and mezlocillin (P<.05 and P<.01, respectively). Over the years, a trend toward an increasing resistance to antibiotics was observed among gram-negative organisms. CONCLUSIONS The trend of increasing bacterial resistance to commonly used antibiotics necessitates the implementation of a rational empirical treatment strategy, based on local susceptibility data, reserving certain agents for emerging resistant pathogens.

Neonatal outcome of inborn and transported very-low-birth-weight infants: relevance of perinatal factors.

OBJECTIVE To compare the neonatal outcome (survival, intraventricular hemorrhage and bronchopulmonary dysplasia) of inborn and outborn very-low-birth-weight infants accounting for sociodemographic, obstetric and perinatal variables. STUDY DESIGN Ninety-one premature infants with birth weights of 750-1250 g delivered between 1990 and 1994 in a hospital providing neonatal intensive care were compared with 76 premature babies delivered in a referring hospital. In the statistical analysis, variables with a statistically significant association with the outcome variables and dissimilar distributions in the two hospitals were identified and entered together with the hospital of birth as explanatory variables in a logistic regression. RESULTS No statistically significant differences between the outcome variables of the two populations examined were observed, whether before or after accounting for the covariates. The odds ratios (outborns relative to inborns) were 1.18 for mortality, 1.25 for bronchopulmonary dysplasia and 1.53 for severe intraventricular hemorrhage. In the multivariate analyses, respiratory distress syndrome was significantly associated with mortality; both low birth weight and the presence of respiratory distress syndrome were associated with the development of bronchopulmonary dysplasia; the evolvement of severe intraventricular hemorrhage was associated with respiratory distress syndrome, initial low Apgar score, advanced multiparity and delivery at the 28-29th week compared to the 23rd-27th week. Antenatal steroid administration had a protective effect. CONCLUSION Our results concur with the notion that a tertiary center is the optimal location for delivery of the high risk neonate. Improvement in medical and nursing care prenatally and at delivery and transportation, including frequent administration of antenatal steroids and earlier administration of surfactant prior to transportation, may minimize the disadvantage of delivery in a referring hospital.

Elimination of vancomycin-resistant enterococci from a neonatal intensive care unit following an outbreak

A policy of weekly faecal cultures for vancomycin-resistant enterococci (VRE) was instituted following the investigation of an outbreak of VRE in our neonatal intensive care unit in 2005. We found that 11 of 18 patients were infected or colonised during the outbreak, including three cases of bloodstream infection and one case of meningitis. This report describes the utility of the surveillance policy in maintaining a VRE-free environment. The outbreak investigation showed that all VRE isolated were Enterococcus faecium of the vanA type. Pulsed-field gel electrophoresis suggested that the outbreak was caused by a single strain. Control of the outbreak was achieved by enhanced contact isolation precautions, cohorting of patients and staff, improved environmental decontamination and closure of the unit to new admissions. The patients with bloodstream infections and meningitis were treated successfully with linezolid. Approximately one year after the outbreak, weekly surveillance detected two patients with faecal carriage of VRE whose periods of admission overlapped. Early intensive intervention was associated with disappearance of the organism from the neonatal intensive care unit. No further cases of colonisation or disease have occurred in the unit in the two and a half years since then.

Carboxyhemoglobin levels in neonatal immune hemolytic jaundice treated with intravenous gammaglobulin

In order to examine the effect of intravenous immunoglobulin (IVIG) on the rate of hemolysis in immune hemolytic hyperbilirubinemia, we measured the carboxyhemoglobin levels of 5 newborn infants who were subjected to IVIG treatment. The pretreatment rate of hemolysis, in the 5 patients with isoimmune hemolytic jaundice (3 patients with Rh hemolytic disease of the newborn and 2 patients with ABO hemolytic disease of the newborn), as reflected by caboxyhemoglobin levels was higher than the rate of hemolysis in normal newborn infants. In 4 out of the 5 patients treated with IVIG, there was a rapid decline (> 30%) of carboxyhemoglobin levels, a pattern which was different from that observed in normal newborn infants with no hemolytic jaundice and in 3 untreated patients with ABO hemolytic disease of the newborn. None of the treated patients required an exchange transfusion. Our preliminary results support the theory that the attenuation of jaundice observed following IVIG treatment in patients with immune hemolytic hyperbilirubinemia is caused, at least in part, by the reduction in hemolysis.

