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Biomedicines
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Drug-Resistant Bacterial Infections and Alternative Therapies—2nd Edition
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Drug-Resistant Bacterial Infections and Alternative Therapies—2nd Edition

A special issue of Biomedicines (ISSN 2227-9059). This special issue belongs to the section "Microbiology in Human Health and Disease".

Deadline for manuscript submissions: 31 December 2026 | Viewed by 3794

Special Issue Editor

Dr. Vijay Singh Gondil

E-Mail Website
Guest Editor
Department of Microbiology and Immunology, University of Rochester Medical Center, Rochester, NY 14620, USA
Interests: antibiotic-resistance; bacterial infections; drug discovery; biofilms; alternative therapeutic agents; combinational therapy
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues

Antibiotic resistance has emerged as a global healthcare challenge, and therapeutic options for treating antibiotic-resistant infections are becoming scarce. Antibiotic resistance limits the effectiveness of existing antibiotics and complicates the treatment of infectious diseases. Addressing antibiotic resistance requires a multifaceted approach, and the development of novel alternatives to antibiotics is crucial to combat resistance. Such alternatives include the discovery/development of novel antibacterial agents, phages, enzybiotics, plant extracts, antibacterial nanoparticles, etc. These antibacterial agents may be beneficial in treating infections when used alone or in combination with available therapeutic options.

This Special Issue is focused on publishing primary research and review articles that explore novel therapeutic agents that could be used as alternatives to conventional antibiotics for managing drug-resistant bacterial infections. We welcome articles on topics including, but not limited to, the following:

  • Applications of phages as therapeutic agents and their synergy with antibiotics;
  • Applications of enzybiotics as therapeutic agents and their synergy with antibiotics;
  • Plant-based antibacterial agents;
  • Antibacterial nanoparticle- and alternative-agent-loaded delivery systems;
  • Drug discovery and the development of new antibacterial agents;
  • The treatment of biofilms and biofilm-associated infections with alternative agents.

Dr. Vijay Singh Gondil
Guest Editor

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 250 words) can be sent to the Editorial Office for assessment.

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. Biomedicines 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 2600 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

  • alternative agents
  • antibiotics
  • phages
  • endolysins
  • phytochemicals
  • drug discovery
  • nanoparticles
  • biofilms

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Published Papers (3 papers)

