Ivacaftor-elexacaftor-tezacaftor and tacrolimus combination in cystic fibrosis.

The CFTR modulator combination elexacaftor/tezacaftor/ivacaftor (ETI) is a genetic mutation-targeted treatment in cystic fibrosis that results in profound improvements in clinical outcomes. Each of the compounds are substrates of CYP3A4/5, the cytochrome P450 enzyme family for which tacrolimus is also a substrate. The use of these compounds in an individual with a solid organ transplant has not been previously studied and there is potential for a drug interaction. In this report, we describe a pediatric liver transplant recipient with clinical decline related to cystic fibrosis who improved substantially with ETI, without significant impact on the systemic exposure of either ETI or tacrolimus.

Student organization prevalence and structures in US schools of pharmacy.

INTRODUCTION: Accreditation Council for Pharmacy Education (ACPE) Standards 2016 emphasize co-curricular programming to complement formal curriculums. Programming engagement through student pharmacist organizations is foundational to many schools' co-curriculum. Adequate funding, membership engagement, and governance structures are vital factors that, in turn, help these groups thrive over time. However, minimal literature exists depicting financial support, governance, and membership engagement for benchmarking purposes. The current study's objective was to examine these parameters at a national level among schools of pharmacy. METHODS: Student affairs personnel identified through the American Association of Colleges of Pharmacy Student Services Special Interest Group received a link to an anonymous Qualtrics survey. Survey data comparing programs were analyzed descriptively and via t-test (continuous data) and Fisher's exact test (nominal data) using Graph Pad Prism 8. RESULTS: Seventy-three schools completed the survey. The majority (53%) were public institutions. Limiting the number of organizations allowed on campus occurred at 39.7% of schools. Regarding formation/funding policies, 75% published policies for organization formation, and 53% published policies for financial support. Use of an "umbrella" format for governance was present in 36% of responding schools. The average number of organizations per school was 11, conducting an average of 10.4 chapter meetings/month. The percent of enrolled students on average belonging to a given organization ranged from 2.2% to over 40%. Ninety-three percent reported that organizations assist in the inculcation of professionalism among student pharmacists. CONCLUSIONS: Pharmacy schools are inconsistent in their approach to student organization formation, funding policies, and governance.

Chromobacterium Violaceum Sepsis: Rethinking Conventional Therapy to Improve Outcome.

BACKGROUND: Chromobacterium violaceum (C. violaceum) is a facultative anaerobic gram-negative bacterium found in soil and water, especially in tropical and subtropical areas. Although infection in humans is rare, it is associated with significant morbidity. The bacterium is known for its resistance to multiple antimicrobials, and the possibility of relapse and reinfection. Presence of bacteremia, disseminated infection, and ineffective antimicrobial agents are predictors of mortality. CASE REPORT: We report the case of a previously healthy 11-year-old male with C. violaceum sepsis who was exposed to stagnant water. He presented with severe septic shock and developed multi-organ system failure. Initial presumptive diagnosis was staphylococcal infection secondary to presence of skin abscesses resulting in antibiotic coverage with vancomycin, clindamycin, nafcillin and ceftriaxone. He also had multiple lung and liver abscesses. Once C. violaceum was identified, he received meropenem and ciprofloxacin, and was later discharged on ertapenem and trimethoprim-sulfamethoxazole (TMP-SMX) to complete a total of six months of antibiotics. He was diagnosed with chronic granulomatous disease (CGD) and is currently on prophylactic TMP-SMX and itraconazole. He has not had any relapses since his initial presentation. CONCLUSIONS: This case highlights the importance of considering C. violaceum as a relevant human pathogen, and considering it early in temperate regions, particularly in cases of fulminant sepsis associated with multi-organ abscesses. Once C. violaceum is identified, appropriate antimicrobial therapy should be started promptly, and sufficient duration of treatment is necessary for successful therapy.

Epidemiology of infections due to extended-spectrum Beta-lactamase-producing bacteria in a pediatric intensive care unit.

