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Pathogens
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Advanced Antimicrobial Agents: Combatting Multi-Drug Resistant Bacterial Infections
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Advanced Antimicrobial Agents: Combatting Multi-Drug Resistant Bacterial Infections

A special issue of Pathogens (ISSN 2076-0817). This special issue belongs to the section "Bacterial Pathogens".

Deadline for manuscript submissions: 30 November 2025 | Viewed by 7132

Special Issue Editor

Dr. Nachiket Vaze

E-Mail Website
Guest Editor
Division of Environmental and Population Health Biosciences, Environmental and Occupational Health Sciences Institute (EOHSI), Rutgers University, Piscataway, NJ 08854, USA
Interests: antimicrobial technology development; antibiotic resistance; nanotechnology; bioaerosols
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Despite the advances in antibiotic development, infectious diseases continue to affect hundreds of millions of people each year with serious outcomes, impacting public health adversely. Incorrect prescription of antibiotics and their overuse have led to the dangerous rise in antibiotic resistance. The most alarming aspect of this is the rise in multi-drug-resistant (MDR) infections. Due to the interconnected nature of the modern economy, the MDR pathogens are spreading rapidly across the globe, causing pandemics. Thus, there is a vital need to develop novel advanced antimicrobial agents for inactivating MDR pathogens.

Although this is an issue of vital importance to the field of public health, there is no focused effort in highlighting such research in the literature. In this Special Issue, we would like to highlight cutting edge research being carried out at the forefront of the battle against these MDR pathogens. Novel approaches such as nanotechnology, advanced pharmaceutical approaches, UV, and other such technologies are some research areas intended to be covered by this issue.

We look forward to featuring your exciting research in this field, which would be of great interest to the readers of the journal and the broad scientific community in general. Thank you.

Dr. Nachiket Vaze
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 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. Pathogens 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 2200 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

  • multi-drug resistance
  • antimicrobial susceptibility
  • nanoformulations
  • UV disinfection
  • antibiotic synergy

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Published Papers (4 papers)

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Research

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19 pages, 10016 KB  
Article
A Novel Enterococcus Phage Endolysin Lys22 with a Wide Host Range Against Mixed Biofilm of Enterococcus faecalis, Staphylococcus aureus, and Acinetobacter baumannii
by Ziqin Yang, Xue Du, Nannan Hu, Meng-Ai Feng, Jiaoyang Xu, Hailin Jiang, Na Zhang, Honglan Huang, Jinghua Li and Hongyan Shi
Pathogens 2025, 14(10), 1060; https://doi.org/10.3390/pathogens14101060 - 20 Oct 2025
Viewed by 446
Abstract
The global surge in multidrug-resistant (MDR) bacterial pathogens has created an urgent imperative for innovative antimicrobial strategies. Enterococcus faecalis, Staphylococcus aureus, and Acinetobacter baumannii demonstrate remarkable antibiotic resistance and dominate hospital-acquired infections. These bacteria often form biofilms, a complex community structure [...] Read more.
The global surge in multidrug-resistant (MDR) bacterial pathogens has created an urgent imperative for innovative antimicrobial strategies. Enterococcus faecalis, Staphylococcus aureus, and Acinetobacter baumannii demonstrate remarkable antibiotic resistance and dominate hospital-acquired infections. These bacteria often form biofilms, a complex community structure that shields them from immune system phagocytosis, resists antibiotic penetration, and enhances their survival in hostile environments. In clinical cases, these bacteria often form mixed biofilms and lead to treatment failures. Phages and their derivatives have emerged as promising candidates in the fight against drug-resistant bacteria. Lys22, an endolysin derived from an enterococcus phage, has been cloned and demonstrated to possess a broad host range, effectively targeting E. faecalis, various Staphylococcus species, and A. baumannii. When applied to the biofilms formed by these bacteria, Lys22 was found to significantly inhibit both simple and complex biofilms in vitro. Virulent genes, including agrA, sarA, and icaA in S. aureus; asa1, cylA, and gelE in E. faecalis; and OmpA and lpsB in A. baumannii were also downregulated by Lys22. Notably, Lys22 also exhibited a robust protective effect against dual or triple infections involving E. faecalis, S. aureus, and A. baumannii in a zebrafish embryos model, highlighting its potential as a therapeutic agent in combatting multi-bacterial infections. Full article
(This article belongs to the Special Issue Advanced Antimicrobial Agents: Combatting Multi-Drug Resistant Bacterial Infections)
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Review

