Successful Treatment of Invasive MRSA Infections in Children Using Area Under the Vancomycin Concentration-Time Curve Divided by the Minimum Inhibitory Concentration (AUC/MIC) to Measure Vancomycin Exposure

Background: Vancomycin is the treatment of choice for invasive methicillin-resistant Staphylococcus aureus (MRSA) infections. Previous guidelines issued by the Infectious Diseases Society of America (IDSA) recommended targeting vancomycin serum trough concentrations of 15–20 mg/L; however, troughs <15 mg/L are also associated with increased odds of renal toxicity. To minimize toxicity, recently updated ASHP/IDSA/PIDS vancomycin dosing guidelines recommend the use of an area under the vancomycin concentration-time curve divided by the minimum inhibitory concentration (AUC/MIC) pharmacodynamic index to measure vancomycin exposure, with an AUC/MIC ratio >400 correlating with clinical efficacy. However, data on vancomycin therapeutic drug monitoring (TDM) in children are limited. Our institutional practice since January 2009 has been to use AUC/MIC, rather than serum trough concentrations, to guide vancomycin dosing. In this study, we describe clinical outcomes in vancomycin-treated children with invasive MRSA infections using this dosing method. Methods: We performed a retrospective chart review of children hospitalized with invasive MRSA infections between 2006 and 2019 at Rady Children’s Hospital in San Diego, California. Clinical, microbiologic, and pharmacologic data including the site of MRSA infection, clinical failure or cure, occurrence of acute kidney injury (AKI), vancomycin MIC, vancomycin AUC, and serum trough concentrations were collected. Results: In total, 61 invasive MRSA cases were reviewed: 20 were admitted January 2016 through December 2008, and 41 were admitted January 2009 through June 2019 (Figure 1). Most patients did not have medical comorbidities. The most common types of infections were primary bacteremia (34%) and osteomyelitis (32%). Of 61 children, 50 (82%) had positive clinical outcomes regardless of vancomycin dosing method. Of 20 patients, 8 (40%) admitted prior to January 2009 developed AKI, compared with 5 (12%) of 41 patients admitted after January 2009. Conclusions: In our retrospective review, most patients had clinically successful outcomes regardless of which dosing strategy was used. We found higher rates of renal toxicity in patients who were admitted prior to 2009, with TDM based on measuring peak and trough concentrations, compared with those using AUC/MIC for TDM. Our findings suggest that AUC/MIC TDM for invasive MRSA infections may be associated with lower rates of renal toxicity.Funding: NoDisclosures: None

Developing a Consistent, Reproducible Botulinum Toxin Type a Dosing Method for Upper Limb Tremor by Kinematic Analysis

Botulinum toxin type A (BoNT-A) injection patterns customized to each patient’s unique tremor characteristics produce better efficacy and lower adverse effects compared to the fixed-muscle-fixed-dose approach for Essential Tremor (ET) and Parkinson’s disease (PD) tremor therapy. This article outlined how a kinematic-based dosing method to standardize and customize BoNT-A injections for tremors was developed. Seven ET and eight PD participants with significant tremor reduction and minimal perceived weakness using optimized BoNT-A injections determined by clinical and kinematic guidance were retrospectively selected to develop the kinematic-based dosing method. BoNT-A dosages allocated per joint were paired to baseline tremor amplitudes per joint. The final kinematic-based dosing method was prospectively utilized to validate BoNT-A injection pattern selection without clinical/visual assessments in 31 ET and 47 PD participants with debilitating arm tremors (totaling 122 unique tremor patterns). Whole-arm kinematic tremor analysis was performed at baseline and 6-weeks post-injection. Correlation and linear regression analyses between baseline tremor amplitudes and the change in tremor amplitude 6-weeks post-injection, with BoNT-A dosages per joint, were performed. Injection patterns determined using clinical assessment and interpretation of kinematics produced significant associations between baseline tremor amplitudes and optimized BoNT-A dosages in all joints. The change in elbow tremor was only significantly associated with the elbow total dose as the change in the wrist and shoulder tremor amplitudes were not significantly associated with the wrist and shoulder dosages from the selected 15 ET and PD participants. Using the kinematic-based dosing method, significant associations between baseline tremor amplitudes and the change (6-weeks post-first treatment) in tremor at each joint with BoNT-A dosages for all joints was observed in all 78 ET and PD participants. The kinematic-based dosing method provided consistency in dose selection and subsequent tremor reduction and can be used to standardize tremor assessments for whole-arm tremor treatment planning.

Comparison between conventional dosing versus personalized pharmacokinetic dosing of vancomycin: a pilot study from a Malaysian private hospital

Pharmacist led vancomycin dosing is not a common practice in private hospital settings of the Malaysian healthcare system. The lack of this pharmacist led system has led to conventional vancomycin dosing without considering the differences in patients pharmacokinetic parameters. This study aims to compare the differences in vancomycin doses between conventional dosing and pharmacist-led personalized pharmacokinetic dosing. A retrospective pilot study was conducted on inpatient adults who were prescribed with intravenous vancomycin in a private hospital. Personalized vancomycin doses were retrospectively calculated by using the pharmacokinetic parameters and was then compared with the actual conventional doses used in the patients. The area under concentration curve over 24 hours/minimum inhibitory concentration (AUC24/MIC) ratio achieved by the doses was also compared. The targeted AUC24/MIC ratio was 400-600 to ensure efficacy and safety of the therapy. A total of 24 patients with a median age of 55.50 years were conveniently sampled. The patients were mostly male (58.3%) and were admitted to the neurosurgical ward (33.3%). Vancomycin was mainly prescribed as empirical treatment (58.3%) for a median treatment period of 5.00 days (IQR 4.00 – 7.00 days). The conventional doses had significant (p < 0.001) lower median total daily dose (2000 mg versus 2500 mg) and lower AUC24/MIC ratio (385 versus 495) as compared to personalized doses. In conclusion, the personalized pharmacokinetic dosing method was significantly more able to achieve the targeted AUC24/MIC ratio. Vancomycin personalized dosing should be considered in the Malaysian private hospital setting.

