Liposomal amphotericin B (AmBisome) in the treatment of neonatal candidiasis in very low birth weight infants.

UNLABELLED: AmBisome (2.5-7 mg/kg/day as a continuous 1 h infusion) was evaluated prospectively from September 1994 to January 1998 in 24 very low birth weight infants (mean birth weight 847+/-244 g, mean gestational age 26 weeks) with systemic candidiasis. Mean age at onset of candidemia was 17 days. One patient had two episodes of candidiasis. Thirteen infants failed previous antifungal therapy with amphotericin B (with or without 5-flucytosine). Candida spp. were isolated from the blood in all 25 episodes and from skin abscesses and urine in four infants each, respectively. There were 13 isolates of Candida albicans, ten of Candida parapsilosis, two of Candida tropicalis and one of Candida glabrata. One infant had a mixed infection with C. albicans and C. parapsilosis. The mean duration of therapy was 21 days; the cumulative AmBisome dose was 94 mg/kg. Fungal eradication was achieved in 92% of the episodes; mean duration of AmBisome therapy until achieving eradication was 9 days. Twenty (83%) infants were considered clinically cured at the end of treatment. No major adverse effects were recorded; one infant developed increased bilirubin and hepatic transaminases levels during therapy. Four (17%) infants died; in two of them (8%) the cause of death was directly attributed to systemic candidiasis. CONCLUSION: AmBisome represents an effective, safe and convenient antifungal agent in the therapy of systemic fungal infections in very low birth weight infants.

Urinary free cortisol (UFC) values in newborns under stress.

UNLABELLED: Children with adrenocortical insufficiency are commonly instructed to increase three to five times baseline glucocorticoid replacement dose during periods of stress such as surgery or febrile illness. The present study was undertaken to determine whether these recommendations reflect the actual change in urinary free cortisol (UFC) output during stress in neonates and to test the effect of stress on the diurnal variation of cortisol in this age group. DESIGN AND PATIENTS: Twenty-four hour urinary free cortisol (UFC) excretion was determined in 75 neonates during the first 2 days of life. Thirty were healthy and 45 were neonates with respiratory distress. In 60 babies the 24-h UFC was collected in 6-h fractions for the determination of diurnal variation of urinary cortisol. RESULTS: The mean change in UFC was 4.5 times higher in the sick babies than in the controls. A distinct diurnal variation of UFC was noted in both healthy and sick babies. CONCLUSIONS: In contrast with previous publications a distinct diurnal pattern was noted in the majority of neonates.

Neutropenia complicating Rh-hydrops fetalis: the effect of treatment with recombinant human granulocyte colony-stimulating factor (rhG-CSF).

Neutropenia is a less commonly encountered feature of Rh hemolytic disease of the newborn, and its management may be problematic. Two newborn infants with neutropenia complicating Rh incompatibility-induced hydrops fetalis were treated with intravenous recombinant human granulocyte colony-stimulating factor (rhG-CSF), 5 micrograms/kg/day for 5 days. Both patients responded to therapy with a rapid and persistent increase of their neutrophil counts to normal values. The treatment was well tolerated and no adverse clinical events were observed. rhG-CSF induces a significant increase in peripheral absolute neutrophil counts of neutropenic neonates with Rh hydrops fetalis and was well tolerated. The contribution of rhG-CSF to clinical recovery warrants further investigation.

The in vivo effect of recombinant human granulocyte-colony stimulating factor in neutropenic neonates with sepsis.

