Pablo J Sánchez

The Ohio State University, Columbus, Ohio, United States

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Publications (137)889.92 Total impact

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    ABSTRACT: Background: Current guidelines for prevention of neonatal group B streptococcal disease recommend diagnostic evaluations and empirical antibiotic therapy for well-appearing, chorioamnionitis-exposed newborns. Some clinicians question these recommendations, citing the decline in early-onset group B streptococcal disease rates since widespread intrapartum antibiotic prophylaxis implementation and potential antibiotic risks. We aimed to determine whether chorioamnionitis-exposed newborns with culture-confirmed, early-onset infections can be asymptomatic at birth. Methods: Multicenter, prospective surveillance for early-onset neonatal infections was conducted during 2006-2009. Early-onset infection was defined as isolation of a pathogen from blood or cerebrospinal fluid collected ≤72 hours after birth. Maternal chorioamnionitis was defined by clinical diagnosis in the medical record or by histologic diagnosis by placental pathology. Hospital records of newborns with early-onset infections born to mothers with chorioamnionitis were reviewed retrospectively to determine symptom onset. Results: Early-onset infections were diagnosed in 389 of 396 586 live births, including 232 (60%) chorioamnionitis-exposed newborns. Records for 229 were reviewed; 29 (13%) had no documented symptoms within 6 hours of birth, including 21 (9%) who remained asymptomatic at 72 hours. Intrapartum antibiotic prophylaxis exposure did not differ significantly between asymptomatic and symptomatic infants (76% vs 69%; P = .52). Assuming complete guideline implementation, we estimated that 60 to 1400 newborns would receive diagnostic evaluations and antibiotics for each infected asymptomatic newborn, depending on chorioamnionitis prevalence. Conclusions: Some infants born to mothers with chorioamnionitis may have no signs of sepsis at birth despite having culture-confirmed infections. Implementation of current clinical guidelines may result in early diagnosis, but large numbers of uninfected asymptomatic infants would be treated.
    No preview · Article · Dec 2015 · PEDIATRICS
  • Joseph B Cantey · Andrea Ronchi · Pablo J Sánchez

    No preview · Article · Oct 2015
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    ABSTRACT: Importance: Extremely preterm infants contribute disproportionately to neonatal morbidity and mortality. Objective: To review 20-year trends in maternal/neonatal care, complications, and mortality among extremely preterm infants born at Neonatal Research Network centers. Design, setting, participants: Prospective registry of 34 636 infants, 22 to 28 weeks' gestation, birth weight of 401 to 1500 g, and born at 26 network centers between 1993 and 2012. Exposures: Extremely preterm birth. Main outcomes and measures: Maternal/neonatal care, morbidities, and survival. Major morbidities, reported for infants who survived more than 12 hours, were severe necrotizing enterocolitis, infection, bronchopulmonary dysplasia, severe intracranial hemorrhage, cystic periventricular leukomalacia, and/or severe retinopathy of prematurity. Regression models assessed yearly changes and were adjusted for study center, race/ethnicity, gestational age, birth weight for gestational age, and sex. Results: Use of antenatal corticosteroids increased from 1993 to 2012 (24% [348 of 1431 infants]) to 87% (1674 of 1919 infants]; P < .001), as did cesarean delivery (44% [625 of 1431 births] to 64% [1227 of 1921]; P < .001). Delivery room intubation decreased from 80% (1144 of 1433 infants) in 1993 to 65% (1253 of 1922) in 2012 (P < .001). After increasing in the 1990s, postnatal steroid use declined to 8% (141 of 1757 infants) in 2004 (P < .001), with no significant change thereafter. Although most infants were ventilated, continuous positive airway pressure without ventilation increased from 7% (120 of 1666 infants) in 2002 to 11% (190 of 1756 infants) in 2012 (P < .001). Despite no improvement from 1993 to 2004, rates of late-onset sepsis declined between 2005 and 2012 for infants of each gestational age (median, 26 weeks [37% {109 of 296} to 27% {85 of 320}]; adjusted relative risk [RR], 0.93 [95% CI, 0.92-0.94]). Rates of other morbidities declined, but bronchopulmonary dysplasia