Molecular epidemiology of antibiotic-resistant gram-negative bacilli in a neonatal intensive care unit during a nonoutbreak period.

OBJECTIVE: Gram-negative organisms that are resistant to parenteral antibiotics are a growing threat to hospitalized patients. This study was conducted to define the epidemiologic characteristics of these organisms during a nonoutbreak period in a neonatal intensive care unit (NICU). METHODS: Nasopharyngeal and rectal swab specimens were obtained 3 times a week from every infant in a tertiary care NICU during a 12-month period. Specimens were processed to identify aerobic Gram-negative species resistant to gentamicin, piperacillin-tazobactam, or ceftazidime. Selected clinical parameters were tested for their association with colonization with a resistant organism. Restriction endonuclease digests of genomic DNA were derived from isolates of the most frequently occurring species. The fragments were analyzed by pulsed-field gel electrophoresis (PFGE) to determine the genetic relatedness of the various isolates and thereby determine the length of colonization, the frequency of horizontal transmission, and the size and duration of clusters. RESULTS: A total of 101 infants (8.6%) of 1180 admissions were colonized with at least 1 antibiotic-resistant bacillus before NICU discharge. Multiple parameters indicating a prolonged, complicated NICU course were associated with resistant colonization, including gestational age, length of stay, and exposure to several classes of antibiotics. Colonization with resistant bacilli occurred as early as the first NICU day, but acquisition continued throughout the infants' stay. A total of 436 isolates were analyzed by PFGE. On the basis of this molecular analysis, it was determined that duration of colonization was usually very short; the median for all species tested was <1 week. In addition, cross-colonization occurred in only 12% of all PFGE-analyzed isolates. Most clusters of cross-colonized infants were small, with the majority involving only 2 patients. CONCLUSIONS: During endemic periods, acquisition of antibiotic-resistant Gram-negative bacilli in the NICU may occur very soon after admission, but colonization continues over many weeks of NICU stay. The duration of colonization with resistant bacilli is short, and horizontal transmission is unusual. These characteristics suggest a gradual but temporary incorporation of these organisms from the NICU environment into the nascent newborn microflora over time with little cross-colonization. These observations may aid the rational development of infection-control strategies to contain the reservoir of resistant Gram-negative organisms in the NICU.antibiotic resistance, Gram-negative bacilli, neonatal intensive care, antibiotic utilization, colonization, pulsed-field gel electrophoresis.

Etiology of fever and opportunities for reduction of antibiotic use in a pediatric intensive care unit.

OBJECTIVE: To determine the cause of fever in critically ill children and to identify opportunities for reducing antibiotic use in this population. DESIGN: Prospective case series. SETTING: A tertiary-care medical-surgical pediatric intensive care unit (PICU). PATIENTS: Children admitted to the PICU who experienced fever (axillary temperature >38.3 degrees C). MEASUREMENTS: Consecutive children who were febrile at any point in their PICU stay were investigated over two winter seasons. Etiology of the fever was determined by physical examination and routine microbiology and radiographic tests. Three subgroups were reviewed to approximate the number of antibiotic-days that could have been reduced; namely, those with an indeterminate source, those with a documented viral infection, and those receiving a prolonged course of antibiotics. A set of standards reflecting common antibiotic use then was applied to these three patient groups. RESULTS: Of 211 subjects, the majority (83.3%) had either a definitive or suspected focus for their fever, and nearly all of these patients were judged to have an infectious etiology. The study population received a total of 2,036 antibiotic-days. Despite the high incidence of infectious causes of fever in our subjects, however, approximately 15% of total antibiotic-days could have been reduced by applying common-use standards. CONCLUSIONS: Fever in the PICU was usually of defined focus and infectious in origin. However, among febrile patients in the PICU, substantial opportunity exists for reduction of antibiotic use. Trials determining the safety of antibiotic reduction in this population should be pursued vigorously.

Heart rate variability in cocaine-exposed newborn infants.

