A Comparison of Currently Available and Investigational Fecal Microbiota Transplant Products for Recurrent Clostridioides difficile Infection.

Clostridioides difficile infection (CDI) is an intestinal infection that causes morbidity and mortality and places significant burden and cost on the healthcare system, especially in recurrent cases. Antibiotic overuse is well recognized as the leading cause of CDI in high-risk patients, and studies have demonstrated that even short-term antibiotic exposure can cause a large and persistent disturbance to human colonic microbiota. The recovery and sustainability of the gut microbiome after dysbiosis have been associated with fewer CDI recurrences. Fecal microbiota transplantation (FMT) refers to the procedure in which human donor stool is processed and transplanted to a patient with CDI. It has been historically used in patients with pseudomembranous colitis even before the discovery of Clostridioides difficile. More recent research supports the use of FMT as part of the standard therapy of recurrent CDI. This article will be an in-depth review of five microbiome therapeutic products that are either under investigation or currently commercially available: Rebyota (fecal microbiota, live-jslm, formerly RBX2660), Vowst (fecal microbiota spores, live-brpk, formerly SER109), VE303, CP101, and RBX7455. Included in this review is a comparison of the products' composition and dosage forms, available safety and efficacy data, and investigational status.

Bictegravir/Emtricitabine/Tenofovir Alafenamide for HIV-1: What is the Hidden Potential of This Emerging Treatment?

Bictegravir/emtricitabine/tenofovir alafenamide (B/F/TAF) is a single-tablet antiretroviral therapy regimen. B/F/TAF has become a popular treatment choice because of its small tablet size, high barrier to resistance, favorable tolerability, and limited drug-drug interaction profile. Continued research on B/F/TAF has revealed additional potential for this regimen. This review presents recent literature supporting the use of B/F/TAF as an option for consolidating therapy and maintaining virologic suppression in individuals despite M184V/I mutations. Additionally, children are a unique patient population with limited antiviral options. Standard dose B/F/TAF has demonstrated similar drug exposure in children and adolescents as adults, and low-dose B/F/TAF is approved for children living with HIV greater than two years of age and weighing at least 14 kg. Data supporting this recommendation is described in this review. Finally, despite a lack of prospective data, B/F/TAF may have a role in the future of pre- and post-exposure prophylaxis. This review discusses these discoveries and the continued exploration of the hidden potential of B/F/TAF.

Efficacy of bezlotoxumab to prevent recurrent Clostridioides difficile infection (CDI) in patients with multiple prior recurrent CDI.

Among 23 patients with multiply recurrent Clostridioides difficile infection (mrCDI) who received bezlotoxumab at the end of antibiotic treatment a sustained clinical response of 91 % at 30 days and 78 % at 90 days was achieved. Bezlotoxumab administered at the end of antibiotic treatment was effective in patients with mrCDI.

Commonly Reported Mosquito-Borne Viruses in the United States: A Primer for Pharmacists.

Mosquito-borne diseases are a public health concern. Pharmacists are often a patient's first stop for health information and may be asked questions regarding transmission, symptoms, and treatment of mosquito borne viruses (MBVs). The objective of this paper is to review transmission, geographic location, symptoms, diagnosis and treatment of MBVs. We discuss the following viruses with cases in the US in recent years: Dengue, West Nile, Chikungunya, LaCrosse Encephalitis, Eastern Equine Encephalitis Virus, and Zika. Prevention, including vaccines, and the impact of climate change are also discussed.

Personalizing prevention: Advances in pharmacotherapy for HIV prevention.

The HIV epidemic continues to pose a significant burden on the healthcare system. Although the incidence of annual new infections is decreasing, health disparities persist and most new infections remain concentrated into different racial, ethnic, and minority groups. Pre-exposure prophylaxis (PrEP), which involves those at high risk of acquiring HIV to take chronic medications to prevent acquisition of the virus, is key to preventing new HIV infections. The purpose of this article is to review medication therapies for PrEP and examine their role in personalizing PrEP in different patient populations. Additionally, new medications currently under development for PrEP are reviewed, as well as treatment as prevention (TasP) and post-exposure prophylaxis (PEP). There are currently four medications available for PrEP: the oral options of co-formulated emtricitabine/tenofovir disoproxil fumarate (FTC/TDF) or emtricitabine/tenofovir alafenamide (FTC/TAF); injectable long-acting cabotegravir (CAB-LA); and the vaginal ring dapivirine (DPV-VR). FTC/TAF is not currently indicated for persons at risk for HIV through vaginal sex due to lack of studies, but trials are currently ongoing. DPV-VR is available in Zimbabwe and South Africa and has been endorsed by the World Health Organization but is not currently available in the United States. Several agents are also in development for use in PrEP: the novel long-acting injectable lenacapavir, a first-in-class capsid inhibitor, which has no cross-resistance to any existing HIV drug class; the subdermal implant islatravir, a first-in-class translocation inhibitor; and VRC01, a broadly neutralizing antibody (bnAb) which has been evaluated in proof-of-concept studies that may lead to the development of more potent bnAbs. Overall, PrEP is highly effective at preventing HIV infection in high-risk populations. Identifying optimal PrEP regimens in different patient populations is complex and must consider patient-specific factors and medication cost and access considerations. Lastly, providers should consider individual patient preferences with regard to prevention to improve access, retention in care, and adherence.

