scholarly journals ColistinDose, a Mobile App for Determining Intravenous Dosage Regimens of Colistimethate in Critically Ill Adult Patients: Clinician-Centered Design and Development Study (Preprint)

2020 ◽  
Author(s):  
Xueliang Hua ◽  
Chen Li ◽  
Jason M Pogue ◽  
Varun S Sharma ◽  
Ilias Karaiskos ◽  
...  
Keyword(s):  
Renal Function ◽  
Critically Ill ◽  
Mobile App ◽  
Adult Patients ◽  
Patient Treatment ◽  
Population Pharmacokinetic ◽  
Safety Issues ◽  
Population Pharmacokinetic Study ◽  
Dosage Regimens ◽  
Calculation Results

BACKGROUND Determining a suitable dose of intravenous colistimethate is challenging because of complicated pharmacokinetics, confusing terminology, and the potential for renal toxicity. Only recently have reliable pharmacokinetic/pharmacodynamic data and dosing recommendations for intravenous colistimethate become available. OBJECTIVE The aim of this work was to develop a clinician-friendly, easy-to-use mobile app incorporating up-to-date dosing recommendations for intravenous colistimethate in critically ill adult patients. METHODS Swift programming language and common libraries were used for the development of an app, ColistinDose, on the iPhone operating system (iOS; Apple Inc). The compatibility among different iOS versions and mobile devices was validated. Dosing calculations were based on equations developed in our recent population pharmacokinetic study. Recommended doses generated by the app were validated by comparison against doses calculated manually using the appropriate equations. RESULTS ColistinDose provides 3 major functionalities, namely (1) calculation of a loading dose, (2) calculation of a daily dose based on the renal function of the patient (including differing types of renal replacement therapies), and (3) retrieval of historical calculation results. It is freely available at the Apple App Store for iOS (version 9 and above). Calculated doses accurately reflected doses recommended in patients with varying degrees of renal function based on the published equations. ColistinDose performs calculations on a local mobile device (iPhone or iPad) without the need for an internet connection. CONCLUSIONS With its user-friendly interface, ColistinDose provides an accurate and easy-to-use tool for clinicians to calculate dosage regimens of intravenous colistimethate in critically ill patients with varying degrees of renal function. It has significant potential to avoid the prescribing errors and patient safety issues that currently confound the clinical use of colistimethate, thereby optimizing patient treatment.

scholarly journals ColistinDose, a Mobile App for Determining Intravenous Dosage Regimens of Colistimethate in Critically Ill Adult Patients: Clinician-Centered Design and Development Study

10.2196/20525 ◽  
2020 ◽  
Vol 8 (12) ◽  
pp. e20525
Author(s):  
Xueliang Hua ◽  
Chen Li ◽  
Jason M Pogue ◽  
Varun S Sharma ◽  
Ilias Karaiskos ◽  
...  
Keyword(s):  
Renal Function ◽  
Critically Ill ◽  
Mobile App ◽  
Adult Patients ◽  
Patient Treatment ◽  
Population Pharmacokinetic ◽  
Safety Issues ◽  
Population Pharmacokinetic Study ◽  
Dosage Regimens ◽  
Calculation Results

Background Determining a suitable dose of intravenous colistimethate is challenging because of complicated pharmacokinetics, confusing terminology, and the potential for renal toxicity. Only recently have reliable pharmacokinetic/pharmacodynamic data and dosing recommendations for intravenous colistimethate become available. Objective The aim of this work was to develop a clinician-friendly, easy-to-use mobile app incorporating up-to-date dosing recommendations for intravenous colistimethate in critically ill adult patients. Methods Swift programming language and common libraries were used for the development of an app, ColistinDose, on the iPhone operating system (iOS; Apple Inc). The compatibility among different iOS versions and mobile devices was validated. Dosing calculations were based on equations developed in our recent population pharmacokinetic study. Recommended doses generated by the app were validated by comparison against doses calculated manually using the appropriate equations. Results ColistinDose provides 3 major functionalities, namely (1) calculation of a loading dose, (2) calculation of a daily dose based on the renal function of the patient (including differing types of renal replacement therapies), and (3) retrieval of historical calculation results. It is freely available at the Apple App Store for iOS (version 9 and above). Calculated doses accurately reflected doses recommended in patients with varying degrees of renal function based on the published equations. ColistinDose performs calculations on a local mobile device (iPhone or iPad) without the need for an internet connection. Conclusions With its user-friendly interface, ColistinDose provides an accurate and easy-to-use tool for clinicians to calculate dosage regimens of intravenous colistimethate in critically ill patients with varying degrees of renal function. It has significant potential to avoid the prescribing errors and patient safety issues that currently confound the clinical use of colistimethate, thereby optimizing patient treatment.

scholarly journals Population Pharmacokinetic Study of Ceftriaxone in Elderly Patients, Using Cystatin C-Based Estimates of Renal Function To Account for Frailty

2020 ◽  
Vol 64 (10) ◽  
Author(s):  
Shu Jin Tan ◽  
Matthew Cockcroft ◽  
Madhu Page-Sharp ◽  
Glenn Arendts ◽  
Timothy M. E. Davis ◽  
...  
Keyword(s):  
Renal Function ◽  
Elderly Patients ◽  
Cystatin C ◽  
Pharmacokinetic Study ◽  
Severe Renal Impairment ◽  
Population Pharmacokinetic ◽  
Pharmacokinetic Studies ◽  
Total Exposure ◽  
Population Pharmacokinetic Study ◽  
Trough Concentrations