OBJECTIVES: To determine the proportion of infections caused by extended-spectrum ß-lactamase (ESBL)-producing Klebsiella or Escherichia coli Gram-negative organisms in the pediatric intensive care unit (PICU), and to identify risk factors for these infections. METHODS: A retrospective, single-center chart review of patients admitted to a PICU in a 5-year period with infections caused by Klebsiella species or E coli was completed. Data collected include demographics, length of stay, outcome, and relevant risk factors previously defined in the literature. RESULTS: A total of 110 isolates were cultured from 94 patients. A total of 53% of the isolates were E coli, and the remainder were Klebsiella subspecies. Of the 110 isolates, 13 isolates (11.8%) in 7 patients were ESBL positive. The ESBL-producing isolates were equally distributed amongE coli and Klebsiella and were primarily cultured from tracheal aspirates. Most of the ESBL-positive isolates (9 of 13; 69%) were cultured from patients who received ceftazidime and/or cefotaxime in the preceding 30 days. Patients infected with E coli had higher PRISM 1 scores and were more likely to have a Foley catheter, whereas infections with Klebsiella were more common in mechanically ventilated males. Although not statistically significant, 80% of patients who were infected with non-ESBL-producing organisms survived to hospital discharge versus 57% of those infected with ESBL-producing E coli and Klebsiella. CONCLUSIONS: Almost 12% of E coli and Klebsiella isolates in this patient population tested positive for ESBL production. ESBL production was equally distributed between E coli and Klebsiella species. These organisms were cultured from 7% of the study patients. As reported in previous studies, patients infected with ESBL-producing organisms most often had received prior cephalosporins and had a longer length of stay in the PICU.

Pediatric intensive care simulation course: a new paradigm in teaching.

OBJECTIVE: True pediatric emergencies are rare. Because resident work hours are restricted and national attention turns toward patient safety, teaching methods to improve physician performance and patient care are vital. We hypothesize that a critical-care simulation course will improve resident confidence and performance in critical-care situations. INTERVENTIONS: We developed a monthly pediatric intensive care unit simulation course for second-year pediatric residents that consisted of weekly 1-hour sessions during both of the residents' month-long pediatric intensive care unit rotations. All scenarios used high-fidelity pediatric simulators and immediate videotape-assisted debriefing sessions. In addition, simulated intraosseous line insertion and endotracheal intubations were also performed. RESULTS: All residents improved their comfort level and confidence in performing individual key resuscitation tasks. The largest improvements were seen with their perceived ability to intubate children and place intraosseous lines. Both of these skills improved from baseline and compared to third-year-resident controls who had pediatric intensive care unit rotations but no simulations (P = .05 and P = .07, respectively). Videotape reviews showed only 54% ± 12% of skills from a scenario checklist performed correctly. CONCLUSIONS: Our simulation-based pediatric intensive care unit training course improves second-year pediatric residents' comfort level but not performance during codes, as well as their perceived intubation and intraosseous ability. Videotape reviews show discordance between objective performance and self-assessment. Further work is necessary to elucidate the reasons for this difference as well as the appropriate role for simulation in the new graduate medical education climate, and to create new teaching modalities to improve resident performance.

Meperidine restriction in a pediatric hospital.

BACKGROUND: Much has been published revealing concerns surrounding the use of meperidine due to associated toxicities, drug interactions, and lack of proven efficacy. Thus, many adult institutions have chosen to remove or limit the use of this agent, while little has been published about the restriction of meperidine in pediatrics. Many clinicians feel there are still clinical situations in which this agent may be useful. OBJECTIVE: To describe methods taken in a pediatric hospital to restrict the use of meperidine and review literature describing uses of meperidine as a second-line agent. METHODS: In our pediatric institution, a policy to restrict the use of meperidine was developed, approved, and implemented. An assessment of meperidine's use 6 months prior to policy implementation was done, along with a postinitiation review of use. RESULTS: Data revealed that the use of meperidine dropped from 646 doses in 84 patients to 226 doses in 27 patients after restriction, as anticipated. Previous to implementation of these restrictions, orthopedics physicians ordered the majority of meperidine prescriptions, while the gastroenterology service ordered the majority of meperidine prescriptions after implementation of the restriction policy. However, the use of the required form was not widely adopted, with only 30% of practitioners utilizing it postrestriction. Widespread restriction of meperidine and education about use of the form at this institution are still under way. CONCLUSION: Not only are there limited reasons for using meperidine, there are acceptable alternatives for every known indication. Limiting meperidine's use via a restriction policy and/or removal from the institution formulary can help limit the use of this potentially toxic agent in the pediatric patient.

