Liposomal Amphotericin B Induced Acute Reactions

Three formulations of amphotericin B are available: liposomal, lipid complex and conventional. The liposomal amphotericin B is more preferred agent than other formulations because of its tolerability, safety and potent antifungal activity. However, the liposomal amphotericin B can cause infusion-related reactions. In this case report, we aimed to report a patient who developed infusion-related reactions during the treatment with the liposomal amphotericin B but eventually tolerated the prolonged infusion. In this case report, we present a patient who developed an infusion-related reaction during The liposomal amphotericin B treatment. A 26-year-old male patient with acute promyelocytic leukemia was hospitalized for the third course of chemotherapy. Due to the invasive fungal infection history in previous hospitalizations, the liposomal amphotericin B 400 mg (IV, 5 mg/kg) once daily was initiated as secondary antifungal prophylaxis. Swelling in infusion site and chest pain were reported within 10 minutes of the liposomal amphotericin B administration, and the infusion rate was slowed down to 400 mg/6 hours from 400 mg/2 hours. All these reactions disappeared with prolonged infusion time. The patient received a total of 7 liposomal amphotericin B doses subsequently without any reaction during the chemotherapy cycle. In our experience, the liposomal amphotericin B-induced infusion-related reactions can be resolved by prolonging the infusion time.

Evaluation of the Robustness of Therapeutic Drug Monitoring Coupled with Bayesian Forecasting of Busulfan with Regard to Inaccurate Documentation

Background Inaccurate documentation of sampling and infusion times is a potential source of error in personalizing busulfan doses using therapeutic drug monitoring (TDM). Planned times rather than the actual times for sampling and infusion time are often documented. Therefore, this study aimed to evaluate the robustness of a limited sampling TDM of busulfan with regard to inaccurate documentation. Methods A pharmacometric analysis was conducted in NONMEM® 7.4.3 and “R” by performing stochastic simulation and estimation with four, two and one sample(s) per patient on the basis of a one-compartment- (1CMT) and two-compartment (2CMT) population pharmacokinetic model. The dosing regimens consisted of i.v. busulfan (0.8 mg/kg) every 6 h (Q6H) or 3.2 mg/kg every 24 h (Q24H) with a 2 h- and 3 h infusion time, respectively. The relative prediction error (rPE) and relative root-mean-square error (rRmse) were calculated in order to determine the accuracy and precision of the individual AUC estimation. Results A noticeable impact on the estimated AUC based on a 1CMT-model was only observed if uncertain documentation reached ± 30 min (1.60% for Q24H and 2.19% for Q6H). Calculated rPEs and rRmse for Q6H indicate a slightly lower level of accuracy and precision when compared to Q24H. Spread of rPE’s and rRmse for the 2CMT-model were wider and higher compared to estimations based on a 1CMT-model. Conclusions The estimated AUC was not affected substantially by inaccurate documentation of sampling and infusion time. The calculated rPEs and rRmses of estimated AUC indicate robustness and reliability for TDM of busulfan, even in presence of erroneous records.

Staffing and Capacity Planning for SARS-CoV-2 Monoclonal Antibody Infusion Facilities: A Performance Estimation Calculator based on Discrete-Event Simulations

Objective: The COVID-19 pandemic has significantly stressed healthcare systems. The addition of monoclonal antibody (mAb) infusions, which prevent severe disease and reduce hospitalizations, to the repertoire of COVID-19 countermeasures offers the opportunity to reduce system stress but requires strategic planning and use of novel approaches. Our objective was to develop a web-based decision-support tool to help existing and future mAb infusion facilities make better and more informed staffing and capacity decisions. Materials and Methods: Using real-world observations from three medical centers operating with federal field team support, we developed a discrete-event simulation model and performed simulation experiments to assess performance of mAb infusion sites under different conditions. Results: 162,000 scenarios were evaluated by simulations. Our analyses revealed that it was more effective to add check-in staff than to add additional nurses for middle-to-large size sites with ≥ 2 infusion nurses; that scheduled appointments performed better than walk-ins when patient load was not high; and that reducing infusion time was particularly impactful when load on resources was only slightly above manageable levels. Discussion: Physical capacity, check-in staff, and infusion time were as important as nurses for mAb sites. Health systems can effectively operate an infusion center under different conditions to provide mAb therapeutics even with relatively low investments in physical resources and staff. Conclusion: Simulations of mAb infusion sites were used to create a capacity planning tool to optimize resource utility and allocation in constrained pandemic conditions, and more efficiently treat COVID-19 patients at existing and future mAb infusion sites.

Does prolonged infusion time really improve the efficacy of meropenem therapy? A prospective study in critically ill patients

Background: Meropenem is a carbapenem antibiotic that has demonstrated excellent in vitro activity against gram-negative clinical isolates and is commonly used in critically ill patients. This study aimed to find the pharmacokinetic/ pharmacodynamic of meropenem in critically ill patients and whether prolonged injection duration is really beneficial to meropenem therapy. Method: We included 209 samples in 64 patients in this prospective study. PPK analysis and Monte Carlo dosing simulations were developed using Phoenix.Results: A two-compartment model described the data adequately. Clearance (CL), volume (V), clearance of peripheral compartment (CL2), volume of peripheral compartment (V2) were 6.15 L/h, 2.83 L/h, 17.40L, and 17.48L, respectively. Creatinine clearance and uric acid were significant covariates. Patients with creatinine clearance of 60 ml/min or less and uric acid greater than 400 μmol/l could achieve the target > 90% under the minimum inhibitory concentration (MIC) of 8 mg/L, even with the administration dose of 500 mg/8 h with a 2-h infusion. Prolonging the infusion time significantly improved the therapeutic effect when MIC＜4. However, for the pharmacodynamic (PD) effects of 100% fT > MIC and 100% fT > 4MIC, no significant statistical difference was observed in critically ill patients.Conclusions: Critically ill patients with lower creatinine clearance and higher uric acid levels were likely to need a lower dosage of meropenem. Prolonged infusion time were not always beneficial for those who need a higher therapeutic target (100% fT > MIC,100% fT > 4 MIC) or with MIC 4mg/L. Increasing dose or alternative therapeutic strategies may be required for critically ill patients with drug-resistant or severe infections. The study is of great significance to guide the rational use of meropenem in critically ill patients.Trial registration: The trial was registered in the China Clinical Trial (ChiCTR1900020672). Registered on 12 January 2019.

