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New Approaches to Fighting Infectious Diseases: Overcoming the Antimicrobial Resistance...
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New Approaches to Fighting Infectious Diseases: Overcoming the Antimicrobial Resistance in Current Treatments

A special issue of Pharmaceuticals (ISSN 1424-8247). This special issue belongs to the section "Medicinal Chemistry".

Deadline for manuscript submissions: 20 February 2025 | Viewed by 12219

Special Issue Editors

Dr. Antonia Efstathiou

E-Mail Website
Guest Editor
Immunology of Infection Group, Department of Microbiology, Hellenic Pasteur Institute, 11521 Athens, Greece
Interests: infectious diseases; drug discovery; vaccine development; antimicrobial resistance; host-pathogen interaction; immunology; extracellular vesicles
Dr. Dimitra K. Toubanaki

E-Mail Website
Guest Editor
Immunology of Infection Group, Department of Microbiology, Hellenic Pasteur Institute, 11521 Athens, Greece
Interests: infectious diseases; host-pathogen interactions; fish immunology; biomarkers identification; therapeutics; transcriptomics

Special Issue Information

Dear Colleagues,

In recent years, the rise of antimicrobial resistance (AMR) has posed a significant challenge to the effective treatment of infectious diseases. As traditional treatments, i.e., antibiotics, chemotherapy and pharmaceuticals, become less effective, researchers and healthcare professionals have been exploring innovative strategies to combat infectious diseases caused by bacteria, viruses and parasites. As more and more infectious diseases emerge and spread throughout the world, and considering the increasing ability of pathogens to overcome the effect of current treatments, the development of alternative therapies and enhancement of the current ones has gained immense attention in the scientific community. Therefore, over the last few years, researchers have focused on different approaches to combat AMR on infectious diseases (rational drug design in silico, identification of novel targets to fight the pathogens, research into new natural antimicrobial agents, antimicrobial peptides, combinatorial therapies with synergistic properties, alternative and more potent drug carriers, etc.). Overall, combating antimicrobial resistance requires a multifaceted approach. By embracing new therapies, optimizing existing treatments and implementing effective preventive measures, we can enhance our ability to fight infectious diseases and mitigate the challenges posed by antimicrobial resistance.

For this Special Issue, we invite research investigators focusing on these fields to submit original research articles or reviews describing and discussing the most recent advancements and developments in basic science and biomedical applications concerning infectious diseases and treatment approaches in the AMR era.

Dr. Antonia Efstathiou
Dr. Dimitra K. Toubanaki
Guest Editors

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Pharmaceuticals is an international peer-reviewed open access monthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2900 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • infectious diseases
  • antimicrobial resistance
  • parasites
  • viruses
  • bacteria
  • treatment approaches
  • therapeutics
  • chemotherapy
  • targeted drug design
  • natural products

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Published Papers (5 papers)

