Challenges and Future Prospects of Antibacterial Therapy, 2nd Edition

Topic Information

Dear Colleagues,

Antibiotic resistance has become one of the most pressing global health issues. The increase in multidrug-resistant (MDR) pathogens has resulted in higher rates of death and illness due to unsuccessful treatments, placing a significant strain on healthcare systems around the world. A key factor in this crisis is the improper and excessive use of antibiotics—not only in medical settings but also in non-medical fields such as agriculture and food production—which has hastened the development and dissemination of resistance. Although there is an urgent demand, creating new and effective treatments against MDR bacteria remains a challenging and ongoing task. Biofilms are microbial communities that adhere to surfaces and resist antibiotics, contributing to chronic infections. Targeting biofilm formation is vital for combating MDR pathogens and improving treatment outcomes. This topic aims to collect pioneering research and thorough reviews that focus on the latest progress in developing novel, biocompatible antimicrobial agents and strategies aimed at counteracting emerging MDR pathogens and biofilm formation. Areas of interest include, but are not limited to, the design, synthesis, and production of new antimicrobial materials and platforms; their biocompatibility assessment; and the evaluation of their therapeutic uses.

Prof. Dr. Kwang-sun Kim
Dr. Zehra Edis
Topic Editors

Keywords

Participating Journals

Journal Name	Impact Factor	CiteScore	Launched Year	First Decision (median)	APC
Antibiotics antibiotics	4.6	8.7	2012	16.4 Days	CHF 2900	Submit
International Journal of Molecular Sciences ijms	4.9	9.0	2000	17.8 Days	CHF 2900	Submit
Microbiology Research microbiolres	2.2	2.8	2010	20.2 Days	CHF 1800	Submit
Microorganisms microorganisms	4.2	7.7	2013	20 Days	CHF 2700	Submit
Nanomaterials nanomaterials	4.3	9.2	2010	14 Days	CHF 2400	Submit
Pharmaceuticals pharmaceuticals	4.8	7.7	2004	16 Days	CHF 2900	Submit
Pharmaceutics pharmaceutics	5.5	10.0	2009	15.7 Days	CHF 2900	Submit

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Published Papers (8 papers)

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All Antibiotics IJMS Microbiology Research Pharmaceuticals Pharmaceutics Nanomaterials Microorganisms

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10 pages, 1045 KB  

Open AccessCommunication

Monocaprin, Monolaurin, and Monomyristin Eradicate Staphylococcus aureus Persister Cells Through Membrane Disruption

by Dae-Yoon Kim and Tae-Jong Kim

Pharmaceuticals 2026, 19(5), 690; https://doi.org/10.3390/ph19050690 - 28 Apr 2026

Viewed by 304

Abstract

Background/Objectives: Staphylococcus aureus persister cells significantly undermine antimicrobial therapy through their transient antibiotic tolerance, contributing to chronic and recurrent infections. Although monoglycerides have shown potential as membrane-active antimicrobial agents, their effect on persister cells remains insufficiently understood. Methods: In this study, [...] Read more.

Background/Objectives: Staphylococcus aureus persister cells significantly undermine antimicrobial therapy through their transient antibiotic tolerance, contributing to chronic and recurrent infections. Although monoglycerides have shown potential as membrane-active antimicrobial agents, their effect on persister cells remains insufficiently understood. Methods: In this study, we evaluated the anti-persister activities of monocaprin, monolaurin, and monomyristin against S. aureus persister cells. Mechanistic analyses were performed using membrane permeability assays and fluorescence microscopy. Results: All three monoglycerides reduced persister cell survival, with varying degrees depending on fatty acid chain length. Monolaurin exhibited the greatest anti-persister activity, whereas monocaprin and monomyristin exerted concentration-dependent bactericidal effects. Mechanistic analyses revealed that these compounds increased membrane permeability, thereby compromising cell viability in S. aureus persister cells. In contrast, Tween 80 attenuated both the bactericidal effect and the increase in membrane permeability, supporting the involvement of membrane disruption in their mode of action. Conclusions: The antibacterial activity of monocaprin, monolaurin, and monomyristin against S. aureus is closely associated with membrane damage. These membrane-active monoglycerides represent promising antimicrobial candidates for the eradication of S. aureus persister cells. Full article