increased between 2009 and 2012 for infants at 26 to 27 weeks' gestation (26 weeks, 50% [130 of 258] to 55% [164 of 297]; P < .001). Survival increased between 2009 and 2012 for infants at 23 weeks' gestation (27% [41 of 152] to 33% [50 of 150]; adjusted RR, 1.09 [95% CI, 1.05-1.14]) and 24 weeks (63% [156 of 248] to 65% [174 of 269]; adjusted RR, 1.05 [95% CI, 1.03-1.07]), with smaller relative increases for infants at 25 and 27 weeks' gestation, and no change for infants at 22, 26, and 28 weeks' gestation. Survival without major morbidity increased approximately 2% per year for infants at 25 to 28 weeks' gestation, with no change for infants at 22 to 24 weeks' gestation. Conclusions and relevance: Among extremely preterm infants born at US academic centers over the last 20 years, changes in maternal and infant care practices and modest reductions in several morbidities were observed, although bronchopulmonary dysplasia increased. Survival increased most markedly for infants born at 23 and 24 weeks' gestation and survival without major morbidity increased for infants aged 25 to 28 weeks. These findings may be valuable in counseling families and developing novel interventions. Trial registration: clinicaltrials.gov Identifier: NCT00063063.
    Full-text · Article · Sep 2015 · JAMA The Journal of the American Medical Association
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    ABSTRACT: Congenital CMV infection is traditionally diagnosed byvirus detection in saliva or urine. Virus culture was positive in significantly fewer urine samples collected using cotton balls in diapers (54.2%) than with samples collected by bags (95.7%) from newborns screened positive for CMV in saliva. However, PCR was positive in 95% of urine samples regardless of the collection method.
    No preview · Article · May 2015 · The Pediatric Infectious Disease Journal
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    ABSTRACT: As part of the CMV and Hearing Multicenter Screening (CHIMES) study, 72,239 newborns were screened for cytomegalovirus by rapid culture and real-time PCR of saliva samples. Of the 266 infants with congenital cytomegalovirus infection, discordance between rapid culture and PCR was observed in 14 children, and 13 were identified only by PCR, demonstrating the superiority of the PCR assay.
    No preview · Article · May 2015 · The Pediatric Infectious Disease Journal
  • Eduardo Lopez-Medina · Joseph B. Cantey · Pablo J. Sánchez
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    ABSTRACT: This retrospective study characterized the clinical course of 13 neonates who died with herpes simplex virus infection from 2001 to 2011, representing a 26% case-fatality rate. Fatal disease developed at ≤48 hours of age in one-third of infants, was mostly disseminated disease, and occurred despite early administration of high-dose acyclovir therapy. Copyright © 2015 Elsevier Inc. All rights reserved.
    No preview · Article · Apr 2015 · The Journal of pediatrics
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    ABSTRACT: Background We previously reported on the overall incidence, management, and outcomes in infants with cardiovascular insufficiency (CVI). However, there are limited data on the relationship of the specific different definitions of CVI to short-term outcomes in term and late preterm newborn infants. Objective This study aims to evaluate how four definitions of CVI relate to short-term outcomes and death. Study Design The previously reported study was a multicenter, prospective cohort study of 647 infants ≥ 34 weeks gestation admitted to a Neonatal Research Network (NRN) newborn intensive care unit (NICU) and mechanically ventilated (MV) during their first 72 hours. The relationship of five short-term outcomes at discharge and four different definitions of CVI were further analyzed. Results All the four definitions were associated with greater number of days on MV and days on O2. The definition using a threshold blood pressure (BP) measurement alone was not associated with days of full feeding, days in the NICU or death. The definition based on the treatment of CVI was associated with all the outcomes including death. Conclusions The definition using a threshold BP alone was not consistently associated with adverse short-term outcomes. Using only a threshold BP to determine therapy may not improve outcomes. Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.
