Role of therapeutic drug monitoring in the treatment of multi-drug resistant tuberculosis.

Tuberculosis (TB) is a leading cause of mortality worldwide, and resistance to anti-tuberculosis drugs is a challenge to effective treatment. Multi-drug resistant TB (MDR-TB) can be difficult to treat, requiring long durations of therapy and the use of second line drugs, increasing a patient's risk for toxicities and treatment failure. Given the challenges treating MDR-TB, clinicians can improve the likelihood of successful outcomes by utilizing therapeutic drug monitoring (TDM).

Clinical considerations and pharmacokinetic interactions between HIV and tuberculosis therapeutics.

Introduction: Tuberculosis (TB) is a leading infectious disease cause of mortality worldwide, especially for people living with human immunodeficiency virus (PLWH). Treating TB in PLWH can be challenging due to numerous drug interactions.

Areas Covered: This review discusses drug interactions between antitubercular and antiretroviral drugs.

Cefepime Daily Exposure and the Associated Impact on the Change in Sequential Organ Failure Assessment Scores and Vasopressors Requirement in Critically Ill Patients Using Repeated-Measures Mixed-Effect Modeling.

Importance: Sepsis and septic shock are major healthcare problems that need early and appropriate management.

Objectives: To evaluate the association of daily cefepime pharmacokinetic/pharmacodynamic (PK/PD) parameters with change in Sequential Organ Failure Assessment (SOFA) score and vasopressors requirement.

Design Setting And Participants: This is a retrospective study.

Association of piperacillin and vancomycin exposure on acute kidney injury during combination therapy.

Objectives: Acute kidney injury (AKI) is a well-documented adverse effect observed with piperacillin/tazobactam in combination with vancomycin. The pharmacokinetics of these antibiotics when given in combination have not been previously evaluated. The purpose of this study was to compare the exposure of vancomycin + piperacillin/tazobactam in patients with and without AKI.

Impact of Beta-Lactam Target Attainment on Resistance Development in Patients with Gram-Negative Infections.

Background: The objective was to identify associations between beta-lactam pharmacokinetic/pharmacodynamic (PK/PD) targets and Gram-negative bacteria resistance emergence in patients.

Methods: Retrospective data were collected between 2016 to 2019 at the University of Florida Health-Shands Hospital in Gainesville, FL. Adult patients with two Gram-negative isolates receiving cefepime, meropenem, or piperacillin-tazobactam and who had plasma beta-lactam concentrations were included.

A Randomized Clinical Trial of Bayesian-Guided Beta-Lactam Infusion Strategy and Associated Bacterial Resistance and Clinical Outcomes in Patients With Severe Pneumonia.

Background: Antimicrobial resistance is a growing health concern worldwide. The objective of this study was to evaluate the effect of beta-lactam infusion on the emergence of bacterial resistance in patients with severe pneumonia in the intensive care unit.

Methods: Adult intensive care patients receiving cefepime, meropenem, or piperacillin-tazobactam for severe pneumonia caused by Gram-negative bacteria were randomized to receive beta-lactams as an intermittent (30 minutes) or continuous (24 hours) infusion.

The effect of anti-tuberculosis drug pharmacokinetics on QTc prolongation.

Background: Implementation of newer anti-tuberculosis (TB) drugs may prolong the QT interval, increasing the risk of arrythmias and sudden cardiac death. The potential for cardiac adverse events has prompted recommendations for frequent cardiac monitoring during treatment. However, unknowns remain, including the association between drug concentrations and QT interval.

Making the case for precision dosing: visualizing the variability of cefepime exposures in critically ill adults.

Objective: To investigate and describe the variability in cefepime exposures among 'real-world', critically ill patients by using population pharmacokinetic modelling and simulations, and with translation of these findings to visualizations.

Methods: A cohort of adult medical ICU patients who received cefepime with therapeutic drug monitoring was studied. Two compartment models were developed to estimate cefepime clearance (Model 1) and simulate cefepime exposures among 1000 patients, each with identical creatinine clearance of 60 mL/min and receiving a regimen of cefepime 1 gram IV over 30 minutes, every 8 hours (Model 2).

Pharmacokinetics and pharmacodynamics of adult dolutegravir tablets in treatment-experienced children with HIV weighing at least 20 kg.

Objective: Limited pharmacokinetic/pharmacodynamic data are a barrier to the scale-up of dolutegravir-based antiretroviral therapy (ART) in children. We examined the pharmacokinetics/pharmacodynamics of the adult film-coated dolutegravir 50 mg tablets in children with HIV infection weighing at least 20 kg.

Design: A prospective, observational, pharmacokinetic, and safety study.

Beta-lactam target attainment and associated outcomes in patients with bloodstream infections.

Objectives: To evaluate the association between early and cumulative beta-lactam pharmacokinetic/pharmacodynamic (PK/PD) parameters and therapy outcomes in bloodstream infection (BSI).

Methods: Adult patients who received cefepime, meropenem, or piperacillin/tazobactam for BSI and had concentrations measured were included. Beta-lactam exposure was generated and the time that free concentration remained above the minimum inhibitory concentration (fT) and four multiples of MIC (fT) were calculated for times 0-24 h and 0-7 days of therapy.

Cerebrospinal fluid concentrations of fluoroquinolones and carbapenems in tuberculosis meningitis.

Tuberculosis meningitis (TBM) is the most lethal form of TB. It is difficult to treat in part due to poor or uncertain drug penetration into the central nervous system (CNS). To help fill this knowledge gap, we evaluated the cerebrospinal fluid (CSF) concentrations of fluoroquinolones and carbapenems in patients being treated for TBM.

Use of therapeutic drug monitoring to characterize cefepime-related neurotoxicity.

Study Objectives: Data evaluating cefepime thresholds associated with neurotoxicity remain limited. The objectives of this study were to evaluate the incidence of cefepime-related neurotoxicity (CRN) in patients with plasma cefepime concentrations, assess the relationship between cefepime exposure and CRN, investigate clinical factors associated with CRN, and describe electroencephalogram (EEG) abnormalities in CRN.

Design: This was a retrospective study of adult inpatients admitted between 2016 and 2018 who received cefepime therapeutic drug monitoring (TDM).

Meropenem Population Pharmacokinetics and Simulations in Plasma, Cerebrospinal Fluid, and Brain Tissue.

Meropenem is a broad spectrum carbapenem used for the treatment of cerebral infections. There is a need for data describing meropenem pharmacokinetics (PK) in the brain tissue to optimize therapy in these infections. Here, we present a meropenem PK model in the central nervous system and simulate dosing regimens.

Using Machine Learning To Define the Impact of Beta-Lactam Early and Cumulative Target Attainment on Outcomes in Intensive Care Unit Patients with Hospital-Acquired and Ventilator-Associated Pneumonia.

Hospital-acquired pneumonia (HAP) and ventilator-associated pneumonia (VAP) are the most common intensive care unit (ICU) infections. We aimed to evaluate the association of early and cumulative beta-lactam pharmacokinetic/pharmacodynamic (PK/PD) parameters with therapy outcomes in pneumonia. Adult ICU patients who received cefepime, meropenem, or piperacillin-tazobactam for HAP or VAP and had its concentration measured were included.