Point prevalence survey of antibiotics use among hospitalised neonates and children in Saudi Arabia: findings and implications.

Background: Neonates and children are more susceptible to a variety of infections, leading to frequent antibiotic prescriptions. However, the inappropriate use of antibiotics leads to antibiotic resistance and higher mortality rates. Therefore, this study aimed to determine the prevalence of antibiotic use, and current antibiotic prescribing practices among neonates and children admitted in the selected hospitals of Saudi Arabia. Methods: A cross-sectional study was conducted from September to November 2023 to assess the prevalence of antibiotic use, and the current antibiotic prescribing practices across six hospitals of Saudi Arabia. Results: The study included 499 children and neonates, with 94.6% receiving antibiotic prescriptions. The most frequently prescribed antibiotic class was third-generation cephalosporin (31.5%), with ceftriaxone being the most commonly prescribed antibiotic (15%). The majority of patients were prescribed one antibiotic (81.4%), and the intravenous route (96.4%) was the primary route for administration. The majority of patients were prescribed antibiotics empirically (69.7%), and community-acquired infections (64.2%) were the most common type of infection for antibiotic prescription. Similarly, sepsis (39.2%) was the most common indication for antibiotics, and the majority of prescribed antibiotics (61.7%) belonged to the 'Watch' category as per WHO AWaRe classification. Conclusion: Our study revealed excessive antibiotic consumption in neonates and children, therefore quality improvement programmes including antimicrobial stewardship programmes are urgently needed to address ongoing issues.

A Glance at the Development and Patent Literature of Tecovirimat: The First-in-Class Therapy for Emerging Monkeypox Outbreak.

Monkeypox disease (MPX) is currently considered a global threat after COVID-19. European Medicines Agency (EMA) approved Tecovirimat in capsule dosage form (200 mg) as the first treatment for MPX in January 2022. This article highlights Tecovirimat's development and patent literature review and is believed to benefit the scientists working on developing MPX treatments. The literature for Tecovirimat was gathered from the website of SIGA Technologies (developer of Tecovirimat), regulatory agencies (EMA, United States Food and Drug Administration (USFDA), and Health Canada), PubMed, and freely accessible clinical/patent databases. Tecovirimat was first recognized as an anti-orthopoxvirus molecule in 2002 and developed by SIGA Technologies. The USFDA and Health Canada have also recently approved Tecovirimat to treat smallpox in 2018 and 2021, respectively. The efficacy of Tecovirimat was verified in infected non-human primates (monkeys) and rabbits under the USFDA's Animal Rule. Most clinical studies have been done on Tecovirimat's safety and pharmacokinetic parameters. The patent literature has revealed inventions related to the capsule, injection, suspension, crystalline forms, amorphous form, and drug combinations (Tecovirimat + cidofovir) and process for preparing Tecovirimat. The authors foresee the off-label use of Tecovirimat in the USA and Canada for MPX and other orthopoxvirus infections. The authors also trust that there is immense scope for developing new Tecovirimat-based treatments (new drug combinations with other antivirals) for orthopoxvirus and other viral diseases. Drug interaction studies and drug resistance studies on Tecovirimat are also recommended. Tecovirimat is believed to handle the current MPX outbreak and is a new hope of biosecurity against smallpox or orthopoxvirus-related bioterrorism attack.

An insight into the discovery, clinical studies, compositions, and patents of macozinone: A drug targeting the DprE1 enzyme of Mycobacterium tuberculosis.

Decaprenyl-phosphoryl-ribose 2'-epimerase (DprE1) inhibitors are an innovative and futuristic orally active group of antituberculosis agents. A few DprE1 inhibitors are in the clinical trial for tuberculosis (TB), including macozinone. This review highlights the discovery, developmental status, clinical studies, patents, and prospects of macozinone (MCZ). The patent and non-patent literature search was done by entering keywords such as macozinone; MCZ; PBTZ169; PBTZ-169 in Pubmed, Espacenet, Patentscope, and the USPTO databases. However, data on Sci-Finder was searched using CAS registry number: 1377239-83-2. MCZ clinical trial studies were retrieved from the clinicaltrials.gov database using the exact keywords. The chemical structure of MCZ was disclosed in 2009. Accordingly, patents/patent applications published from 2009 to June 12, 2022, have been discussed herein. MCZ and MCZ hydrochloride salt patents were granted in 2014 and 2019, respectively, in the USA. The patent literature and the clinical trial studies suggest capsule, tablet, and suspension formulations of crystalline MCZ and its hydrochloride salt as the possible and prospective dosage forms to treat TB. Some combinations of MCZ with other drugs (chloroquine, telacebec, tafenoquine, TBI-166, and sanfetrinem) with improved anti-TB efficacy have been documented. Based on the literature covered in this review article on the clinical studies and patents applied/granted to MCZ, it can be inferred that MCZ seems to be a promising DprE1 inhibitor and could help to tackle the emerging dilemma of drug-resistant either as a monotherapy or in combination with additional anti-TB agents. Furthermore, the authors anticipate the development of new combinations, salts, and polymorphs of MCZ as anti-TB agents shortly. This review article might prove beneficial to the scientific community as it summarizes chemistry, pharmacology and provides an update on the clinical studies and patents/patent applications of one of the emerging anti-TB drugs in one place.

CXCL4/Platelet Factor 4 is an agonist of CCR1 and drives human monocyte migration.

Activated platelets release micromolar concentrations of the chemokine CXCL4/Platelet Factor-4. Deposition of CXCL4 onto the vascular endothelium is involved in atherosclerosis, facilitating monocyte arrest and recruitment by an as yet, unidentified receptor. Here, we demonstrate that CXCL4 drives chemotaxis of the monocytic cell line THP-1. Migration and intracellular calcium responses induced by CXCL4 were pertussis toxin-sensitive, implicating a GPCR in signal transduction. Cell treatment with chondroitinase ABC ablated migration, suggesting that cis presentation of CXCL4 by cell surface glycosaminoglycans to a GPCR is required. Although CXCR3 has been previously described as a CXCL4 receptor, THP-1 cells were unresponsive to CXCR3 ligands and CXCL4-induced migration was insensitive to a CXCR3 antagonist, suggesting that an alternative receptor is involved. Interrogating CC-class chemokine receptor transfectants, we unexpectedly found that CXCL4 could induce the migration of CCR1-expressing cells and also induce CCR1 endocytosis. Extending our findings to primary human monocytes, we observed that CXCL4 induced CCR1 endocytosis and could induce monocyte chemotaxis in a CCR1 antagonist-sensitive manner. Collectively, our data identify CCR1 as a previously elusive monocyte CXCL4 receptor and suggest that CCR1 may play a role in inflammation where the release of CXCL4 is implicated.