    No preview · Article · Mar 2015 · American Journal of Perinatology
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    ABSTRACT: The treatment of symptomatic congenital cytomegalovirus (CMV) disease with intravenous ganciclovir for 6 weeks has been shown to improve audiologic outcomes at 6 months, but the benefits wane over time. We conducted a randomized, placebo-controlled trial of valganciclovir therapy in neonates with symptomatic congenital CMV disease, comparing 6 months of therapy with 6 weeks of therapy. The primary end point was the change in hearing in the better ear ("best-ear" hearing) from baseline to 6 months. Secondary end points included the change in hearing from baseline to follow-up at 12 and 24 months and neurodevelopmental outcomes, with each end point adjusted for central nervous system involvement at baseline. A total of 96 neonates underwent randomization, of whom 86 had follow-up data at 6 months that could be evaluated. Best-ear hearing at 6 months was similar in the 6-month group and the 6-week group (2 and 3 participants, respectively, had improvement; 36 and 37 had no change; and 5 and 3 had worsening; P=0.41). Total-ear hearing (hearing in one or both ears that could be evaluated) was more likely to be improved or to remain normal at 12 months in the 6-month group than in the 6-week group (73% vs. 57%, P=0.01). The benefit in total-ear hearing was maintained at 24 months (77% vs. 64%, P=0.04). At 24 months, the 6-month group, as compared with the 6-week group, had better neurodevelopmental scores on the Bayley Scales of Infant and Toddler Development, third edition, on the language-composite component (P=0.004) and on the receptive-communication scale (P=0.003). Grade 3 or 4 neutropenia occurred in 19% of the participants during the first 6 weeks. During the next 4.5 months of the study, grade 3 or 4 neutropenia occurred in 21% of the participants in the 6-month group and in 27% of those in the 6-week group (P=0.64). Treating symptomatic congenital CMV disease with valganciclovir for 6 months, as compared with 6 weeks, did not improve hearing in the short term but appeared to improve hearing and developmental outcomes modestly in the longer term. (Funded by the National Institute of Allergy and Infectious Diseases; ClinicalTrials.gov number, NCT00466817.).
    Full-text · Article · Mar 2015 · New England Journal of Medicine
  • Joseph B Cantey · Alan M Klein · Pablo J Sánchez
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    ABSTRACT: Polymerase chain reaction testing of blood for herpes simplex virus (HSV) is recommended for newborns delivered to mothers with active genital HSV lesions at delivery. We report an infant who had a positive blood HSV polymerase chain reaction test before the onset of clinical signs of HSV disease. Copyright © 2015 Elsevier Inc. All rights reserved.
    No preview · Article · Feb 2015 · Journal of Pediatrics
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    ABSTRACT: Understanding the causes and timing of death in extremely premature infants may guide research efforts and inform the counseling of families. We analyzed prospectively collected data on 6075 deaths among 22,248 live births, with gestational ages of 22 0/7 to 28 6/7 weeks, among infants born in study hospitals within the National Institute of Child Health and Human Development Neonatal Research Network. We compared overall and cause-specific in-hospital mortality across three periods from 2000 through 2011, with adjustment for baseline differences. The number of deaths per 1000 live births was 275 (95% confidence interval [CI], 264 to 285) from 2000 through 2003 and 285 (95% CI, 275 to 295) from 2004 through 2007; the number decreased to 258 (95% CI, 248 to 268) in the 2008-2011 period (P=0.003 for the comparison across three periods). There were fewer pulmonary-related deaths attributed to the respiratory distress syndrome and bronchopulmonary dysplasia in 2008-2011 than in 2000-2003 and 2004-2007 (68 [95% CI, 63 to 74] vs. 83 [95% CI, 77 to 90] and 84 [95% CI, 78 to 90] per 1000 live births, respectively; P=0.002). Similarly, in 2008-2011, as compared with 2000-2003, there were decreases in deaths attributed to immaturity (P=0.05) and deaths complicated by infection (P=0.04) or central nervous system injury (P<0.001); however, there were increases in deaths attributed to necrotizing enterocolitis (30 [95% CI, 27 to 34] vs. 23 [95% CI, 20 to 27], P=0.03). Overall, 40.4% of deaths occurred within 12 hours after birth, and 17.3% occurred after 28 days. We found that from 2000 through 2011, overall mortality declined among extremely premature infants. Deaths related to pulmonary causes, immaturity, infection, and central nervous system injury decreased, while necrotizing enterocolitis-related deaths increased. (Funded by the National Institutes of Health.).
