Recent Advances in Anti-Infective Drug Discovery - Online First

Fever of Unknown Origin (FUO) was first defined in 1961 as a temperature greater than 38.3°C on several occasions, lasting for more than 3 weeks, or failure to reach a diagnosis despite one week of inpatient investigation. The time frame has recently been revised to include patients whose illness remains undiagnosed after either a minimum of three outpatient visits or three days of hospitalization. The purpose of this study was to describe the etiology, frequency, and pattern of different causes, particularly infectious causes, and to determine the relative incidence of various causes of FUO in the mid-Delta area of Egypt.

This retrospective cohort study included all FUO cases registered in the file system over a seven-year period from 2015 to 2022 at Mahala-Kubra Fever Hospital, as well as all admitted FUO cases at the Tropical Medicine and Infectious Diseases Department of Tanta University during 2021 and 2022.

A total of 383 FUO cases were included in the study. Among these, the leading causes of FUO were infections (n = 334, 87.2%), followed by neoplasms (n = 26, 6.8%). Autoimmune and miscellaneous causes ranked third (n = 9, 2.3%), and undiagnosed cases were the least common (n = 5, 1.3%). The two most common infectious causes in this study were urinary tract infection (n = 136, 40.7%) and brucellosis (n = 115, 34.4%). Typhoid fever (n = 29, 8.7%), pneumonia (n = 15, 4.2%), and abscesses (n = 10, 3.0%) were also frequent causes of FUO. Hematological malignancies were the most common malignant causes of FUO, with lymphoma being the most prevalent (n = 10, 38.5%), followed by leukemia (n = 8, 30.8%).

Fever (pyrexia) of unknown origin remains one of the most challenging complexities in medical diagnosis. Infections, particularly Urinary Tract Infections (UTIs) and brucellosis, are the primary causes of FUO in this study. It is also important to recognize that hematological malignancies are a significant cause of FUO.

Viral infections continue to be a major global health issue, causing over five million fatalities and millions of hospitalizations every year. Existing vaccines and commonly used antiviral drugs often exhibit significant side effects and limited efficacy. In contrast, recent studies have shown that plant extracts and their bioactive compounds possess considerable antiviral activity, along with a favourable safety profile for long-term use. These findings have spurred increased interest in the discovery and development of novel plant-derived antiviral agents.

This review emphasizes the significance of plant-derived antiviral compounds and their corresponding therapeutic targets. It provides a comprehensive overview of recent research on phytochemicals with potential antiviral activity against a wide range of viruses. By consolidating current findings, this review serves as a unified and up-to-date resource on contemporary plant-based antiviral bioactive compounds used in the treatment of human viral infections.

The antiviral efficacy of selected phytoactive compounds was analysed through detailed molecular mechanism studies, supported by in vitro and/or in vivo experimental models. Key herbs were reviewed for their active compounds and antiviral activities against specific viruses like influenza, HIV, HBV, HCV, HSV SARS-CoV-2, and measles. The study also analyzed the results, comparing their mechanisms of action, such as immune modulation, inhibition of viral entry, or interference with replication, while also discussing limitations and gaps in current research.

Evidence from the literature suggests that the notable selectivity of herbal bioactive compounds toward viral target proteins may underlie their antiviral activity. Additionally, findings from in silico, in vitro, and in vivo studies indicate that these compounds exert their effects by binding to specific host cell components, thereby protecting the host from viral infection. This review identifies and summarizes over 150 plant-derived antiviral bioactive compounds, along with their respective mechanisms of action, that have demonstrated efficacy against various selected viruses.

Plant-derived compounds, such as alkaloids, flavonoids, phenolics, terpenoids, and coumarins, exhibit significant antiviral potential. Given the limited number of approved antiviral drugs, cellular and molecular evidence supports herbal bioactives as promising alternatives for developing effective antiviral therapies, offering a natural and safer approach to combating viral infections.

Antimicrobial Resistance (AMR) has emerged as a critical global health challenge, with bacteria, viruses, fungi, and parasites developing the capacity to survive antimicrobial treatments. This resistance, largely driven by increased antibiotic usage, threatens public health by diminishing the effectiveness of current infection management strategies.

This study aims to evaluate the antimicrobial resistance patterns of prevalent pathogens in a secondary care hospital, highlighting the essential role of clinical pharmacists in addressing AMR through the implementation of Antibiotic Stewardship Programs (ASPs) to promote responsible antibiotic use.

This prospective study analyzed 80 positive microbial culture reports from six months. Ethical approval was granted by the Institutional Ethical Committee (Ref: ECR/288/Indt/TN/2018/RR-21/001, dated April 6, 2023). Inclusion criteria covered adults (≥18 years) with confirmed infections across various sites, including bloodstream, urinary, respiratory, and soft tissue. Exclusion criteria eliminated reports with no pathogen growth. Data were analyzed using SPSS software version 26.0, with statistical measures applied to assess resistance patterns and correlations across infection types.

Of the 80 positive cultures, Escherichia coli 35.0%) was most frequently isolated, followed by Klebsiella pneumoniae (12.5%), Pseudomonas aeruginosa (8.8%), Proteus mirabilis (8.8%), and Klebsiella oxytoca (7.5%). The isolated pathogens displayed high resistance to ampicillin (82.5%), cefixime (80.0%), ceftriaxone (78.8%), and ceftazidime (71.3%), with a strong sensitivity to amikacin (86.3%) and meropenem (70.0%).

The rise of third-generation cephalosporin-resistant pathogens signals an urgent need for sustained AMR monitoring and robust ASPs in healthcare settings, particularly in developing regions. The study underscores the importance of rational antibiotic use and continuous AMR surveillance to curb resistant infections and protect public health.

Tinea infections are superficial fungal infections caused by three species of fungi (i.e. Epidermophyton, Microsporum, and Trichophyton) collectively termed dermatophytes. Dermatophytes are fungi that cause skin, nail bed, and hair infections. These infections are classified based on infection site, including tinea pedis (foot), tinea corporis (body), tinea capitis (head), and tinea cruris (groin). Dermatophytes can spread by direct contact with other people (anthropophilic organisms), animals (zoophilic organisms), and soil (geophilic organisms), as well as indirectly from fomities.

This review aims to summarize the allopathic drugs along with their mechanism of action and herbal drugs including their parts of the plant used for the treatment of tinea infections.

The literature review was performed using the following databases: PubMed (https://pubmed.ncbi.nlm.nih.gov/), and Google Scholar (https://scholar.google.com/), to identify the various drugs involved in the treatment of dermatophytosis along with their mechanisms. Results:

The following keywords were applied in the search strategy: “Tinea”, “Dermatophytosis”, “Ringworm infection”, “Pathogenesis of tinea”, “Tinea pedis”, and “Tinea capitis”. This article also reviews several formulations that are available in the market for treating ringworm infection.

The current review provides information about the classification of dermatophytosis based on infection site and environmental habitat, pathogenesis, immunopathogenesis of dermatophytes, and herbals and allopathic drugs used for their treatment.