Ibrexafungerp: A narrative overview.

Ibrexafungerp (IBX) is a new antifungal drug that recently entered the antifungal landscape. It disrupts fungal cell wall synthesis by non-competitive inhibition of the ß-(1,3)-D-glucan (BDG) synthase enzyme. It has demonstrated activity against a range of pathogens including Candida and Aspergillus spp., as well as retaining its activity against azole-resistant and echinocandin-resistant strains. It also exhibits anti-biofilm properties. Pharmacokinetic (PK) studies revealed favorable bioavailability, high protein binding, and extensive tissue distribution with a low potential for CYP-mediated drug interactions. It is characterized by the same mechanism of action of echinocandins with limited cross-resistance with other antifungal agents. Resistance to this drug can arise from mutations in the FKS genes, primarily FKS2 mutations in Nakaseomyces glabrata. In vivo, IBX was found to be effective in murine models of invasive candidiasis (IC) and invasive pulmonary aspergillosis (IPA). It also showed promising results in preventing and treating Pneumocystis jirovecii infections. Clinical trials showed that IBX was effective and non-inferior to fluconazole in treating vulvovaginal candidiasis (VVC), including complicated cases, as well as in preventing its recurrence. These trials positioned it as a Food and Drug Administration (FDA)-approved option for the treatment and prophylaxis of VVC. Trials showed comparable responses to standard-of-care in IC, with favorable preliminary results in C. auris infections in terms of efficacy and tolerability as well as in refractory cases of IC. Mild adverse reactions have been reported including gastrointestinal symptoms. Overall, IBX represents a significant addition to the antifungal armamentarium, with its unique action, spectrum of activity, and encouraging clinical trial results warranting further investigation.

Recent advances in the treatment of Ebola disease: A brief overview.

Ebola disease (EBOD) remains a significant and ongoing threat to African countries, characterized by a mortality rate of 25% to 90% in patients with high viral load and significant transmissibility. The most recent outbreak, reported in Uganda in September 2022, was declared officially over in January 2023. However, it was caused by the Sudan Ebola virus (SUDV), a culprit species not previously reported for a decade. Since its discovery in 1976, the management of EBOD has primarily relied on supportive care. Following the devastating outbreak in West Africa from 2014 to 2016 secondary to the Zaire Ebola virus (EBOV), where over 28,000 lives were lost, dedicated efforts to find effective therapeutic agents have resulted in considerable progress in treating and preventing disease secondary to EBOV. Notably, 2 monoclonal antibodies-Ebanga and a cocktail of monoclonal antibodies, called Inmazeb-received Food and Drug Administration (FDA) approval in 2020. Additionally, multiple vaccines have been approved for EBOD prevention by various regulatory bodies, with Ervebo, a recombinant vesicular stomatitis virus-vectored vaccine against EBOV being the first vaccine to receive approval by the FDA in 2019. This review covers the key signs and symptoms of EBOD, its modes of transmission, and the principles guiding supportive care. Furthermore, it explores recent advancements in treating and preventing EBOD, highlighting the unique properties of each therapeutic agent and the ongoing progress in discovering new treatments.

Metallo-beta-lactamases: mechanisms, treatment challenges, and future prospects.

INTRODUCTION: Metallo-beta-lactamases (MBLs) are responsible for resistance to almost all beta-lactam antibiotics. Found predominantly in Gram-negative bacteria, they severely limit treatment options. Understanding the epidemiology, risk factors, treatment, and prevention of infections caused by MBL-producing organisms is essential to reduce their burden. AREAS COVERED: The origins and structure of MBLs are discussed. We describe the mechanisms of action that differentiate MBLs from other beta-lactamases. We discuss the global epidemiology of MBL-producing organisms and their impact on patients' outcomes. By exposing the mechanisms of transmission of MBLs among bacterial populations, we emphasize the importance of infection prevention and control. EXPERT OPINION: MBLs are spreading globally and challenging the majority of available antibacterial agents. Genotypic tests play an important role in the identification of MBL production. Phenotypic tests are less specific but may be used in low-resource settings, where MBLs are more predominant. Infection prevention and control are critical to reduce the spread of organisms producing MBL in healthcare systems. New combinations such as avibactam-aztreonam and new agents such as cefiderocol have shown promising results for the treatment of infections caused by MBL-producing organisms. New antibiotic and non-antibiotic agents are being developed and may improve the management of infections caused by MBL-producing organisms.

