Antibiotics

11 pages, 337 KiB

Open AccessArticle

Early Administration of Rifampicin Does Not Induce Increased Resistance in Septic Two-Stage Revision Knee and Hip Arthroplasty

by Leonard Grünwald, Benedikt Paul Blersch and Bernd Fink

Antibiotics 2025, 14(6), 610; https://doi.org/10.3390/antibiotics14060610 (registering DOI) - 16 Jun 2025

Abstract

Background/Objectives: Periprosthetic joint infection (PJI) is a severe complication that follows arthroplasty and occurs in approximately 2% of all cases. One of several cornerstones of therapy is an optimized antibiotic regimen. Early administration of rifampicin—together with a combination of an antibiotic to [...] Read more.

Background/Objectives: Periprosthetic joint infection (PJI) is a severe complication that follows arthroplasty and occurs in approximately 2% of all cases. One of several cornerstones of therapy is an optimized antibiotic regimen. Early administration of rifampicin—together with a combination of an antibiotic to which the specific microorganism is susceptible—accompanying a two-stage revision surgery, remained controversial due to the potential risk of emerging resistance. However, the exact time to start rifampicin treatment often remains unclear and might be crucial in the treatment regimen. Methods: In a retrospective study design, a total of 212 patients receiving a two-stage revision surgery after a diagnosis of PJI (60.8% THA, 39.2% TKA) received an individual rifampicin combination therapy after initial debridement and removal of all foreign material, starting rifampicin on the second day postoperatively. Results: At the time of spacer explantation, two patients had developed rifampicin resistance (0.9%). At follow-up (M = 55.4 ± 21.8 months) after reimplantation, three patients had developed rifampicin resistance (1.4%). Concerning the development of reinfection, in general, in the study group and the necessity for further treatment, a total of 25 patients showed signs of reinfection (11.8%). Conclusions: Only 0.9% after the first stage and 1.4% at follow-up after the second stage of all 212 patients with accompanying long-term rifampicin combination therapy developed a rifampicin resistance. Therefore, rifampicin administration could be started on the second postoperative day when sufficient concentrations of the accompanying antibiotics can be expected. Full article

(This article belongs to the Special Issue Advances in the Field of Biofilm-Associated Musculoskeletal Infections)

► Show Figures

Figure 1

15 pages, 292 KiB

Open AccessReview

Is Osteoarthritis a State of Joint Dysbiosis?

by Mincong He, Frank Kolhoff, Michael A. Mont and Javad Parvizi

Antibiotics 2025, 14(6), 609; https://doi.org/10.3390/antibiotics14060609 (registering DOI) - 15 Jun 2025

Abstract

Osteoarthritis (OA) has traditionally been defined as a degenerative joint disease driven by mechanical wear, aging, and metabolic disturbances. However, emerging evidence suggests that joint dysbiosis, a dysregulation in the joint microbiome, may play an important role in OA pathogenesis. This review explores [...] Read more.

Osteoarthritis (OA) has traditionally been defined as a degenerative joint disease driven by mechanical wear, aging, and metabolic disturbances. However, emerging evidence suggests that joint dysbiosis, a dysregulation in the joint microbiome, may play an important role in OA pathogenesis. This review explores the mechanisms linking dysbiosis to OA. We examine the presence and origin of joint dysbiosis, also highlighting the gut–joint and oral–joint axes as potential routes for microbial translocation. However, challenges remain in distinguishing causation from correlation and addressing microbial contaminants in microbiome studies. Future research should prioritize longitudinal studies and multiomics integration to elucidate the complex interplay between microbial communities and joint health. Full article

(This article belongs to the Special Issue Bone and Joint Infections: The Challenges of Prevention, Diagnosis and Treatment and Opportunities for Future Research)

► Show Figures

Figure 1

30 pages, 2650 KiB

Open AccessReview

The Role of Livestock Antibiotic Use in Microbiota Dysbiosis and Neuroinflammation

by Serena Silvestro, Carmelo Biondo, Angelina Midiri, Borrello Lucia and Giuseppe Mancuso

Antibiotics 2025, 14(6), 608; https://doi.org/10.3390/antibiotics14060608 (registering DOI) - 15 Jun 2025

Abstract

Antibiotic overuse in livestock is a major concern, as it contributes to the emergence of antibiotic resistance and may adversely affect both animal and human health. One important consequence is its impact on the gut microbiota, a complex microbial ecosystem essential for maintaining [...] Read more.