The effects of recombinant granulocyte-colony stimulating factor (rhG-CSF) in neonatal neutropenia with presumed sepsis, which has a poor prognosis, were investigated. The study involved 14 neonates with presumed sepsis and neutropenia. Findings were compared with those from 24 historical controls. rhG-CSF (5 micrograms/ kg/day i.v. for 5 days) was administered immediately following diagnosis. Complete blood counts were obtained before and 24, 48, 72, 96 and 120 h after initiation of treatment. Neutrophil storage pool (NSP) was assessed (in 4 patients) before and after treatment. Statistical analysis was performed using one way analysis of variance. Treatment led to an increase in absolute neutrophil count (ANC) levels in 13/14 patients. At the end of treatment, the mean ANC was higher than that of controls (P = 0.007). There was a marked increase in the NSP of between 32% and 65% (P = 0.005). There were two clinical failures, one of whom was considered to have died from his underlying condition. There were no reports of clinical or haematological toxicity during treatment or follow up.

["CHARGE" association].

CHARGE association represents a group of congenital anomalies with no clear etiology. The broad array of abnormalities, which involves several systems, has been the basis for the acronym CHARGE: coloboma, heart anomaly, choanal atresia, retarded growth and development, hypoplastic genitalia and ear malformation. We present 3 children with CHARGE association to illustrate the phenotypic variability and note the multidisciplinary treatment they received. It is recommended that this entity be approached in an interdisciplinary, integrated way to allow for faster diagnosis and better prognosis.

Twenty-one years of monitoring congenital malformations (1974-1994): The Israel Birth Defects Monitoring System, affiliated with the International Clearinghouse.

The first 21 years of monitoring of congenital malformations by a hospital-based program affiliated to the International Clearinghouse is analyzed. The foundation activities, methodology, data and time trends are presented and precautions in interpretation of this information are emphasized. The great majority of congenital malformations, including Down syndrome, have stable rates making the search of their causes and the development of intervention methods much harder. The practical implications of these data and the appropriate recommendations are discussed.

Sepsis at a neonatal intensive care unit: a four-year retrospective study (1989-1992).

During the 4-year period 1989-1992, 18,227 neonates were born at Kaplan Hospital and 614 (3.4%) were admitted to the neonatal intensive care unit. During this period, 120 episodes (6.6/1000 live births) of neonatal sepsis were recorded in 109 neonates (6/1000 live births). The incidence of early-onset sepsis was 19/109 (17%). The main pathogens of early-onset sepsis were S. agalactiae (42%) and E. coli (32%). Seven of the 8 S. agalactiae cases were recorded during 1989-1990. The main pathogens of late-onset sepsis were Klebsiella spp. (31%), coagulase-negative staphylococci (18%) and Candida spp (16%). There were 11 cases (10%) of meningitis, 5 due to Klebsiella spp. The overall fatality rate due to sepsis was 14% (0.8/1000 live births) with an early-onset sepsis death rate of 37%. The mortality from S. agalactiae sepsis was 63%. The main trends recorded during the period of the study were 1) the emergence of S. agalactiae as the main pathogen of early-onset sepsis, followed by a sharp decrease in its incidence during the last part of the study, 2) the emergence of extremely virulent, multi-antibiotic-resistant Klebsiella organisms, and 3) the persistent high incidence of Candida sepsis.

An outbreak of antibiotic multiresistant Klebsiella at the Neonatal Intensive Care Unit, Kaplan Hospital, Rehovot, Israel, November 1991 to April 1992.

From November 1991 through April 1992, 8 infants developed systemic infections due to antibiotic multiple resistant Klebsiellaa (MRK). All were premature and 6 of the 8 weighed less than 1100 g; 7 of the 8 had received previous antibiotic therapy. Five infections occurred during the first week of life. MRK were isolated from blood (8 cases), tracheal secretions (TS-6), stool (3), and CSF (1). All Klebsiella blood isolates were resistant to ampicillin, mezlocillin, and cefotaxime, 7 of 8 to ceftazidime and amikacin, and 4 of 7 to aztreonam; all isolates were sensitive to quinolones and imipenem. Four infants died. In all 4 of the isolates, they were sensitive only to quinolones and imipenem, and the empiric therapy used for suspected sepsis proved to be inappropriate. The outbreak was terminated by temporary closure of NICU in May 1992. Strict hand washing practices were reemphasized, and the previous empiric antibiotic protocol used for suspected sepsis (mezlocillin plus amikacin, and lately ceftazidime plus amikacin) was changed to imipenem and amikacin in the risk population. At closure, 5 additional infants had MRK in stools and/or tracheal suction specimens. Development of MRK organisms should dictate a rational use of empiric antibiotics for neonatal infections in NICU.