(This article belongs to the Topic Challenges and Future Prospects of Antibacterial Therapy, 2nd Edition)

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26 pages, 1016 KB  

Open AccessReview

Burn Infections and Sepsis: Challenges and Future Prospects of Antibacterial Therapy

by Ghazaleh Dadashizadeh, Margarita Elloso and Marc G. Jeschke

Antibiotics 2026, 15(4), 383; https://doi.org/10.3390/antibiotics15040383 - 9 Apr 2026

Viewed by 1065

Abstract

Infectious complications remain a principal determinant of late morbidity and mortality following major thermal injury, reflecting a convergence of barrier disruption, microbial adaptation, and host immune dysfunction. The post-burn environment creates a uniquely permissive niche for pathogen persistence, characterized by altered tissue perfusion, [...] Read more.

Infectious complications remain a principal determinant of late morbidity and mortality following major thermal injury, reflecting a convergence of barrier disruption, microbial adaptation, and host immune dysfunction. The post-burn environment creates a uniquely permissive niche for pathogen persistence, characterized by altered tissue perfusion, biofilm formation, and dynamic shifts in microbial ecology toward multidrug-resistant organisms. Concurrently, profound and evolving changes in host immunity and metabolism reshape both susceptibility to infection and response to therapy. This review integrates current evidence across pathophysiology, microbiology, diagnostics, and treatment, with a focus on challenges that limit effective infection control in burn patients. Particular attention is given to diagnostic uncertainty arising from overlap between sterile inflammation and true infection, the clinical implications of biofilm-associated tolerance, and the impact of burn-specific pharmacokinetic variability on antimicrobial efficacy. We further examine emerging diagnostic and therapeutic innovations, including host-response profiling, rapid molecular detection platforms, and next-generation anti-infective strategies targeting microbial virulence, biofilm structure, and host immune pathways. Despite substantial scientific advances, translation into clinical practice remains constrained by limited burn-specific trials, heterogeneous definitions, and systemic barriers to antimicrobial development. Collectively, these challenges underscore the need for integrated, precision-based approaches that combine early source control, individualized antimicrobial optimization, and advanced diagnostic frameworks. Future progress will depend on coordinated efforts to standardize definitions, generate high-quality multicenter data, and align innovation with clinical applicability across diverse healthcare settings. Full article

(This article belongs to the Topic Challenges and Future Prospects of Antibacterial Therapy, 2nd Edition)

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27 pages, 7495 KB  

Open AccessArticle

Comparative Stability and Quality Assessment of Powder–Liquid Double-Chamber Bag Versus Traditional Meropenem Infusions: Implications for Critical Care and Individualized Dosing

by Xiaokai Ren, Xiao Li, Liting Zhang, Xiaofei Zhao, Lei Zhang and Zhanjun Dong

Pharmaceutics 2026, 18(3), 382; https://doi.org/10.3390/pharmaceutics18030382 - 20 Mar 2026

Viewed by 601

Abstract

Background: Maintaining therapeutic meropenem plasma concentrations requires prolonged infusion, but stability concerns exist between preparation and administration. This study compared the stability and operability of ready-to-use powder–liquid double-chamber bag (DCB) infusions versus traditional powder-for-injection (PFI) meropenem under clinical conditions. Methods: Infusions [...] Read more.

Background: Maintaining therapeutic meropenem plasma concentrations requires prolonged infusion, but stability concerns exist between preparation and administration. This study compared the stability and operability of ready-to-use powder–liquid double-chamber bag (DCB) infusions versus traditional powder-for-injection (PFI) meropenem under clinical conditions. Methods: Infusions at clinically relevant concentrations were stored at 2–8 °C, 25 ± 5 °C, and 40 ± 2 °C for 12 h. Stability assessments included appearance, pH, osmolality, insoluble particle count, meropenem content (HPLC), and impurity A level. Results: DCBs demonstrated superior content uniformity, significantly fewer insoluble particles (p < 0.05), and greater operational simplicity compared to PFI. Refrigeration maintained meropenem content > 95% and effectively suppressed impurity formation for up to 12 h. However, at both room temperature and elevated temperature, impurity A exceeded pharmacopoeial limits within 2 h, particularly at higher concentrations. An innovative bedside solvent volume adjustment method enabled DCBs to deliver high-concentration infusions, facilitating individualized critical care dosing. Conclusions: Compared with traditional powder injection formulations, the Meropenem powder–liquid dual-chamber bag offers more convenient operation under routine preparation conditions and poses a lower risk of contamination during the preparation process. Its stability is more sensitive to storage temperature, requiring strict adherence to refrigeration conditions. When stored under standardized conditions, the dual-chamber bag can better ensure drug efficacy stability and medication safety, making it particularly suitable for clinical emergency use and standardized workflow management. Full article