Survival, functional capacity, and quality of life after cardiac surgery followed by long-term intensive care stay.

BACKGROUND: The rising prevalence of multimorbid patients undergoing cardiac surgery often leads to prolonged postoperative intensive care unit (ICU) treatment. The fate of these patients after discharge is poorly investigated. This study is aimed to assess survival, functional outcome, and quality of life (QOL) in patients after an ICU stay of at least 5 days. MATERIALS AND METHODS: Between August 2009 and July 2010, 1,092 patients underwent various cardiac procedures. Of these patients, 119 required ICU treatment of at least 5 days. Preoperative characteristics as well as postoperative course were analyzed and the discharged patients were contacted after 1 year to gain information about survival, functional capacity, and QOL. RESULTS: European system for cardiac operative risk evaluation I of the patients was 22.3 ± 16.7. Mean ICU stay was 19 ± 20 days. Forty three patients (36.1%) died in the hospital, 1-year overall survival was 46.2%, and 1-year survival of the discharged patients was 72.4%. Barthel mobility index was 85, showing a satisfactory mobilization. QOL, assessed with short form 12 questionnaire, was comparable with the reference group. CONCLUSION: Long-term ICU treatment after cardiac surgery is related to a high in-hospital and follow-up mortality. The physical and psychological recovery of the survivors is encouraging, justifying the extensive engagement of hospital resources.

Impact of high intensity transient signals on the choice of mechanical aortic valve substitutes.

OBJECTIVE: High intensity transient signals (HITS) observed during extracorporeal circulation and following mechanical valve replacement are suspected of causing cognitive dysfunction (deterioration of episodic and working memory). This study evaluates the role played by valve design (bileaflet versus tilting disc) and other parameters in the incidence of HITS. METHODS: Thirty patients were selected for the study as follows: 18 males, 58-78 years of age; ten St. Jude Medical, ten CarboMedics, ten Medtronic Hall (MH); all size 23, in optimum orientation (Ann Thorac Surg 68 (1999) 1069); all in sinus rhythm; no coronary or carotid artery disease; all in sinus rhythm, international normalized ratio greater than 2.5 and all at least 9 months postoperative. All patients had bilateral HITS measurement in both middle cerebral arteries via transcranial doppler for 30 min. If five HITS or more were observed during the initial 10 min, patients were subjected to 100% oxygen breathing followed by 10 min of normal air breathing. Simultaneously, HITS were measured in the right radial and femoral arteries. RESULTS: Patients with bileaflet valve substitutes revealed HITS rates varying from 32 to 108 counts/h. There was only one HITS observed in the MH valve group during the 5h observation period (0.2 HITS/h). There were no HITS detected in either the radial or the femoral arteries in any patient. After breathing 100% oxygen, HITS significantly decreased or completely disappeared (0-30 HITS/h). When normal air breathing was resumed HITS reappeared or increased. With an intravenous infusion of 100 mg of lysine acetylsalicylate (Aspisol, Bayer Leverkusen, Germany), HITS decreased by 16 to 41%. CONCLUSIONS: We conclude that bileaflet mechanical valve prostheses produce HITS even in their optimum orientation. HITS following bileaflet valve replacement have an unstable nature and might be composed of nitrogen and platelets. Tilting disc valves in their optimum orientation provide almost physiological conditions with HITS measured in the same range as bioprosthesis.