BACKGROUND: Infants born to cocaine-using mothers have a 3- to 8-fold increase in sudden infant death syndrome. Its underlying cause, in part, may be attributed to abnormal autonomic function. We proposed to study heart rate variability, reflecting autonomic control of the heart, in cocaine-exposed infants. METHODS: From 1997 to 2000, we studied 217 asymptomatic, term infants, of whom 68 had intrauterine cocaine exposure (group I). Their data were compared with infants exposed to drugs other than cocaine (group II, n = 77) and no drugs (group III, n = 72). Twenty-four-hour heart rate variability was measured within 72 hours of birth. RESULTS: Cocaine-exposed infants, as compared with the 2 control groups, had an overall significant decrease (P <.05) in global heart rate variability and a lower standard deviation of all valid N-N intervals in the recording (41.9 +/- 1.4 ms vs 47.6 +/- 1.3 ms and 46.9 +/- 1.3 ms, respectively). Vagal parameters such as high-frequency power and the square root of the mean of the squared differences between adjacent N-N intervals were also lower in newborns with heavy in utero cocaine exposure. CONCLUSIONS: Decreased heart rate variability was seen in cocaine-exposed infants. Whether low heart rate variability is a marker for increased risk of sudden death in infants (as it is in adults with structural heart disease) is unknown and requires further investigation.

Effect of cross-sectional imaging on negative appendectomy and perforation rates in children.

PURPOSE: To compare negative appendectomy and perforation rates in children who underwent ultrasonography (US), computed tomography (CT), or no imaging before urgent appendectomy. MATERIALS AND METHODS: All children who underwent urgent appendectomy during a 4(1/2)-year period were identified in a surgical billing database. Pathology reports were coded as negative or as showing acute inflammation or perforation. Imaging up to 14 days before appendectomy or abscess drainage was noted, and imaging-based diagnoses were compared with pathologic findings. Patient age and sex were recorded. RESULTS: Two hundred ninety-nine children, 176 (59%) male and 123 (41%) female (mean age, 10.4 years; age range, 1--21 years), underwent urgent appendectomy. One hundred twenty-six (42%) underwent no imaging, 121 (41%) underwent US with or without CT, and 52 (17%) underwent CT only; 44 (15%) underwent both US and CT. There were significantly higher rates of appendectomy with normal pathologic findings ("negative appendectomy") in patients who underwent no imaging (14% [18 of 126]) or US (17% [20 of 121]) versus the rates in those who underwent CT only (2% [one of 52]) (P =.02 and P =.007, respectively). The negative appendectomy rate was 7% in 96 patients who underwent CT with or without prior US. The perforation rates were not significantly different. CONCLUSION: As compared with children who underwent no preoperative imaging and those who underwent US, children who underwent CT had a significantly lower negative appendectomy rate, without a significantly higher perforation rate.

Developing language skills of cocaine-exposed infants.

OBJECTIVE: To assess whether there is an association of level of fetal cocaine exposure to developmental precursors of speech-language skills at 1 year of age, after controlling for confounding factors. DESIGN: In a prospective, longitudinal, quasi-experimental, matched cohort design, 3 cocaine exposure groups were defined by maternal self-report and infant meconium assay: nonexposure (n = 131), heavier exposure (n = 66), >the 75th percentile for maternal self-report and >the 70th percentile of benzoylecgonine concentration, and all others as lighter exposure (n = 68). At 1 year of age, the Preschool Language Scale-3 was administered by examiners unaware of infant drug status. RESULTS: Independent of confounding drug, medical, and environmental factors, more heavily exposed infants had lower auditory comprehension scores than nonexposed infants and lower total language scores than lighter and nonexposed infants. More heavily exposed infants were also more likely to be classified as mildly delayed by total language score than nonexposed infants. There were positive linear relationships between the concentration of benzoylecgonine in meconium and all outcomes and between maternal report of severity of prenatal cocaine use with poorer auditory comprehension indicating a relationship between amount of exposure and poorer outcomes. CONCLUSIONS: This study documents significant behavioral teratogenic effects of fetal cocaine exposure on attentional abilities underlying auditory comprehension skills considered to be precursors of receptive language. Pediatricians are in a unique position to monitor early development of cocaine-exposed infants and make timely referrals for intervention.

