Experience with Implementing a Beta-lactam Therapeutic Drug Monitoring Service in a Burn Intensive Care Unit: A Retrospective Chart Review.

Thermal injuries alter pharmacokinetics, complicating the prediction of standard antibiotic dose effectiveness. Therapeutic drug monitoring (TDM) has been proposed to prevent subtherapeutic dosing of antibiotic therapy, but remains scarcely studied in the burn patient population. A retrospective chart review of burn patients receiving beta-lactam TDM from 2016 to 2019 was conducted.

Therapeutic drug monitoring in patients with tuberculosis and concurrent medical problems.

Introduction: Therapeutic drug monitoring (TDM) has been recommended for treatment optimization in tuberculosis (TB) but is only is used in certain countries e.g. USA, Germany, the Netherlands, Sweden and Tanzania.

Pharmacokinetics of Efavirenz 600 mg Once Daily During Pregnancy and Post Partum in Ghanaian Women Living With HIV.

Purpose: The updated World Health Organization guidelines recommend efavirenz (EFV) 400 mg as the preferred alternate first-line antiretroviral therapy to dolutegravir, with EFV 600 mg recommended only in special situations. We examined the pharmacokinetic (PK) properties of EFV 600 mg/d during pregnancy and post partum to inform EFV dosing decisions in pregnant women.

Methods: Ghanaian pregnant women with HIV infection initiating tenofovir disoproxil fumarate 300 mg/lamivudine 300 mg/EFV 600 mg fixed-dose combination tablet once daily were enrolled.

A Pharmacology Perspective of Simultaneous Tuberculosis and Hepatitis C Treatment.

Tuberculosis (TB) and hepatitis C virus (HCV) infection are both major public health problems. Despite high rates of co-infection there is scarce literature addressing the convergence of the two diseases. One particularly unexplored area is the potential for simultaneous treatment of TB and HCV which would allow for leveraging an extensive global TB treatment infrastructure to help scale up HCV treatment.

Recent Progress in Natural-Product-Inspired Programs Aimed To Address Antibiotic Resistance and Tolerance.

Bacteria utilize multiple mechanisms that enable them to gain or acquire resistance to antibiotic therapies during the treatment of infections. In addition, bacteria form biofilms which are surface-attached communities of enriched populations containing persister cells encased within a protective extracellular matrix of biomolecules, leading to chronic and recurring antibiotic-tolerant infections. Antibiotic resistance and tolerance are major global problems that require innovative therapeutic strategies to address the challenges associated with pathogenic bacteria.

A Highly Potent Class of Halogenated Phenazine Antibacterial and Biofilm-Eradicating Agents Accessed Through a Modular Wohl-Aue Synthesis.

Unlike individual, free-floating planktonic bacteria, biofilms are surface-attached communities of slow- or non-replicating bacteria encased within a protective extracellular polymeric matrix enabling persistent bacterial populations to tolerate high concentrations of antimicrobials. Our current antibacterial arsenal is composed of growth-inhibiting agents that target rapidly-dividing planktonic bacteria but not metabolically dormant biofilm cells. We report the first modular synthesis of a library of 20 halogenated phenazines (HP), utilizing the Wohl-Aue reaction, that targets both planktonic and biofilm cells.

Structure-Activity Relationships of a Diverse Class of Halogenated Phenazines That Targets Persistent, Antibiotic-Tolerant Bacterial Biofilms and Mycobacterium tuberculosis.

Persistent bacteria, including persister cells within surface-attached biofilms and slow-growing pathogens lead to chronic infections that are tolerant to antibiotics. Here, we describe the structure-activity relationships of a series of halogenated phenazines (HP) inspired by 2-bromo-1-hydroxyphenazine 1. Using multiple synthetic pathways, we probed diverse substitutions of the HP scaffold in the 2-, 4-, 7-, and 8-positions, providing critical information regarding their antibacterial and bacterial eradication profiles.

Discovery of quinoline small molecules with potent dispersal activity against methicillin-resistant Staphylococcus aureus and Staphylococcus epidermidis biofilms using a scaffold hopping strategy.

Staphylococcus aureus and Staphylococcus epidermidis are recognized as the most frequent cause of biofilm-associated nosocomial and indwelling medical device infections. Biofilm-associated infections are known to be highly resistant to our current arsenal of clinically used antibiotics and antibacterial agents. To exacerbate this problem, no therapeutic option exists that targets biofilm-dependent machinery critical to Staphylococcal biofilm formation and maintenance.