Aplasia cutis congenita, elevated alpha-fetoprotein, and a distinct amniotic fluid acetylcholinesterase electrophoretic band.

Aplasia cutis congenita affecting the elbows, knees, hips, and gluteal area was observed in a female newborn, product of a twin pregnancy. One of the twins was a fetus papyraceous detected at 15 weeks of pregnancy. During the course of the pregnancy, maternal thrombocytosis was diagnosed and treated with aspirin. alpha-Fetoprotein was elevated in maternal serum and amniotic fluid, and a distinct electrophoretic acetylcholinesterase band was seen in amniotic fluid. These findings are in agreement with the classification of aplasia cutis congenita as proposed by Frieden et al in which type V is related to the presence of a fetus papyraceous or placental infarcts. The findings in the present case may be explained by the effect of the dead twin on the surviving fetus and the extensive denuded skin areas. Long-term follow-up of the infant showed that the lesions were cured, most of them with minimal scars. Increased risk for aplasia cutis congenita should be considered when elevated maternal and amniotic fluid alpha-fetoprotein and a distinct electrophoretic band of acetylcholinesterase are found. Especially when one of the twins is dead.

Clinical outcome and follow-up of prenatal hydronephrosis.

Between 1987 and 1991, 160 hydronephrotic kidneys were diagnosed prenatally and confirmed postnatally in 100 infants. The aim of the study was to describe the natural history and management of primary hydronephrosis detected prenatally. We devised a new classification of obstructive uropathy outcome using ultrasonography and the diethylenetriamine penta-acetic acid scan. Accordingly, we classified the patients as having mild, moderate or severe hydronephrosis. Nine patients had pyeloplasties and 5 had ureteric reimplantations. We conclude that in most cases there is no need for immediate surgery, and that the initial approach to the management of congenital hydronephrosis should be conservative. We suggest that anti-bacterial prophylaxis be conventionally given to infants with vesicoureteral reflux and for the first 6 months of life to infants demonstrating moderate to severe newborn primary hydronephrosis.

Evaluation of prenatally diagnosed hydronephrosis by morphometric measurements of the kidney.

A large number of hydronephrotic kidneys (108) were diagnosed prenatally in 69 infants between 1987 and 1991 and subsequently confirmed postnatally. Prenatal morphometric measurements were done in order to find reliable parameters for the detection of a group at risk for surgical treatment. A second aim of the study was to describe the natural history and management of hydronephrosis detected prenatally. We devised a classification of postnatal obstructive uropathy using ultrasonography and the renal scan. Accordingly, we classified the patients as having mild, moderate or severe hydronephrosis. A renal pelvic antero-posterior diameter (APD) of 9 mm or more, and a pelvic-to-renal APD ratio of 0.45 before 32 weeks of gestation and 0.52 thereafter, were found to be useful for the detection of severe outcome. Our new parameter, a pelvic-to-renal volume ratio of greater than 0.08, can also be used for this purpose.

Neonatal noma.

Neonatal noma is a rare clinical syndrome affecting term and preterm infants. It causes gangrene of the orofacial tissues accompanied by sepsis and a high mortality rate. A preterm 35-week infant, severely growth retarded in utero, developed clinical signs of sepsis with ulcers all over the oral mucosa caused by local infection with Pseudomonas aeruginosa. The lesions healed with cicatricial sequelae of the mouth, sequestration of teeth, and retraction of perimandibular soft tissues.

Evaluation of two rapid tests for detection of maternal endocervical group B streptococcus: enzyme-linked immunosorbent assay and gram stain.