Placental lesions associated with abnormal growth in twins.

Abnormal growth in one or both twins may contribute to the increased morbidity and mortality observed in twin gestation. Our objective in this retrospective study of all twin pregnancies delivered at our hospital (n = 240) over a 2-year period was to study the relationship between placental lesions and abnormal growth. Standardized placental examinations were performed in 192 cases (80%), which constituted the study population. Two growth abnormalities were studied: discordant growth as defined by > 15% difference in birth weight and small-for-gestational-age (SGA) birth as defined by birth weight less-than the 10th percentile for gestational age. The majority of twin pregnancies with either discordant growth (41/57 cases) or SGA birth (26/35 cases) had dichorionic placentas. In monochorionic placentas studied by injection there was no significant relationship between vascular anastomoses and discordant growth. Placental weight for small discordant and SGA twins was equivalent or increased relative to infant weight, a pattern not suggestive of maternal vascular underperfusion. Eight lesions, five considered to represent chronic placental disease and three considered to represent intrauterine adaptation, were studied as possible predictors of abnormal growth. The overall prevalence of these lesions in twin placentas was less than that seen in singleton births. Concordance between twin placentas for most lesions was higher than would be expected, based on their prevalence in singleton placentas. Two lesions were associated with discordant growth in both univariate and multivariate analyses: peripheral cord insertion (OR 3.6, 95% CI 1.7-7.6) and avascular villi (AV; OR 3.2, 95% CI 1.0-10.3). Three placental lesions were associated with SGA infants at the univariate level: peripheral cord insertion, avascular villi, and maternal vascular underperfusion. Only peripheral cord insertion (OR 9.8, 95% CI 4.1-23.4) and AV (OR 3.7, CI 1.0-13.7) were significant in the multivariate analysis. The relative increase in peripheral cord insertion and AV with abnormal growth was observed for both monochorionic and dichorionic placentas. Subgroups of discordant infants with and without SGA were both associated with peripheral cord insertion while only those with SGA had an increase in AV. Both peripheral cord insertion and AV were increased in the subgroup with SGA but no discordancy. In summary, two placental lesions, peripheral cord insertion indicating a spatially limited intrauterine compartment and AV indicating occlusion of fetal vessels in the placenta, were associated with abnormal growth in twins.

Neurobehavioral outcomes of cocaine-exposed infants.

The present study investigated the neurobehavioral outcomes of fetal cocaine exposure. Attempts were made to control, by design or statistical analysis, for significant confounders. Timing and amount of drug exposures were considered, and biologic measures of exposure were quantified to classify exposure severity. One hundred sixty-one non-cocaine and 158 cocaine-exposed (82 heavily and 76 lightly exposed) infants were seen at a mean-corrected age of 43 weeks post-conception and administered the Neurobehavioral Assessment (NB Assessment). Heavily cocaine-exposed infants had more jitteriness and attentional problems than lightly and non-exposed infants. They also had more movement and tone abnormalities, and sensory asymmetries than non-exposed infants. Heavily exposed infants were more likely to be identified with an abnormality than non-exposed infants and there was a trend toward heavily exposed infants being more likely to be identified with an abnormality than lightly exposed infants. Furthermore, there was a trend for heavily exposed infants to be less likely to be testable than non-exposed infants. After the confounding and mediating factors were considered, heavily cocaine-exposed infants were four times as likely to be jittery and nearly twice as likely to demonstrate any abnormality than lightly and non-exposed infants, but all other effects were no longer significant. Higher concentrations of the cocaine metabolites of cocaine, cocaethylene, and benzoylecgonine (BZE) were related to higher incidence of movement and tone abnormalities, jitteriness, and presence of any abnormality. Higher cocaethylene levels were related to attentional abnormalities and higher meta-hydroxybenzoylecgonine (m-OH-BZE) was related to jitteriness. Drug effects on attention were mediated by maternal psychological distress, suggesting that this factor should be considered in future studies of drug exposure effects.

Imaging evaluation of suspected appendicitis in a pediatric population: effectiveness of sonography versus CT.

