bluuebunny/crossref_metadata_2025_split huggingface dataset:
Beyond Susceptible and Resistant, Part I: Treatment of Infections Due to Gram-Negative Organisms With Inducible β-Lactamases
Authors: MacDougall Conan 
Published: October 2020

ABSTRACTInactivation of β-lactams by the action of β-lactamase enzymes is the most common mode of resistance to these drugs among Gram-negative organisms. The genomes of some key clinical pathogens such as Enterobacter and Pseudomonas encode AmpC, an inducible chromosomal β-lactamase. The potent activity of AmpC against broad-spectrum β-lactams complicates treatment of organisms with this gene. Antibiotic exposure can select for mutants expressing high levels of this enzyme, leading to the emergence of resistant isolates and failure of therapy, even when the initial isolate is fully susceptible. The risk of selecting for resistant organisms varies according to the particular β-lactam used for treatment. This article reviews the microbiology of these enzymes, summarizes clinical data on the frequency emergence of resistance, and discusses considerations for antimicrobial treatment of these organisms.
Reversing the Myths Obstructing the Determination of Optimal Age- and Disease-Based Drug Dosing in Pediatrics
Authors: Reed Michael D. 
Published: October 2020

ABSTRACTThe need for critical, well-designed comprehensive clinical pharmacology research in pediatrics that encompasses the age continuum, from the most premature infant through adolescence, may be more important today than ever. New drug regimens often require greater adherence to specific dose guidelines to maximize efficacy and minimize toxic potential. The climate that allowed the propagation of the “therapeutic orphan” concept is now mostly of historical perspective. Nevertheless, the negative impact of this concept continues to linger due to continued propagation of many, now outdated myths surrounding the effective study of optimal drug dosing in pediatrics. Advances in clinical medicine combined with the advances in study design, sampling, and analysis has dramatically improved the paradigm for clinical pharmacology research in infants and children. Capitalizing upon and thoughtfully using these many advances while dispelling these myths will result in greater research focused on optimal drug therapy in pediatric practice.
Clevidipine for Perioperative Blood Pressure Control in Infants and Children Undergoing Cardiac Surgery for Congenital Heart Disease
Authors: Tobias Joseph D. , Schechter William S. , Phillips Alistair , Weinstein Samuel , Michler Robert , Berkenbosch John W. , Montoya Carlos 
Published: October 2020

ABSTRACT

OBJECTIVE
To determine the efficacy and adverse effect profile of clevidipine when used for perioperative blood pressure (BP) control during surgery for congenital heart disease (CHD).

METHODS
We retrospectively reviewed our experience with the perioperative use of clevidipine in pediatric-aged patients undergoing surgery for CHD.

RESULTS
The study cohort included 14 patients ranging from 11 months to 15 years (7.4 ± 4.6 years) and weighing from 5 to 41 kg (21.8 ± 11.1 kg). Clevidipine was administered as a continuous infusion for control of either postoperative BP or intraoperative mean arterial pressure (MAP) during cooling and cardiopulmonary bypass (CPB). It was administered as a bolus for BP control during emergence from anesthesia following cardiac surgery. The continuous infusion was started at 1 mcg/kg/min and increased in increments of 0.5 to 1 mcg/kg/min as needed. For postoperative BP control, dosing requirements varied from 1 to 7 mcg/kg/min (mean = 2.0 ± 1.2 mcg/kg/min). The target BP was achieved within 5 minutes in all patients. Two patients were treated with intravenous or oral propranolol for an increase in heart rate (HR) while receiving clevidipine. Despite doses up to 10 mcg/kg/min, effective control of MAP could not be achieved during CPB and cooling (core body temperature 28°C to 32°C). Bolus doses of clevidipine (10 to 15 mcg/kg) controlled BP during emergence from anesthesia with a decrease of the MAP from 97 ± 6 mm Hg to 71 ± 5 mm Hg (p&lt;0.01).

