A Retrospective Cohort Study Comparing Dual Therapy With Ceftaroline With Vancomycin or Daptomycin Monotherapy for High-Grade or Persistent MRSA Bacteremia.

Background: Methicillin-resistant Staphylococcus aureus (MRSA) bacteremia is a serious clinical infection associated with a high risk of mortality. Dual therapy is often used in patients with persistent bacteremia. Objective: This study aimed to compare the outcomes of vancomycin or daptomycin monotherapy with those of dual therapy with ceftaroline in high-grade or persistent MRSA bacteremia. Methods: We conducted a retrospective cohort study at a university teaching hospital between January 2014 and June 2021, involving adults initially treated with vancomycin or daptomycin. Patients were categorized into monotherapy and dual therapy groups. The primary outcome was 30-day mortality. Secondary outcomes included microbiological relapse and antibiotic-related adverse events. Results: In a group of 155 patients, 30-day mortality rates were similar between the monotherapy (23.4%) and dual therapy (22.6%) groups, with comparable microbiological relapse rates (6.5%). In inverse probability of treatment weighting analysis, we found no significant association between dual therapy and mortality (adjusted risk ratio [ARR] 1.38, 95% CI 0.64-2.41, P = 0.38) or microbiological relapse (ARR 0.95, 95% CI 0.31-2.73, P = 0.93). Dual therapy was associated with a lower risk of antibiotic-related adverse events (ARR 0.45, 95% CI 0.21-0.89, P = 0.02). Infectious diseases (ID) consultation was associated with a reduced mortality risk (ARR 0.27, 95% CI 0.07-0.95, P = 0.04). Conclusions: Dual therapy with ceftaroline did not reduce mortality risk compared with monotherapy in patients with MRSA bacteremia. However, patients with ID consultations showed a 73% reduction in mortality rates. Large-scale, prospective, and randomized controlled trials are needed to provide conclusive evidence regarding the potential benefits of dual therapy with ceftaroline for MRSA bacteremia.

Short versus long duration of ceftaroline combination therapy and outcomes in persistent or high-grade MRSA bacteremia: A retrospective single-center study.

BACKGROUND: Methicillin-resistant Staphylococcus aureus (MRSA) is associated with high mortality rates. Despite antibiotic therapy, persistent bacteremia is challenging to treat. Combination therapy with ceftaroline has emerged as a potential treatment option; however, the optimal duration and clinical implications after bacteremia clearance are unknown. METHODS: This retrospective cohort study examined patients with high-grade or persistent MRSA bacteremia who were treated with ceftaroline combination therapy at the University of New Mexico Hospital between January 2014 and June 2021. Patients were categorized into short- (<7 days) or long-duration (≥7 days) groups based on the duration of combination therapy after bacteremia clearance. Outcomes included 30-day all-cause mortality, bacteremia recurrence, post-bacteremia clearance length of stay, and adverse events. RESULTS: A total of 32 patients were included in this study. The most common sources of bacteremia were bone/joint and endovascular (28.1%, 9/32 each). The median duration of combination therapy after clearance was seven days (IQR 2.8, 11). Patients in the long-duration group had a lower Charlson comorbidity index (1.0 vs 5.5, p = 0.017) than those in the short-duration group. After adjusting for confounders, there was no significant difference in the 30-day all-cause mortality between the groups (AOR 0.17, 95% CI 0.007-1.85, p = 0.18). No association was found between combination therapy duration and recurrence (OR 2.53, 95% CI 0.19-inf, p = 0.24) or adverse drug events (OR 3.46, 95% CI 0.39-74.86, p = 0.31). After controlling for total hospital length of stay, there was no significant difference in the post-bacteremia clearance length of stay between the two groups (p = 0.37). CONCLUSIONS: Prolonging ceftaroline combination therapy after bacteremia clearance did not significantly improve outcomes in patients with persistent or high-grade MRSA bacteremia. The limitations of this study warrant cautious interpretation of its results. Larger studies are needed to determine the optimal duration and role of combination therapy for this difficult-to-treat infection.

Pneumococcal Polysaccharide Vaccination (PPSV23) in High-Risk Pediatric Patients With Diabetes.