OBJECTIVE: The purpose of this study was to compare the diagnostic accuracy of graded compression sonography with that of helical CT for the diagnosis of appendicitis in a pediatric and young adult population. SUBJECTS AND METHODS: Between June 1996 and April 1999, 386 pediatric and young adult patients with suspected appendicitis were examined using sonography, CT, or both: 233 underwent sonography only, 71 underwent CT only, and 82 underwent sonography and CT. All sonograms and CT scans were prospectively interpreted as showing positive or negative findings for appendicitis by one of six pediatric radiologists. CT and sonographic findings were correlated with surgical and histopathologic findings or findings at clinical follow-up. RESULTS: Helical CT had a significantly higher sensitivity (95% versus 78%, p = 0.009) and accuracy (94% versus 89%, p = 0.05) than graded compression sonography for the diagnosis of appendicitis in children, adolescents, and young adults. The specificity of both techniques was 93%. Twenty of 82 patients who underwent both sonography and CT had discordance between the findings of the two examinations. The CT results were correct in a significantly greater number of patients with discordant examinations (17/20 patients [85%]). CONCLUSION: Helical CT has a significantly higher sensitivity and accuracy than graded compression sonography for the diagnosis of appendicitis in a pediatric and young adult population, particularly in children more than 10 years old.

Ethyl linoleate in meconium: a biomarker for prenatal ethanol exposure.

BACKGROUND: Fetal alcohol syndrome, fetal alcohol effects, alcohol-related neurodevelopmental disorder, and alcohol-related birth defects, all terms referring to the spectrum of consequences of in utero exposure to ethanol, are a major public health burden. There is currently no laboratory test to identify newborns exposed to ethanol in utero. Meconium was analyzed for ethyl linoleate, a metabolite of ethanol, as a biological marker for fetal ethanol exposure. METHODS: Samples of meconium were obtained from 248 infants and analyzed for fatty acid ethyl esters. Detailed maternal alcohol, tobacco, and drug use histories were obtained within 1 month of giving birth. RESULTS: The detection of ethyl linoleate in meconium was called a positive test. The mean number of drinks reported per week in the month before pregnancy, the first trimester, and overall were significantly higher in the positive group (unadjusted: 9.2 +/- 1.9 vs. 4.3 +/- 1.4, p = 0.004; 7.3 +/- 1.7 vs. 3.8 +/- 1.2, p = 0.03; and 6.1 +/- 1.3 vs. 3.0 +/- 1.0, p = 0.006). A positive test was not associated with marijuana, cocaine, or tobacco use. Sensitivity and specificity of the test were 72% and 51% to distinguish women who reported 1 or more drinks/week in the third trimester from women who denied use, and 68% and 48% to distinguish women who used > or =1 drink/week from women who used <1 drink/week in the month before pregnancy. CONCLUSIONS: The presence of ethyl linoleate in meconium is the first reported biological marker for maternal ethanol use during pregnancy. Because of the inherent inaccuracy associated with the use of self-reporting, the establishment of true values of sensitivity and specificity will require validation where the presence, quantity, and timing of exposure to alcohol is known. Further validation of this marker will permit identification and intervention of at-risk infants.

Factors that predict preexisting colonization with antibiotic-resistant gram-negative bacilli in patients admitted to a pediatric intensive care unit.