CONCLUSIONS
Clevidipine is effective for perioperative BP control in infants and children with CHD; however, it does not appear effective in controlling MAP during cooling and CPB.
Use of Intravesicular Amikacin Irrigations for the Treatment and Prophylaxis of Urinary Tract Infections in a Patient with Spina Bifida and Neurogenic Bladder: A Case Report
Authors: Huynh Donna , Morgan Jill A. 
Published: October 2020

ABSTRACT
This case report describes the use of intravesicular amikacin irrigations to treat and prevent urinary tract infections (UTIs) in a pediatric patient with spina bifida and neurogenic bladder. A 15 year old Hispanic female was admitted for a UTI caused by Enterobacter cloacae and multiple-drug resistant Pseudomonas aeruginosa. A 7 day course of daily intravenous amikacin and ceftazidime was initiated along with twice daily intravesicular amikacin irrigations (15 mg/30 mL) with a dwell time of 2 hours. The patient improved and was discharged on prophylactic Bactrim SS (sulfamethoxazole/trimethoprim) 1 tablet daily and intravesicular amikacin irrigations (15 mg/30 mL) once every other day. Approximately 2 months after discharge, the patient developed another UTI from multidrug resistant Escherichia coli and was treated with a 14 day course of daily intravenous ciprofloxacin accompanied by daily intravesicular amikacin irrigations. Adjunctive therapy with either once daily or twice daily intravesicular amikacin irrigations successfully treated the patient's UTI. However, prophylactic treatment with intravesicular amikacin failed to prevent future UTIs in this patient.
Arthritis Associated With Antithyroid Therapy in a 15-Year-Old Girl
Authors: Ploegstra Wieteke M. , Boontje Ronald P. , Kamps Arvid W.A. 
Published: October 2020

ABSTRACT
A 15-year-old white girl with autoimmune thyroiditis developed arthritis 3 weeks after starting therapy with the antithyroid drug thiamazole. Because an adverse drug reaction of thionamide therapy was suspected, thiamazole was withdrawn, and symptoms disappeared rapidly. Thionamide therapy is indicated for hyperthyroidism and has been widely used since 1948. Reported adverse drug reactions range from mild to potentially life threatening. Arthritis is an uncommon but serious side effect and can develop as a part of the antithyroid arthritis syndrome or as a part of antineutrophil cytoplasmic antibody-associated vasculitis that is induced by antithyroid drugs. Little is known about the exact pathogenesis. Therapy consists of prompt discontinuation of the drug, where upon symptoms rapidly disappear. Because of possible cross-reactivity with alternative thionamides, another form of treatment for hyperthyroidism is recommended. Clinical awareness is important, and prompt withdrawal of the antithyroid drug is necessary when serious side effects occur.
Antipsychotic Treatment of Adolescent Dual Diagnosis Patients
Authors: Price Scott A. , Brahm Nancy C. 
Published: October 2020

BACKGROUNDA diagnosis of schizophrenia requires development of a pharmacotherapy regimen that balances many factors in the therapeutic decision-making process. Patient age and the presence or absence of comorbid chemical dependency represent two factors. Comorbid chemical dependency can have a profound impact on the successful treatment of schizophrenia, making patients with dual diagnoses of schizophrenia and chemical dependence a uniquely challenging population. There is little information regarding treatment of schizophrenia and chemical dependence in the pediatric population. Existing data from pediatric and adult populations may facilitate a well-guided and knowledgeable approach to treating pediatric dual diagnosis patients.METHODSA review of the literature for medication trials evaluating antipsychotic medication used to treat schizophrenia in childhood and adolescence as well as antipsychotic use in the treatment of the dual diagnoses of schizophrenia and chemical dependence was done. Databases for Ovid MEDLINE, PubMed, and PsycInfo were searched using the terms “addiction,” “adolescence,” “childhood,” “dual diagnosis,” “schizophrenia,” and “substance abuse.” Results were limited to English-language articles.RESULTSSeven articles were identified related to psychotic disorders and substance abuse in pediatric populations. Psychosis measurement instruments included the Brief Psychiatric Rating Scale, Positive and Negative Syndrome Scale, and Clinical Global Impression. Mean improvements were insignificant in most cases. Medication trials included clozapine, olanzapine, risperidone, and molindone. Trial safety concerns included metabolic effects, increased prolactin levels, and akathisia. One study with random assignment to olanzapine was discontinued early because of substantial weight gain without evidence of superior efficacy. Clozapine treatment was associated with more adverse drug events.CONCLUSIONThere is a great need for more research and use of available data to develop safe and effective treatment guidelines for childhood and adolescent dual diagnosis patients. When appropriate decisions are made regarding treatment of patients with comorbid schizophrenia and chemical dependence, both conditions may benefit with increased remission.
A Review of Candida Prophylaxis in the Neonatal Intensive Care Population
Authors: Chicella Michael F. , Woodruff Eloise D. , Desai Mital M. 
Published: October 2020