Lidocaine for dinutuximab associated pain? A multicenter retrospective observational cohort study

Dinutuximab, an immune-mediated therapy used in the treatment of high-risk neuroblastoma targets the protein disialoganglioside (GD2) present on neuroblastoma cells, neurons, and peripheral nerve fibers. Off target effects could lead to severe nerve pain. Pain regimens including continuous infusion opioids are required during the first treatment course. Our institution utilizes a combination of intravenous (IV) lidocaine infusions and morphine for the treatment of dinutuximab-associated neuropathic pain. The primary outcome of this study was to compare morphine equivalents for cycle one of dinutuximab at an institution that uses IV lidocaine (primary) versus those that do not (comparison). Secondary outcomes included both dinutuximab infusion time and safety of IV lidocaine. A retrospective, multi-centered, electronic chart review was performed at three tertiary academic medical centers. Patients between 0-18 years of age during their first course of dinutuximab were included to evaluate the primary outcome of adjuvant morphine equivalents needed. Total morphine equivalents at the primary institution were 1.87 mg/kg vs 1.79 mg/kg at the comparison institutions (p=0.413). Dinutuximab infusion time was significantly lower at the primary institution: 610.5 minutes vs 676.23 minutes (p=0.046). Only one patient at the primary institution experienced nausea, vomiting and paresthesias. This study did not find a statistically significant difference in morphine equivalents between patients who received IV lidocaine and those who did not. However, we did find that use of IV lidocaine resulted in a statistically significant lower dinutuximab infusion time and that it is a safe adjuvant medication in the treatment of dinutuximab-associated neuropathic pain.

Effects of uric acid, creatinine clearance, and infusion duration on the population pharmacokinetics of meropenem in critically ill patients

Background: Meropenem is a carbapenem antibiotic that has demonstrated excellent in vitro activity against gram-negative clinical isolates and is commonly used in critically ill patients. This study aimed to find the pharmacokinetic/ pharmacodynamic of meropenem in critically ill patients and whether prolonged injection duration is really beneficial to meropenem therapy. Method: We included 209 samples in 64 patients in this prospective study. PPK analysis and Monte Carlo dosing simulations were developed using Phoenix.Results: A two-compartment model described the data adequately. Clearance (CL), volume (V), clearance of peripheral compartment (CL2), volume of peripheral compartment (V2) were 6.15 L/h, 2.83 L/h, 17.40L, and 17.48L, respectively. Creatinine clearance and uric acid were significant covariates. Patients with creatinine clearance of 60 ml/min or less and uric acid greater than 400 μmol/l could achieve the target > 90% under the minimum inhibitory concentration (MIC) of 8 mg/L, even with the administration dose of 500 mg/8 h with a 2-h infusion. Prolonging the infusion time significantly improved the therapeutic effect when MIC＜4. However, for the pharmacodynamic (PD) effects of 100% fT > MIC and 100% fT > 4MIC, no significant statistical difference was observed in critically ill patients.Conclusions: Critically ill patients with lower creatinine clearance and higher uric acid levels were likely to need a lower dosage of meropenem. Prolonged infusion time were not always beneficial for those who need a higher therapeutic target (100% fT > MIC,100% fT > 4 MIC) or with MIC 4mg/L. Increasing dose or alternative therapeutic strategies may be required for critically ill patients with drug-resistant or severe infections. The study is of great significance to guide the rational use of meropenem in critically ill patients.Trial registration: The trial was registered in the China Clinical Trial (ChiCTR1900020672). Registered on 12 January 2019.

Impact of rapid infliximab infusions on access at a large academic tertiary medical center

Purpose Infliximab promotes remission in patients with inflammatory bowel disease (IBD) and rheumatologic disease (RD). Rapid infliximab infusions (RI) reduce infusion time from 2 hours to 1 hour and can enhance access to care, as defined by capacity, safety, and patient characteristics. Our hypothesis for the study described here was that use of RI can enhance access for patients. Methods Data on all patients receiving infliximab for IBD or RD at our outpatient infusion center from February 2016 to August 2017 were retrospectively analyzed. Demographic and clinical information were collected. Results Of 348 patients who received infliximab, 205 had IBD and 143 had RD. In terms of capacity, 40% of patients received RI, resulting in a 16.1% decrease in average daily infusion time and a 9.8% increase in average daily available scheduled infusion chair time (P = 0.720). In terms of safety, 4 patients switched back to standard infusions after RI, after 3 specifically had reactions to RI. In terms of patient characteristics, more patients with RD versus IBD received RI (P = 0.020). Among the patients with RD, a lower proportion receiving RI were female (P = 0.043). For the patients with IBD, a higher proportion receiving RI were white (P = 0.048). Among both patients with RD and patients with IBD, a higher proportion receiving RI had private insurance (P = 0.016 and P = 0.018, respectively). Conclusion RI were safe and increased available chair time. Females with RD, patients of non-White race with IBD, and patients with public insurance were less likely to receive RI. Future directions include patient surveys and evaluation of implicit bias against patient factors that may impact access to RI.