Rachel G. Greenberg

Traumatic Lumbar Punctures in Neonates: Test Performance of the Cerebrospinal Fluid White Blood Cell Count

Background: Cerebrospinal fluid (CSF) findings are often used to diagnose meningitis in neonates given antibiotics before the lumbar puncture is performed. Traumatic lumbar punctures are common and complicate interpretation of CSF white blood cell counts. The purpose of this study is to evaluate the diagnostic utility of adjusting CSF white blood cell counts based on CSF and peripheral red blood cell counts. Methods: Cohort study of lumbar punctures performed between 1997 and 2004 at 150 neonatal intensive care units managed by the Pediatrix Medical group. Traumatic lumbar punctures were defined as CSF specimens with ≥500 red blood cells/mm3. CSF white blood cell counts were adjusted downward for traumatic lumbar punctures using several commonly used methods. We calculated sensitivity, specificity, likelihood ratios, and area under the receiver operating characteristic curve of unadjusted and adjusted CSF white blood cell counts for predicting meningitis in neonates with traumatic lumbar punctures. Results: Of 6374 lumbar punctures, 2519 (39.5%) were traumatic. 114/6374 (1.8%) were positive for meningitis; 50 neonates with traumatic lumbar punctures had meningitis. The areas under the receiver operating characteristic curve for white blood cell count unadjusted and adjusted by all methods were similar. Conclusions: Adjustment of CSF white blood cell counts to account for increased red cells does not improve diagnostic utility. Adjustment can result in loss of sensitivity with marginal gain in specificity. Adjustment of WBC counts in the setting of a traumatic lumbar puncture does not aid in the diagnosis of bacterial and fungal meningitis in neonates.

Vasopressin for Refractory Hypotension in Extremely Low Birth Weight Infants

Intravenous vasopressin at 0.01 to 0.04 units/kg/h increased median mean blood pressure from 26 mm Hg (range 18-44) to 41 mm Hg (range 17-90) by 12 hours of infusion (P=.002) and allowed weaning of catecholamines in a group of extremely low birth weight infants with refractory hypotension.

Effect of Catheter Dwell Time on Risk of Central Line–Associated Bloodstream Infection in Infants

BACKGROUND AND OBJECTIVE: Central venous catheters in the NICU are associated with significant morbidity and mortality because of the risk of central line–associated bloodstream infections (CLABSIs). The purpose of this study was to determine the effect of catheter dwell time on risk of CLABSI. METHODS: Retrospective cohort study of 13 327 infants with 15 567 catheters (93% peripherally inserted central catheters [PICCs], 7% tunneled catheters) and 256 088 catheter days cared for in 141 NICUs. CLABSI was defined using National Health Surveillance Network criteria. We defined dwell time as the number of days from line insertion until either line removal or day of CLABSI. We generated survival curves for each week of dwell time and estimated hazard ratios for CLABSI at each week by using a Cox proportional hazards frailty model. We controlled for postmenstrual age and year, included facility as a random effect, and generated separate models by line type. RESULTS: Median postmenstrual age was 29 weeks (interquartile range 26–33). The overall incidence of CLABSI was 0.93 per 1000 catheter days. Increased dwell time was not associated with increased risk of CLABSI for PICCs. For tunneled catheters, infection incidence was significantly higher in weeks 7 and 9 compared with week 1. CONCLUSIONS: Clinicians should not routinely replace uninfected PICCs for fear of infection but should consider removing tunneled catheters before week 7 if no longer needed. Additional studies are needed to determine what daily maintenance practices may be associated with decreased risk of infection, especially for tunneled catheters.

Repeat lumbar punctures in infants with meningitis in the neonatal intensive care unit

Objective:The purpose of this study is to examine the results of repeat lumbar puncture in infants with initial positive cerebrospinal fluid (CSF) cultures in order to determine the clinical characteristics and outcomes of infants with repeat positive cultures.Study Design:Cohort study of infants with an initial positive CSF culture undergoing repeat lumbar puncture between 1997 and 2004 at 150 neonatal intensive care units managed by the Pediatrix Medical group. We compared the clinical outcomes of infants with repeat positive cultures and infants with repeat negative cultures.Result:We identified 118 infants with repeat CSF cultures. Of these, 26 infants had repeat positive cultures. A higher proportion with repeat positive cultures died compared with those with repeat negative cultures, 6/23 (26%) vs. 6/81 (7%), respectively (P=0.02).Conclusion:Among infants with a positive CSF culture, a repeat positive CSF culture is common. The presence of a second positive culture is associated with increased mortality.

Outcomes of catheter-associated infections in pediatric patients with short bowel syndrome.

Children with short bowel syndrome requiring long-term total parenteral nutrition are at high risk for catheter-associated infections. The optimal management of catheter infections in this patient population is unknown. We conducted a retrospective observational study in children with short bowel syndrome to compare outcomes of catheter-associated infections treated with catheter removal plus antibiotic therapy versus antibiotic therapy alone.

Neonatal candidiasis: diagnosis, prevention, and treatment.

