Antifungal resistance, combinations and pipeline: oh my!

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.

Missed Opportunities for Antifungal Stewardship during the COVID-19 Era.

Significant increases in antibacterial use were observed during the COVID-19 pandemic. However, subsequent analyses found this increase in antibiotic use to be excessive in comparison with the relatively low rates of bacterial coinfection. Although patients who are critically ill with COVID-19 may be at an increased risk for pulmonary aspergillosis, antifungal use in these populations remained underreported, particularly in later phases of the pandemic. This single-center, population-level cohort analysis compares the monthly use rates of mold-active antifungal drugs in the medical intensive care unit during April 2019-March 2020 (baseline) with those during April 2020-November 2022. The antifungal drugs included in the analysis were liposomal amphotericin B, anidulafungin, isavuconazonium, posaconazole, and voriconazole. We found that during 2020-2022, the usage of antifungal drugs was not significantly different from baseline for all included agents except isavuconazonium, which was used significantly more (p = 0.009). There were no changes in diagnostic modalities between the two time periods. The reported prevalence of and mortality from COVID-19-associated pulmonary aspergillosis (CAPA) may have resulted in higher rates of prescribing antifungal drugs for critically ill patients with COVID-19. Antimicrobial stewardship programs should develop and apply tools to facilitate more effective and appropriate antifungal use.

Diabetic foot infections: A microbiologic review.

Diabetes mellitus continues to be an increasingly common comorbidity. Diabetic foot infections are one of the most common causes of hospitalization in this population, and account for a significant portion of increased hospitalization and healthcare expenditure. Complications, such as osteomyelitis, can necessitate the use of multiple, prolonged antibiotic courses. These courses often consist of broad-spectrum, empiric therapy determined by organisms considered to be commonly associated with these types of infections. Extended periods of broad-spectrum antibiotic regimens can contribute to antibiotic resistance and ultimately limit future treatment options. Furthermore, patient specific risk factors can impact the microbiologic diversity found in these infections. As a result, it is difficult to determine if a single empiric regimen is appropriate for all instances of diabetic foot infections. OBJECTIVES AND METHODS: This review analyzes global literature relating to the culture methods, incidence, risk factors, resistance patterns, and geographic distribution of the microorganisms isolated from diabetic foot infections using the PRISMA statement for systematic review and meta-analysis reporting. RESULTS: Staphylococcus aureus remains a significant pathogen, with a growing incidence of Pseudomonas aeruginosa and MDR gram-negative bacilli. CONCLUSIONS: Though some individualized risk factors can be useful, local epidemiology and resistance patterns remain essential for antibiotic treatment considerations.

A Community Pharmacist's Guide to Oral COVID-19 Antivirals.

The recent approval of novel, oral antivirals for the treatment of COVID-19 has significantly altered the outpatient management of patients diagnosed with COVID-19. From a community pharmacy perspective, the two treatment options for mild to moderate COVID-19 are Paxlovid™ (nirmatrelvir/ritonavir) and Lagevrio™ (molnupiravir). While the availability of these antivirals has expanded community pharmacists' capability to provide care for patients diagnosed with COVID-19, many community pharmacists may struggle to effectively operationalize these agents in practice. This commentary provides a review of Paxlovid™ and Lagevrio™ clarifying the differences between each medication and their respective places in therapy, as well as suggestions and best-practices to operationalize the provision of these services in community pharmacies. These considerations are necessary to support and inform community pharmacy practice when providing oral COVID-19 antiviral therapy.

An evaluation of antipseudomonal dosing on the incidence of treatment failure.

INTRODUCTION: Significant mortality is associated with delays in appropriate antibiotic therapy in Pseudomonas aeruginosa infections. The impact of empiric dosing on clinical outcomes has been largely unreported. METHODS: This retrospective cohort compared treatment failure in patients receiving guideline-concordant or guideline-discordant empiric therapy with cefepime, meropenem, or piperacillin/tazobactam. Patients with culture-positive P. aeruginosa between 1 July 2013 and 31 July 2019 were eligible for inclusion. Patients with cystic fibrosis, polymicrobial infection, and urinary or pulmonary colonization were excluded. The composite primary outcome was treatment failure, defined as (1) therapy modification due to resistance/perceived treatment failure, (2) increased/unchanged qSOFA, or (3) persistent fever 48 h after initiating appropriate therapy. Secondary outcomes included rate of infectious diseases consultation, all-cause inpatient mortality, mechanical ventilation requirement, and infection-related intensive care unit and hospital lengths of stay. RESULTS: In total, 198 patients were included: 90 guideline-concordant and 108 guideline-discordant. Baseline characteristics were balanced. Treatment failure was more common in the guideline-discordant than the guideline-concordant group (62% versus 48%; p = 0.04). This remained significant when adjusting for supratherapeutic dosing (p = 0.02). Infectious diseases consultation was higher in the guideline-discordant group (46% versus 29%, p = 0.01), while intensive care unit length of stay was longer in the guideline-concordant group (4.5 versus 3 days, p = 0.03). Additional secondary outcomes were similar. CONCLUSION: Treatment failure was significantly higher in patients receiving guideline-discordant empiric antipseudomonal dosing. Guideline-directed dosing, disease states, and patient-specific factors should be assessed when considering empiric antipseudomonal dosing.