CONCRETO PRODUZIDO COM AGREGADO GRAÚDO LATERÍTICO EM SANTARÉM, PARÁ

RESUMO: Avaliou-se a substituição da brita basáltica existente no concreto por material alternativo em abundância no município de Santarém-PA: a laterita. Foi avaliado o desempenho do concreto incorporado com agregado laterítico in natura em substituição parcial ao agregado graúdo de brita basáltica nos teores de 20% e 50%. Realizou-se a caracterização dos agregados graúdo e miúdo. De acordo com o método da ABCP, determinou-se o traço de referência em massa 1:1,71:3,03:0,53; confeccionou-se corpos-de-prova cilíndricos 10x20 cm utilizando 3 traços diferentes, de modo a substituir a brita basáltica pelo agregado laterítico, em 20% e 50%. Para cada traço foram quantificados a sua consistência, por meio do ensaio de abatimento do tronco de cone, resistência à compressão axial, resistência à tração por compressão diametral e módulo de elasticidade aos 28 dias. A substituição do agregado convencional de brita basáltica por agregado laterítico em seu estado natural promoveu diminuição da resistência a compressão simples, da resistência à tração por compressão diametral e do módulo de elasticidade com a inclusão do agregado laterítico na mistura. Destaca-se que acima de determinado teor de substituição o concreto torna-se inviável devido a necessidade de adicionar aditivo plastificante para manter a consistência desejada e que as duas misturas incorporadas com agregado laterítico se mostraram muito semelhantes após os 28 dias, no que tange a ganhos de resistência a compressão. ABSTRACT: This study is about the replacement of basaltic origin crushed stone by alternative material present in the municipality of Santarém, Pará State: the laterite. The aim were to evaluate the performance of concrete incorporated with natural lateritic aggregate, replacing the of crushed stone in 20% and 50%. The first stage was characterizing the coarse and fine aggregates that made up the studied concrete. According to ABCP dosing method it was determined the mass reference trait 1: 1.71: 3.03: 0.53; bodies of 10x20 cm were made for cylindrical test, using three different strokes so that the basaltic crushed stone gradually replaced by the lateritic aggregate in proportions of 20% and 50%. For each trait its consistency was quantified by means of the tapering test, axial compression strength, diametric compression tensile strength and the modulus of elasticity at 28 days. Was observed that the replacement of the conventional aggregate basalt crushed stone for aggregate of laterite in natural state promoted a decrease in the value of simple compressive strength, diametric tensile strength and modulus of elasticity with inclusion of a larger amount of lateritic aggregate in the mixture. It is noteworthy that above a certain substitution content, the concrete becomes not feasible due to the need for a large increase in the amount of plasticizer additive to the desired consistency is maintained and the two blends incorporated with lateritic showed very similar after 28 days in terms of gains in compressive strength.

VARIABLES IMPACTING GFR ESTIMATION METHOD FOR DRUG DOSING IN CKD: ARTIFICIAL NEURAL NETWORK PREDICTION MODEL

Objective: This study aimed to measure concordance between different renal function estimates in terms of drug doses and determine the potential significant clinical differences. Methods: Around one hundred and eighty patients (≥ 18 y) with chronic kidney disease (CKD) were eligible for inclusion in this study. A paired-proportion cohort design was utilized using an artificial intelligence model. CKD patients refined into those who have drugs adjusted for renal function. For superiority of Cockcroft-Gault (CG) vs. modified diet in renal disease (MDRD) guided with references for concordance or discordance of the two equations and determined the dosing tiers of each drug. Validated artificial neural networks (ANN) was one outcome of interest. Variable impacts and performed reassignments were compared to evaluate the factors that affect the accuracy in estimating the kidney function for a better drug dosing. Results: The best ANN model classified most cases to CG as the best dosing method (79 vs. 72). The probability was 85% and the top performance was slightly above 93%. Creatinine levels and CKD staging were the most important factors in determining the best dosing method of CG versus MDRD. Ideal and actual body weights were second (24%). Whereas drug class or the specific drug was an important third factor (14%). Conclusion: Among many variables that affect the optimal dosing method, the top three are probably CKD staging, weight, and the drug. The contrasting CKD stages from the different methods can be used to recognize patterns, identify and predict the best dosing tactics in CKD patients.

Comparative Study of Maize Agronomics Performance Under Low Nitrogen Soil Availability, in Southern Savanna of Dr Congo

To determine the growing and yield performance of low nitrogen tolerant maize varieties under fertilized and unfertilized conditions, a study was conducted at the Mvuazi Research Center. Nine varieties were tested with and without fertilizer using the micro-dosing method, following the randomized complete block design with two factors. The results showed a difference among varieties in both crop conditions. The average yield with fertilizer was higher than the yield without fertilizer. The varieties LNTP-W C4 and LNTP-Y C7 registered 5.9 t/ha and 3.6 t/ha respectively under fertilized crop conditions and 7.14t/ha and 7.12t/ha under unfertilized crop conditions. Thus, using Low-N can minimize production costs by improving the productivity of soils low in Nitrogen typical of conditions of the southwestern savanna.