OBJECTIVETo review the efficacy and safety of antifungal prophylaxis in the neonatal intensive care setting.DATA SOURCESEnglish-language literature was accessed using MEDLINE (January 1988– December 2010). The following Medical Subject Heading (MeSH) search terms were used: “amphotericin B,” “fluconazole,” “nystatin,” “itraconazole,” “caspofungin,” “voriconazole,” “Candida,” “prevention and control,” and “critically ill.” Literature was further limited to studies focusing on patient birth to 6 months of age. Abstracts and original research articles were included. Preference was given to published controlled trials. Articles providing descriptions of the safety and effectiveness of antifungal prophylaxis in neonatal intensive care patients were also used in this review.RESULTSTwenty-two studies have evaluated the impact of antifungal prophylaxis on Candida colonization or invasive infections in the Neonatal Intensive Care Unit (NICU). The two antifungal agents most commonly studied were nystatin and fluconazole. All of the nystatin studies demonstrated that nystatin is effective at reducing fungal colonization and invasive fungal infections. All of the studies designed to evaluate the impact of fluconazole prophylaxis on fungal colonization demonstrated a reduction in the incidence of fungal colonization with fluconazole prophylaxis. A total of 12 of 16 studies that evaluated the impact of fluconazole prophylaxis on the incidence of invasive fungal infections demonstrated a reduction in invasive fungal infections with fluconazole prophylaxis. Two studies found no difference between fluconazole and nystatin when used for prophylaxis.CONCLUSIONAntifungal prophylaxis appears to be effective in reducing the incidence of Candida colonization and invasive Candida infections in the NICU. Antifungal prophylaxis also appears to be safe in the NICU population. The impact of antifungal prophylaxis on resistance patterns could be significant and needs to be evaluated long term before widespread prophylaxis can be recommended.
National Survey of Extended-Interval Aminoglycoside Dosing in Pediatric Cystic Fibrosis Pulmonary Exacerbations
Authors: Prescott William A 
Published: October 2020

OBJECTIVESThe Cystic Fibrosis Foundation recently deemed the use of extended-interval dosing (EID) of aminoglycosides acceptable for the treatment of cystic fibrosis (CF) pulmonary exacerbations, but current practices across United States (US) pediatric CF accredited care centers and affiliate programs are unknown. The objectives of this research are to characterize the practice trends, dosing strategies, therapeutic drug monitoring practices, and adverse drug reaction monitoring of EID of aminoglycosides in the treatment of pulmonary exacerbations across US pediatric CF programs.METHODSA 38-question online survey was distributed on behalf of the author by the CF Foundation to all US pediatric CF accredited care centers and affiliate programs.RESULTSOf the 70 participating CF programs (42.2% survey response rate), 94.3% reported using EID of aminoglycosides (as once-daily or twice-daily dosing), whereas 84.3% reported using once-daily EID in their pediatric CF population. The frequency of EID use increased with patient age. Tobramycin dosed 10 mg/kg per day every 24 hours, infused over the course of 30 minutes, in combination with an antipseudomonal beta-lactam, was the most commonly cited regimen. Monitoring of aminoglycoside serum concentrations was reported by 98.5% of programs, with a tobramycin peak of 25 to 30 mg/L and trough of less than 1 mg/L targeted most frequently. Nephrotoxicity was commonly monitored through serum creatinine measurements, whereas ototoxicity was monitored by audiometry in approximately one-half of programs.CONCLUSIONSThis study indicates that the use of EID of aminoglycosides across US pediatric CF accredited care centers and affiliate programs is common, particularly among adolescents, with tobramycin being the preferred agent.
Development and Implementation of a Pharmacist-Managed, Neonatal and Pediatric, Opioid-Weaning Protocol
Authors: Johnson Melissa R. , Nash David R. , Laird Mary R. , Kiley Robert C. , Martinez Michael A. 
Published: October 2020