Use of simulation to enhance learning in a pediatric elective.

OBJECTIVES: To assess the impact on learning of adding a pediatric human patient simulation to a pharmacy course. DESIGN: Pharmacy students enrolled in a pediatric elective participated in 1 inpatient and 1 outpatient scenario using a pediatric patient simulator. Immediately following each case, reflective debriefing occurred. ASSESSMENT: Forty-two students participated in the simulation activity over 2 academic years. A pretest and posttest study design was used, with average scores 4.1 + or - 1.2 out of 9 on pretest and average 7.0 + or - 1.5 out of 9 on posttest (p < 0.0001). Ninety-five percent (40/42) of students' scores improved. Students felt the learning experiences were positive and realistic. CONCLUSIONS: Pharmacy students' knowledge and application skills improved through use of pediatric simulation exercises.

Severe invasive community-associated methicillin-resistant Staphylococcus aureus infections in previously healthy children.

OBJECTIVE: An increase in community-associated methicillin-resistant Staphylococcus aureus (CA-MRSA) infections has been reported in the literature. Most severe, life-threatening infections were previously thought to be associated with chronically ill or frail patients. Our pediatric intensive care unit (PICU) has seen a recent dramatic increase in primary, severe invasive CA-MRSA infections in healthy children. DESIGN/SETTING: A retrospective chart review of all previously healthy patients admitted to our 19-bed combined medical-surgical PICU with a primary diagnosis of severe invasive, culture-proven CA-MRSA disease during the past 6 years. RESULTS: Eleven previously healthy patients were admitted to our PICU with severe, primary, invasive CA-MRSA infections from March 2006 through September 2007, in contrast to no patients meeting these criteria in the preceding 5 years. The mortality rate was 27%, compared with an overall PICU mortality rate during the study period of <7%. The mean PICU length of stay of these patients was 14.9 days, compared with an average PICU length of stay of 2.4 days. Despite initiation of treatment with vancomycin at admission to the PICU in all but one case, patients took a mean of 5.7 days to convert to negative blood cultures. Eight patients had bacteremia longer than 4 days. Six of the patients developed bilateral necrotizing pneumonia requiring prolonged mechanical ventilation. CONCLUSIONS: Severe CA-MRSA infections in healthy children are increasing at an alarming rate in our institution. This acute rise in incidence, coupled with an alarmingly high associated mortality rate, raises important questions about the initial empirical antibiotic therapy we use in caring for patients presenting with suspected life-threatening CA-MRSA disease. Vancomycin monotherapy may not be adequate treatment for severe CA-MRSA infections.

Correlation of vancomycin dosing to serum concentrations in pediatric patients: a retrospective database review.

OBJECTIVES: Appropriate antimicrobial dosing maximizes therapeutic benefit while minimizing development of antimicrobial resistance. Common pediatric references recommend vancomycin dosing of 40 mg/kg/day divided every 6 to 8 hours for non-central nervous system infections, while some clinicians report utilizing higher initial doses to optimize efficacy. This study compares vancomycin serum concentrations following traditional dosing of 10 mg/kg/dose every 6 to 8 hours versus 15 to 20 mg/kg/dose every 6 to 8 hours. STUDY DESIGN: Retrospective database review of vancomycin serum concentrations in pediatric patients. RESULTS: Three hundred fifty-seven patients were analyzed. The mean peak concentration of the 10 mg/kg groups every 6 and every 8 hours were below 25 mg/L, whereas the mean peak concentrations of the 15 mg/ kg groups every 6 and 8 hours were within the 25-40 mg/L range (p < 0.001). The mean trough concentration of the 10 mg/kg group every 6 hours was within the 5-15 mg/L range while the 10 mg/kg group dosed every 8 hours was below target. However, the mean trough concentrations of the 15 mg/kg group dosed every 6 and 8 hours were both within the 5-15 mg/L range (p < 0.001). CONCLUSIONS: Vancomycin doses of 15 mg/kg every 6 to 8 hours produce peak and trough serum concentrations within target range more often than 10 mg/kg every 6 to 8 hours.

