Anti-Infective Agents - Volume 23, Issue 5, 2025
Volume 23, Issue 5, 2025
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A Review on Emerging Challenges and Innovations in the Management of Carbapenem-resistant Enterobacteriaceae Infections in Hospital Settings
Carbapenem-resistant Enterobacteriaceae represent a crucial global public health issue. The challenges associated with carbapenem-resistant Enterobacteriaceae are multifaceted. This review article aims to explore and comprehend the emerging challenges and the latest developments in the management of carbapenem-resistant Enterobacteriaceae infections. A comprehensive literature search was conducted using databases such as PubMed, Cochrane Library, and Embase. Studies published from database inception until May 2024 were included. Articles were selected based on relevance, study design, and quality. Data from clinical trials, observational studies, and reviews were synthesized to provide a detailed overview of the current state of knowledge on carbapenem-resistant Enterobacteriaceae. The review identifies key epidemiological trends, including geographic variations and risk factors associated with carbapenem-resistant Enterobacteriaceae. Mechanisms of resistance are elucidated, focusing on carbapenemase production and other related factors. Current treatment options are assessed, with an emphasis on newer antibiotic combinations such as ceftazidime/avibactam, meropenem/vaborbactam, ceftolozane/tazobactam, and cefepime/enmetazobactam. The review also highlights emerging therapeutic approaches, including novel antibiotics and non-traditional approaches like phage therapy, fecal microbiota transplantation, probiotics, antimicrobial peptides, vaccines, and herbal drugs. Additionally, the review also reflects on effective infection prevention and control strategies. While research efforts to explore newer combinations and alternate approaches to treat carbapenem-resistant Enterobacteriaceae infections are crucial, the importance of stringent infection prevention and control strategies cannot be overstated. This dual focus is essential to address both the immediate and long-term challenges posed by carbapenem-resistant Enterobacteriaceae.
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Epidemiologic Investigation of Eye Symptoms Related to COVID-19 among Outpatient Population
Authors: Fatemeh Eslami, Salman Khazaei, Anahita Eslamighayour and Tahere MohammadiIntroductionSince 2019, with the spread of coronavirus and the emergence of new strains worldwide, various studies have identified the effects of this virus on multiple organs of the body.
ObjectiveIndividuals with COVID-19 experience various symptoms in their body systems. Some of these symptoms can affect the visual system and lead to blurry vision, dry eyes, foreign body sensations, tearing, etc. These symptoms can cause early eye fatigue and reduce the quality of academic and occupational performance.
MethodsThis study aimed to investigate the ocular symptoms and treatments in outpatients with mild to moderate COVID-19 at the Vali-e-asr Clinic in Hamadan City. The study was cross-sectional with the ethics code IR.UMSHA.REC.1401.913, and was conducted from April, 2021, until the required sample size was achieved. Patients were selected using an available non-probability sampling method.
Results and DiscussionThe findings indicated that the pandemic had a significant impact on the employment status of individuals, particularly full-time and part-time employees or workers, as well as university students. Additionally, in our study, significant increases in various eye symptoms, including blurred vision, fluctuating vision, the need to increase text size while reading, and eye irritation, were reported.
ConclusionBased on our study on the impact of COVID-19 on dry eye, we found a significant increase in dry eye symptoms among patients with a history of COVID-19. It is essential to raise awareness among individuals, healthcare professionals, and policymakers about the possible consequences of the pandemic on eye health and to implement appropriate measures to mitigate these effects.
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Anti-HIV Treatment: History, Current Advances and Targets
Authors: Apurva Wasnik, Kalyani Thombre, Krishna Radheshyam Gupta and Milind Janrao UmekarHuman Immunodeficiency Virus (HIV) is a retrovirus that is well known to be the causative agent for acquired immunodeficiency syndrome. In this review, we discussed the HIV virus, its transmission, events that lead to AIDS, the historical aspect of its emergence, current prospects in antiretroviral drugs, and its evolution up until current treatment strategies. We have also discussed the recent research related to new molecules, which showed potent anti-HIV activity and have the potential to become a key targetfor drugdevelopment. New studies have explored novel drug target sites and the benefits of using artificial intelligence and machine learning in drug discovery and design, leading to better results and advancements in treatment.