OBJECTIVE: The Advisory Committee on Immunization Practices recommends the pneumococcal polysaccharide vaccine (PPSV23) following the pneumococcal conjugate vaccine (PCV13) for pediatric patients aged 2 to 18 years with high-risk medical conditions. The PPSV23 is not a routine immunization for all pediatric patients and children who meet criteria for high-risk conditions may not consistently receive the PPSV23 vaccine, despite current recommendations. The goal of this study was to determine PPSV23 -vaccination rates in the high-risk pediatric patients with type 1 or type 2 diabetes. METHODS: A single-center retrospective cohort study was conducted. Patients were included if they were 2 to 18 years of age on January 1, 2019, with a diagnosis of diabetes, and had ≥1 encounters within the health care system in 2019. The primary outcome was PPSV23 vaccination rates in the high-risk diabetic pediatric population. Secondary outcomes included identifying missed opportunities for vaccinations and the incidence of invasive pneumococcal infections. RESULTS: A total of 366 patients met criteria for study inclusion. Patients had a mean age of 13.3 years and were predominantly white (69.8%). A total of 32 (8.7%) patients had documentation of PPSV23 vaccination. Baseline characteristics were comparable between the two groups. There were 32 cases of pneumonia charted before patients received the PPSV23 and one case reported after patients received the PPSV23 vaccination. CONCLUSIONS: PPSV23 vaccination rates were low in this high-risk diabetic pediatric group, with many -documented missed opportunities for vaccination. This may be attributed to the vaccine not being a -routinely recommended for all pediatric patients.

Pneumococcal Pure Polysaccharide Vaccination in Pediatric Patients With Chronic Heart Disease.

INTRODUCTION: This study aimed to describe pneumococcal polysaccharide vaccine-23 (PPSV23) vaccination use in high-risk pediatric patients with chronic heart disease (CHD). METHOD: This was a single-center retrospective cohort study. Patients were included if they were aged 2-18 years and were diagnosed with CHD. The primary outcome was PPSV23 vaccination. Secondary outcomes included missed opportunities and the incidence of infections. RESULTS: Three hundred ninety-two patients were included; the mean age was 8.8 years. Only 40 patients (10.2%) had documentation of PPSV23 vaccination. Patients had a median number of three clinic visits in 2019. There were 114 cases of pneumonia documented in patients before receiving PPSV23 and one case reported after PPSV23 vaccination. DISCUSSION: PPSV23 vaccination in high-risk pediatric patients with CHD was low, with many documented missed opportunities for vaccination. This may be attributed to the PPSV23 not being a routine vaccination on the pediatric schedule.

Stability Testing of Sirolimus in Medium-Chain Triglyceride Oil Using High-Performance Liquid Chromatography.

OBJECTIVE: Recently, a premature neonate, born at 26.5 weeks, was treated with sirolimus for kaposiform hemangioendothelioma with Kasabach-Merritt phenomenon at the University of New Mexico Children's Hospital. Because of the lipophilic properties of the drug and an inability to draw the correct dose needed for the neonate with the standard 1 mg/mL concentration, sirolimus was diluted to 0.01 mg/mL (10 mg/L) in medium-chain triglyceride (MCT) oil. The objective of this study was to evaluate the stability of sirolimus diluted in MCT oil. METHODS: Commercially available sirolimus oral solution was diluted with MCT oil from 1 mg/mL to 10 mg/L. The diluted samples were prepared by measuring 0.1 mL of the commercial product in an oral syringe and mixing with 9.9 mL of MCT oil. The 3 diluted samples were placed in amber glass vials, stored at 10°C, and analyzed over 14 days. RESULTS: The initial concentration of the 3 samples ranged from 8.5 to 10.8 mg/L sirolimus, or 85% to 108% of the target value. No significant differences were seen between average concentrations on the days tested. However, the average drug concentration fell to approximately 90% of the theoretical 10 mg/L target concentration between days 7 and 10. CONCLUSIONS: This study shows that sirolimus oral solution diluted with MCT oil to a final concentration of 10 mg/L was stable for at least 7 days when stored at 10°C, suggesting that the beyond-use date should be 7 days.

Evaluation of Anticoagulant Monitoring in Pediatric Patients Receiving Enoxaparin for Treatment of Venous Thrombosis.