    Full-text · Article · Jan 2015 · New England Journal of Medicine
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    ABSTRACT: Inhaled nitric oxide (INO), a selective pulmonary vasodilator, has revolutionized the treatment of neonatal hypoxemic respiratory failure (NHRF). However, there is lack of sustained improvement in 30 to 46% of infants. Aerosolized prostaglandins I2 (PGI2) and E1 (PGE1) have been reported to be effective selective pulmonary vasodilators. The objective of this study was to evaluate the feasibility of a randomized controlled trial (RCT) of inhaled PGE1 (IPGE1) in NHRF. Two pilot multicenter phase II RCTs are included in this report. In the first pilot, late preterm and term neonates with NHRF, who had an oxygenation index (OI) of >=15 and <25 on two arterial blood gases and had not previously received INO, were randomly assigned to receive two doses of IPGE1 (300 and 150 ng/kg/min) or placebo. The primary outcome was the enrollment of 50 infants in six to nine months at 10 sites. The first pilot was halted after four months for failure to enroll a single infant. The most common cause for non-enrollment was prior initiation of INO. In a re-designed second pilot, co-administration of IPGE1 and INO was permitted. Infants with suboptimal response to INO received either aerosolized saline or IPGE1 at a low (150 ng/kg/min) or high dose (300 ng/kg/min) for a maximum duration of 72 hours. The primary outcome was the recruitment of an adequate number of patients (n = 50) in a nine-month-period, with fewer than 20% protocol violations. No infants were enrolled in the first pilot. Seven patients were enrolled in the second pilot; three in the control, two in the low-dose IPGE1, and two in the high-dose IPGE1 groups. The study was halted for recruitment futility after approximately six months as enrollment targets were not met. No serious adverse events, one minor protocol deviation and one pharmacy protocol violation were reported. These two pilot RCTs failed to recruit adequate eligible newborns with NHRF. Complex management RCTs of novel therapies for persistent pulmonary hypertension of the newborn (PPHN) may require novel study designs and a longer period of time from study approval to commencement of enrollment.Trial registration: ClinicalTrials.gov: Pilot one: NCT number: 00598429 https://clinicaltrials.gov/ct2/show/NCT00598429?term=PGE1&rank=5registered on 10 January 2008. Last updated: 3 February 2011.Pilot two: NCT number: 01467076 https://clinicaltrials.gov/ct2/show/NCT01467076?term=PGE1&rank=717 October 2011. Last updated: 13 February 2013.
    Full-text · Article · Dec 2014 · Trials
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    ABSTRACT: A non-standardized approach to caring for infants after pyloromyotomy for pyloric stenosis was associated with prolonged postoperative length of stay (pLOS) at our institution. We studied the impact of a standardized postoperative care protocol on pLOS, patients' clinical course, and nursing care. A retrospective chart review identified that 27% of infants who underwent uncomplicated pyloromyotomy had prolonged pLOS, defined as more than one postoperative midnight. A comprehensive postoperative care protocol was developed for infants undergoing pyloromyotomy. Patients were recruited prospectively and those with complications were excluded. A sample size of 70 in each cohort (historic and prospective) allowed 80% power to detect a 50% reduction in the proportion of patients with prolonged pLOS (α=0.05). The prospective group and historic cohort were compared using nonparametric statistics. The historic cohort had 70 patients and the prospective cohort had 66. Protocol implementation resulted in fewer patients with prolonged pLOS, shorter time to feeds, fewer feeds to discharge, less emesis, and improved nursing documentation. Implementation of a postoperative care protocol improved various aspects of patient care and nursing care studied. Protocols outline a patient's course and serve as a common platform for communication among care providers; they can facilitate, expedite, and enhance patient care. Copyright © 2014 Elsevier Inc. All rights reserved.