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Exploring the Therapeutic Potential of Benzimidazole Hybrids as Antimicrobial Agents: An In-Depth Analysis
Authors: Sugat Shukla, Arun Kumar, Mohd Akil, Mohammad Owais, Benjamin Siddiqui, Shikhar Verma, Kuldeep Singh and Iqbal AzadIntroductionHeterocyclic compounds play an essential role in biological systems and occur widely in nature. They are fundamental in the development of pharmaceuticals aimed at combating microbial infections and other with the potential biological activities. Pharmacological evaluations have demonstrated their efficacy against diverse bacterial strains. This study investigates the antimicrobial properties of various benzimidazole hybrids.
ObjectiveThis review article is expected to make a substantial contribution to the advancement of antibacterial medications. The research's goal is to improve the efficacy of combating bacterial infections by utilizing the potent properties of benzimidazole-based hybrid scaffolds. In the end, this will aid in reducing the global incidence of this contagious illness.
MethodsSeveral nitrogen-containing heterocyclic compounds display substantial potential as antibacterial agents. These compounds possess fused benzene and imidazole nuclei. These nuclei could change the number of electrons they have, which in turn affects their physiochemical characteristics. The versatility of drugs arises from their capacity to interact with receptors in various modalities, which is a key factor in drug pharmacological screening.
Results and DiscussionPyrazole, imidazole, oxazole, thiazole, indole, and benzimidazole are examples of compounds that include nitrogen species. These nitrogen-containing compounds engage in metabolic interactions with other molecules within the cell. Nevertheless, an overabundance of reactive nitrogen species can cause cytotoxicity, causing harm to vital biological macromolecules. But benzimidazole is traditionally the most effective, with a wide range of important qualities, including antibacterial, anti-HIV, anticancer, antimalarial, antiviral, antifungal, antioxidant, anti-inflammatory, and anti-tubercular activities.
ConclusionThis study focuses on the efficacy of novel benzimidazole-based hybrid scaffolds in inhibiting microbial growth. The study primarily focuses on recent studies carried out from 2009 to 2024. The study highlights the effectiveness of different benzimidazole-based hybrids using minimum inhibitory concentration (MIC) values. More in-depth studies also show that adding electron-withdrawing groups (EWGs) to the nitrogenous framework might make them more effective. Further research is necessary to design strong, least-toxic benzimidazole-based hybrids that can either kill or inhibit multidrug-resistant (MDR) bacteria.
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An Emerging Outbreak of H7 and H9 Avian Influenza Viruses among Different Countries: A Review
Authors: Rishi Kant, Prashanjit Roy, Amandeep Kaur, Hardik Kumar and Ranjeet KumarAvian Influenza (AI) viruses are a class of viruses that have been discovered in birds. A valuable insight gained from previous pandemics is that every pandemic influenza virus now under study has viral genes derived from Avian Influenza Viruses (AIVs). Avian Influenza (AI) consists of Haemagglutinin (H1–H16) and all 9-neuraminidase influenza. We provide an overview of the epidemiology and outcomes of AIV infections in different countries. Worldwide, 3417 human cases were reported, over which a thousand people died as a result of viruses carrying the Hemagglutinin (HA) gene of subtypes H7-H9. Since the data was recorded in 1966, the first human cases were reported in 1998 up to December 2023 (with 128 reported human infections globally), most occurring in China. The Y280 lineage of H9N2 AI was first identified in 2020 in South Korea. These viruses have killed at least 622 million domestic birds and triggered multiple illness outbreaks in wild and domestic poultry. Low Pathogenic Avian Influenza (LPAI) is a milder virus that mostly affects the respiratory system. Three waves of influenza outbreaks have been caused by the H7 influenza viruses, which are transmitted by wild birds and have affected multiple continents. On May 22, 2024, India's National Focal Point reported a case of avian influenza A(H9N2) in a person from West Bengal, India.
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Synthesis of Novel Cyclic Imide-containing Thiazole and Benzothiazoles for Antimicrobial Evaluation and Computational Docking Studies
Authors: Smita Pawar, Amol Kale, Srushti Jadhav, Shital Shendge, Nilesh Shinde, Rushikesh Lande and Pratik KapaseBackground/IntroductionMany compounds with thiazole, benzothiazole, and cyclic imide have been found to exhibit potent antimicrobial activity, such as Cefotaxime, Moiramide, Ritonavir, etc.
AimsAs per the aim of this study, the cyclic imides with thiazole and benzothiazole moiety were designed and synthesized.