Histamine 2 receptor antagonists vs intravenous proton pump inhibitors in a pediatric intensive care unit: a comparison of gastric pH.

PURPOSE: The aim of this study was to assess gastric pH in critically ill pediatric patients receiving intravenous stress ulcer medication. MATERIALS AND METHODS: A prospective study was done in 48 patients with a gastric tube in place who were receiving either ranitidine or a proton pump inhibitor and no enteral nutrition. Daily peak and trough gastric pHs were measured. RESULTS: The median age was 7 years 5 months (range, 1 month to 19 years), the median weight was 31 kg (range, 3-130 kg), and the median pediatric risk of mortality 2 (PRISM2) score was 12.5 (range, 0-31). All patients were intubated and 8 received dialysis. The average trough pH was 4.4 +/- 1.6 in the ranitidine group, 4.9 +/- 1.8 in the once daily proton pump inhibitor group, and 5.0 +/- 1.2 in the twice daily proton pump inhibitor group (P = .16). The average peak pH was 5.3 +/- 1.8 in the ranitidine group, 5.9 +/- 1.6 in the once daily proton pump inhibitor group, and 6.0 +/- 1.0 in the twice daily proton pump inhibitor group (P = .06). Three (10%) of 28 trough pH measurements in the twice daily proton pump inhibitor group were more acidic than 4 vs 24 (40%) of 60 in the ranitidine group, and 22 (40%) of 56 in the once daily proton pump inhibitor group (P = .02). One (4%) of 27 peak pH measurements in the twice daily proton pump inhibitor group were more acidic than 4 vs 13 (20%) of 61 in the ranitidine group, and 9 (16%) of 56 in the once daily proton pump inhibitor group (P = .12). Three patients (6%; 95% confidence interval, 0.51%-16%) developed upper gastrointestinal bleeding, and 4 patients (8%; 95% confidence interval, 0%-13%) developed ventilator-acquired pneumonia. CONCLUSIONS: Many critically ill pediatric patients receiving stress ulcer prophylaxis have a trough or peak gastric pH more acidic than 4.

The use of enteral naloxone to treat opioid-induced constipation in a pediatric intensive care unit.

OBJECTIVE: To describe the effects of enteral naloxone used to treat opioid-induced constipation in pediatric intensive care patients. DESIGN: Retrospective chart review. SETTING: Pediatric intensive care unit. PATIENTS: Twenty-three patients who received opioid therapy and enteral naloxone in our institution from January 2003 to February 2004 were compared with a randomly sampled control group matched for age, weight, sex, and length of stay who received opioids but had not received enteral naloxone. INTERVENTIONS: None. MEASUREMENTS: Daily stool output, daily opiate usage, nutrition, adjuvant laxative use, and side effects were assessed. RESULTS: Patients stayed an average of 5 days (range, 0-13 days) in the pediatric intensive care unit before enteral administration of naloxone was instituted and received it for an average of 9 consecutive days (range, 3-30 days). Mean stool output for study patients before administration of enteral naloxone was 0.14 +/- 0.38 stools per day, whereas after its initiation it was 1.60 +/- 1.14 stools per day (p < .001). However, two patients developed significant opiate withdrawal symptoms after receiving enteral naloxone. The average stool output for control patients was 0.53 +/- 1.21 stools per day. CONCLUSIONS: Enteral naloxone may be effective in increasing stool output in opioid-induced constipation but carries the risk of introducing withdrawal symptoms. Further studies are needed to evaluate this agent for opioid-induced constipation in the intensive care unit.

Fatal hypermagnesemia caused by an Epsom salt enema: a case illustration.

The authors describe a case of fatal hypermagnesemia caused by an Epsom salt enema. A 7-year-old male presented with cardiac arrest and was found to have a serum magnesium level of 41.2 mg/dL (33.9 mEq/L) after having received an Epsom salt enema earlier that day. The medical history of Epsom salt, the common causes and symptoms of hypermagnesemia, and the treatment of hypermagnesemia are reviewed. The easy availability of magnesium, the subtle initial symptoms of hypermagnesemia, and the need for education about the toxicity of magnesium should be of interest to physicians.