Search

Antimicrobial resistance is a global threat that requires urgent attention to slow the spread of resistant pathogens. The United States Centers for Disease Control and Prevention (CDC) has emphasized clinician-driven antimicrobial stewardship approaches including the reporting and proper documentation of antimicrobial usage and resistance. Additional efforts have targeted the development of new antimicrobial agents, but narrow profit margins have hindered manufacturers from investing in novel antimicrobials for clinical use and therefore the production of new antibiotics has decreased. In order to combat this, both antimicrobial drug discovery processes and healthcare reimbursement programs must be improved. Without action, this poses a high probability to culminate in a deadly post-antibiotic era. This review will highlight some of the global health challenges faced both today and in the future. Furthermore, the new Infectious Diseases Society of America (IDSA) guidelines for resistant Gram-negative pathogens will be discussed. This includes new antimicrobial agents which have gained or are likely to gain FDA approval. Emphasis will be placed on which human pathogens each of these agents cover, as well as how these new agents could be utilized in clinical practice.

Febrile neutropenia (FN) is associated with mortality rates as high as 40%, highlighting the importance of appropriate clinical management in this patient population. The morbidity and mortality of FN can be attributed largely to infectious processes, with specific concern for infections caused by pathogens with antimicrobial resistance. Expeditious identification of responsible pathogens and subsequent initiation of empiric antimicrobial therapy is imperative. There are four commonly used guidelines, which have variable recommendations for empiric therapy in these populations. All agree that changes could be made once patients are stable and/or with an absolute neutrophil count (ANC) over 500 cells/mcL. Diagnostic advances have the potential to improve knowledge of pathogens responsible for FN and decrease time to results. In addition, more recent data show that rapid de-escalation or discontinuation of empiric therapy, regardless of ANC, may reduce days of therapy, adverse effects, and cost, without affecting clinical outcomes. Antimicrobial and diagnostic stewardship should be performed to identify, utilize, and respond to appropriate rapid diagnostic tests that will aid in the definitive management of this population.

Abstract Cannabidiol and related cannabinoids are under exploration for the treatment of a number of disease states. The cannabinoid-quinone HU-331 has been studied as a potential anticancer therapeutic. Previous studies provide evidence that HU-331 displays anticancer activity without some of the known adverse events associated with traditional anticancer agents. In this brief review, we will explore the literature related to the activity of HU-331 in purified systems, cancer cell lines, and animal models. For example, HU-331 displays inhibitory activity against human topoisomerase IIα, a known anticancer drug target. Further, in multiple cell model systems, the IC50 value for HU-331 was less than 10 μM. In addition, mouse model systems demonstrate the ability of HU-331 to shrink tumors without causing cardiotoxicity. In addition, we will briefly review the activity of some key analogs and derivatives of HU-331 for various disease states. Taken together, the published studies support further exploration of HU-331 for the treatment of cancer and possibly other disease states.

Delays in the treatment of proven invasive fungal disease have been shown to be harmful. However, empiric treatment for all patients at risk of infection has not demonstrated benefit. This study evaluates the effects of a micafungin stewardship initiative on the duration of therapy and clinical outcomes at the University of Mississippi Medical Center in Jackson, Mississippi. This single-center quasi-experiment evaluated patients who received micafungin. Adult inpatients who received at least one treatment dose of micafungin in the pre-intervention (1 October 2020 to 30 September 2021) or post-intervention (1 October 2021 to 30 April 2022) groups were included. Patients were placed on micafungin for prophylaxis and those who required definitive micafungin therapy were excluded. An algorithm was used to provide real-time recommendations in order to assess change in the treatment days of micafungin therapy. A total of 282 patients were included (141 pre-group versus 141 post-group). Over 80% of the patients included in the study were in an intensive care unit, and other baseline characteristics were similar. The median number of treatment days with micafungin was 4 [IQR 3-6] in the pre-group and 3 [IQR 2-6] in the post-group (p = 0.005). Other endpoints, such as time to discontinuation or de-escalation, hospital mortality, and hospital length of stay, were not significantly different between the groups. An antifungal stewardship initiative can be an effective way to decrease unnecessary empiric antifungal therapy for patients who are at risk of invasive fugal disease.

Invasive fungal infections are a strong contributor to healthcare costs, morbidity and mortality, especially amongst hospitalized patients. Historically, Candida was responsible for approximately 15% of all nosocomial bloodstream infections. In the past 10 years, the epidemiology of Candida species has altered, with increasing prevalence of resistant species. With rising fungal resistance, especially in Candida spp., the demand for novel antifungal therapies has exponentially increased over the last decade. Newer antifungal agents have become an attractive option for patients needing long-term therapy for infections or those requiring antifungal prophylaxis. Despite advances in coverage of non-Candida pathogens with newer agents, clinical scenarios involving multidrug-resistant fungal pathogens continue to arise in practice. Combination antifungal therapy can lead to a host of side-effects, some of which can be drug limiting. Additional antifungal therapies with enhanced fungal spectrum of activity and decreased rates of adverse effects are warranted. Fosmanogepix, ibrexafungerp, olorofim and rezafungin may help fill some of these gaps in the antifungal armamentarium. This article is part of the Challenges and strategies in the management of invasive fungal infections Special Issue: https://www.drugsincontext.com/special_issues/challenges-and-strategies-in-the-management-of-invasive-fungal-infections