ObjectivesLiterature findings suggest the potential antimicrobial properties of thiazole and benzothiazole, which inspired us to design and synthesize imides with succinic anhydride, phthalic anhydride, and maleic anhydride.
MethodsThree series of synthetic compounds were synthesized i.e. substituted 1-(4-(p-tolyl)thiazol-2-yl)pyrrolidine-2,5-dione (SI 1-6), 2-(4-phenylthiazol-2-yl)isoindoline-1,3-dione (PI 1-6), and 1-(benzo[d]thiazol-2-ylamino)-1H-pyrrole-2,5-dione (MI 1–5) and characterized with IR, NMR, Mass spectroscopy. All synthesized derivatives were evaluated to check the antimicrobial properties against Gram +ve, Gram -ve bacteria, and fungi species by determining the zone of inhibition and minimum inhibitory concentration. Docking was carried out to check binding affinities with targets ‘DNA Gyrase and Penicillin Binding Protein 3’.
Results and DiscussionZone of inhibition showed that all the synthesized compounds are active against bacteria and fungi. Compound SI-4 showed a maximum zone of inhibition. Most of the compounds showed MIC at 6.25 and 12.5 µg/ml. A docking study revealed that compounds PI-4 and PI-2 showed good dock scores towards DNA Gyrase and Penicillin Binding Protein 3, respectively.
ConclusionAll synthesized compounds showed significant antimicrobial properties. The anti-microbial evaluation showed that compounds SI-4, PI-,2, and MI-1 possess good antimicrobial activity. Electron withdrawing substitutions may enhance the antimicrobial property.
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Regulation's Effects on the Trends in Community Antibiotic Consumption in the European Union and the United States
This study presents the compiled information from the EU and the US on antibiotic dispensation across the countries and trends between 2011 and 2020 as per the latest available data. Antibiotic misuse continues to be a significant global health challenge, exacerbated by insufficient regulatory measures and a lack of public awareness. Utilizing data on antibiotic dispensation, we analyze the correlation between national regulatory conditions and levels of antibiotic use, with a particular focus on amoxicillin, the most frequently prescribed antibiotic. Our findings reveal that while there has been an overall decrease in amoxicillin consumption in recent years, significant disparities persist among countries. For instance, from 2015 to 2020, the U.K., France, and Germany reported some of the highest rates of antibiotic consumption, significantly above the EU average. This highlights the critical role of effective regulatory measures in mitigating overuse and promoting responsible prescribing practices. Statistical analyses indicate that robust national regulations correlate with lower rates of antibiotic consumption, underscoring the necessity for continued monitoring and policy development. The study also emphasizes the importance of future surveillance efforts aimed at preventing antibiotic overuse and addressing the growing threat of antimicrobial resistance. Overall, this study contributes to understanding how regulatory actions can shape antibiotic consumption patterns and inform strategies for improving public health outcomes in both the EU and US contexts.
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A Review on Therapeutic Potential of Plumbago zeylanica Extracts and Sustainable Production Methods
Authors: Chetana Tripathi, Sachin Kumar Jain and Sudha VengurlekarHerbal medicines have earned a timeless place in healthcare, valued for their biocompatibility and widespread use in treating cancer and related conditions. Plumbago zeylanica, widely recognized as white leadwort or doctorbush, holds a prominent place in traditional medicine systems worldwide, revered for its diverse therapeutic properties. This widespread use, however, coupled with unsustainable harvesting practices, has raised concerns about the plant's long-term survival in its natural habitat. Their enduring presence is particularly evident in countries like India, Pakistan, Bangladesh, Sri Lanka, and Australia, where they are deeply rooted in ethnomedical traditions. P. zeylanica stands out as a rich source of bioactive compounds, including naphthoquinones, flavonoids, alkaloids, and terpenoids, with plumbagin identified as a key driver of its medicinal properties. Plumbagin exhibits a remarkable pharmacological profile, demonstrating significant efficacy as an anticancer, antidiabetic, antimalarial, and antimicrobial agent, making it a promising candidate for drug development. The literature reveals that the root and root bark also have a wider claim in traditional medicines against various diseases as a memory enhancer, anti-inflammatory, wound healing, anti-infertility, blood coagulation, and anti-oxidant activities. This review provides a comprehensive overview of P. zeylanica, encompassing its traditional uses, phytochemical composition, and the pharmacological activities of its key bioactive constituents, with a particular focus on plumbagin. We delve into the scientific evidence supporting its therapeutic applications, highlighting its potential in treating a wide range of diseases. Furthermore, we discuss the progress made in developing sustainable production methods for plumbagin for medicinal purposes from P. zeylanica.