    No preview · Article · Dec 2014 · Journal of Pediatric Surgery
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    ABSTRACT: Objective: Prophylactic indomethacin reduces severe intraventricular hemorrhage but may increase spontaneous intestinal perforation (SIP) in extremely low birth weight (ELBW) infants. Early feedings improve nutritional outcomes but may increase the risk of SIP. Despite their benefits, use of these therapies varies largely by physician preferences in part because of the concern for SIP. Methods: This was a cohort study of 15,751 ELBW infants in the Eunice Kennedy Shriver National Institute of Child Health and Human Development Neonatal Research Network from 1999 to 2010 who survived beyond 12 hours after birth. The risk of SIP was compared between groups of infants with and without exposure to prophylactic indomethacin and early feeding in unadjusted analyses and in analyses adjusted for center and for risks of SIP. Results: Among infants exposed to prophylactic indomethacin, the risk of SIP did not differ between the indomethacin/early-feeding group compared with the indomethacin/no-early-feeding group (adjusted relative risk [RR] 0.74, 95% confidence interval [CI] 0.49-1.11). The risk of SIP was lower in the indomethacin/early-feeding group compared with the no indomethacin/no-early-feeding group (adjusted RR 0.58, 95% CI 0.37-0.90, P = .0159). Among infants not exposed to indomethacin, early feeding was associated with a lower risk of SIP compared with the no early feeding group (adjusted RR 0.53, 95% CI 0.36-0.777, P = .0011). Conclusions: The combined or individual use of prophylactic indomethacin and early feeding was not associated with an increased risk of SIP in ELBW infants.
    No preview · Article · Oct 2014 · Pediatrics
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    ABSTRACT: Background: Congenital CMV infection is a leading cause of sensorineural hearing loss (SNHL) and neurodevelopmental impairment in childhood. Information on CMV detection in cerebrospinal fluid (CSF) and its association with outcomes is limited. The objective of this study was to determine the significance of CMV detection in CSF of infants with congenital CMV infection. Methods: Retrospective review of cases of congenital CMV infection diagnosed at Nationwide Children’s Hospital, Parkland Memorial Hospital/Children’s Medical Center Dallas, and the University of Oklahoma Health Sciences Center from 1996-2014. Diagnosis of congenital CMV was made by culture or PCR from urine or saliva within the first 3 weeks of age. Detection of CMV in CSF was performed by culture or PCR. Clinical, laboratory, radiographic, and audiologic data was reviewed. Infants in whom CMV was detected in CSF were compared to those whose CSF was negative for CMV. Results: Twenty-two infants with congenital CMV infection who had a lumbar puncture performed and CSF tested for CMV were enrolled. All 22 infants had clinically apparent ("symptomatic") disease. 10 (45%) infants had CMV detected in CSF (CSF+) and were compared to the 12 infants whose CSF was CMV-negative (CSF-). The CSF+ infants did not differ from those whose CSF was CMV negative (CMV-) in age at diagnosis (median/range; 1.5 [1-8] vs.1 [1-17]; p>0.05), platelet count (p=0.47), alanine aminotransferase (p=0.11), direct bilirubin concentration (p=0.08), or CSF analyses including white blood cell count (p=0.98), protein content(p=0.39), or glucose concentration (p=0.31). Of the CSF+ infants, 6 (60%) had SNHL, while 10 (83%) CSF- infants had SNHL. Abnormalities on CNS imaging studies, either ultrasound/CT/MRI, were comparable between groups. Conclusion: CMV was frequently detected in CSF of infants with clinically apparent congenital CMV infection. However, its detection was not associated with increased rate of SNHL or neuroimaging abnormalities. Larger studies that incorporate neurodevelopmental assessments are needed to determine the potential role of CSF evaluation in the management of infants with congenital CMV infection.