(This article belongs to the Topic Challenges and Future Prospects of Antibacterial Therapy, 2nd Edition)

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23 pages, 1685 KB  

Open AccessReview

Current Status and Perspectives of Antibacterial Agents Belonging to 2-Oxazolidinones

by Jessica Ceramella, Annaluisa Mariconda, Domenico Iacopetta, Maria Marra, Alessia Catalano, Paola Checconi, Stefano Aquaro, Carmela Saturnino, Pasquale Longo and Maria Stefania Sinicropi

Pharmaceuticals 2026, 19(3), 432; https://doi.org/10.3390/ph19030432 - 6 Mar 2026

Viewed by 950

Abstract

In the last three decades, 2-oxazolidinones have emerged as an important class of inhibitors of bacterial protein synthesis, effective in the treatment of multidrug-resistant (MDR) bacterial infections. From a public health perspective, the importance of 2-oxazolidinones is related to the treatment of tuberculosis [...] Read more.

In the last three decades, 2-oxazolidinones have emerged as an important class of inhibitors of bacterial protein synthesis, effective in the treatment of multidrug-resistant (MDR) bacterial infections. From a public health perspective, the importance of 2-oxazolidinones is related to the treatment of tuberculosis (TB), primarily MDR-TB and extensively drug-resistant XDR-TB. Linezolid, the first oxazolidinone antibiotic approved by FDA, is still used in therapy despite common adverse events, such as myelosuppression and serotonergic toxicity, as well as the increasing percentage of linezolid-resistant bacteria (Staphylococcus aureus, enterococci and methicillin-resistant S. aureus). Tedizolid phosphate was the second commercially available oxazolidinone antibiotic approved, followed by other oxazolidinones (contezolid, radezolid, ranbezolid, sutezolid, delpazolid, cadazolid, TBI-233 and MK-7762) that are in clinical study. Contezolid is approved in China and cadazolid has entered phase III clinical trials. This comprehensive review intends to provide an overview of the compounds belonging to this class already in use in therapy and/or clinical studies and to portray the most significant and recent outcomes regarding new oxazolidinones under study. Three literature databases, i.e., PubMed/MEDLINE, Google Scholar and Scopus, were used for the literature search, particularly focusing on the last five years, and screened using different keywords. The design of new drugs belonging to this class may be of considerable interest to researchers and clinicians, contributing to the discovery of new antibiotics that retain antibacterial activity but have fewer side effects. Full article

(This article belongs to the Topic Challenges and Future Prospects of Antibacterial Therapy, 2nd Edition)

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17 pages, 2748 KB  

Open AccessArticle

Impact of Modified Lactoperoxidase Systems on Glycolytic Metabolism and Virulence Factors in Streptococcus mutans

by Marcin Rafał Magacz, Anna Skalniak, Paweł Mamica, Wiktoria Pepasińska, Anna Maria Osyczka, Grzegorz Tylko and Wirginia Krzyściak

Int. J. Mol. Sci. 2026, 27(2), 799; https://doi.org/10.3390/ijms27020799 - 13 Jan 2026

Viewed by 406

Abstract

The lactoperoxidase system (LpoS) is an enzymatic antimicrobial mechanism of saliva that oxidizes (pseudo)halide substrates to reactive compounds capable of limiting microbial growth. This study evaluated how different LpoS variants—utilizing iodide (LpoS-I⁻), thiocyanate (LpoS-SCN⁻), selenocyanate (LpoS-SeCN⁻), and [...] Read more.

