Daniel K Benjamin

..Related to this class, future research is needed in order to better assess dosing, safety, schedules and areas of use of these agents in infants admitted to the neonatal intensive care unit...

..As a result, there have been over 100 product labeling changes. The publication status of studies completed for pediatric exclusivity has not been evaluated...

..Although the number of infants for whom safety data are reported is small, higher doses of micafungin appear safe and well tolerated in this population...

..We quantified risk factors that predict infection in premature infants at high risk and compared clinical judgment with a prediction model of invasive candidiasis...

....

..We evaluated 16 patients with Candida IE nested within a cohort of 2,022 patients with IE. Prosthetic valve IE was more common in patients with Candida (50% vs 17%); mortality was 37% for patients with Candida...

..This article discusses infections that might be seen in this population and gives options for diagnosis and treatment...

..These data suggest that micafungin dosages of 7 and 10 mg/kg/day are well tolerated and provide exposure levels that have been shown (in animal models) to be adequate for central nervous system coverage...

..Neonatal candidiasis is associated with substantial morbidity and mortality rates. Neurodevelopmental follow-up data for a large multicenter cohort have not been reported...

..More importantly, our ability to combine data across trials allowed us to evaluate and potentially improve trial design...

..aureus infections are caused by capsular polysaccharide (CPS) types 5 and 8. Altastaph is a polyclonal investigational human immunoglobulin G (IgG) with high levels of opsonizing S. aureus CPS types 5 and 8 IgG...

..The model was most pertinent to children 36 months of age or younger, and was conducted in children receiving monotherapy and dual therapy...

..This is one reason why the otoscopic examination is difficult to teach. Available techniques can assess diagnostic exams when there is no gold standard-one of these is latent class analysis...

....

..Although guidelines for empirical therapy exist for patients with fever and neutropenia, these do not exist for neonates...

..We evaluated the current medical literature in an effort to critique the literature and to document the reported prevalences of end-organ damage after neonatal candidemia...

....

..Any positive PCR test requires virologic confirmation and serologic follow-up...

..We evaluated variation in age, weight, and weight-for-age z-score at Fontan across institutions, and the impact of these variables on postoperative morbidity and mortality...

..Describe cerebrospinal fluid parameters in infants with culture-proven Group B streptococcal meningitis in the era of intrapartum antibiotic prophylaxis...

..Cerebrospinal fluid parameters used to diagnose meningitis in the absence of dependable cerebrospinal fluid cultures are unreliable. Caution should be employed when interpreting cerebrospinal fluid parameters in the premature neonate...

..Early and late onset sepsis results in significant mortality in extremely preterm infants, but little is known about sepsis outcomes in late preterm infants...

..Diagnosis of late-onset sepsis can be challenging. The complete blood cell count and differential have been previously evaluated as diagnostic tools for late-onset sepsis in small, single-center reports...

..The ECMO circuit can alter drug pharmacokinetics; thus, standard fluconazole dosing in children on ECMO may result in suboptimal drug exposure. This study determined the pharmacokinetics of fluconazole in infants on ECMO...

..Invasive candidiasis is a leading cause of mortality and morbidity in neonatal intensive care units. Treatment recommendations are limited by a lack of comparative outcomes data...

..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...

..The goal of this study was to determine the normal ranges for cell count parameters in neonates with VP shunts and CSF reservoirs, as well as to determine the predictive value of CSF parameters as markers of infection...

..aureus bacteremia...

..We evaluated the population pharmacokinetics (PK) of piperacillin using targeted sparse sampling and scavenged samples obtained from preterm infants ≤ 32 weeks of gestational age at birth and <120 postnatal days...

..To assess the impact of empiric antifungal therapy for invasive candidiasis on subsequent outcomes in premature infants...

..The optimal management of Candida infective endocarditis (IE) is unknown...

..Infants with methicillin-resistant S. aureus infection had a longer median duration of bacteremia (4.5 versus 1 day, P = 0.01), but no difference in length of hospital stay, mortality, or neurodevelopmental impairment...

....

..The purpose of this study was to determine the safety and effectiveness of meropenem in young infants with suspected or complicated intra-abdominal infections...

..To determine whether premature infants with invasive Candida infection caused by strains with increased virulence properties have worse clinical outcomes than those infected with less virulent strains...