    No preview · Conference Paper · Oct 2014
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    ABSTRACT: Background: Congenital CMV infection (cCMV) is a common congenital infection and a significant contributor to non-genetic sensorineural hearing loss (SNHL). Real-time PCR of newborn saliva specimens has been shown to be highly sensitive and specific compared to culture based methods for CMV screening. Although both saliva and urine samples are known to be acceptable for identifying infants with cCMV, it is thought that urine samples may contain more virus and thus, are optimal for cCMV screening. The objective is to compare viral load (VL) levels between saliva and urine samples from a large cohort of infants with cCMV infection identified through a newborn screening program. Methods: As part of the NIDCD CHIMES study, newborns at 7 U.S. medical centers were screened for CMV by saliva and dried blood spot PCR. Infants who screened positive were enrolled in a follow-up study to confirm congenital infection by testing saliva and urine samples using a previously described real-time PCR assay. CMV viral load in saliva samples obtained at screening and enrollment was compared to urine collected at enrollment in follow-up. Results: Of the 100,332 newborns screened for CMV from 2007 to 2011, viral load levels in both saliva and urine samples were available in 73% (336/462) of infants with confirmed cCMV. Of these, 36% (121/336) were enrolled within the first 3 weeks of life. The median viral load level in saliva at screening and enrollment (2.x106 IU/ml and 1.1x107 IU/ml, respectively) was significantly higher than in urine (8.3x105 IU/ml; p < 0.0001). There was no significant difference between VL in saliva and urine in infants with and without symptomatic disease and with and without congenital SNHL. In the smaller cohort of infants enrolled within 3 weeks of birth, median saliva VL at screening and enrollment (1.1x106 IU/ml vs. 9.3x106 IU/ml, respectively) was higher than urine VL (7.9x105IU/ml; p < 0.0001) . Conclusion: Infants with congenital CMV infection shed large amounts of virus in both saliva and urine. However, saliva samples contained higher viral load than urine, are easier to collect and do not require DNA extraction. Therefore, we propose that saliva should be considered the ideal specimen and real-time PCR of saliva is appropriate for both newborn screening and diagnosis of cCMV.
    No preview · Conference Paper · Oct 2014
  • Joseph Cantey · Sean Nguyen · Phillip Wozniak · Pablo J. Sanchez
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    ABSTRACT: Background: Prolonged antibiotic therapy among preterm infants in the NICU is associated with adverse outcomes including death and necrotizing enterocolitis. The optimal metric to measure antibiotic use in the NICU and thus guide stewardship efforts is unknown. The purpose of this study was to apply two different metrics of antibiotic use to a large cohort of NICU infants and compare the results. Methods: Prospective collection and analysis of all antibiotics provided to every infant admitted to the NICU at Parkland Memorial Hospital, Dallas during a 14 month period (SCOUT study). Pertinent clinical and outcome data were collected. Two different metrics for determining antibiotic use were calculated for all antibiotics: 1) days of therapy (DOT) and 2) number of calendar days (CD) that the antibiotics were administered. DOT was calculated by dividing the dosing interval by 24 hours, then multiplying by the number of doses, summed for each antibiotic. CD was determined by the number of days in which a dose of an antibiotic was administered. For example, a 6-dose course of q8 hour ampicillin begun Monday evening and completed Wednesday morning would equal 2 DOT (8 ÷ 24 x 6 = 2) and 3 CD (Mon, Tue, Wed = 3). Results: 1521 infants were admitted during the study period; 364 (24%) received no systemic antibiotics and were excluded. 1157 infants (76%) accounted for 19,788 hospital days and received 1439 separate antibiotic courses. The total volume of antibiotic administered was 9394 by DOT and 5915 by CD. Agent-specific antibiotic use by DOT and CD is shown (Table). Antibiotic No. of courses DOT CD % difference All 1439 9394 5915 -37% Gentamicin 1399 4468 4551 2% Ampicillin 1233 3579 4417 31% Oxacillin 181 676 874 23% Vancomycin 41 249 276 11% Piperacillin/tazobactam 36 171 195 14% 1st generation cephalosporins 18 10 23 130% Penicillin 12 69 77 12% 3rd generation cephalosporins 6 10 13 30% Meropenem 5 26 30 14% Metronidazole 4 38 42 11% Other 14 98 115 17% Conclusion: Antibiotic use in the NICU varies substantially by the metric used. When used to describe a course of antibiotics, CD does not account for the number of agents. When used for specific agents, CD overestimates therapy volume by 13% on average. Our ongoing evaluation of which metric best predicts adverse outcomes is important to guide antibiotic stewardship efforts.