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17 pages, 275 KB  
Review
Ceftazidime/Avibactam Monotherapy Versus Other Antibiotics: Where Do We Stand?
by Georgios Vougiouklakis, Constantinos Tsioutis, Nayia Vasileiadi, Konstantinos Alexakis, Nikolaos Spernovasilis and Aris P. Agouridis
Pathogens 2025, 14(11), 1119; https://doi.org/10.3390/pathogens14111119 - 3 Nov 2025
Viewed by 344
Abstract
The global rise of multi-drug resistant (MDR) pathogens, including the widespread resistance to beta-lactams through the production of β-lactamases, like extended spectrum β-lactamases (ESBLs), has led to the increasing use of last-line antibiotics such as carbapenems. Subsequently, the worldwide emergence of carbapenemase-producing pathogens [...] Read more.
The global rise of multi-drug resistant (MDR) pathogens, including the widespread resistance to beta-lactams through the production of β-lactamases, like extended spectrum β-lactamases (ESBLs), has led to the increasing use of last-line antibiotics such as carbapenems. Subsequently, the worldwide emergence of carbapenemase-producing pathogens poses a formidable challenge. The combination ceftazidime/avibactam (CAZ/AVI) has emerged as a pivotal agent in the management of multidrug-resistant Gram-negative infections. Avibactam, a novel β-lactamase inhibitor, demonstrates a wider spectrum of activity against Ambler Class A, C, and partially D β-lactamases in comparison to older inhibitors, thus enhancing the antimicrobial activity of ceftazidime against organisms producing ESBL and carbapenemases, such as oxacillinase (OXA)-type and Klebsiella pneumoniae Carbapenemase (KPC). This review synthesizes findings from randomized controlled trials and cohort studies, evaluating the efficacy of CAZ/AVI across diverse clinical settings, including complicated intra-abdominal infections, urinary tract infections, nosocomial pneumonia, skin and soft tissue infections, and bloodstream infections. The non-inferiority of CAZ-AVI with respect to carbapenems and superiority over polymyxins in terms of both clinical outcomes and safety are outlined, along with evidence supporting the use of CAZ/AVI in high-risk populations such as immunocompromised and critically ill patients. Overall, CAZ/AVI represents a compelling therapeutic option with favorable efficacy and safety, thus appearing as a reasonable frontline treatment for resistant Gram-negative infections. Full article
(This article belongs to the Special Issue Advanced Antimicrobial Agents: Combatting Multi-Drug Resistant Bacterial Infections)
16 pages, 3105 KB  
Review
Novel Therapies for Prosthetic Joint Infections Caused by Methicillin-Resistant Staphylococcus aureus
by Xi Xiang, Xin Jin, Qi Yang, Lili Zou, Yueqing Wang, Tianxu Wang and Xun Sun
Pathogens 2025, 14(11), 1102; https://doi.org/10.3390/pathogens14111102 - 29 Oct 2025
Viewed by 250
Abstract
Periprosthetic joint infection (PJI) is a serious complication following total joint replacement, with methicillin-resistant Staphylococcus aureus (MRSA) being the primary pathogen. The treatment challenges posed by MRSA’s antibiotic resistance further highlight the critical importance of research in this field. Current antibiotic therapies for [...] Read more.
Periprosthetic joint infection (PJI) is a serious complication following total joint replacement, with methicillin-resistant Staphylococcus aureus (MRSA) being the primary pathogen. The treatment challenges posed by MRSA’s antibiotic resistance further highlight the critical importance of research in this field. Current antibiotic therapies for periprosthetic joint infection caused by methicillin-resistant Staphylococcus aureus (MRSA-PJI) are limited by considerable side effects, such as high costs and the development of resistance. Therefore, there is an urgent need to explore novel alternative or adjunctive therapies. This review provides a comprehensive overview of several innovative therapeutic strategies. These include monoclonal antibody therapies that target specific bacterial components; phage therapy, which can either independently or synergistically degrade biofilms and enhance antimicrobial efficacy, characterized by its high specificity; antimicrobial peptides, capable of disrupting bacterial membrane integrity and exhibiting dual antibiofilm activity, with a reduced tendency to induce resistance; and nanoparticles and hydrogels, which function as drug delivery systems for sustained release, thereby improving both preventive and therapeutic outcomes. However, these novel therapies also face challenges such as high production costs and limited stability, underscoring the need for further research and optimization. Future efforts should focus on additional studies, clinical trials, and the development of robust regulatory frameworks to fully realize the potential of these treatments for MRSA-PJI. Full article
(This article belongs to the Special Issue Advanced Antimicrobial Agents: Combatting Multi-Drug Resistant Bacterial Infections)
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33 pages, 1065 KB  
Review
Disarming Staphylococcus aureus: Review of Strategies Combating This Resilient Pathogen by Targeting Its Virulence
by Abdelaziz Touati, Nasir Adam Ibrahim and Takfarinas Idres
Pathogens 2025, 14(4), 386; https://doi.org/10.3390/pathogens14040386 - 15 Apr 2025
Cited by 8 | Viewed by 5606
Abstract
Staphylococcus aureus is a formidable pathogen notorious for its antibiotic resistance and diverse virulence mechanisms, including toxin production, biofilm formation, and immune evasion. This article explores innovative anti-virulence strategies to disarm S. aureus by targeting critical virulence factors without exerting bactericidal pressure. Key [...] Read more.
Staphylococcus aureus is a formidable pathogen notorious for its antibiotic resistance and diverse virulence mechanisms, including toxin production, biofilm formation, and immune evasion. This article explores innovative anti-virulence strategies to disarm S. aureus by targeting critical virulence factors without exerting bactericidal pressure. Key approaches include inhibiting adhesion and biofilm formation, neutralizing toxins, disrupting quorum sensing (e.g., Agr system inhibitors), and blocking iron acquisition pathways. Additionally, interventions targeting two-component regulatory systems are highlighted. While promising, challenges such as strain variability, biofilm resilience, pharmacokinetic limitations, and resistance evolution underscore the need for combination therapies and advanced formulations. Integrating anti-virulence strategies with traditional antibiotics and host-directed therapies offers a sustainable solution to combat multidrug-resistant S. aureus, particularly methicillin-resistant strains (MRSA), and mitigate the global public health crisis. Full article
(This article belongs to the Special Issue Advanced Antimicrobial Agents: Combatting Multi-Drug Resistant Bacterial Infections)
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