Antibiotic overuse in livestock is a major concern, as it contributes to the emergence of antibiotic resistance and may adversely affect both animal and human health. One important consequence is its impact on the gut microbiota, a complex microbial ecosystem essential for maintaining host health. A growing body of research highlights the critical role of a balanced gut microbiota in maintaining the integrity of the gut-microbiota–brain axis, a bidirectional communication network between the gastrointestinal tract and the central nervous system (CNS). Antibiotics introduced through the food chain and the environment can disrupt microbial balance, leading to dysbiosis and systemic inflammation. In this context, the concept of “One Health” is emphasized, which recognizes the deep interconnection between the health of humans, animals, and the environment to address the global problem of antibiotic resistance. Several animal studies highlight how dysbiosis can induce neuroinflammation and potentially damage the gut–brain barrier. This review explores the mechanisms by which antibiotic use in livestock alters the gut microbiota and compromises the gut-microbiota–brain axis integrity, outlining the implications for public health and the possible link with neurodegenerative conditions. Full article

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

► Show Figures

Figure 1

13 pages, 950 KiB

Open AccessArticle

Surveillance of Multidrug-Resistant Genes in Clinically Significant Gram-Negative Bacteria Isolated from Hospital Wastewater

by Shriya C. Shetty, Lakshya S. Gowda, Ankeeta Menona Jacob, Kalidas Shetty and A. Veena Shetty

Antibiotics 2025, 14(6), 607; https://doi.org/10.3390/antibiotics14060607 (registering DOI) - 15 Jun 2025

Abstract

Background/Objectives: Antimicrobial resistance (AMR) has become a serious public health threat worldwide. Among the various surveillance domains, hospital wastewater (HWW) has been overlooked, and it is the major reason for the threats posed by AMR. Therefore, the HWW domain is of paramount importance [...] Read more.

Background/Objectives: Antimicrobial resistance (AMR) has become a serious public health threat worldwide. Among the various surveillance domains, hospital wastewater (HWW) has been overlooked, and it is the major reason for the threats posed by AMR. Therefore, the HWW domain is of paramount importance for tackling the AMR. In this regard, the present study investigated the occurrence of Gram-negative bacteria from HWW and evaluated the isolates’ multi-drug-resistant (MDR) pattern in the study environment. Methods: This descriptive study involves HWW samples (n = 24) consecutively collected across 6 months. The samples were cultured for bacteria, identified, and subjected to antimicrobial susceptibility testing via Kirby–Bauer. PCR confirmed the presence of drug-resistance genes in Gram-negative bacterial isolates. Results: High rates of Enterobacterales resistant to carbapenems and cephalosporins observed in isolates from final treated effluent. The molecular screening showed tetD, tetE, tetG, catA1, catA2, bla_NDM-1, quinolones, qnrA, qnrB, qnrS, and qepa. Conclusions: Overall, our results suggest that microbiological surveillance and identification of resistance genes of clinically important pathogens in HWW can be a general screening method for early determination of under-detected antimicrobial resistance profiles in hospitals and early warning of outbreaks and difficult-to-treat infections. Full article

(This article belongs to the Special Issue Tracking Reservoirs of Antimicrobial Resistance Genes in Environment)