ABSTRACT Ceftriaxone is widely used for respiratory and urinary infections in elderly and frail patients, but there are few pharmacokinetic studies. A prospective population pharmacokinetic study of ceftriaxone in adults over 65 years old was undertaken. Dried blood spots collected at baseline (predose) and 0.5, 1, 4, 8, and 24 h after administration of 1 g of ceftriaxone were assayed using a validated liquid chromatography-mass spectroscopy analytical method. Frailty was classified using the Edmonton frailty scale and grip strength via a hand dynamometer. Estimates of glomerular filtration rate were determined using creatinine-based and cystatin C-based equations. Of 26 patients recruited, 23 (88%) were vulnerable or very frail. Estimates of drug clearance improved significantly with a cystatin C-based estimate of renal function that accounted for frailty. Simulations indicate that the combined effects of ranges of size and renal function resulted in a 6-fold range in peak ceftriaxone concentrations and 9-fold range in total exposure (area under the concentration-time curve [AUC]). For elderly patients with moderate or severe renal impairment, 48-h dosing results in greater trough concentrations and total exposure than the trough concentrations and total exposure in patients with normal renal function receiving 24-h dosing. Cystatin C-based measures of renal function improved predictions of ceftriaxone clearance in elderly patients.

scholarly journals Impact of Maximizing Css/MIC Ratio on Efficacy of Continuous Infusion Meropenem Against Documented Gram-Negative Infections in Critically Ill Patients and Population Pharmacokinetic/Pharmacodynamic Analysis to Support Treatment Optimization

2021 ◽  
Vol 12 ◽  
Author(s):  
Pier Giorgio Cojutti ◽  
Milo Gatti ◽  
Matteo Rinaldi ◽  
Tommaso Tonetti ◽  
Cristiana Laici ◽  
...  
Keyword(s):  
Renal Function ◽  
Critically Ill ◽  
Critically Ill Patients ◽  
Population Pharmacokinetic ◽  
Treatment Optimization ◽  
Gram Negative ◽  
Cart Analysis ◽  
Pharmacodynamic Analysis ◽  
Favorable Clinical Outcome ◽  
Support Treatment

Introduction: optimal treatment of Gram-negative infections in critically ill patients is challenged by changing pathophysiological conditions, reduced antimicrobial susceptibility and limited therapeutic options. The aim of this study was to assess the impact of maximizing Css/MIC ratio on efficacy of continuous infusion (CI) meropenem in treating documented Gram-negative infections in critically ill patients and to perform a population pharmacokinetic/pharmacodynamic analysis to support treatment optimization.Materials and Methods: Classification and regression tree (CART) analysis was used to identify whether a cutoff of steady-state meropenem concentration (Css)-to-minimum inhibitory concentration (MIC) (Css/MIC) ratio correlated with favorable clinical outcome. A non-parametric approach with Pmetrics was used for pharmacokinetic analysis and covariate evaluation. The probability of target attainment (PTA) of the identified Css/MIC ratio was calculated by means of Monte Carlo simulations. Cumulative fraction of response (CFRs) were calculated against common Enterobacterales, P. aeruginosa and A. baumannii as well.Results: a total of 74 patients with 183 meropenem Css were included. CART analysis identified a Css/MIC ratio ≥4.63 as cutoff value significantly associated with favorable clinical outcomes. Multivariate regression analysis confirmed the association [OR (95%CI): 20.440 (2.063–202.522); p < 0.01]. Creatinine clearance (CLCR) was the only covariate associated with meropenem clearance. Monte Carlo simulations showed that, across different classes of renal function, dosages of meropenem ranging between 0.5 and 2 g q6h over 6 h (namely by CI) may grant PTAs of Css/MIC ratios ≥4.63 against susceptible pathogens with an MIC up to the EUCAST clinical breakpoint of 2 mg/L. The CFRs achievable with these dosages were very high (>90%) against Enterobacterales across all the classes of renal function and against P. aeruginosa among patients with CLCR < 30 ml/min/1.73 m2, and quite lower against A. baumannii.Discussion: our findings suggest that Css/MIC ratio ≥4.63 may be considered the pharmacodynamic target useful at maximizing the efficacy of CI meropenem in the treatment of Gram-negative infections in critically ill patients. Dosages ranging between 0.5 g q6h and 2 g q6h by CI may maximize the probability of favorable clinical outcome against meropenem-susceptible Gram-negative pathogens among critically ill patients having different degrees of renal function.

Reply to Baklouti et al., “Why Is It Desirable To Do the External Evaluation of a Population Pharmacokinetic Model?”

2021 ◽  
Author(s):  
Pier Giorgio Cojutti ◽  
Matteo Rinaldi ◽  
Eleonora Zamparini ◽  
Nicolò Rossi ◽  
Sara Tedeschi ◽  
...  
Keyword(s):  
Pharmacokinetic Study ◽  
Population Pharmacokinetic Model ◽  
Pharmacokinetic Model ◽  
Optimal Treatment ◽  
Adult Patients ◽  
Population Pharmacokinetic ◽  
External Evaluation ◽  
Population Pharmacokinetic Study ◽  
Osteoarticular Infections ◽  
French Group

We thank Baklouti et al. (1) for commenting on our population pharmacokinetic study of dalbavancin for optimal treatment of adult patients with staphylococcal osteoarticular infections (2) and for suggesting that our model tends to underestimate the concentrations observed in a group of French patients (French group).…

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