The lactoperoxidase system (LpoS) is an enzymatic antimicrobial mechanism of saliva that oxidizes (pseudo)halide substrates to reactive compounds capable of limiting microbial growth. This study evaluated how different LpoS variants—utilizing iodide (LpoS-I⁻), thiocyanate (LpoS-SCN⁻), selenocyanate (LpoS-SeCN⁻), and a thiocyanate–iodide mixture (LpoS-SCN⁻ + I⁻)—affect virulence, metabolism, and biofilm structure in Streptococcus mutans. Using qRT-PCR, pyruvate assays, MTT reduction, and confocal microscopy, we found that LpoS-I⁻ most effectively reduced atpD and ldh expression, impaired acid tolerance, and decreased lactate and pyruvate production. LpoS-SCN⁻ and LpoS-SeCN⁻ also downregulated atpD and gtfB, although LpoS-SeCN⁻ upregulated ldh. Despite minimal structural biofilm disruption, LpoS-I⁻ markedly inhibited intracellular and extracellular pyruvate accumulation, suggesting altered glycolytic flux. These findings indicate that iodide-based LPO systems modulate key metabolic and regulatory pathways in S. mutans and may hold potential for inclusion in anticaries oral formulations. Full article

(This article belongs to the Topic Challenges and Future Prospects of Antibacterial Therapy, 2nd Edition)

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21 pages, 1017 KB  

Open AccessReview

CRISPR–Cas-Mediated Reprogramming Strategies to Overcome Antimicrobial Resistance

by Byeol Yoon, Jang Ah Kim and Yoo Kyung Kang

Pharmaceutics 2026, 18(1), 95; https://doi.org/10.3390/pharmaceutics18010095 - 11 Jan 2026

Cited by 1 | Viewed by 1638

Abstract

Antimicrobial resistance (AMR) is escalating worldwide, posing a serious threat to global public health by driving infections that are no longer treatable with conventional antibiotics. CRISPR–Cas technology offers a programmable and highly specific therapeutic alternative by directly targeting the genetic determinants responsible for [...] Read more.

Antimicrobial resistance (AMR) is escalating worldwide, posing a serious threat to global public health by driving infections that are no longer treatable with conventional antibiotics. CRISPR–Cas technology offers a programmable and highly specific therapeutic alternative by directly targeting the genetic determinants responsible for resistance. Various CRISPR systems can restore antibiotic susceptibility and induce selective bactericidal effects by eliminating resistance genes, disrupting biofilm formation, and inhibiting virulence pathways. Moreover, CRISPR can suppress horizontal gene transfer (HGT) by removing mobile genetic elements such as plasmids, thereby limiting the ecological spread of AMR across humans, animals, and the environment. Advances in delivery platforms—including conjugative plasmids, phagemids, and nanoparticle-based carriers—are expanding the translational potential of CRISPR-based antimicrobial strategies. Concurrent progress in Cas protein engineering, spatiotemporal activity regulation, and AI-driven optimization is expected to overcome current technical barriers. Collectively, these developments position CRISPR-based antimicrobials as next-generation precision therapeutics capable of treating refractory bacterial infections while simultaneously suppressing the dissemination of antibiotic resistance. Full article

(This article belongs to the Topic Challenges and Future Prospects of Antibacterial Therapy, 2nd Edition)

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27 pages, 4082 KB  

Open AccessArticle

Biogenic Selenium Nanoparticles from Lactiplantibacillus plantarum as a Potent Antimicrobial Agent Against Methicillin-Resistant Staphylococcus aureus

by Gyeong-min Kim, SeCheol Oh and Kwang-sun Kim

Pharmaceutics 2026, 18(1), 14; https://doi.org/10.3390/pharmaceutics18010014 - 22 Dec 2025

Cited by 2 | Viewed by 1121

Abstract

Background: Methicillin-resistant Staphylococcus aureus (MRSA) remains a major global health concern owing to its multidrug resistance and persistence despite continued antibiotic development. Eco-friendly nanomaterials such as selenium nanoparticles (SeNPs) have emerged as promising antimicrobial alternatives because of their high biocompatibility and lower toxicity [...] Read more.