► Show Figures

Graphical abstract

33 pages, 1374 KiB

Open AccessReview

Antimicrobials in Livestock Farming and Resistance: Public Health Implications

by Marilena Trinchera, Silvia De Gaetano, Elenoire Sole, Angelina Midiri, Serena Silvestro, Giuseppe Mancuso, Teresa Catalano and Carmelo Biondo

Antibiotics 2025, 14(6), 606; https://doi.org/10.3390/antibiotics14060606 (registering DOI) - 14 Jun 2025

Abstract

The accelerated spread of bacterial resistance has been demonstrated to reduce the effectiveness of antibiotic treatments for infections, resulting in higher morbidity and mortality rates, as well as increased costs for livestock producers. It is expected that the majority of future antimicrobial use [...] Read more.

The accelerated spread of bacterial resistance has been demonstrated to reduce the effectiveness of antibiotic treatments for infections, resulting in higher morbidity and mortality rates, as well as increased costs for livestock producers. It is expected that the majority of future antimicrobial use will be in animal production. The management of antimicrobial resistance (AMR) in the livestock sector poses significant challenges due to the multifaceted nature of the problem. In order to identify appropriate solutions to the rise of antimicrobial resistance, it is imperative that we have a comprehensive understanding of the disease dynamics underpinning the ways in which antimicrobial resistance is transmitted between humans and animals. Furthermore, in consideration of the anticipated requirement to satisfy the global demand for food, it is imperative that we guarantee that resistance is not transmitted or propagated during the treatment and disposal of animal waste, particularly from intensive farming. It is also crucial to formulate a research agenda to investigate how antibiotic resistance in animal faeces from livestock farming is affected by intensified farming activities. The review analyses the environment’s role in the transmission resistance chain and reviews methodologies for disrupting the link. A particular focus is placed on the limitations of the applied methodologies to reduce antimicrobial resistance in global animal production. Full article

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

► Show Figures

Figure 1

10 pages, 1559 KiB

Open AccessArticle

Is It Possible to Optimize the Elaboration and Preservation of a Vancomycin Catheter Lock Solution?

by Marta Díaz-Navarro, David Samitier, Félix García-Moreno, María Sanjurjo, Patricia Muñoz, Beatriz Torroba and María Guembe

Antibiotics 2025, 14(6), 605; https://doi.org/10.3390/antibiotics14060605 (registering DOI) - 14 Jun 2025

Abstract

Background/Objectives: Vancomycin (V) is widely used for catheter lock therapy. However, its ad hoc preparation in pharmacy departments involves discarding most of an intravenous vial and contributes to high workload. We aimed to assess the V concentration and minimum inhibitory biofilm concentration [...] Read more.

Background/Objectives: Vancomycin (V) is widely used for catheter lock therapy. However, its ad hoc preparation in pharmacy departments involves discarding most of an intravenous vial and contributes to high workload. We aimed to assess the V concentration and minimum inhibitory biofilm concentration (MIBC) of a frozen V lock solution. Methods: Two V-2 mg/mL solutions were tested: (1) V + heparin 100 IU/mL and (2) V + citrate 2%. Solutions were frozen at −20 °C, followed by 48 h refrigeration, and analyses were performed at baseline and after 2, 4, 8, and 12 weeks (experiment 1). In addition, after the 12-week freezing period, solution 1 was also preserved for 1 and 2 weeks at both 4 °C and room temperature (experiment 2). V concentration was assessed by HPLC-DAD at 205 nm and validated with forced degradation tests. A <10% variation indicated significant change. MBIC was determined by XTT staining of 24 h biofilms exposed to decreasing concentrations of each solution. Microorganisms tested included methicillin-susceptible and -resistant Staphylococcus aureus (MSSA, MRSA), Staphylococcus epidermidis ATCC35984 (SE), and a highly biofilm-forming clinical S. epidermidis strain (SEclin). MIBC was defined as ≥50% reduction in metabolic activity. Results: In experiment 1, while V concentration remained stable over time, MIBC values varied, notably increasing from 8 weeks for all strains. Moreover, in experiment 2, significant reductions in both V concentration and MIBC were detected in the 2-week period. Conclusions: V lock solution appears to be able to be 12-weeks frozen followed by up to 1 week at refrigeration or room temperature. This facilitates the optimization of vial preparation in hospital pharmacy laboratories. Full article