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Silymarin and Isoniazid Combination for the Treatment of Drug-Resistant Tuberculosis: A Mini Review
Authors: Pooja Jatav and Ruchi Khare ShrivastavaTuberculosis remains a global health concern, necessitating the exploration of novel therapeutic strategies. Multidrug-resistant and extensively drug-resistant strains of Mycobacterium tuberculosis pose a growing challenge in tuberculosis treatment. Drug resistance can reduce the effectiveness of isoniazid, a commonly used first-line anti-tuberculosis drug, in treating tuberculosis. Silymarin, a flavonoid complex obtained from milk thistle, has drawn great interest owing to its rich anticancer, antioxidant, anti-inflammatory, and hepatoprotective properties. Recent studies have indicated that silymarin, when used with first-line anti-TB drugs such as isoniazid, may strengthen the treatment. This mini-review intends to assess the currently available evidence base and the extent to which it supports the use of silymarin as synergistic with isoniazid in the treatment of tuberculosis. We further elaborate on pharmacological activities and describe possible ways silymarin would exert an antibacterial action against Mycobacterium tuberculosis, the causative microorganism of tuberculosis. Further analysis is conducted on in vitro, in vivo, and clinical studies that contain information regarding the effectiveness and security of this drug combination. Finally, we consider the barriers, patterns, and contours connected with silymarin-isoniazid combination therapy development, silymarin justification dominance formulations, reliable doses, and necessary clinical trials to verify silymarin efficacy and safety in different categories of patients suffering from tuberculosis.
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Sesquiterpene Coumarins as Promising Antiviral Agents: An In-silico Study
Authors: Dara Dastan and Ahmad EbadiIntroductionSesquiterpene coumarins are a unique class of natural compounds with a wide range of biological activities. These C15 terpenes are connected by ether or carbon-carbon bonds to coumarin derivatives. Sesquiterpene coumarins that include a 7-hydroxylcoumarin (umbelliferone) moiety have significant antiviral properties. The natural flexibility of these compounds reduces the likelihood of developing resistance, which is often seen in viruses due to high mutation rates.
ObjectiveThe lessons learned from the coronavirus pandemic experience emphasize the importance of preparedness for future viral outbreaks in the medical community. Consequently, fast and reliable assessment methods, such as in silico techniques, are crucial in drug discovery.
MethodsIn this study, we used in silico studies to evaluate the potential antiviral effects of various sesquiterpene coumarins.
ResultsThe binding free energy to the spike protein of SARS-CoV-2 suggested that 5′-hydroxyumbelliprenin (2), conferol (9), 8′-acetoxy-5′-hydroxyumbelliprenin (3), and Sanandajine (1) could be promising antiviral candidates.
ConclusionThese compounds have unique physicochemical characteristics and occupy distinct chemical spaces compared to synthetic libraries; therefore, the criteria for drug-likeness need to be adjusted for this series of compounds.
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In situ Gelling Systems for the Treatment of Ocular Pain and Inflammation: A Review
Authors: Sakshi Singh Chouhan and Ruchi Khare ShrivastavaOcular drug delivery presents significant challenges due to the intricate anatomy and protective barriers of the eye, which limit drug penetration and retention. Addressing common issues like ocular pain and inflammation, conditions that substantially impact the quality of life, requires innovative approaches. This review focuses on in situ gel systems as a promising solution for ocular drug delivery, specifically for managing pain and inflammation. In situ gels, which transition from liquid to gel upon contact with the eye, offer distinct advantages over traditional formulations, such as prolonged residence time, sustained drug release, enhanced drug retention, and minimized systemic side effects. These benefits contribute to enhanced therapeutic efficacy and increased patient comfort. It also examines various polymers and gelling mechanisms used in in situ gels, including temperature-sensitive, pH-sensitive, and ion-activated polymers. While there is significant promise in the development of in situ gel systems, several challenges must be addressed, including the optimization of viscosity, the assurance of biocompatibility, and the precise adjustment of drug release profiles. Future research is geared toward integrating novel polymers, designing stimuli-responsive systems, and advancing targeted drug delivery strategies. These innovations aim to further improve the effectiveness and patient compliance of in situ gel systems for ocular applications, offering a viable alternative for sustained and comfortable management of ocular pain and inflammation.