OBJECTIVES: A venous thromboembolism (VTE) is a blood clot that occurs secondary to vessel wall injury often from a central line insertion. Enoxaparin is often considered a first-line treatment in pediatrics for VTE due to its favorable kinetic profile. Enoxaparin monitoring for pediatric patients is accomplished through anti-Xa monitoring in which monitoring practices may vary between institutions. The objective of this study is to evaluate covariates in pediatric patients to determine which variables are most likely to be associated with enoxaparin dose changes as a result of anti-Xa monitoring. METHODS: A single center, retrospective chart review was conducted in pediatric patients treated with enoxaparin for VTE over a 10-year period and who were assessed to determine covariates that lead to dose changes based on anti-Xa levels. Secondary outcomes described monitoring patterns at the University of New Mexico Children's Hospital. RESULTS: Sixty-eight patients met inclusion criteria in which results showed that patients aged 2 to 5.9 months (p = 0.026), who had critical care status (p = 0.009), and who were of Native American ethnicity (p = 0.016) were likely to have an enoxaparin dose change at least once during their treatment regimen. The mean number of levels drawn were 7.5 per patient over a 6- to 12-week period, and doses were not frequently changed based on a confirmatory lab draw. However, many doses were adjusted based on the week 1 post-therapeutic level. CONCLUSIONS: Patients of Native American ethnicity, younger than 6 months, and those admitted to the PICU were likely to have dose changes based on anti-Xa levels.

Use of Sirolimus in a Premature Neonate With Kaposiform Hemangioedema.

Kaposiform hemangioendothelioma (KHE) is a rare, vascular malignancy that is often associated with coagulopathies and thrombocytopenia secondary to platelet trapping. Typically, a person diagnosed with KHE with Kasabach-Merritt phenomenon (KMP) presents with a reddish-purplish lesion, thrombocytopenia, and elevated D-dimer, which can lead to high morbidity and mortality. Sirolimus has been identified as a treatment option for KHE with or without KMP for reduction in lesion size and hematologic parameters. In this case report, a female born at 26.5 weeks was noted at birth to have a purpuric lesion on her right upper back and flank area. She was diagnosed with biopsy-confirmed KHE with KMP. She was started on sirolimus 0.01 mg (0.02 mg/kg; 0.14 mg/m2) once a day, and because of high trough concentrations treatment was held until concentrations decreased. Sirolimus was then microdiluted to a 0.01 mg/mL concentration in medium-chain triglyceride oil for administration. Prior to discharge from the hospital the commercially available product was dispensed for home use. After 6 months of treatment, she achieved a reduction in lesion size and improvement in hematologic parameters, and treatment was stopped at 9 months.

A Distinctive Approach to Venous Thromboembolism Treatment in a Pediatric, Hemodialysis Patient: A Case Report.

Enoxaparin is a low molecular weight heparin (LMWH) that is the mainstay for treatment of pediatric patients with a venous thromboembolism, which provides better compliance compared with the use of unfractionated heparin (UFH) in long-term anticoagulation. Although data are limited in pediatric patients with renal insufficiency, enoxaparin can be used in this population. Data related to its use in hemodialysis (HD) pediatric patients is almost non-existent. A major concern for enoxaparin use in patients with renal insufficiency or for those on HD is bleeding. A few studies in adults showed an increased risk of bleeding, but the risk was similar to that of UFH when the two were compared. This case report describes the use of enoxaparin in an 8-year-old female who is on hemodialysis, without any bleeding or clotting complications. Although systematic trials are needed to support the safety and efficacy of LMWH in pediatric patients with renal dysfunction or on HD, this case will provide limited information for enoxaparin use in this population.

Open-Label Study of the Stability of Sublingual Nitroglycerin Tablets in Simulated Real-Life Conditions.

Contemporary practice favors refilling sublingual nitroglycerin (SL NTG) every 3 to 6 months. This recommendation is based on antiquated data that does not consider the reformulated tablet and the improved manufacturing process. Our objective was to investigate the stability of SL NTG over time using simulated real-life scenarios in comparison to controlled storage conditions. This was an open-label study of 100- and 25-count commercial SL NTG bottles stored in either controlled temperature and relative humidity conditions, or carried in a pocket or purse. SL NTG potency (chemical stability) was assessed using high performance liquid chromatography and physical stability was assessed by changes in tablet weights over time through the labeled expiration date. Both chemical and physical stability of SL NTG were affected by environmental and physical factors. High temperature storage resulted in the most rapid loss of potency. Tablets carried in a pant pocket lost potency faster than those carried in a purse. Potency was also dependent on headspace of the bottle. Tablets stored in the original bottle in a temperate environment could be expected to maintained potency for more than 2 years when carried in a purse, irrespective of package size. When carried in a pant pocket, potency of a 25-count bottle was maintained for 2 years, whereas potency of a 100-count bottle fell below acceptable limits at 12 months. In conclusion, since potency is dependent on temperature, headspace, and carrying practices, frequency of SL NTG refills should be based on individual patient behavior.