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Research

Jump to: Review

18 pages, 3362 KiB  
Article
Novel Tricyclic Flavonoids as Promising Anti-MRSA Agents
by Cristina-Veronica Moldovan, Loredana-Elena Mantea, Mihaela Savu, Peter G. Jones, Laura Gabriela Sarbu, Marius Stefan and Mihail Lucian Birsa
Pharmaceuticals 2024, 17(10), 1276; https://doi.org/10.3390/ph17101276 - 26 Sep 2024
Viewed by 545
Abstract
Background: Methicillin-resistant Staphylococcus aureus (MRSA) is considered the main cause of nosocomial and community-associated infections. Because of antimicrobial resistance, MRSA infections are difficult or impossible to treat, leading to high mortality rates and significant economic and societal costs. In view of the MRSA [...] Read more.
Background: Methicillin-resistant Staphylococcus aureus (MRSA) is considered the main cause of nosocomial and community-associated infections. Because of antimicrobial resistance, MRSA infections are difficult or impossible to treat, leading to high mortality rates and significant economic and societal costs. In view of the MRSA challenge to public health all over the world, the identification of new and effective anti-MRSA agents is a high medical priority. Objectives: A new series of tricyclic flavonoids with a methyl substituent on ring A of the flavonoid skeleton was synthesized to assess their antimicrobial properties. Methods: The structures of novel synthetic tricyclic flavonoids and their 3-dithiocarbamic flavanones were proven by X-ray structural analyses. Minimum inhibitory concentration (MIC) and minimum bactericidal/fungicidal concentration (MBC/MFC) were used to evaluate antimicrobial activity. Growth kinetic and time–kill assays were employed to confirm the antibacterial effectiveness. The mechanism of action was investigated using fluorescence microscopy. Results: Our results show that the tricyclic flavonoids exhibited important antibacterial and antifungal activities, with MIC and MBC values as low as 1.95 µg/mL and 3.90 µg/mL recorded for compound 5e against a multidrug-resistant MRSA strain. Flavonoid 5e induced a more important bacteriostatic effect compared with chloramphenicol, inhibiting the bacterial growth for up to 24 h at concentrations equivalent to 2 × MIC. Also, 5e exhibited a significant bactericidal activity, with no viable cells evidenced after 6 h of incubation in the presence of MBC and a total kill effect recorded up to 24 h. The anti-MRSA activity may be explained by the cell membrane impairment induced by 5e. Conclusions: All the data support the idea that flavonoid 5e is a reliable candidate to develop effective anti-MRSA agents, but further studies are necessary. Full article
(This article belongs to the Special Issue New Approaches to Fighting Infectious Diseases: Overcoming the Antimicrobial Resistance in Current Treatments)
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6 pages, 230 KiB  
Communication
Aztreonam Combinations with Avibactam, Relebactam, and Vaborbactam as Treatment for New Delhi Metallo-β-Lactamase-Producing Enterobacterales Infections—In Vitro Susceptibility Testing
by Małgorzata Brauncajs, Filip Bielec, Marlena Malinowska and Dorota Pastuszak-Lewandoska
Pharmaceuticals 2024, 17(3), 383; https://doi.org/10.3390/ph17030383 - 17 Mar 2024
Cited by 4 | Viewed by 2089
Abstract
Antimicrobial resistance is a major global health issue. Metallo-β-lactamases (MBL), in particular, are problematic because they can inactivate all classes of β-lactams except aztreonam. Unfortunately, the latter may be simultaneously inactivated by serine β-lactamases. The most dangerous known MBL is New Delhi Metallo-β-lactamase [...] Read more.
Antimicrobial resistance is a major global health issue. Metallo-β-lactamases (MBL), in particular, are problematic because they can inactivate all classes of β-lactams except aztreonam. Unfortunately, the latter may be simultaneously inactivated by serine β-lactamases. The most dangerous known MBL is New Delhi Metallo-β-lactamase (NDM). This study aimed to test the in vitro susceptibility to aztreonam in combination with novel β-lactamase inhibitors (avibactam, relebactam, and vaborbactam) in clinical strains of Enterobacterales NDM which is resistant to aztreonam. We investigated 21 NDM isolates—including Klebsiella pneumoniae, Escherichia coli, and Citrobacter freundii—which are simultaneously resistant to aztreonam, ceftazidime/avibactam, imipenem/relebactam, and meropenem/vaborbactam. MICs for aztreonam combinations with novel inhibitors were determined using the gradient strip superposition method. The most effective combination was aztreonam/avibactam, active in 80.95% strains, while combinations with relebactam and vaborbactam were effective in 61.90% and 47.62%, respectively. In three studied strains, none of the studied inhibitors restored aztreonam susceptibility. Aztreonam/avibactam has the most significant antimicrobial potential for NDM isolates. However, combinations with other inhibitors should not be rejected in advance because we identified strain susceptible only to tested combinations with inhibitors other than avibactam. Standardization committees should, as soon as possible, develop official methodology for antimicrobial susceptibility testing for aztreonam with β-lactamase inhibitors. Full article
(This article belongs to the Special Issue New Approaches to Fighting Infectious Diseases: Overcoming the Antimicrobial Resistance in Current Treatments)
14 pages, 659 KiB  
Article
Shorter and Longer Antibiotic Durations for Respiratory Infections: To Fight Antimicrobial Resistance—A Retrospective Cross-Sectional Study in a Secondary Care Setting in the UK
by Rasha Abdelsalam Elshenawy, Nkiruka Umaru and Zoe Aslanpour
Pharmaceuticals 2024, 17(3), 339; https://doi.org/10.3390/ph17030339 - 6 Mar 2024
Cited by 1 | Viewed by 4034
Abstract
As antimicrobial resistance (AMR) escalates globally, examining antibiotic treatment durations for respiratory infections becomes increasingly pertinent, especially in the context of the COVID-19 pandemic. In a UK secondary care setting, this retrospective study was carried out to assess the appropriateness of antibiotic treatment [...] Read more.
As antimicrobial resistance (AMR) escalates globally, examining antibiotic treatment durations for respiratory infections becomes increasingly pertinent, especially in the context of the COVID-19 pandemic. In a UK secondary care setting, this retrospective study was carried out to assess the appropriateness of antibiotic treatment durations—shorter (≤5 days) versus longer (6–7 days and >8 days)—for respiratory tract infections (RTIs) in 640 adults across 2019 and 2020, in accordance with local antimicrobial guidelines. The analysis employed these guidelines and clinical evidence to examine the effectiveness and suitability of antibiotic prescribing practices. This study considered the ‘Shorter Is Better’ approach, noting an increased rate of patient discharges associated with shorter antibiotic regimens (≤5 days). It further demonstrates that shorter treatments are as effective as longer ones for conditions such as COPD exacerbation, COVID-19 pneumonia, and hospital-acquired pneumonia (HAP), except in cases of community-acquired pneumonia (CAP) and unspecified diagnoses. Nevertheless, this study raises concerns over an observed increase in mortality risk with shorter treatment durations. Although these mortality differences were not statistically significant and might have been influenced by the COVID-19 pandemic, the need for extended research with a larger sample size is highlighted to confirm these findings. This study also emphasises the critical need for accurate and specific diagnoses and considering risk assessments at admission, advocating for tailored, evidence-based antibiotic prescribing to ensure patient safety. It contributes to antimicrobial stewardship efforts by reinforcing the importance of adapting antibiotic use to current healthcare challenges and promoting a global commitment to fight antimicrobial resistance. This approach is crucial for enhancing patient outcomes and saving lives on a global scale. Full article
(This article belongs to the Special Issue New Approaches to Fighting Infectious Diseases: Overcoming the Antimicrobial Resistance in Current Treatments)
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Graphical abstract

