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Antibiotic Resistance and Misuse

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

Deadline for manuscript submissions: closed (31 December 2025) | Viewed by 17594

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Special Issue Editors

Dr. Bogdan Vintila

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1. Faculty of Medicine, Lucian Blaga University, 2A, Lucian Blaga Str., 550169 Sibiu, Romania
2. Anesthesia and Intensive Care Department, County Clinical Emergency Hospital, 2–4, Corneliu Coposu Bld., 550245 Sibiu, Romania
Interests: anesthesia and intensive care; pharmacology; infectious diseases; airway management; sepsis; hemodynamics
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Dr. Claudiu Morgovan

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Faculty of Medicine, Lucian Blaga University, 2A, Lucian Blaga Str., 550169 Sibiu, Romania
Interests: pharmacology; drug safety; antimicrobial resistance; drug efficacy
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Dr. Anca-Maria Arseniu

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Faculty of Medicine, Lucian Blaga University of Sibiu, Sibiu, Romania
Interests: drug delivery; drug design and synthesis; structural characterization; biological activity evaluation; structure-activity relationship; medicinal chemistry; pharmacovigilance
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

As a specialist in anesthesia and intensive care and holding a PhD focused on the risks associated with exposure to antibiotics commonly used in intensive care settings, I am honored to invite you to contribute to this Special Issue of the Pharmaceuticals journal, which is dedicated to examining the timely topics of antibiotic resistance and misuse.

Antibiotic resistance is worsened by the misuse and overuse of antibiotics in clinical settings and is one of the most significant public health challenges we face today. This Special Issue aims to provide valuable insights to the medical community through a diverse collection of research articles, reviews, and case studies from leading experts in the field. This topic highlights the need for responsible antibiotic use, effective infection prevention and control, and assessment of the antimicrobial resistance phenomenon. These contributions seek to bring clarity to the complex nature of antibiotic resistance, exploring its molecular mechanisms, the effects of antibiotic stewardship programs, and innovative strategies for developing new antimicrobial agents and therapies.

This Special Issue set out to explore the consequences of antibiotic misuse in various care settings and to highlight recent advancements in diagnostic techniques that allow for faster identification of resistant infections, enabling more targeted and effective treatment approaches.

Dr. Bogdan Vintila
Dr. Claudiu Morgovan
Dr. Anca-Maria Arseniu
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 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. 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

antibiotic resistance
antibiotic misuse
antimicrobial stewardship
infection control
resistance mechanisms
diagnostic innovations
therapeutic strategies
policy reforms
clinical outcomes

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Published Papers (5 papers)

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Research

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21 pages, 1183 KB

Open AccessArticle

Resistance, Ineffectiveness, and Off-Label Use Related to Cephalosporins from the Reserve Group—A Pharmacovigilance Signal Detection Study on EudraVigilance Database

by Anca Maria Arseniu, Bogdan Ioan Vintila, Anca Butuca, Laurentiu Stoicescu, Adina Frum, Adriana Aurelia Chis, Rares Arseniu, Felicia Gabriela Gligor, Steliana Ghibu, Claudiu Morgovan and Carmen Maximiliana Dobrea

Pharmaceuticals 2026, 19(1), 155; https://doi.org/10.3390/ph19010155 - 15 Jan 2026