Infection with Candida species is associated with significant morbidity and mortality in infants. The incidence of Candida infection varies widely across centers, likely due to differences in practice related to modifiable risk factors such as exposure to empiric antibiotics and length of parenteral nutrition. Early diagnosis of Candida and prompt treatment with appropriate antifungal agents, such as fluconazole, amphotericin B deoxycholate, and micafungin, are critical for improved outcomes. This paper reviews the current literature relating to the prevention, diagnosis, and treatment of Candida infections in the neonatal intensive care unit.

Late-onset Sepsis in Extremely Premature Infants: 2000–2011

Background: Late-onset sepsis (LOS) is an important cause of death and neurodevelopmental impairment in premature infants. The purpose of this study was to assess overall incidence of LOS, distribution of LOS-causative organisms and center variation in incidence of LOS for extremely premature infants over time. Methods: In a retrospective analysis of infants 401–1000 g birth weight and 22–28 6/7 weeks of gestational age born at 12 National Institute of Child Health and Human Development Neonatal Research Network centers in the years 2000–2005 (era 1) or 2006–2011 (era 2) who survived >72 hours, we compared the incidence of LOS and pathogen distribution in the 2 eras using the &khgr;2 test. We also examined the effect of birth year on the incidence of LOS using multivariable regression to adjust for nonmodifiable risk factors and for center. To assess whether the incidence of LOS was different among centers in era 2, we used a multivariable regression model to adjust for nonmodifiable risk factors. Results: Ten-thousand one-hundred thirty-one infants were studied. LOS occurred in 2083 of 5031 (41%) infants in era 1 and 1728 of 5100 (34%) infants in era 2 (P < 0.001). Birth year was a significant predictor of LOS on adjusted analysis, with birth years 2000–2009 having a significantly higher odds of LOS than the reference year 2011. Pathogens did not differ, with the exception of decreased fungal infection (P < 0.001). In era 2, 9 centers had significantly higher odds of LOS compared with the center with the lowest incidence. Conclusions: The incidence of LOS decreased over time. Further investigation is warranted to determine which interventions have the greatest impact on infection rates.

Therapeutic Index Estimation of Antiepileptic Drugs: A Systematic Literature Review Approach.

ObjectivesOur study aimed to determine whether data obtained from the medical literature can be used to estimate the therapeutic index of 5 antiepileptic drugs (AEDs): carbamazepine, lamotrigine, phenobarbital, phenytoin, and valproate. MethodsWe performed a literature search using PubMed and EMBASE to collect published safety, efficacy, and therapeutic monitoring data for 5 AEDs and extracted all relevant information into a drug- and study-specific drug database. For each AED, we summarized (1) type, severity, and incidence of toxicity-related adverse events and toxicity-associated range of drug doses or concentrations; (2) effective versus toxic concentration and dose (therapeutic range); and (3) therapeutic drug monitoring practices. We defined therapeutic index as the ratio of the minimum toxic concentration to the minimum effective concentration. ResultsWe reviewed a total of 810 full-text articles and extracted data from 163. The literature suggests that the therapeutic index of phenytoin is 2. The therapeutic indices of phenobarbital and valproate exceed 2. There were insufficient data to precisely quantify the therapeutic indices of carbamazepine and lamotrigine. ConclusionsFor some drugs, this approach offers a low-cost method of therapeutic index estimation. Our results can serve as preliminary data for future trials and as guidance for US Food and Drug Administration decision making regarding narrow therapeutic index classification.

Risk factors for group B streptococcal disease in neonates of mothers with negative antenatal testing

Objective:The aim of this study was to identify risk factors for early-onset group B Streptococcus (EOGBS) disease in neonates of mothers with negative antenatal screening.Study Design:We performed a retrospective cohort study of neonates born to mothers with negative antenatal GBS screening between 2002 and 2012. Our primary outcome was EOGBS infection. We used multivariable logistic regression to assess factors associated with EOGBS.Results:EOGBS was confirmed in 492 of the 179 818 neonates that met the study inclusion criteria. Risk factors for EOGBS included black race (reference: white, odds ratio (OR) =1.81 (95% confidence interval: 1.43, 2.31)), maternal age <18 years (reference: >35 years, OR=2.63 (1.54, 4.51)) and maternal age 18 to 35 years (reference: >35 years, OR=1.94 (1.30, 2.88)).Conclusion:Maternal age <18 years and black race were the strongest predictors of EOGBS. Further research investigating contributors to the discordance between screening results and neonatal outcomes in these populations is needed.

Dosing antibiotics in neonates: review of the pharmacokinetic data

Antibiotics are often used in neonates despite the absence of relevant dosing information in drug labels. For neonatal dosing, clinicians must extrapolate data from studies for adults and older children, who have strikingly different physiologies. As a result, dosing extrapolation can lead to increased toxicity or efficacy failures in neonates. Driven by these differences and recent legislation mandating the study of drugs in children and neonates, an increasing number of pharmacokinetic studies of antibiotics are being performed in neonates. These studies have led to new dosing recommendations with particular consideration for neonate body size and maturation. Herein, we highlight the available pharmacokinetic data for commonly used systemic antibiotics in neonates.