12 pages, 244 KiB  
Article
Comparison and Analysis of Antibiotic Consumption in Two Italian Hospital Settings in Relation to the Fight of Antimicrobial Resistance
by Francesco Ferrara, Roberta Pasquinucci, Maurizio Capuozzo, Giacomo Polito, Gabriele Bagaglini, Marcello Vaccaro, Adriana Coluccia, Roberto Langella, Ugo Trama, Eduardo Nava and Andrea Zovi
Pharmaceuticals 2024, 17(2), 183; https://doi.org/10.3390/ph17020183 - 30 Jan 2024
Cited by 1 | Viewed by 1318
Abstract
Introduction: The emergence and spread of drug-resistant pathogens due to the improper use of antibiotics have become increasingly apparent in recent years. Objective: This retrospective comparative analysis aimed to assess and compare antibiotic prescription trends in Italy across two different regions [...] Read more.
Introduction: The emergence and spread of drug-resistant pathogens due to the improper use of antibiotics have become increasingly apparent in recent years. Objective: This retrospective comparative analysis aimed to assess and compare antibiotic prescription trends in Italy across two different regions based on geographic area and healthcare structure. One region represents a large hospital institution, while the other represents a populous local Italian health agency. The study also examined the impact of documented antibiotic stewardship programs and efforts to promote responsible antibiotic use at all levels, in alignment with international goals. Antibiotic consumption data were collected from the Umberto I Polyclinic Hospital and the ASL Napoli 3 South Local Health Agency. Methods: To compare consumption between regions, a standardized comparison using the Defined Daily Dose (DDD) was employed. The internal management system of each healthcare facility records all prescriptions and drug dispensations, and these data were extrapolated for this retrospective study. Results: A comparative assessment between the first half of 2022 and 2023 (January–June) highlighted a significant increase in beta-lactam antibiotic consumption, showing a twofold rise compared to the previous year’s term. Regarding prescription averages, there was a noticeable increase of +29.00% in hospitalizations and +28.00% in hospital discharges within the ASL Napoli 3 South. Conversely, at Policlinico Umberto I, there was a marginal increase of +1.60% in hospitalizations and a decrease of −7.40% in hospital discharges. Conclusions: The study offers valuable insights into expenditure patterns and antibiotic consumption, underscoring the need for enhanced prescribing practices and awareness campaigns to address the issue of antibiotic resistance. The findings stress the importance of implementing international guidelines to combat the growing threat of antibiotic resistance and ensure the effective management of infectious diseases. Full article
(This article belongs to the Special Issue New Approaches to Fighting Infectious Diseases: Overcoming the Antimicrobial Resistance in Current Treatments)

Review

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16 pages, 344 KiB  
Review
New Approaches to Overcoming Antimicrobial Resistance in Endophthalmitis
by Noraliz Garcia O’Farrill, Mariana Abi Karam, Victor M. Villegas, Harry W. Flynn, Jr., Andrzej Grzybowski and Stephen G. Schwartz
Pharmaceuticals 2024, 17(3), 321; https://doi.org/10.3390/ph17030321 - 1 Mar 2024
Viewed by 3131
Abstract
Endophthalmitis is a rare but vision-threatening infection characterized by marked inflammation of intraocular fluids and tissues, uncommonly seen following surgery and intravitreal injection. Antimicrobials are used worldwide in the prophylaxis and treatment of bacterial and fungal infections of the eye and are standard [...] Read more.
Endophthalmitis is a rare but vision-threatening infection characterized by marked inflammation of intraocular fluids and tissues, uncommonly seen following surgery and intravitreal injection. Antimicrobials are used worldwide in the prophylaxis and treatment of bacterial and fungal infections of the eye and are standard treatment in the preoperative and postoperative care of surgical patients. However, antimicrobials are reported to be overprescribed in many parts of the world, which contributes to antimicrobial resistance (AMR). AMR complicates the prophylaxis and treatment of endophthalmitis. This article examines the prevalence and mechanisms of AMR in ocular microorganisms, emphasizing the importance of understanding AMR patterns for tailored treatments. It also explores prophylaxis and management strategies for endophthalmitis, with a discussion on the use of intracameral antibiotic administration. The use of prophylactic intracameral antibiotics during cataract surgery is common in many parts of the world but is still controversial in some locations, especially in the US. Finally, it highlights the role of stewardship in ophthalmology and its benefits in the treatment of endophthalmitis. Full article
(This article belongs to the Special Issue New Approaches to Fighting Infectious Diseases: Overcoming the Antimicrobial Resistance in Current Treatments)
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