Journal of Pediatric Pharmacology and Therapeutics最新文献

Objective: To report efficacy, safety, and dosing of angiotensin II (AT-II) in pediatric patients with refractory vasodilatory shock.

Methods: This was a single center retrospective cohort study using automated, high-fidelity hemodynamic data in a large tertiary pediatric academic medical center. Pediatric patients who required multimodal vasopressor therapy for fluid refractory vasodilatory shock and received AT-II between June 2017 and November 2022 were included. High-fidelity hemodynamic data were captured via the Etiometry T3 platform. Vasoactive-inotropic score (VIS), AT-II dosing, demographics, clinical characteristics, and potential adverse effects were collected from the electronic medical record.

Results: Fourteen pediatric patients with a median age of 11.6 years (range, 13 days-16.8 years) received AT-II at a dose of 2.5 to 80 ng/kg/min for a median of 32 hours (range, 3.1-72.4). Ten of 14 patients (71%) responded favorably to AT-II therapy, experiencing a clinically significant decrease in VIS or increase in mean arterial blood pressure. The median age of responders was significantly higher than that of nonresponders (12.5 years vs 0.4 years; p = 0.002), and responders had a higher baseline VIS (56 vs 33; p = 0.008) than nonresponders. One patient (7%) experienced peripheral ischemia.

Conclusions: Angiotensin II has a potential role in the management of pediatric patients with vasodilatory shock resistant to multimodal vasopressor therapy. Demographic and clinical characteristics predicting response in the pediatric population require careful, prospective evaluation.

Objective: The University of Oklahoma College of Pharmacy created the Pediatric Degree Option Program (PDOP) to enhance the knowledge and skills of students in pediatric pharmacy. The purpose of the study was to identify the pediatric-focused research and scholarship activities and outcomes of PDOP graduates.

Methods: This was a retrospective study of PDOP graduates from 2011-2022. The primary objective was to identify the overall number of activities conducted during the PDOP. Secondary objectives included the overall number of peer-reviewed and non-peer reviewed publications, and comparison of the median number of scholarship activities per PDOP graduate between those who did and did not complete a PGY1 residency. Inferential statistics were performed using Mann-Whitney U and Chi-square or Fischer's exact test as appropriate, with an a priori p value <0.05.

Results: Fifty-two PDOP graduates completed the program. Following graduation, 23 (44.2%) individuals completed a postgraduate year-one (PGY1) residency. PDOP graduates completed a total of 53 research and scholarship activities. The majority (n=44; 83.0%) were original research projects, and 41 (77.4%) graduates published ≥1 manuscript. There was a significant difference in manuscript authorship between graduates who did and did not complete a residency (18 versus 7, p<0.001). Seventeen (26.2%) of the PDOP scholarship projects involved collaboration with a PGY1/postgraduate year-two (PGY2) resident.

Conclusions: This study demonstrated that students enrolled in a curricular track were exposed to various aspects of the research and scholarship process. Many of the activities resulted in a publication or presentation for the PDOP graduate.

Staphylococcus aureus infection is one of the most common and serious infections that arises in children and is associated with high morbidity. S. aureus is the leading cause of acute hematogenous osteomyelitis in children. In the absence of concerns regarding resistance to methicillin, an anti-staphylococcal isoxazolyl penicillin, such as oxacillin or nafcillin, is the drug of choice for treatment of S. aureus osteomyelitis. However, first-generation cephalosporins, such as cefazolin, can also be used. There are limited antimicrobial options available for osteomyelitis and persistent or intermittent bacteremia when surgical intervention for source control is not indicated or feasible. Hence, there is a need to improve our knowledge of synergistic antimicrobial combinations to guide clinical practice and improve outcomes, particularly among children. We present the case of an 11-year-old child with persistence of acute hematogenous vertebral osteomyelitis with discitis and bacteremia, despite appropriate treatment with an anti-staphylococcal beta-lactam. Blood cultures were sterilized, and symptoms resolved after the addition of ertapenem 1 g daily for 7 days. To our knowledge, this is the first report of using ertapenem in combination with an anti-staphylococcal beta-lactam to specifically treat persistent methicillin-susceptible S. aureus (MSSA) vertebral osteomyelitis with bacteremia. Similar success has been reported using this combination to treat adults with persistent MSSA bacteremia and preterm low-birth-weight infants with late-onset neonatal sepsis; hence, our report provides further support for the benefit of this combination in staphylococcal infections.

Objective: Monoclonal antibody therapy has been used to treat COVID-19, with paucity of literature about its use in children. This retrospective study sought to evaluate the effectiveness of preventing hospitalization and safety of monoclonal antibody (mAb) treatment (bamlanivimab-etesevimab and casirivimab-imdevimab) for COVID-19 in patients ≤18 years of age.

Methods: Between January 1 and December 31, 2021, patients were selected for mAb therapy, based on the referring provider's clinical assessment of high risk for progression to severe COVID-19. The choice of mAb was determined by drug availability, compounding feasibility, and documented in vitro activity against circulating SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2) variants. All patients received a single-dose infusion. Primary outcomes included hospital readmissions and emergency department (ED) visits within 90 days of treatment. The secondary outcome was safety/adverse events.

Results: Of 141 patients who received mAbs in 2021, only 3 experienced ongoing COVID-19 symptoms. Only 1 patient necessitated escalated care owing to persistent COVID-19 symptoms post infusion. There were no infusion-related side effects or hospitalizations in the 90 days post infusion.

