Fosmanogepix: The Novel Anti-Fungal Agent's Comprehensive Review of in Vitro, in Vivo, and Current Insights From Advancing Clinical Trials.

Fosmanogepix, a prodrug of Manogepix (MGX), is a groundbreaking antifungal agent with broad-spectrum activity against yeasts, including Cryptococcus and Candida, as well as molds. It exhibits effectiveness against drug-resistant strains, such as Candida strains resistant to echinocandins and Aspergillus strains resistant to azoles. Furthermore, fosmanogepix shows activity against pathogens that typically resist other classes of drugs, such as Scedosporium, Lomentospora prolificans, and Fusarium, although its efficacy against Mucorales varies. In animal models, fosmanogepix has demonstrated notable effectiveness against disseminated infections caused by various Candida species, Coccidioides immitis, and Fusarium solani. It has also shown efficacy in pulmonary infection models involving Aspergillus fumigatus, Aspergillus flavus, Scedosporium prolificans, Scedosporium apiospermum, and Rhizopus arrhizus. Clinical trials have revealed excellent oral bioavailability (>90%), enabling a seamless transition between intravenous and oral formulations without compromising blood concentrations. Fosmanogepix exhibits favorable profiles in terms of drug interactions, tolerability, and extensive distribution in various tissues, making it an appealing choice for treating invasive fungal infections. This comprehensive review aims to examine the outcomes of published data on fosmanogepix, encompassing in vitro, in vivo, and clinical investigations.

Invasive Aspergillosis in Liver Transplant Recipients in The Current Era.

Invasive aspergillosis (IA) is a rare but fatal disease among liver transplant recipients (LiTRs). We performed a multi-center 1:2 case-control study comparing LiTRs diagnosed with proven/probable IA and controls with no invasive fungal infection. We included 62 IA cases and 124 matched controls. Disseminated infection occurred only in eight cases (13%). 12-week all-cause mortality of IA was 37%. In multivariate analyses, systemic antibiotics usage (adjusted odds ratio [aOR], 4.74; p=0.03) and history of pneumonia (aOR, 48.7; p=0.01) were identified as independent risk factors associated with the occurrence of IA. Moreover, reoperation (aOR, 5.99; p=0.01), systemic antibiotics usage (aOR, 5.03; p=0.04), and anti-mold prophylaxis (aOR, 11.9; p=0.02) were identified as independent risk factors associated with the occurrence of early IA. Among IA cases, Aspergillus colonization (adjusted hazard ration [aHR], 86.9; p<0.001), ICU stay (aHR, 3.67; p=0.02), disseminated IA (aHR, 8.98; p<0.001), and dialysis (aHR, 2.93; p=0.001) were identified as independent risk factors associated with 12-week all-cause mortality; while recent receipt of tacrolimus (aHR, 0.11; p=0.001) was protective. Mortality among LiTRs with IA remains high in the current era. The identified risk factors and protective factors may be useful for establishing robust targeted anti-mold prophylactic and appropriate treatment strategies against IA.

Epidemiological Perspectives: A Four-Year Insight Into Hepatitis C Surveillance in the Kingdom of Saudi Arabia.

Introduction Hepatitis C is a viral disease caused by the hepatitis C virus (HCV), a member of the Flaviviridae family. This compact, enveloped RNA virus possesses a positive single-stranded genome and can be transmitted through various means, including blood exposure, sexual contact, and vertical transmission. The disease is associated with significant morbidity and mortality, imposing substantial costs on the healthcare system. In Saudi Arabia, HCV is a notifiable disease; however, there is a scarcity of recent reports on HCV trends in the country. This study aims to provide updated insights into the infection patterns of HCV across demographics, regions, and genders in Saudi Arabia. Methods A retrospective analysis was conducted to investigate the epidemiological trends of HCV infection in Saudi Arabia. Data were obtained from the Saudi Ministry of Health (MOH), encompassing the timeframe from 2019 to 2022. A descriptive analysis of HCV infection, organized by year, age group, and gender, was conducted using the data reported to the MOH. Results Between 2019 and 2022, there was a significant decrease of 56.9% in the overall rate of hepatitis C cases in Saudi Arabia. The rate dropped from 9.94 to 4.29 cases per 100,000 people during this period. Males consistently had higher reported cases compared to females, although there was a notable decline in cases for both genders from 2019 to 2022. The highest incidence of HCV was found in individuals aged 45 years and above. However, there was a decline in cases among this age group, with the number dropping from 2,195 cases in 2019 to 946 cases in 2022. In terms of regional variations, Riyadh, Makkah, Jeddah, Alsharqiya, and Taif had the highest incidence of HCV cases. Some regions experienced an increase in cases between 2021 and 2022, particularly Jeddah, Taif, and Al-Ahsaa. Conclusion This study reveals a significant reduction in reported HCV cases in Saudi Arabia from 2019 to 2022. However, gender disparities persist, with males having a higher number of reported cases. There is also a notable decline in HCV cases among children and adolescents, which can be attributed to preventive measures. The findings emphasize the importance of region-specific strategies, as certain areas, such as Riyadh, Makkah, Jeddah, Alsharqiya, and Taif, continue to have a high number of reported cases. Proactive measures, surveillance, and public awareness campaigns remain crucial in addressing HCV as a significant public health challenge in the Kingdom.

Molecular epidemiology and outcome of carbapenem-resistant Enterobacterales in Saudi Arabia.

BACKGROUND: The burden of carbapenem resistance is not well studied in the Middle East. We aimed to describe the molecular epidemiology and outcome of carbapenem-resistant Enterobacterales (CRE) infections from several Saudi Arabian Centers. METHODS: This is a multicenter prospective cohort study conducted over a 28-month period. Patients older than 14 years of age with a positive CRE Escherichia coli or Klebsiella pneumoniae culture and a clinically established infection were included in this study. Univariate and multivariable logistic models were constructed to assess the relationship between the outcome of 30-day all-cause mortality and possible continuous and categorical predictor variables. RESULTS: A total of 189 patients were included. The median patient age was 62.8 years and 54.0% were male. The most common CRE infections were nosocomial pneumonia (23.8%) and complicated urinary tract infection (23.8%) and 77 patients (40.7%) had CRE bacteremia. OXA-48 was the most prevalent gene (69.3%). While 100 patients (52.9%) had a clinical cure, 57 patients (30.2%) had died within 30 days and 23 patients (12.2%) relapsed. Univariate analysis to predict 30-day mortality revealed that the following variables are associated with mortality: older age, high Charlson comorbidity index, increased Pitt bacteremia score, nosocomial pneumonia, CRE bacteremia and diabetes mellitus. In multivariable analysis, CRE bacteremia remained as an independent predictor of 30 day all-cause mortality [AOR and 95% CI = 2.81(1.26-6.24), p = 0.01]. CONCLUSIONS: These data highlight the molecular epidemiology and outcomes of CRE infection in Saudi Arabia and will inform future studies to address preventive and management interventions.