OBJECTIVES: To compare the length of wean and abstinence severity in neonatal and pediatric patients with neonatal abstinence syndrome or iatrogenic opioid dependence treated with a pharmacist-managed, methadone-based protocol compared with physician-managed patients treated with either methadone or dilute tincture of opium (DTO).
METHODS: This was a prospective, single-centered, interventional evaluation of 54 pharmacist-managed patients versus 53 retrospective, physician-managed patients. Wean duration and severity of neonatal abstinence syndrome were compared between groups using the Student t test.
RESULTS: Significantly shorter wean duration in in utero-exposed pharmacist-managed patients compared with patients on physician-managed DTO (11.7 days vs 24.2 days, p &lt; 0.001), but not compared with patients on physician-managed methadone (11.7 days vs 47 days, p = 0.101). No statistically significant difference was seen in wean duration in iatrogenic-exposed pharmacist-managed patients compared with patients on either physician-managed DTO or methadone (8.69 days vs 14 days, p = 0.096) and (8.69 days vs 9.82 days, p = 0.34), respectively. There were significantly fewer abstinence scores &gt;12 in pharmacist-managed patients versus physician-managed DTO, but not physician-managed methadone (2.05 vs 17.3, p = 0.008 and 2.05 vs 74.3, p = 0.119, respectively). Significantly fewer abstinence scores ≥8 × 3 consecutively were seen in pharmacist-managed patients compared with patients on either physician-managed DTO or methadone (2.89 vs 11.9, p = 0.01 and 2.89 vs 24, p &lt; 0.001, respectively).
CONCLUSIONS: Use of a pharmacist-managed, methadone-based weaning protocol standardizes patient care and has the potential to decrease abstinence severity and shorten duration of wean versus physician-managed patients exposed to opioids in utero. Additionally, a methadone wean of 10% to 20% per day was well tolerated in both neonatal and pediatric patients.
Vancomycin Dosing in Healthy-Weight, Overweight, and Obese Pediatric Patients
Authors: Eiland Lea S. , Sonawane Kalyani B. 
Published: October 2020

OBJECTIVES: With an increase in vancomycin resistance and the prevalence of obesity in children, alterations of vancomycin dosing regimens may be necessary to achieve target serum concentrations. The primary objective of this study was to describe initial vancomycin dosing with resulting serum concentrations in healthy-weight and overweight/obese children. Secondary objectives include comparing vancomycin dosing regimens of healthy-weight and overweight/obese patients that produced target trough serum concentrations and evaluating the likelihood of attaining target concentrations by patient characteristics.
METHODS: This retrospective review evaluated healthy-weight and overweight/obese patients, aged 2 to 18 years, who had vancomycin trough serum concentrations obtained between 2005 and 2010. Vancomycin dosing, initial trough serum concentrations, pharmacokinetic parameters, and patient demographics were collected for analysis. Target trough serum concentrations were defined as 10 to 20 mg/L.
RESULTS: The study included 98 patients (48 healthy weight, 50 overweight/obese) of which only 14 patients (14.2%, 6 healthy weight, 8 obese) reached a target trough serum concentration with empiric dosing. No difference was found between the mean daily dosing of vancomycin that produced target trough serum concentrations in healthy-weight or overweight/obese patients (53.63 mg/kg/day vs 51.6 mg/kg/day, respectively). Demographic or clinical characteristics were not found to be associated with the likelihood of target trough serum concentration attainment.
CONCLUSIONS: Vancomycin dosing in healthy-weight and overweight/obese pediatric patients did not reach target trough serum concentrations most of the time. In obtaining initial target serum concentrations, no dosing difference was identified for overweight/obese patients compared with healthy-weight patients. Alternate dosing strategies, therapeutic monitoring, and clinical outcomes should continue to be evaluated in this population.
A Filtration System That Greatly Reduces Aluminum in Calcium Gluconate Injection, USP Used to Prepare Parenteral Nutrition Solutions
Authors: Yokel Robert A. , Harris Wesley R. , Spilling Christopher D. , Abramov Vasiliy P. , Lone Jason M. , Kuhn Robert J. 
Published: October 2020