Conclusion: Monoclonal antibodies appear to be safe and effective in preventing hospitalizations in COVID-19-positive children.

Pharmacy students, residents, and new practitioners may feel overwhelmed with patients in the pediatric critical care setting due to the disease states, variation in acuity based on patient factors, and complex medication regimens. The FASTHUG MAIDENS mnemonic is a standardized and validated tool that was developed in 2011 for pharmacists to use when evaluating critically ill adult patients. However, there are no studies evaluating the use of this tool in pediatric critical care setting. This article aims to provide trainees and new practitioners with a new and distinct mnemonic tool, IN-DEPTH, to use when evaluating critically ill pediatric patients and identifying areas for treatment optimization. In addition, this article will provide rationale and examples to enhance the user's understanding of the components and subcomponents of the mnemonic. Ultimately, the goal of the IN-DEPTH mnemonic is to help provide some structure for pharmacy trainees or new practitioners that are less experienced with critical or pediatric care and provide the opportunity to have a meaningful impact in the care of critically ill pediatric patients.

Continuous kidney replacement therapy (CKRT) can influence pharmacokinetics (PK), including clearance (CL) of antibiotics like piperacillin (PIP). Both CKRT intensity, or "dialysis dose," and residual kidney function can alter PIP PK and pharmacodynamic (PD) target attainment (TA), defined by the percentage of time free PIP concentrations exceed the minimum inhibitory concentration (% fT > MIC). In existing reports, children receiving PIP and CKRT are usually oligoanuric, so PIP PK/PD in non-oligoanuric patients receiving high-intensity CKRT is unknown. This report analyzes free PIP PK/PD in a child with robust kidney function who received 30-minute infusions of 100 mg/kg PIP-tazobactam every 6 hours while on high-intensity CKRT after liver-kidney transplant for primary hyperoxaluria. Model-informed PK software was used to estimate PK/PD parameters for periods on and off CKRT. PIP CL on CKRT was 66% higher than off CKRT (5.59 L/hr vs 3.36 L/hr). Nearly 100% fT > 1xMIC (using 8 mg/L for Enterobacterales) was achieved whether on or off CKRT, but only 60% fT > 4xMIC was achieved on CKRT. CKRT CL was 40% of total CL on CKRT and 51% of the CKRT dialysis dose, suggesting PIP elimination was mostly renal despite high-intensity dialysis. Monitoring of free PIP concentrations may help ensure proper TA in non-oligoanuric patients receiving high-dose CKRT.

Objective: Nigella sativa (NS) has been widely used and investigated in several pediatric studies; however, its safety and efficacy in pediatrics are yet to be evaluated. This systematic review evaluates the clinical uses, safety, and efficacy of NS in pediatrics.

Methods: The search was conducted across 4 databases, including PubMed, Web of Science, Scopus, and Cochrane, up to September 6, 2023, and included clinical trials using NS in pediatrics. A methodological quality assessment was performed using the Cochrane risk of bias tool for randomized trials (Rob 2). A meta-analysis was conducted to evaluate safety. The systematic review follows the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines.

Results: Two hundred sixty-five studies were screened for eligibility, including 125 papers from Scopus, 31 from PubMed, 37 from Cochrane, and 72 from the Web of Science. Sixty-eight duplicate papers were eliminated, and 185 studies were excluded. Three studies were added from snowballing. Fifteen clinical trial studies were included in this review. Limited studies have been conducted on NS in pediatrics. Based on the meta-analysis, no statistically significant side effects have occurred. Different doses and forms of NS were used, and most studies have reported improvements in the outcomes.

Conclusion: More high-quality studies are needed to establish the efficacy of using NS in different diseases, along with its effective dose and form. The studies in this review report no severe adverse effects and no statistically significant occurrence of side effects. However, further studies are needed to fully understand the safety of using NS in pediatrics.

Objective: People with cystic fibrosis (pwCF) have impaired bacterial mucociliary clearance, which can result in colonization with pathogens like Pseudomonas aeruginosa and methicillin-resistant Staphylococcus aureus (MRSA) in the lower airway. Although guidelines for the eradication of P. aeruginosa in CF are well-established, MRSA eradication guidelines are lacking. This study aimed to determine the rates of MRSA eradication in pwCF based on a prescribed antibiotic regimen.

Methods: This retrospective chart review included pwCF with a first lifetime positive MRSA respiratory culture or first positive MRSA respiratory culture after at least 1 year of MRSA negativity (minimum of 4 negative respiratory cultures) obtained at Nationwide Children's Hospital between August 1, 2012, and February 28, 2022. Secondary outcomes assessed the impact of adding topical decontamination on MRSA eradication and the time to a subsequent MRSA-positive respiratory culture after completing the eradication regimen.

Results: Sixty-two patients were included, and 16% achieved MRSA eradication. Intravenous vancomycin transitioned to oral trimethoprim-sulfamethoxazole achieved the highest eradication rate of 75% (p = 0.008). Antibiotics consisting of dual therapy with rifampin and topical decontamination had a higher rate of eradication (25%) compared with antibiotics alone, antibiotics with topical decontamination, or no antibiotics. Four patients had no subsequent MRSA-positive cultures, including 2 patients who did not receive antibiotics.

Conclusions: The transition from intravenous vancomycin to oral trimethoprim-sulfamethoxazole had the highest rate of MRSA eradication. Overall rates of MRSA eradication at 12 months in patients CF using antibiotics with or without topical decontamination are low.