Viewed by 642

Abstract

Background/Objectives: Antimicrobial resistance (AMR) is considered a major threat by the healthcare community. In this context, the AWaRe (Access, Watch, Reserve) classification of antibiotics is a valuable tool that can assist physicians during the clinical decision process and pharmacists in promoting the rational use of antibiotics. Pharmacovigilance studies based on real-world evidence offer valuable insight into the AMR phenomenon. The aim of this study was the assessment of the resistance, ineffectiveness, and off-label use signals of all five cephalosporins belonging to the Reserve group (ceftazidime/avibactam, ceftaroline, cetolozane/tazobactam, ceftobiprole, and cefiderocol). Methods: The study was conducted using descriptive approaches on EudraVigilance data and disproportionality analyses comparing each of the fourteen cephalosporins in the Watch group. Results: Ceftazidime/avibactam (n = 904, 38.6%) topped the reports, followed by ceftaroline (n = 559, 23.9%) and ceftolazane/tazobactam (n = 560, 23.9%). The lowest number of reports was submitted for cefiderocol (n = 176, 7.5%) and ceftobiprole (n = 146, 6.2%). The resistance to ceftazidime/avibactam, cefiderocol, and ceftolozane/tazobactam was reported with a higher probability than all others, the strongest signal being observed for cefiderocol against cefixime (ROR: 171.25, 95% CI 79.64–368.27). All cephalosporins from the Reserve group (except ceftobiprole) have higher probability for reporting ineffectiveness than cephalosporins from the Watch group; the strongest signal was observed for cefiderocol–cefditoren (ROR: 14.70, 95% CI 6.73–32.11). All cephalosporines from the Reserve group had a higher probability of reporting off-label use by comparison with the ones from the Watch group, except for two cases of no disproportionate signal between cefiderocol–cefoperazone and cefiderocol–ceftizoxime; the strongest signal was observed for ceftolozane/tazobactam–cefotaxim (ROR: 43.61, 95% CI 30.14–63.09). Conclusions: This analysis supplements information from clinical trials and current clinical practice, underscoring the critical need for rigorous antibiotic stewardship programs. Notably, even restricted use of cephalosporins demonstrated therapeutic failure and inappropriate utilization. Full article

(This article belongs to the Special Issue Antibiotic Resistance and Misuse)

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15 pages, 1308 KB

Open AccessArticle

Trends in Antimicrobial Resistance of Acinetobacter baumannii and Pseudomonas aeruginosa from Bloodstream Infections: An Eight-Year Study in a Romanian Tertiary Hospital

by Alina Maria Borcan, Elena Rotaru, Laura Georgiana Caravia, Mihai-Cezar Filipescu and Mădălina Simoiu

Pharmaceuticals 2025, 18(7), 948; https://doi.org/10.3390/ph18070948 - 24 Jun 2025

Cited by 6 | Viewed by 2445

Abstract

Background: Bloodstream infections (BSIs) caused by multidrug-resistant non-fermenting Gram-negative bacilli, particularly Pseudomonas aeruginosa and Acinetobacter baumannii, represent a growing public health concern, especially in tertiary care settings. This study aimed to describe the epidemiological and antimicrobial resistance trends of P. aeruginosa and A. baumannii isolated from blood cultures over an eight-year period (2017–2024) at a tertiary infectious disease hospital in Bucharest, Romania, especially in the context of the disruption caused by the SARS-CoV-2 pandemic. Methods: A retrospective study was conducted on 43,951 blood cultures processed at the National Institute of Infectious Diseases. Species identification and antibiotic susceptibility testing (AST) were performed using VITEK2, MALDI-TOF MS, and supplementary phenotypic methods. AST interpretation followed EUCAST guidelines. Results: Out of all of the positive blood cultures, 112 (3.63%) were P. aeruginosa and 158 (5.12%) A. baumannii. Multidrug-resistance (MDR) was identified in 46% of P. aeruginosa and 90.73% of A. baumannii isolates. Resistance trends varied, with P. aeruginosa showing a decrease in MDR rates post-COVID-19 pandemic and following antimicrobial stewardship implementation. In contrast, A. baumannii displayed persistently high resistance, with carbapenem and aminoglycoside resistance rates reaching 100% by 2024. Colistin resistance, though low overall, increased in the latter years. Conclusions: The findings highlight the dynamic nature of antimicrobial resistance among P. aeruginosa and A. baumannii. Effective infection control and antimicrobial stewardship programs are crucial in curbing the rise of MDR strains, particularly amid healthcare system disruptions such as the COVID-19 pandemic. Full article

(This article belongs to the Special Issue Antibiotic Resistance and Misuse)