OBJECTIVE: The study objective was to reduce aluminum (Al) in Calcium Gluconate Injection, US Pharmacopeia (USP) used in the preparation of parenteral nutrition (PN) solutions.
METHODS: A flow-through filter containing an immobilized chelator that complexes Al from Calcium Gluconate Injection, USP as it flows through the filter was designed, refined by design modifications, and extensively tested. When a small-volume parenteral vial containing 100 mL of Calcium Gluconate Injection, USP is connected on the inlet side of the filter, and the outlet side is connected to an evacuated receiving vial, the filtered solution is drawn into the receiving vial. This constitutes a complete system to remove Al from Calcium Gluconate Injection, USP.
RESULTS: The extent of Al removal is flow rate dependent. At a flow rate of 1 mL/min approximately 85% of the Al was removed from calcium gluconate solution. PN solutions have been reported to deliver 15 to 23 mcg/kg/day Al to neonates. Given that Calcium Gluconate Injection, USP provides 85% of the Al in neonatal PN solutions, removal of 85% of the Al from this source was calculated to reduce Al delivered to most neonates to &lt;5 mcg/kg/day.
CONCLUSIONS: A point-of-use, self-contained, single-use, disposable, Al-complexing filter has been created. It was calculated to reduce Al delivered in PN solutions by 72%, resulting in daily Al delivery below the level that results in Al accumulation associated with central nervous system and bone toxicity to all but the smallest (&lt;1 kg) infants.
Proton Pump Inhibitor Prescribing Patterns in Newborns and Infants
Authors: Illueca Marta , Alemayehu Berhanu , Shoetan Nze , Yang Huiying 
Published: October 2020

OBJECTIVES: In 2011, the Food and Drug Administration (FDA) approved intravenous esomeprazole 0.5 mg/day for children aged &gt;1 month and oral esomeprazole for infants aged 1 month to &lt;1 year at doses of 2.5, 5, and 10 mg based on weight. Prior to 2011, proton pump inhibitors (PPIs) were not approved for use in infants aged &lt;1 year. This study determined PPI usage rates prior to the FDA approval among newborns and infants in both the inpatient and outpatient settings and compared PPI and histamine-2 receptor antagonist (H2RA) usage in the inpatient setting.
METHODS: We conducted a retrospective analysis of PPI prescribing patterns for newborns and infants from 2003 to 2008 using data from the Premier Perspective Inpatient Hospital Database and the PharMetrics Patient-Centric Database for inpatient and outpatient data, respectively. PPI use and diagnoses were determined from clinical and charge records from more than 500 hospitals. Descriptive statistics were used to summarize the findings.
RESULTS: Our analysis showed that PPIs were prescribed for approximately 5000 newborns (0.13%) and 15,000 infants (2.65%) each year in the hospital setting and 1.6% of newborns and infants, as a group, in the outpatient setting. Newborns and infants receiving PPIs most often had diagnoses of gastroesophageal reflux disease (GERD) and were generally prescribed an adult PPI dose, although the actual dose administered could not be substantiated.
CONCLUSIONS: Although no PPI was approved by the FDA for patients aged &lt;1 year at the time of this study, results of this analysis indicate that PPIs were commonly prescribed for newborns and infants, mostly in hospital, but also in outpatient settings. Most PPIs were prescribed for infants with a diagnosis of GERD.
Optimizing Pediatric Esmolol Dosing Using Computerized Practitioner Order Entry
Authors: Chao Tihua , Perry James C. , Romanowski Gale L. , Tremoulet Adriana H. , Capparelli Edmund V. 
Published: October 2020

OBJECTIVES: The aims of this study were to 1) describe the cardiovascular dose-response of esmolol and dose-limiting adverse effects in pediatric patients; 2) assess an institutional guideline for protocol adherence, efficacy, and achievement of therapeutic targets for pediatric patients with tachyarrhythmias or systemic hypertension; and 3) revise the protocol accordingly.
METHODS: In this prospective study, pediatric/neonatal subjects were identified using a medication utilization report in the electronic medical record and treated with esmolol for blood pressure or rhythm control at Rady Children's Hospital San Diego between November 1, 2012, and February 28, 2013. Inclusion criteria required subjects to be under intensive care and have bedside telemetry monitoring. Data collection consisted of patient demographic information, administration history of esmolol, concurrent administration of other cardiovascular medications, patient cardiovascular goals, and vital signs.
RESULTS: A total of 8 subjects representing 10 administrations of esmolol were included in the study. Whereas esmolol was found to be safe and effective overall for control of hypertension and tachyarrhythmia, protocol adherence was poor, leading to subtherapeutic dosing schemes, dose changes prior to achievement of presumed steady-state pharmacokinetics, and erratic dosing to target effect.
CONCLUSIONS: After the review, the data were revealed at a program-wide conference and consensus was reached on a new, data-driven protocol. As a result of this quality improvement initiative, the new protocol provides more precise dosing and clearly delineated therapeutic targets and is designed to reflect specific esmolol pharmacokinetics. The effort emphasizes the need to construct foundations for follow-up quality improvement efforts in intensive care pharmacology.