(This article belongs to the Section Antibiotic Therapy in Infectious Diseases)

► Show Figures

Figure 1

14 pages, 922 KiB

Open AccessArticle

From Farm to Slaughter: Tracing Antimicrobial Resistance in a Poultry Short Food Chain

by Andrea Laconi, Roberta Tolosi, Claudia Chirollo, Cristiana Penon, Giacomo Berto, Francesco Galuppo and Alessandra Piccirillo

Antibiotics 2025, 14(6), 604; https://doi.org/10.3390/antibiotics14060604 - 13 Jun 2025

Abstract

Background: Short food supply chains are commonly perceived as more sustainable and safer alternatives to conventional production systems, often linked to organic, free-range livestock practices. Materials and methods: This study investigates, for the first time, the distribution of antimicrobial resistance genes [...] Read more.

Background: Short food supply chains are commonly perceived as more sustainable and safer alternatives to conventional production systems, often linked to organic, free-range livestock practices. Materials and methods: This study investigates, for the first time, the distribution of antimicrobial resistance genes (ARGs) and characterizes the microbial communities’ composition, using 16S rRNA sequencing and real-time PCR, respectively. Eleven fecal, 76 slaughterhouse surface, 11 cecal, and 11 carcass samples, from 11 poultry farms belonging to the same short food chain, were analyzed in the study. Results: While cleaning and disinfection procedures appeared to reduce the bacterial load on slaughterhouse surfaces, diverse and potentially resistant bacteria, including genera such as Staphylococcus and Streptococcus, persisted both before and after slaughter. ARGs conferring resistance to high-priority critically important antimicrobials (HPCIAs), such as fluoroquinolones and third-generation cephalosporins, were frequently detected on carcasses, with qnrS (76.15%, 95%CI 68.02-84.28%) and bla_CMY2 (57.8%, 95%CI 48.38-67.22%) being the most prevalent. The slaughtering process emerged as a critical step for ARG dissemination via intestinal bacteria, such as genus Lactobacillus. Additionally, the detection of mcr genes and bla_NDM on carcasses but not in the bird gut samples suggests possible anthropogenic contamination. Discussion: These findings highlight that the evisceration process, slaughterhouse environment, and personnel are all contributing factors in ARG spread and underscore the need for enhanced hygiene protocols and reduced gut ARG carriage in domestic birds to mitigate the risk for the consumer. Full article

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

13 pages, 776 KiB

Open AccessArticle

In Vitro Activity of Cefaclor/Beta-Lactamases Inhibitors (Clavulanic Acid and Sulbactam) Combination Against Extended-Spectrum Beta-Lactamase Producing Uropathogenic E. coli

by Ali Atoom, Bayan Alzubi, Dana Barakat, Rana Abu-Gheyab, Dalia Ismail-Agha, Awatef Al-Kaabneh and Nawfal Numan

Antibiotics 2025, 14(6), 603; https://doi.org/10.3390/antibiotics14060603 - 13 Jun 2025

Abstract

Background: Urinary tract infections (UTIs) caused by the multidrug resistance (MDR) phenotype termed extended-spectrum beta lactamase (ESBL)-producing E. coli is a significant and growing global health concern. In response to the rising prevalence, the novel Beta Lactam-Beta Lactamase inhibitor (BL/BLI) combinations have been [...] Read more.