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Research

11 pages, 240 KB  
Article
Quantifying the Silent Selection Pressure: Antimicrobial Stewardship and Gut Microbiome Integrity in the NICU and PICU
by Fauna Herawati, Faathimah Az’zahra, Maria Anggeraini, Nur Palestin Ayumuyas, Kevin Kantono, Eko Setiawan and Rika Yulia
Biomedicines 2026, 14(5), 1080; https://doi.org/10.3390/biomedicines14051080 - 9 May 2026
Viewed by 629
Abstract
Background: Antimicrobial stewardship in Neonatal (NICU) and Pediatric Intensive Care Units (PICUs) is complicated by rapid physiological maturation and the high vulnerability of the developing gut microbiome. Traditional metrics fails to capture the true utilization density of antibiotics in these settings. This [...] Read more.
Background: Antimicrobial stewardship in Neonatal (NICU) and Pediatric Intensive Care Units (PICUs) is complicated by rapid physiological maturation and the high vulnerability of the developing gut microbiome. Traditional metrics fails to capture the true utilization density of antibiotics in these settings. This study evaluated antimicrobial consumption patterns and alignment with the WHO AWaRe framework in two Indonesian hospitals and its impact towards patients’ length of stay. Methods: A retrospective multicenter study was conducted at a public hospital (Haji Hospital) and a private university hospital (HU Hospital) across 2024–2025. The study population includes all admitted patients (n = 315 in NICU and n = 12 in PICU) to calculate utilization density. Consumption was quantified using Defined Daily Dose (DDD)/100 bed-days, and qualitative assessment was performed using the WHO AWaRe classification. Results: Generalized linear modeling revealed that appropriate antibiotic therapy was significantly associated with a 17% reduction in hospital length of stay (β = −0.187, p = 0.035). At HU Hospital, PICU exhibited a seven-fold higher antimicrobial density (37.56 DDD/100) compared to NICU (5.22 DDD/100). At Haji Hospital, NICU density was 4.95 DDD/100 bed-days. Weight-normalized simulations revealed weight-based dosing disparity with low absolute DDD values in neonates mask a significant biological burden and intense selection pressure on the gut resistome due to immature renal clearance. While Haji Hospital maintained high “Access” category adherence (92.21%), HU Hospital’s PICU showed a high reliance on “Watch” agents (71.27%), specifically Ceftriaxone and Meropenem, which are known drivers of multidrug resistance. Conclusions: Low absolute dosing in neonates does not equate to low therapeutic density or reduced environmental pressure. The heavy use of broad-spectrum agents in the PICU acts as a primary driver for microbiome disruption. To mitigate the emergence of multidrug-resistant organisms, stewardship must transition from adult-indexed metrics (DDD) to more precise measures like Days of Therapy (DOT) and prioritize “Access” protocols to preserve microbiome integrity. Full article
(This article belongs to the Special Issue Drug-Resistant Bacterial Infections and Alternative Therapies—2nd Edition)
9 pages, 600 KB  
Article
Antimicrobial Activity of Natural Extracts Against Catheter-Colonizing Methicillin-Resistant Staphylococcus aureus Clinical Isolates
by José Avendaño-Ortiz, Alba Tribaldo, Luna Ballestero, Luis Antonio Gómez, Ignacio Gracia, Juan Francisco Rodríguez, Natalia Bejarano Ramírez, Raquel Bodoque-Villar, María Ángeles Vaz-Salgado, Rosa del Campo and Francisco Javier Redondo-Calvo
Biomedicines 2025, 13(9), 2150; https://doi.org/10.3390/biomedicines13092150 - 4 Sep 2025
Cited by 1 | Viewed by 1205
Abstract
Background: Intravascular catheters (ICs) are critical medical devices but require frequent replacement due to the risk of bacterial colonization, which can lead to bloodstream infections. This process causes patient discomfort and incurs significant health and economic costs. Aim: To evaluate the inhibitory activity [...] Read more.
Background: Intravascular catheters (ICs) are critical medical devices but require frequent replacement due to the risk of bacterial colonization, which can lead to bloodstream infections. This process causes patient discomfort and incurs significant health and economic costs. Aim: To evaluate the inhibitory activity of natural extracts as potential IC coatings to prevent colonization by methicillin-resistant Staphylococcus aureus (MRSA). Methods: Thirty-six clinical MRSA isolates, obtained from ICs using the Maki technique, were tested. Three natural extracts were evaluated: garlic extract enriched in thiosulfinates (allicin: 7 mg/g), grape extract enriched in proanthocyanidins (92% proanthocyanidins), and propolis extract. Chlorhexidine gluconate (CHG) served as the bactericidal control. The minimum inhibitory concentration (MIC) was determined using the broth microdilution technique with optical density measurements and resazurin-based viability confirmation. The minimum bactericidal concentration (MBC) was assessed from viable cells in wells exceeding the MIC. Results: All tested extracts exhibited bacteriostatic activity against MRSA isolates. The grape extract demonstrated the lowest MIC90 (3.125 mg/mL), followed by propolis extract (MIC90 = 12.5 mg/mL) and garlic extract (MIC90 = 50 mg/mL). Only the propolis extract showed bactericidal activity (MBC = 25 mg/mL). While CHG outperformed the natural extracts, their activity against MRSA suggests potential clinical utility. Conclusion: The natural extracts studied display promising bacteriostatic activity against MRSA isolates from ICs, with propolis extract additionally showing bactericidal effects. Although less potent than CHG, these extracts offer a potential alternative for combating multidrug-resistant pathogens in clinical settings, warranting further investigation for use as IC coatings. Full article
(This article belongs to the Special Issue Drug-Resistant Bacterial Infections and Alternative Therapies—2nd Edition)
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23 pages, 3549 KB  
Article
Immunomodulatory Effects of Escherichia coli Phage GADS24 on Human Dendritic Cells
by Alia M. Aldahlawi, Ghadah A. Alsubhi, Jehan S. Alrahimi, Fatemah S. Basingab and Kawther A. Zaher
Biomedicines 2025, 13(7), 1519; https://doi.org/10.3390/biomedicines13071519 - 21 Jun 2025
Cited by 1 | Viewed by 1319
Abstract
Background: Multidrug-resistant (MDR) Escherichia coli (E. coli) strains pose a significant public health challenge, which has led to the exploration of alternative therapeutic strategies. Due to their antibacterial and immunomodulatory properties, bacteriophages have emerged as promising therapeutic agents. Methods: This study [...] Read more.
Background: Multidrug-resistant (MDR) Escherichia coli (E. coli) strains pose a significant public health challenge, which has led to the exploration of alternative therapeutic strategies. Due to their antibacterial and immunomodulatory properties, bacteriophages have emerged as promising therapeutic agents. Methods: This study investigates the effects of GADS24, a novel lytic bacteriophage of E. coli, on human-monocyte-derived dendritic cells (DCs). DCs are exposed to purified GADS24 phage, bacterial lysate, or a combination of both. Flow cytometry was used to assess the expression of surface markers (HLA-DR, CD80, CD83, and CD86), and ELISA was used to measure cytokine production (IL-10 and IL-12p70). Results: Following treatment with bacterial lysate, a significant increase in DC maturation markers was observed. The GADS24 phage alone induced a moderate upregulation of these markers, decreased IL-10 secretion, and increased IL-12p70. Combining bacterial lysate and phage tempered the maturation response compared to the lysate treatment alone. Conclusion: These findings suggest that GADS24 exerts antibacterial activity and modulates host immunity by influencing DC maturation and cytokine production. Due to its dual antimicrobial and immunomodulatory functions, GADS24 is likely to be a valuable adjunctive therapy for multidrug-resistant (MDR) bacterial infections. Furthermore, in vivo studies are necessary to confirm these promising in vitro results. Full article
(This article belongs to the Special Issue Drug-Resistant Bacterial Infections and Alternative Therapies—2nd Edition)
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