..We sought to determine the risk factors, incidence, and mortality of very late onset bacterial infection (blood, urine, or cerebrospinal fluid culture positive occurring after day of life 120) in preterm infants...

..27) were associated with increased mortality; CONS (HR=1.08) and GP-o (HR=0.97) were not. CONCLUSIONS: Nosocomial GNR bacteremia and candidemia were associated with increased mortality but Gram-positive bacteremia was not...

....

..We evaluated the relationship between empirical antibiotic practices for extremely low birth-weight infants and center incidence of candidiasis...

....

..We were not able to detect a difference in calcineurin inhibitor antifungal activity against isolates from transplant recipients and nontransplant patients...

..We evaluated the diagnostic accuracy of the complete blood cell count and differential in EOS in a large, multicenter population of neonates admitted to the neonatal intensive care unit...

..Candidiasis carries a significant risk of death or neurodevelopmental impairment (NDI) in extremely low birth weight infants (ELBW; <1000 g). We sought to determine the impact of candiduria in ELBW preterm infants...

..Clinical outcomes resulting from such a therapeutic strategy have not been well defined...

..04) and longer hospital stays (19.7 vs 14.5 days; P = .05) compared with early evidence of C albicans. Mortality was similar between the groups...

..Trough concentrations were unpredictable based on dose, highlighting the need to follow values during therapy...

..Minimal-risk methods such as scavenged PK sampling provided meaningful information related to development of metronidazole PK models and dosing recommendations...

..Short-term exposure to placebo in pediatric trials of antihypertensive medications appears to be safe...

..We sought to describe the Pediatric Advisory Committee's recommendations made in response to safety reviews informed by data from the Food and Drug Administration Adverse Event Reporting System in 67 drugs granted exclusivity...

..We sought to determine the cost of performing pediatric exclusivity trials within a single therapeutic area and the subsequent economic return to industry sponsors...

..To estimate the risk of bloodstream infection associated with catheter dwell time in infants...

..The primary objective of this study was to determine the association between catheter associated blood stream infection (CABSI) and catheter-related thrombosis in the Neonatal Intensive Care Unit...

....

..29; 95% CI, 0.15-0.56). Voriconazole is likely to be a better treatment choice for A. terreus infection than is a polyene...

..AAV vector administration in the canine model for GSD Ia resulted in sustained G6Pase expression and improvement in liver histology and in biochemical parameters...

..In February 2006, the U.S. Food and Drug Administration approved the echinocandin anidulafungin for the treatment of patients with candidemia, peritonitis, intra-abdominal abscesses and esophageal candidiasis...

....

....

..Fluconazole is increasingly used to prevent and treat invasive candidiasis in infants. Dosing guidance remains empiric and variable because limited pharmacokinetic data exist...

..In the past decade, the antifungal armamentarium against invasive mycoses has expanded greatly. The purpose of the present report is to review the most recent literature addressing the use of antifungal agents in children...

..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...

..A loading dose of fluconazole is advised for older patients but has not been evaluated in infants. We sought to determine the pharmacokinetics and safety of a fluconazole loading dose in infants at risk for invasive fungal infection...

....

..Race, the need for mechanical ventilation, and younger PCA when the blood culture was obtained were also strongly associated with mortality...

..Coagulase-negative staphylococci (CoNS) are the most commonly isolated pathogens in the neonatal intensive care unit (NICU). CoNS infections are associated with increased morbidity, including neurodevelopmental impairment...

..This critique has been a substantial part of congressional debate on the program, which is due to expire in 2007...

..Changes in WAZ were not associated with laboratory outcomes relevant to pediatric HIV infection. Height velocity should be considered as a component of a composite clinical endpoint in future PACTG trials...

..Abnormal cerebrospinal fluid (CSF) parameters are often used to predict neonatal meningitis and determine length and type of antibiotic therapy in neonates with a positive blood culture and negative CSF culture...

..These preclinical data demonstrated the efficacy of correcting hepatic G6Pase deficiency, and support the further preclinical development of AAV vector-mediated gene therapy for GSD-Ia...

..In addition, diagnostic alternatives to traditional blood culture, experience with antifungal agents for prophylaxis and therapeutic options, including newer antifungal agents, will be presented...

..7 vs. 20.7 days; P < 0.001) and higher inpatient costs ($133,871 vs. $56,725; P < 0.001) but lower mortality (28.3% vs. 43.5%; P < 0.001)...