    No preview · Conference Paper · Oct 2014
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    ABSTRACT: Background: Neonatal enterovirus sepsis has high mortality. Antiviral therapy is not available. Methods: Neonates with suspected enterovirus sepsis (hepatitis, coagulopathy, and/or myocarditis) with onset at ≤15 days of life were randomized 2:1 to receive oral pleconaril or placebo for 7 days. Serial virologic (oropharynx, rectum, urine, serum), clinical, pharmacokinetic, and safety evaluations were performed. Results: Sixty-one subjects were enrolled (43 treatment, 18 placebo), of whom 43 were confirmed enterovirus infected (31 treatment, 12 placebo). There was no difference in day 5 oropharyngeal culture positivity (primary endpoint; 0% in both groups). However, enterovirus-infected subjects in the treatment group became culture negative from all anatomic sites combined faster than placebo group subjects (median 4.0 versus 7.0 days, P = .08), and fewer subjects in the treatment group remained polymerase chain reaction (PCR)-positive from the oropharynx when last sampled (23% versus 58%, P = .02; median, 14.0 days). By intent to treat, 10/43 (23%) subjects in the treatment group and 8/18 (44%) in the placebo group died (P = .02 for 2-month survival difference); among enterovirus-confirmed subjects, 7/31 (23%) in the treatment group died versus 5/12 (42%) in the placebo group (P = .26). All pleconaril recipients attained concentrations greater than the IC90 after the first study day, but 38% were less than the IC90 during the first day of treatment. One subject in the treatment group and three in the placebo group had treatment-related adverse events. Conclusions: Shorter times to culture and PCR negativity and greater survival among pleconaril recipients support potential efficacy and warrant further evaluation.
    No preview · Conference Paper · Oct 2014
  • Joseph B Cantey · Phillip S Wozniak · Pablo J Sánchez
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    ABSTRACT: Background: Prolonged or unnecessary antibiotic use is associated with adverse outcomes in neonates. Our objectives were to quantify all antibiotic use in a Level-III neonatal intensive care unit and to identify scenarios where their use could be reduced. Methods: Surveillance and evaluation of all antibiotic use provided to every infant admitted to a Level-III neonatal intensive care unit from 10/3/11 to 11/30/12 was performed. Types of antibiotics, reasons for their initiation, discontinuation and duration, as well as clinical, laboratory and outcome data were recorded. Antibiotic use was quantified by days of therapy (DOT) per 1000 patient-days (PD). Results: A total of 1607 infants were included. The total antibiotic use was 9165 DOT (343.2 DOT/1000 PD; 5.7 DOT/infant). Seventy-two percent of infants received 1 (43%) or more (29%) courses of antibiotics. Gentamicin (46%), ampicillin (39%) and oxacillin (8%) were the most frequently used agents. Ninety-four percent of antibiotic use (323 DOT/1000 PD) was empiric therapy for suspected infection. Sixty-three percent (216.2 DOT/1000 PD) was discontinued at approximately 48 hours when cultures were sterile (68%>48 hours, 32%≤48 hours). Twenty-six percent of all antibiotic use (89.4 DOT/1000 PD) was therapy for ≥5 days despite sterile cultures; pneumonia (16%) and "culture-negative" sepsis (8%) were the major contributors. Five percent (17.4 DOT/1000 PD) of antibiotic use was for culture-proven sepsis, 5% (16.6 DOT/1000 PD) was penicillin prophylaxis for group B Streptococcus and 1% (3.5 DOT/1000 PD) was preprocedural prophylaxis. Conclusions: Narrow-spectrum therapy accounted for >92% of antibiotic use and would not be monitored by most stewardship programs. Only 5% of antibiotic usage was due to culture-proven infection. Pneumonia and "culture-negative" sepsis were frequent reasons for prolonged therapy; further study of these conditions may allow reduction in treatment duration.