Background: Methicillin-resistant Staphylococcus aureus (MRSA) remains a major global health concern owing to its multidrug resistance and persistence despite continued antibiotic development. Eco-friendly nanomaterials such as selenium nanoparticles (SeNPs) have emerged as promising antimicrobial alternatives because of their high biocompatibility and lower toxicity compared to conventional metallic nanoparticles. In this study, we investigated the inhibitory effects and underlying mechanisms of Lactiplantibacillus plantarum (LP)–derived SeNPs (LP-SeNPs) on MRSA. Methods: SeNPs were biosynthesized using the antibacterial cell-free supernatant (CFS) of LP, which provides naturally reducing and stabilizing biomolecules. The resulting LP-SeNPs were characterized by physicochemical and structural analyses and compared to chemically synthesized SeNPs (Chem-SeNPs). Antibacterial activity was assessed through minimum inhibitory concentration (MIC) testing, time-kill kinetics, and cell viability assays. Results: LP-SeNPs, which were spherical with an average diameter of 107 nm, exhibited selective antibacterial activity against Gram-positive bacteria and showed no effect on Gram-negative strains. Notably, all six MRSA isolates demonstrated high susceptibility, with MIC values approximately 100-fold lower than that of S. aureus ATCC 25923, a non-MRSA reference strain. LP-SeNPs were also non-cytotoxic up to 20-fold the MIC (IC₅₀ > 10 µg/mL). Mechanistic analyses indicated that disruption of the bacterial cell membrane was the primary antibacterial mechanism, supported by additional contributions from reactive oxygen species generation and protein synthesis inhibition. Conclusions: LP-SeNPs represent a sustainable, biocompatible, and potent antibacterial nanoplatform with strong selectivity for Gram-positive pathogens, particularly MRSA. These findings highlight their potential as eco-friendly and targeted therapeutic strategies for combating MRSA infections. Full article

(This article belongs to the Topic Challenges and Future Prospects of Antibacterial Therapy, 2nd Edition)

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11 pages, 235 KB  

Open AccessArticle

Clinical Outcomes of Piperacillin/Tazobactam Treatment in Outpatient Parenteral Antimicrobial Therapy (OPAT) Programs: Comparison of Two Models of Opat Care

by Santiago J. Lora-Escobar, Laura Herrera-Hidalgo, Nerea Castillo-Fernández, Zaira R. Palacios-Baena, Rafael Luque-Márquez, Arístides De Alarcón, Ana Belén Guisado-Gil, Belén Gutierrez-Gutierrez, María Dolores Navarro-Amuedo, Julia Praena-Segovia, Marta Mejías Trueba, Juan Manuel Carmona-Caballero, José Manuel Sánchez Oliva, María Victoria Gil-Navarro and Luis E. López-Cortés

Pharmaceutics 2025, 17(11), 1429; https://doi.org/10.3390/pharmaceutics17111429 - 4 Nov 2025

Viewed by 1186

Abstract

Objectives: Piperacillin/tazobactam (P/T) is a broad-spectrum β-lactam antibiotic frequently used in outpatient parenteral antimicrobial therapy programs (OPAT). We aim to compare the clinical outcomes of P/T treatment in two models of OPAT care in order to maximize the utilization of health resources. [...] Read more.

Objectives: Piperacillin/tazobactam (P/T) is a broad-spectrum β-lactam antibiotic frequently used in outpatient parenteral antimicrobial therapy programs (OPAT). We aim to compare the clinical outcomes of P/T treatment in two models of OPAT care in order to maximize the utilization of health resources. Material and methods: We conducted a prospective observational study with retrospective analysis of a cohort of patients treated with P/T delivered every 24 or 48 h in an OPAT program. The primary outcomes were treatment failure during the OPAT episode and 30 day treatment failure. A bivariate and multivariate logistic regression model was built. A two-sided p < 0.05 was considered statistically significant. Results: Between 2012 and 2022, 247 patients were treated with P/T. Treatment was delivered daily in 176 patients (Group 24) and every two days in 71 patients (Group 48). The rate of treatment failure during OPAT in Group 24 and Group 48 was 12.4% (n = 22) and 5.6% (n = 4), respectively (p = 0.112); and the rate of treatment failure 30 days after OPAT treatment end was 18.2% (n = 32) and 21.1% (n = 15) in Group 24 and Group 48, respectively (p = 0.594). Treatment every 24 or 48 h was not associated with higher treatment failure during OPAT or 30 days after finishing OPAT in either bivariate or multivariate analysis. Conclusions: P/T administration in OPAT programs being replaced every two days is feasible without an increase in treatment failure, relapse, or mortality compared to daily drug replacement. These findings should motivate further research to facilitate the implementation of this novel delivery strategy in OPAT programs. Full article

(This article belongs to the Topic Challenges and Future Prospects of Antibacterial Therapy, 2nd Edition)

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