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Review

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29 pages, 668 KB

Open AccessReview

Bovine Mastitis Therapy at a Crossroads: Pharmacokinetic Barriers, Biofilms, Antimicrobial Resistance, and Emerging Solutions

by Alexandra Ban-Cucerzan, Adriana Morar, Emil Tîrziu, Iulia-Maria Bucur, Sebastian-Alexandru Popa and Kálmán Imre

Pharmaceuticals 2026, 19(1), 175; https://doi.org/10.3390/ph19010175 - 19 Jan 2026

Cited by 3 | Viewed by 1089 | Correction

Abstract

Bovine mastitis remains a major challenge in dairy production despite extensive antimicrobial use, with therapeutic failure increasingly attributed to factors beyond classical antimicrobial resistance (AMR). Growing evidence indicates that treatment inefficacy arises from the combined effects of pharmacokinetic/pharmacodynamic (PK/PD) constraints, biofilm-mediated tolerance, intracellular persistence, and the adaptive capacity of mastitis pathogens. Intramammary therapy is particularly limited by poor tissue penetration, episodic drug elimination via milk flow, and inactivation by milk components, frequently resulting in subtherapeutic exposure at the site of infection. These limitations are amplified in chronic and subclinical mastitis, where biofilms and intracellular reservoirs reduce antimicrobial susceptibility and promote relapse and resistance selection. This narrative review integrates current knowledge on pharmacokinetic and pharmacodynamic (PK/PD) barriers, microbial survival strategies, and antimicrobial resistance (AMR) mechanisms that underlie treatment failure in bovine mastitis. It critically evaluates conventional antimicrobial therapies alongside emerging approaches, including antimicrobial peptides, bacteriophages and endolysins, nanoparticle-based delivery systems, immunomodulators, CRISPR-guided antimicrobials, and drug repurposing strategies. Overall, available evidence highlights the potential of these approaches to enhance therapeutic durability, particularly in settings where biofilm formation, intracellular persistence, and resistance limit conventional treatment efficacy. By mapping research coverage across mastitis phenotypes and therapeutic outcomes, this review identifies key gaps in long-term efficacy and resistance mitigation and underscores the need for PK/PD-guided, biofilm-aware, and resistance-conscious strategies to support durable next-generation mastitis management. Full article

(This article belongs to the Special Issue Antibiotic Resistance and Misuse)

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24 pages, 1487 KB

Open AccessReview

Hypervirulent Klebsiella pneumoniae: Insights into Virulence, Antibiotic Resistance, and Fight Strategies Against a Superbug

by Helal F. Hetta, Fawaz E. Alanazi, Mostafa A. Sayed Ali, Ahmed D. Alatawi, Hashim M. Aljohani, Rehab Ahmed, Nuha A. Alansari, Fahad M. Alkhathami, Alaa Albogmi, Bander M. Alharbi, Hanadi S. Alanzi, Amirah B. Alaqyli and Yasmin N. Ramadan

Pharmaceuticals 2025, 18(5), 724; https://doi.org/10.3390/ph18050724 - 15 May 2025

Cited by 24 | Viewed by 12457

Abstract

Community-acquired infections caused by Klebsiella pneumoniae (K. pneumoniae) have become a significant global health concern, particularly with the emergence of hypervirulent strains (hvKP). These strains are associated with severe infections, such as pyogenic liver abscesses, even in otherwise healthy individuals. Initially reported in Taiwan in the 1980s, hvKP has now spread worldwide. The pathogenicity of hvKP is attributed to an array of virulence factors that enhance its ability to colonize and evade host immune defenses. Additionally, the convergence of hypervirulence with antibiotic resistance has further complicated treatment strategies. As a member of the ESKAPE group of pathogens, K. pneumoniae exhibits high resistance to multiple antibiotics, posing a challenge for healthcare settings. This review provides a comprehensive overview of hvKP, highlighting its structural and pathogenic differences from classical K. pneumoniae strains, key virulence factors, mechanisms of antibiotic resistance, and the increasing threat of multidrug-resistant hvKP. Lastly, we discuss current treatment guidelines and emerging therapeutic strategies to combat this formidable pathogen. Full article

(This article belongs to the Special Issue Antibiotic Resistance and Misuse)

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