..The role of both host and pathogen characteristics in hematogenous seeding following Staphylococcus aureus bacteremia is incompletely understood...

..We determined the economic impact of isolating and cohorting MRSA-colonized neonates on total hospital cost at a 49-bed, level III-IV neonatal intensive care unit...

..This population PK model of fluconazole discriminated the impact of BGA, PNA, and creatinine on drug CL. Our data suggest that dosing in young infants will require adjustment for BGA and PNA to achieve targeted systemic drug exposures...

..Systemic prophylaxis is currently not recommended for any neonatal population, and amphotericin B deoxycholate continues to be used as first-line therapy for the treatment of invasive disease...

..Given the low probability of disease in patients who have had 3 negative PCR tests, documentation of a negative ELISA may not be an appropriate use of medical resources...

..It is well established that adult patients of different races show disparate response to angiotensin-converting enzyme (ACE) inhibitors, however no such studies have been performed in children...

..We evaluated the setting of published studies conducted under the US Pediatric Exclusivity Provision, which provides economic incentives to pharmaceutical companies to conduct drug studies with children...

..The authors report a case of a 16-year-old with chronic mucocutaneous candidiasis who developed a fungemia with Candida tropicalis...

..Candida is an increasingly important nosocomial pathogen within intensive care nurseries. The purpose of this study was to determine the attributable cost of candidemia in neonates...

....

..Our findings reveal that calcineurin appears to play a globally conserved role in the virulence of several pathogenic fungi and yet plays specialized roles in each and can be an excellent target for therapeutic intervention...

..Pediatric resident physicians' clinical diagnostic accuracy of otitis media is unknown. We attempted to correlate the clinical examination of pediatric house staff with pediatric otolaryngologists and tympanometry...

..Neither active nor prior GBV-C infection was associated with a lower rate of HIV acquisition among infants. Thus, GBV-C does not appear to protect against perinatal HIV acquisition...

..The incidence of invasive fungal infections in patients receiving aerosolized amphotericin B formulations as sole prophylaxis was determined...

..The prevalences of asthma and obesity in children have increased significantly during the past 2 decades. The basis for the relationship between pediatric asthma and obesity is not well established...

..The larger body of data in adult patients is used for comparative purposes only in an attempt to understand pediatric implications...

..The primary objective of this study was to assess the safety and pharmacokinetics of an increased (15 mg/kg/d) dose of micafungin...

..The infant's Candida isolate developed resistance to azoles during fluconazole administration and also suffered from severe hypercalcemia during the initiation of caspofungin therapy...

....

..To determine the natural history of renal mycetoma (fungal balls) in the neonate...

..The incidence of cough in children receiving ACEis (reported cough, 3.2%) was similar to that in children receiving ARBs (reported cough, 1.8%) (P = 0.34). Reports of cough were lower in children than in adults...

..This study evaluated the results of six trials of ACE inhibitors in children, using meta-analytic techniques to estimate the effect of race on blood pressure response...

..o. The development of efficacious AAV vector-mediated gene therapy could significantly reduce the impact of long-term complications in GSD-Ia, including hypoglycemia, hyperlipidemia and growth failure...

..7 and 16.3 mcg ml(-1), respectively. Even though the infants received higher doses than adults, their drug concentrations were comparable to those observed in adults treated with regular dosing of daptomycin...

..Thus, chimeric, highly secreted GAA enhanced the efficacy of AAV vector-mediated gene therapy in GSD-II mice...

..These factors may identify those patients with IE for more aggressive treatment...

..Mice deficient in CD35/CD21 showed a 67% decrease in survival compared with normal mice, suggesting that CD35/CD21 is of major importance in the control of S aureus-induced bacteremia...

....

..abstract_text> ..

..The research will provide guidance as to the efficacy, safety, and neurodevelopmental outcomes related to fluconazole use. ..

..The research will evaluate the efficacy, safety, and neurodevelopmental outcomes related to fluconazole use. ..

..The research will provide guidance as to the efficacy, safety, and neurodevelopmental outcomes related to fluconazole use. ..

..abstract_text> ..

..6) To train physicians and pharmacologists in clinical and developmental pharmacology: the centerpiece will be a 3-year pediatric pharmacology fellowship. Drs. Brouwer and Lindley (UNC) will lead this program. ..

..The research will evaluate the efficacy, safety, and neurodevelopmental outcomes related to fluconazole use. ..