OBJECTIVE: To predict which patients hospitalized in a pediatric intensive care unit (ICU) are colonized with antibiotic-resistant gram-negative rods on admission. METHODS: Consecutive children admitted to a pediatric ICU over a 6-month period were entered into the study. A questionnaire soliciting information regarding the child's medical history and home environment was completed by the parent or guardian. Nasopharyngeal and rectal cultures were obtained on each of the first 3 days of ICU admission, and organisms resistant to ceftazidime or tobramycin were identified. Only clonally distinct organisms, as confirmed by pulsed field gel electrophoresis, were analyzed. The association between identification of colonization with an antibiotic-resistant gram-negative rod within 3 days of ICU admission and factors included in the questionnaire was tested by chi2 or t test. RESULTS. In 64 (8.8%) of 727 admissions, an antibiotic-resistant gram-negative bacillus was isolated within the first 3 ICU days. More than half were identified on the day of admission. Colonization was associated with two factors related to the patient's medical history, namely, number of past ICU admissions (1.98 vs.87) and administration of intravenous antibiotics within the past 12 months (67.9% vs 28.2%). No association was found between colonization and exposure to oral antibiotics. In addition, factors related to the child's environment were also associated with presumed importation of an antibiotic-resistant gram-negative rod into the ICU. Specifically, residence in a chronic care facility was strongly associated with colonization (28.3% vs 2.6%); exposure to a household contact who had been hospitalized in the past 12 months also predicted colonization (41.7% vs 18.5%). CONCLUSIONS: These data suggest that a profile can be established characterizing children colonized with resistant gram-negative bacilli before admission to a pediatric ICU. Infection control measures may help to contain these potentially dangerous bacteria once they have been introduced into the unit.

Maternal psychological distress and parenting stress after the birth of a very low-birth-weight infant.

CONTEXT: Few studies document how parents adapt to the experience of a very low-birth-weight (VLBW; <1500 g) birth despite societal concerns about the ethics and justification of intensive care for these infants. OBJECTIVE: To determine the degree and type of stress experienced over time by mothers whose infants vary in degree of prematurity and medical and developmental risk. DESIGN: Longitudinal prospective follow-up study of a cohort of mothers of high- and low-risk VLBW and term infants from birth to 3 years. SETTING: All level III neonatal intensive care units from a large midwestern metropolitan region. PARTICIPANTS: Mothers and infants prospectively and consecutively enrolled in a longitudinal study between 1989 and 1991. High-risk VLBW infants were diagnosed as having bronchopulmonary dysplasia, and comparison groups were low-risk VLBW infants without bronchopulmonary dysplasia and term infants (>36 weeks, >2500 g). MAIN OUTCOME MEASURES: Standardized, normative self-report measures of maternal psychological distress, parenting stress, family impact, and life stressors. RESULTS: Mothers of VLBW infants (high risk, n = 122; low risk, n = 84) had more psychological distress than mothers of term infants (n=123) at 1 month (13% vs 1%; P = .003). At 2 years, mothers of low-risk VLBW infants did not differ from term mothers, while mothers of high-risk infants continued to report psychological distress. By 3 years, mothers of high-risk VLBW children did not differ from mothers of term children in distress symptoms, while parenting stress remained greater. Severity of maternal depression was related to lower child developmental outcomes in both VLBW groups. CONCLUSIONS: The impact of VLBW birth varies with child medical risk status, age, and developmental outcome. Follow-up programs should incorporate psychological screening and support services for mothers of VLBW infants in the immediate postnatal period, with monitoring of mothers of high-risk VLBW infants.

Motor development of cocaine-exposed children at age two years.

OBJECTIVE: This article was designed to investigate effects of prenatal cocaine exposure on motor development of young children from a predominately underprivileged, urban population. METHODOLOGY: A total of 260 infants and young children were initially recruited from either the newborn nursery or the at-risk pediatric clinic of an urban teaching hospital. Prenatal history and birth outcomes were collected from medical records. Demographic characteristics and additional drug histories were obtained from the mothers. The 199 subjects (98 cocaine-exposed and 101 unexposed) who returned at age 2 years were assessed by examiners blinded to drug exposure status using the Peabody Developmental Motor Scales. RESULTS: Compared with control subjects, the cocaine-exposed group performed significantly less well on both the fine and the gross motor development indices. Mean scores for both groups were within the average range on the gross motor index, but greater than 1 standard deviation below average on the fine motor index. Differences were significant on the balance and the receipt and propulsion subscales of the gross motor scale, and on the hand use and the eye-hand coordination subscales of the fine motor scale. Cocaine status independently predicted poorer hand use and eye-hand coordination scores. There also was an effect of alcohol exposure on the receipt and propulsion subscale. CONCLUSIONS: Findings indicate that deficiencies in motor development remain detectable at 2 years of age in children exposed to drugs prenatally. Although other environmental variables may influence motor development, children exposed to cocaine and to alcohol in utero may encounter developmental challenges that impede later achievement.