How to design and implement an outpatient antimicrobial stewardship programme.

Antimicrobial stewardship programmes in the outpatient setting have recently become an area of focus in an effort to improve antimicrobial prescribing. The Centers for Disease Control and Prevention and The Joint Commission have recently addressed this concern and provided a framework for the implementation of an outpatient stewardship programme. This manuscript offers detailed guidance on how to design and implement an outpatient antimicrobial stewardship programme and reviews the literature on current strategies. Challenges related to initiating and maintaining outpatient stewardship efforts are also discussed. This article is part of the Antibiotic stewardship Special Issue: https://www.drugsincontext.com/special_issues/antimicrobial-stewardship-a-focus-on-the-need-for-moderation.

Antiretroviral drug-drug interactions: A comparison of online drug interaction databases.

WHAT IS KNOWN AND OBJECTIVE: Antiretrovirals have a high drug interaction potential, which can lead to increased toxicity and/or decreased efficacy. Multiple databases are available to assess drug-drug interactions. The aim of our study was to compare interaction identification for commonly used ARVs and concomitant medications between six different online drug-drug interaction databases. COMMENT: This was a cross-sectional review using each of the following six databases: LexiComp®, Clinical Pharmacology®, Micromedex®, Epocrates®, University of Liverpool, and University of Toronto. Sixteen antiretroviral drugs and 100 of the DrugStats Database "Top 200 of 2019" list of medications were included. Each of the six databases identified a different number of actual or potential interactions. The number of interactions ranged from 211 to 283. WHAT IS NEW AND CONCLUSIONS: A variety of databases exist with inconsistent identification of actual or potential drug-drug interactions amongst them. It may be beneficial to cross-reference multiple databases prior to making decisions regarding patient care.

Pharmacokinetic evaluation of cefiderocol for the treatment of multidrug resistant Gram-negative infections.

INTRODUCTION: Cefiderocol is a siderophore cephalosporin antibiotic and first of its kind approved by the Food and Drug Administration for the treatment of complicated urinary tract infections (cUTI) and hospital-acquired and ventilator-associated bacterial pneumonia (HABP/VABP) in patients 18 years or older caused by susceptible organisms. Cefiderocol's unique mechanism of iron chelation improves Gram-negative membrane penetration as the bacteria's iron uptake mechanism recognizes the chelated iron antibiotic and iron for entry. This also allows for the evasion of cefiderocol from cell entry-related resistance mechanisms. AREAS COVERED: This review covers the mechanism of action, resistance mechanisms, pharmacokinetics in various patient populations, and pharmacodynamics. Relevant literature evaluating efficacy and safety are discussed. EXPERT OPINION: Limited treatment options are available for the treatment of carbapenem-resistantorganisms. Clinical trials have demonstrated that cefiderocol is no worse than alternative treatment options for cUTIs and HABP/VABP, but more data are currently available to support the use of beta-lactam beta-lactamase inhibitor agents, where susceptible. Mortality differences demonstrated in patients with pneumonia and bloodstream infections must further be explored and logistical and practical considerations regarding susceptibility testing and use as monotherapy vs. combination therapy must be considered prior to confidently recommending cefiderocol for regular use in systemic infections.

Penetration of Antibacterial Agents into Pulmonary Epithelial Lining Fluid: An Update.

A comprehensive review of drug penetration into pulmonary epithelial lining fluid (ELF) was previously published in 2011. Since then, an extensive number of studies comparing plasma and ELF concentrations of antibacterial agents have been published and are summarized in this review. The majority of the studies included in this review determined ELF concentrations of antibacterial agents using bronchoscopy and bronchoalveolar lavage, and this review focuses on intrapulmonary penetration ratios determined with area under the concentration-time curve from healthy human adult studies or pharmacokinetic modeling of various antibacterial agents. If available, pharmacokinetic/pharmacodynamic parameters determined from preclinical murine infection models that evaluated ELF concentrations are also provided. There are also a limited number of recently published investigations of intrapulmonary penetration in critically ill patients with lower respiratory tract infections, where greater variability in ELF concentrations may exist. The significance of these changes may impact the intrapulmonary penetration in the setting of infection, and further studies relating ELF concentrations to clinical response are needed. Phase I drug development programs now include assessment of initial pharmacodynamic target values for pertinent organisms in animal models, followed by evaluation of antibacterial penetration into the human lung to assist in dosage selection for clinical trials in infected patients. The recent focus has been on ß-lactam agents, including those in combination with ß-lactamase inhibitors, particularly due to the rise of multidrug-resistant infections. This manifests as a large portion of the review focusing on cephalosporins and carbapenems, with or without ß-lactamase inhibitors, in both healthy adult subjects and critically ill patients with lower respiratory tract infections. Further studies are warranted in critically ill patients with lower respiratory tract infections to evaluate the relationship between intrapulmonary penetration and clinical and microbiological outcomes. Our clinical research experience with these studies, along with this literature review, has allowed us to outline key steps in developing and evaluating dosage regimens to treat extracellular bacteria in lower respiratory tract infections.