    No preview · Article · Sep 2014 · The Pediatric Infectious Disease Journal
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    ABSTRACT: Objective Obstetric antecedents were analyzed in births where the infant received whole-body cooling for neonatal encephalopathy. Methods This retrospective cohort study included all live-born singleton infants delivered at or beyond 36 weeks gestation from October 2005 through December 2011. Infants who had received whole-body cooling identified by review of a prospective neonatal registry were compared to a control group comprising the remaining obstetric population delivered at greater than 36 weeks but not cooled. Univariable analysis was followed by a staged, stepwise selection of variables with the intent to rank significant risk factors for cooling. Results A total of 86,371 women delivered during the study period and 98 infants received whole-body cooling (1.1/1,000 livebirths). Of these 98 infants, 80 (88%) newborns had moderate encephalopathy and 10 (12%) had severe encephalopathy prior to cooling. Maternal age less than or equal to 15 years, low parity, maternal body habitus (BMI > 40 kg/m2), diabetes, preeclampsia, induction, epidural analgesia, chorioamnionitis, length of labor, and mode of delivery were associated with significantly increased risk of infant cooling during univariable analysis. Catastrophic events to include umbilical cord prolapse (OR 14; 95%CI, 3-72), placental abruption (OR 17; 95%CI, 7-44), uterine rupture (OR 130; 95%CI, 11-1477) were the strongest factors associated with infant cooling after staged-stepwise logistic analysis. Conclusion A variety of intrapartum characteristics were associated with infant cooling for neonatal encephalopathy with the most powerful antecedents being umbilical cord prolapse, placental abruption, and uterine rupture.
    No preview · Article · Aug 2014 · American journal of obstetrics and gynecology
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    ABSTRACT: Objective: Antenatal magnesium (anteMg) is used for various obstetric indications including fetal neuroprotection. Infants exposed to anteMg may be at risk for respiratory depression and delivery room (DR) resuscitation. The study objective was to compare the risk of acute cardiorespiratory events among preterm infants who were and were not exposed to anteMg. Study design: This was a retrospective analysis of prospective data collected in the Eunice Kennedy Shriver National Institute of Child Health and Human Development Neonatal Research Network's Generic Database from April 1, 2011, through March 31, 2012. The primary outcome was DR intubation or respiratory support at birth or on day 1 of life. Secondary outcomes were invasive mechanical ventilation, hypotension treatment, neonatal morbidities, and mortality. Logistic regression analysis evaluated the risk of primary outcome after adjustment for covariates. Results: We evaluated 1544 infants <29 weeks' gestational age (1091 in anteMg group and 453 in nonexposed group). Mothers in the anteMg group were more likely to have higher education, pregnancy-induced hypertension, and antenatal corticosteroids, while their infants were younger in gestation and weighed less (P < .05). The primary outcome (odds ratio [OR], 1.2; 95% confidence interval [CI], 0.88-1.65) was similar between groups. Hypotension treatment (OR, 0.70; 95% CI, 0.51-0.97) and invasive mechanical ventilation (OR, 0.54; 95% CI, 0.41-0.72) were significantly less in the anteMg group. Conclusion: Among preterm infants age <29 weeks' gestation, anteMg exposure was not associated with an increase in cardiorespiratory events in the early newborn period. The safety of anteMg as measured by the need for DR intubation or respiratory support on day 1 of life was comparable between groups.
    No preview · Article · Jul 2014 · American Journal of Obstetrics and Gynecology

Publication Stats

4k Citations
889.92 Total Impact Points

Institutions

  • 2014-2015
    • The Ohio State University
      • Department of Pediatrics
      Columbus, Ohio, United States
    • Nationwide Children's Hospital
      Columbus, Ohio, United States
    • Brown University
      • Department of Pediatrics
      Providence, Rhode Island, United States
  • 1990-2015
    • University of Texas Southwestern Medical Center
      • • Department of Pediatrics
      • • Department of Internal Medicine
      • • Department of Obstetrics and Gynecology
      Dallas, Texas, United States
  • 1999-2014
    • University of Texas at Dallas
      Richardson, Texas, United States
  • 2012
    • University of Alabama at Birmingham
      • Department of Pediatrics
      Birmingham, AL, United States
  • 2008
    • National Cancer Institute (USA)
      베서스다, Maryland, United States
  • 1998
    • Hospital del Niño
      Ciudad de Panamá, Panamá, Panama