Hemodynamic and fibrinolytic consequences of intermittent pneumatic compression: preliminary results.

OBJECTIVE: To elucidate the time course and magnitude of hemodynamic and fibrinolytic changes associated with sequential gradient intermittent pneumatic compression (SGIPC). DESIGN: Two-phase, intervention and response investigation in normal volunteers. MATERIALS AND METHODS: Subjects were assigned to control (phase I) or compression (phase II) groups. Serial blood samples were obtained via femoral venous catheters for tissue plasminogen activator (tPA), plasminogen activator inhibitor (PAI-1), tPA-PAI-1 complex (tPA-PAI), and euglobulin lysis time (ELT) from all subjects and for fibrin degradation products (FbDP) and fibrinogen degradation products (FgDP) from phase II subjects. Duplex venous scanning was carried out on phase II subjects before and during SGIPC. RESULTS: Catheter placement caused elevations in PAI-1 and tPA-PAI, which stabilized within 4 hours of catheter insertion. In phase II, SGIPC induced significant increases in FbDP, FgDP, and tPA-PAI and decreases in ELT and PAI-1, all of which quickly reverted to baseline on termination of compression. Femoral venous blood flow increased by more than 100% with SGIPC. CONCLUSIONS: Sequential gradient intermittent pneumatic compression induces prompt, but short-lived, alterations in both fibrinolytic and hemodynamic function. Noncontinuous SGIPC may result in suboptimal thromboembolic prophylaxis.

An expanded scoring system including an index of nutritional status for patients with cystic fibrosis.

Evaluation of success or failure of therapy for patients with cystic fibrosis (CF) commonly relies on the results of a single pulmonary function test (PFT). Most PFT measurements reflect different functional aspects of the lung. Although no single parameter can summarize all aspects of lung function, a combination of several may provide an advantage by reflecting the overall abnormality of lung function in one number. Cropp et al. (1982, Am Rev Respir Dis 126:211-216) developed a multiparameter pulmonary function score (PFS) using the results of six separate parameters obtained from a PFT. In CF, there is also the potential for declining nutritional status (NS), leading to malnutrition and skeletal muscle wasting. Our aim was to expand the PFS by including weighted information on NS, and to determine whether the expanded score (nutritional-pulmonary function score, NPFS) was more sensitive in detecting change in outcome variables than the PFS. Individual PFT parameters, percent ideal body weight (%IBW), and an index of anaerobic performance (AP) were measured in 21 patients on admission to the hospital and again at discharge. In the group as a whole, in-hospital therapy resulted in improvement (P < 0.01) in individual PFT parameters, %IBW, PFS, and NPFS, and no change in AP. While the PFS more effectively reflected improvement in lung function than did any single PFT parameter, the NPFS resulted in an even more sensitive index of change. Based on these results, we believe that the NPFS, which includes both lung and nutritional status, provides an effective and sensitive index of disease severity that can be used as a unifying measure to: 1) detect disease progression; 2) guide rehabilitation and training; 3) stratify patients for clinical trials; or 4) evaluate the effects of a therapeutic intervention.

Schistosomiasis mansoni and paddy-rice growing in Uganda: an emerging new problem.

In Eastern Uganda, paddy-rice growing, which has only become popular in recent years, seems to be associated with the emergence of schistosomiasis mansoni as a new problem in public health. To estimate the magnitude of this problem, a cross-sectional, baseline survey was carried out in six villages of the Kibimba Rice Scheme. The overall prevalence of Schistosoma mansoni infection was found to be 20%. The highest prevalences and intensities of infection were seen in those aged 5-29 years, with more males infected than females. An attempt was then made to identify the important factors in the aetiology of S. mansoni in this area. Odds ratios indicated that working regularly in the rice paddies, fishing with baskets, and being male were statistically associated with an increased risk of S. mansoni infection. It is clear that schistosomiasis mansoni which is emerging as a new health problem in the study area is closely linked to working in the rice paddies. Encouraging the rice farmers to wear knee-high, waterproof boots while in the fields may help control the disease.