Does parity affect the neonatal outcome of very-low-birth-weight infants ?

OBJECTIVE To evaluate the impact of parity on the neonatal outcome (survival, bronchopulmonary dysplasia and severe intraventricular hemorrhage) of very-low-birth-weight infants, accounting for sociodemographic, obstetric and perinatal variables. STUDY DESIGN One hundred and eleven singleton premature infants with birth weights of 750--1250 grams, delivered between 1990 and 1994 and treated in the Hadassah University Hospitals in Jerusalem, were evaluated. In the analyses, variables with statistically significant association with the outcome variables were identified and entered together with parity as explanatory variables in a logistic regression. The results were analyzed with and without the inclusion of respiratory distress syndrome, representing an index of initial illness severity, in the multivariate model. RESULTS Neonatal mortality was higher in the 2--11 parity group when compared with first born infants. This association was of borderline statistical significance (OR=3.3; P=0.09), and was evident only upon exclusion of respiratory distress syndrome from the equation. There was no association between parity and the development of bronchopulmonary dysplasia. The risk for developing severe intraventricular hemorrhage was higher in offsprings of multiparous women (OR=4.6; P=0,08 for parity 2-4, and OR=7.6; P=0.03 for parity 5--11). Respiratory distress syndrome was significantly associated with all the outcome variables and, to some extent, masked the relevance of pregnancy duration. A short hospitalization period before delivery was associated with increased mortality and with higher incidence of severe intraventricular hemorrhage. High initial Apgar scores appeared protective against severe intraventricular hemorrhage and bronchopulmonary dysplasia. CONCLUSION Our results demonstrate a trend for increased survival of first born premature infants when compared with offsprings of subsequent deliveries, and an association between advanced parity and the development of severe intraventricular hemorrhage. Confirmation of these data by other studies is required before resultant implications are considered.

Gastrointestinal colonization with ESBL-producing Klebsiella in preterm babies—is vancomycin to blame?

In this study, we examine the possible association between treatment with vancomycin and colonization with extended-spectrum beta-lactamase (ESBL)-producing Klebsiella in our neonatal intensive care unit (NICU). Variables compared between newborns which developed rectal colonization and those who did not include: gestational age, birth weight, gender, and total length of hospital stay until positive stool culture or discharge, treatment with vancomycin, and positive blood culture for coagulase-negative Staphylococcus. We found that lower birth weight, younger gestational age, and treatment with vancomycin were statistically significant risk factors for gastrointestinal colonization with ESBL-producing Klebsiella. When applying a multivariate model, treatment with vancomycin, both for a full 10-day course and for a short 3-day empirical treatment, remained statistically significant. Treatment with vancomycin is a risk factor for gastrointestinal colonization with ESBL-producing Klebsiella in premature babies.

Neonatal limb ischemia following maternal indomethacin treatment in twin pregnancies

The prenatal administration of indomethacin in obstetric management has been implicated as a cause of neonatal cardio-pulmonary, gastrointestinal and renal complications. The present report describes two cases of twin pregnancy resulting in premature delivery at the 33rd and 30th week following prolonged maternal indomethacin treatment for 9 and 4 weeks respectively. Neonatal cardiovascular and renal complications were observed and an unusual severe ischemia of a lower limb occured in each of the first twins following insertion of an umbilical arterial line. It is suggested that prolonged antenatal exposure to the drug may increase the systemic arterial constrictive reactivity in some newborn infants and that special caution should be exercised during arterial catheterization of susceptible cases.