Increased Stroke Risk Following Herpes Zoster Infection and Protection With Zoster Vaccine.

BACKGROUND: Studies evaluating stroke following varicella zoster virus (VZV) infection are limited, and the utility of zoster vaccination against this phenomenon is unclear. This study aimed to determine the risk of stroke 30 days following zoster infection and to evaluate the impact of zoster vaccinations on the risk of stroke in VZV-infected patients. METHODS: This retrospective case-control study was conducted from January 2010 to January 2020 utilizing nationwide patient data retrieved from the Veterans Affairs' Corporate Data Warehouse. RESULTS: A total of 2 165 505 patients ≥18 years of age who received care at a Veterans Affairs facility were included in the study, of whom 71 911 had a history of zoster infection. Zoster patients were found to have 1.9 times increased likelihood of developing a stroke within 30 days following infection (odds ratio [OR], 1.93 [95% confidence interval {CI}, 1.57-2.4]; P < .0001). A decreased risk of stroke was seen in patients who received the recombinant zoster vaccine (OR, 0.57 [95% CI, .46-.72]; P < .0001) or the live zoster vaccine (OR, 0.77 [95% CI, .65-.91]; P = .002). CONCLUSIONS: Patients had a significantly higher risk of stroke within the first month following recent herpes zoster infection. Receipt of at least 1 zoster vaccination was found to mitigate this increased risk. Vaccination may therefore be viewed as a protective tool against the risk of neurologic postinfection sequelae.

Optimizing Clinical Outcomes Through Rational Dosing Strategies: Roles of Pharmacokinetic/Pharmacodynamic Modeling Tools.

Significant progress in previous decades has led to several methodologies developed to facilitate the design of optimal antimicrobial dosing. In this review, we highlight common pharmacokinetic/pharmacodynamic (PKPD) modeling techniques and their roles in guiding rational dosing regimen design. In the early drug development phases, dose fractionation studies identify the PKPD index most closely associated with bacterial killing. Once discerned, this index is linked to clinical efficacy end points, and classification and regression tree analysis can be used to define the PKPD target goal. Monte Carlo simulations integrate PKPD and microbiological data to identify dosing strategies with a high probability of achieving the established PKPD target. Results then determine dosing regimens to investigate and/or validate the findings of randomized controlled trials. Further improvements in PKPD modeling could lead to an era of precision dosing and personalized therapeutics.

Significant Publications on Infectious Diseases Pharmacotherapy in 2021.

Purpose: To summarize the most noteworthy infectious diseases (ID) pharmacotherapy articles published in peer-reviewed literature in 2021. Summary: Members of the Houston Infectious Diseases Network (HIDN) nominated articles that were deemed to have significant contributions to ID pharmacotherapy in 2021. These nominations included articles pertaining to both general ID, including coronavirus disease 2019 (COVID-19), and human immunodeficiency virus/acquired immunodeficiency syndrome (HIV/AIDS) pharmacotherapy. A total of 35 articles were nominated by HIDN: 30 articles pertaining to general ID pharmacotherapy and 5 articles with HIV/AIDS focus. To select the most influential articles of 2021, a survey was created and distributed to members of the Society of Infectious Diseases Pharmacists (SIDP). Of the 239 SIDP members who responded to the survey, there were 192 recorded votes for the top 10 general ID pharmacotherapy articles and 47 recorded votes for the top HIV/AIDS article, respectively. The top publications are summarized. Conclusion: Antimicrobial stewardship and the optimal management of infectious disease states continues to be a priority in the midst of the ongoing coronavirus disease 2019 (COVID-19) global pandemic. In light of the sheer volume of ID-related articles published in the past year, this review aims to aid clinicians in remaining up-to-date on key practice-changing ID pharmacotherapy publications from 2021.

Open-source maximum a posteriori-bayesian dosing AdDS to current therapeutic drug monitoring: Adapting to the era of individualized therapy.

Recent updates in the therapeutic drug monitoring (TDM) guidelines for vancomycin have rekindled interest in maximum a posteriori-Bayesian (MAP-Bayesian) estimation of patient-specific pharmacokinetic parameters. To create a versatile infrastructure for MAP-Bayesian dosing of vancomycin or other drugs, a freely available, R-based software package, Advanced Dosing Solutions (AdDS), was created to facilitate clinical implementation of these improved TDM methods. The objective of this study was to utilize AdDS for pre- and post-processing of data in order to streamline the therapeutic management of vancomycin in healthy and obese veterans. Patients from a local Veteran Affairs hospital were utilized to compare the process of full re-estimation versus Bayesian updating of priors on healthy adult and obese patient populations for use with AdDS. Twenty-four healthy veterans were utilized to train (14/24) and test (10/24) the base pharmacokinetic model of vancomycin while comparing the effects of updated and fully re-estimated priors. This process was repeated with a total of 18 obese veterans for both training (11/18) and testing (7/18). Comparison of MAP objective function between the original and re-estimated models for healthy adults indicated that 78.6% of the subjects in the training and 70.0% of the subjects in the testing datasets had similar or improved predictions by the re-estimated model. For obese veterans, 81.8% of subjects in the training dataset and 85.7% of subjects in the testing dataset had similar or improved predictions. Re-estimation of model parameters provided more significant improvements in objective function compared with Bayesian updating, which may be a useful strategy in cases where sufficient samples and subjects are available. The generation of bespoke regimens based on patient-specific clearance and minimal sampling may improve patient care by addressing fundamental pharmacokinetic differences in healthy and obese veteran populations.

Combatting the Rising Tide of Antimicrobial Resistance: Pharmacokinetic/Pharmacodynamic Dosing Strategies for Maximal Precision.

OBJECTIVE: Antimicrobial pharmacokinetics/pharmacodynamics (PK/PD) principles and PK/PD models have been essential in characterizing the mechanism of antibiotic bacterial killing and determining the most optimal dosing regimen that maximizes clinical outcomes. This review summarized the fundamentals of antimicrobial PK/PD and the various types of PK/PD experiments that shaped the utilization and dosing strategies of antibiotics today. METHODS: Multiple databases - including PubMed, Scopus, and EMBASE - were searched for published articles that involved PK/PD modelling and precision dosing. Data from in vitro, in vivo and mechanistic PK/PD models were reviewed as a basis for compiling studies that guide dosing regimens used in clinical trials. RESULTS: Literature regarding the utilization of exposure-response analyses, mathematical modelling and simulations that were summarized are able to provide a better understanding of antibiotic pharmacodynamics that influence translational drug development. Optimal pharmacokinetic sampling of antibiotics from patients can lead to personalized dosing regimens that attain target concentrations while minimizing toxicity. Thus the development of a fully integrated mechanistic model based on systems pharmacology can continually adapt to data generated from clinical responses, which can provide the framework for individualized dosing regimens. CONCLUSIONS: The promise of what PK/PD can provide through precision dosing for antibiotics has not been fully realized in the clinical setting. Antimicrobial resistance, which has emerged as a significant public health threat, has forced clinicians to empirically utilize therapies. Future research focused on implementation and translation of PK/PD-based approaches integrating novel approaches that combine knowledge of combination therapies, systems pharmacology and resistance mechanisms are necessary. To fully realize maximally precise therapeutics, optimal PK/PD strategies are critical to maximize antimicrobial efficacy against extremely-drug-resistant organisms, while minimizing toxicity.