OBJECTIVE: To establish the reliability of two rapid tests for detection of group B streptococcus, the new enzyme-linked immunosorbent assay (ELISA) and the Gram stain. In addition, we wished to determine whether the combination of these tests would increase test sensitivity. METHODS: During a 2-year period, cervical secretions from 660 patients who presented with either premature rupture of membranes or preterm labor at a gestational age of 37 weeks or less were tested by three methods: the Equate ELISA test, a Gram stain smear, and a culture for group B streptococcus. Results of the rapid tests were compared with the corresponding culture results. RESULTS: Cultures were positive for group B streptococcus in 50 patients, a prevalence of 7.5%. The sensitivity for the Equate ELISA test was 24% and for the Gram stain, 20%. Specificity was 95 and 89%, respectively. When results of these tests were combined, the sensitivity increased to 26%. Both rapid tests yielded a high rate of false positives. In more than 50% of false-positive cases, bacteria other than group B streptococcus were isolated. CONCLUSION: Neither the Gram stain nor the Equate ELISA test is sensitive enough to be used as a screening test for the identification of group B streptococcus. Furthermore, the combination of both rapid tests yielded only a slight increase in sensitivity. The high false-positive rate of the ELISA test seems to be related to a cross-reactivity of the anti-group B streptococcal antibody with other cervical bacteria.

Systemic candidal infections associated with use of peripheral venous catheters in neonates: a 9-year experience.

The clinical courses of 25 infants with systemic candidiasis who were treated in the neonatal intensive care unit at Kaplan Hospital, Rehovot, Israel, during the period 1980-1989 were retrospectively analyzed. Twenty-three (92%) weighted less than 1,500 g at birth. Candidemia was associated with prolonged antibiotic therapy, hyperalimentation, and intravenous fat emulsions in all cases and with previous tracheal intubation in 80% of cases. Only one infant had a central venous catheter placed; for all others, hyperalimentation was administered by means of peripheral intravenous catheters. The mean age at onset of systemic candidiasis was 30 +/- 14 days, although an earlier onset (25 +/- 8 days) was noted during the last 3 years of the study period. Candida species were isolated from the blood of 24 infants and from the urine of 10 infants. Microscopic examination of the urine was positive for Candida organisms for three infants and led to a rapid diagnosis. Candidal skin abscesses were present in 11 infants (44%); for two of these infants, the early occurrence of such abscesses prompted the initiation of therapy before confirmation of the diagnosis of systemic candidiasis. All infants were treated with intravenous amphotericin B and oral 5-fluorocytosine. The mortality rate was 20%, but death was directly attributable to candidemia in only three infants (12%).

Occurrence of cerebrohepatorenal (Zellweger) syndrome in the Karaite community in Israel: a genetic hypothesis.

Two infants with the cerebrohepatorenal (Zellweger) syndrome in Karaite families are described. This syndrome has an autosomal recessive mode of inheritance with an estimated incidence of between 1:25,000 and 1:100,000 live births. In addition to a previous report of the syndrome in a Karaite family, this report raises the possibility of a high incidence of Zellweger Syndrome among the Karaites in Israel.

Time trends (1978-86) of anencephaly and spina bifida in four hospitals affiliated with the International Clearinghouse: a warning.

The prevalence and time trends of spina bifida and anencephaly in the central area of Israel have been studied using data derived from four hospitals affiliated with the International Clearinghouse for Birth Defects Monitoring Systems. Spina bifida rates show a continuous increase from 1978 (1.1/10,000) to 1986 (7.4/10,000) with a peak in 1984 (7-fold increase compared with 1978). The logistic regression analysis of proportion of cases revealed a significant linear trend over time (P less than 0.005). Anencephaly rates increased from 1978 to 1981 but later decreased continuously until 1986 when the prevalence returned to the initial level of 1978. This time trend of spina bifida may represent a real alarm; the implications of this observation are discussed.