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Tiny Dots, Big Impact: The Antimicrobial Power of Carbon Dots
Authors: Ranadeep Borgohain, Md. Moidul Islam, Harpreet Kaur, Harmanjot Kaur, Amit Kumar and Sarjana RaikwarCarbon Dots (CDs) are innovative nanoscale carbon-based materials recognized for their exceptional optical properties, biocompatibility, and minimal toxicity. These fluorescent nanoparticles, generally smaller than 10 nm, exhibit strong photoluminescence and absorption capabilities, which make them valuable for diverse applications in biomedicine, sensing, catalysis, and antibacterial technologies. Since their discovery in carbon soot in 2004, CDs have attracted attention for their environmental friendliness and versatile preparation methods, such as top-down (e.g., laser ablation, arc discharge) and bottom-up (e.g., hydrothermal treatment, microwave irradiation) approaches. Functionalized with various surface groups, CDs offer excellent solubility and customizable properties for specific applications. One of the most promising uses of CDs is as antibacterial agents, particularly against multidrug-resistant pathogens in the fight against bacterial infections. Their antibacterial mechanism involves generating Reactive Oxygen Species (ROS), which cause oxidative stress in bacterial cells, ultimately leading to cell death. Studies demonstrate the effective antibacterial action of CDs against bacteria such as E. coli and Staphylococcus aureus, attributed to ROS generation and membrane-penetrating effects. Despite challenges like synthesis consistency and potential toxicity, advancements in eco-friendly production and combination with other antimicrobial agents present exciting possibilities. CDs emerge as sustainable alternatives to traditional antibiotics, offering a valuable tool for advancing infection control in nanotechnology and global health contexts.
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Analysis of Carbapenemase and Extended-spectrum Beta-lactamases-producing Cephalosporin-resistant Strain of Escherichia coli and Klebsiella pneumoniae among Children in a Tertiary Care Centre, South India
Authors: Santhosh J. Thattil, Thekkuttuparambil A. Ajith and Suresh DhanarajIntroductionThe incidence of Extended-spectrum Beta-lactamase (ESBL)- and carbapenemase-producing enterobacteriaceae in enterobacterales is increasing globally, posing a threat to health. Schoolchildren under adolescence show a gradual increase in immunity, and respiratory infections like pneumonia and others are more prevalent in children under five-years of age. However, gastrointestinal disorders primarily affect children under one-year of age.
AimsThe study aimed to analyze the ESBL and carbapenemase-producing cephalosporin-resistant strain of Escherichia coli and Klebsiella pneumoniae, isolated from various specimens of hospitalized children below ten years of age.
MethodsA cross-sectional study on laboratory reports of positive culture specimens from children below ten years of age was conducted to analyze the cephalosporin-resistant strains of E. coli and K. pneumoniae between July, 2023 and July, 2024 in the Microbiology Department of a tertiary care hospital central Kerala, South India. The cephalosporin-resistant strain was analyzed for carbapenemase or ESBL presence using a double disc synergy test. The data were subjected to statistical analysis.
Results and DiscussionA total of 1636 culture reports were analyzed, and growth was found in 672 (41%) specimens. Among the cephalosporin-resistant 187 strains (66%), E. coli and K. pneumoniae were 106 (57%) and 81 (43%), respectively. A significant difference (p <0.05) was noted between cephalosporin-resistant and sensitive E. coli among the various age groups. The difference between cephalosporin-resistant and susceptible K. pneumoniae across different age groups, however, was negligible (p>0.05). Carbapenemase and ESBL-producing E. coli and K. pneumoniae were 39%, 29%, and 48%, respectively. The carbapenemase and ESBL-producing strains were more in children below one year. An insignificant difference (p>0.05) between ESBL (+) and ESBL (-) E. coli or K. pneumoniae was found among various age groups. A similar observation was found between carbapenemase [+] and carbapenemase (-) E. coli or K. pneumoniae. According to the effect value (Cramer's V) determined for each comparison, the association was either very weak or negligible.
ConclusionThe cephalosporin-resistant strains (66%) of E. coli and K. pneumoniae were 57% and 43%, respectively. Specimens of children below one year of age showed more incidence of ESBL-producing K. pneumonia (67%) and carbapenemase-producing E. coli (68%).
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