Background: Urinary tract infections (UTIs) caused by the multidrug resistance (MDR) phenotype termed extended-spectrum beta lactamase (ESBL)-producing E. coli is a significant and growing global health concern. In response to the rising prevalence, the novel Beta Lactam-Beta Lactamase inhibitor (BL/BLI) combinations have been introduced in recent years. While these agents have shown efficacy, their clinical utility is constrained by high cost, limited availability, and emerging resistance mechanisms. The rational of this study was to test the in vitro activity of a cost-effective alternative to currently available BL–BLI combinations against ESBL-producing E. coli isolated from urinary tract infections (UTIs). Objective: This study investigates the in vitro antimicrobial activity of cefaclor (CFC), both as monotherapy and in combination with the β-lactamase inhibitors clavulanic acid (CA) and sulbactam (SUL), against 52 ESBL-producing E. coli isolates derived from urine cultures of patients diagnosed with UTIs. Methods: The susceptibility ranges were measured by disk diffusion and minimal inhibitory concentration (MIC) methods. In addition, the Time kill assay and disk approximation method were performed to measure the synergistic and bactericidal activity of the approached combination. Results: The MIC50 and MIC90 for CFC were improved from more than 128 µg/mL to 8/4 µg/mL when CFC was combined with either CA or SUL. The triple combination format of CFC/CA/SUL showed MIC50 and MIC90 values at 8/4/4 µg/mL and 64/32/32 µg/mL, respectively. The recovered susceptibility percentages were 54%, 54%, and 58% for CFC/CA, CFC/SUL, and CFC/CA/SUL combinations, respectively. Disk approximation and time–kill assay results revealed synergy and bactericidal effects when CFC combined with CA or SUL for isolates that showed susceptibility restorations of CFC when coupled with CA or SUL by the disk diffusion and MIC method. Conclusions: This study proposes a cost-effective combination that could mitigate resistance development and offer a sparing option to last resort treatment choices including carbapenems. However, testing efficacy in a clinical setting is crucial. Full article

► Show Figures

Figure 1

15 pages, 1157 KiB

Open AccessArticle

Antifungal Activity of Selected Naphthoquinones and Their Synergistic Combination with Amphotericin B Against Cryptococcus neoformans H99

by Naira Sulany Oliveira de Sousa, Juan Diego Ribeiro de Almeida, Linnek Silva da Rocha, Izabela de Mesquita Bárcia Moreira, Flávia da Silva Fernandes, Ani Beatriz Jackisch Matsuura, Kátia Santana Cruz, Emersom Silva Lima, Érica Simplício de Souza, Hagen Frickmann and João Vicente Braga de Souza

Antibiotics 2025, 14(6), 602; https://doi.org/10.3390/antibiotics14060602 - 13 Jun 2025

Abstract

Background/Objectives: Cryptococcosis, caused by Cryptococcus neoformans and Cryptococcus gattii species complexes, remains a significant health concern, particularly among immunocompromised patients. The emergence of antifungal resistance and toxicity of conventional treatment underscore the urgent need for novel therapeutic approaches. Combination therapies represent a promising [...] Read more.

Background/Objectives: Cryptococcosis, caused by Cryptococcus neoformans and Cryptococcus gattii species complexes, remains a significant health concern, particularly among immunocompromised patients. The emergence of antifungal resistance and toxicity of conventional treatment underscore the urgent need for novel therapeutic approaches. Combination therapies represent a promising strategy to enhance efficacy and overcome resistance. This study investigated the antifungal activity of five naphthoquinones against nine isolates of Cryptococcus spp. and assessed their synergistic effects with amphotericin B (AmB). Methods: In this study, five selected naphthoquinones were evaluated for their antifungal activity against Cryptococcus spp. isolates using broth microdilution assays to determine minimum inhibitory concentrations (MICs), according to CLSI guidelines. The potential synergistic effect with AmB was assessed using checkerboard assays, with synergy interpreted based on the fractional inhibitory concentration index (FICI). Cytotoxicity was evaluated in MRC-5 human lung fibroblast cells using the MTT assay. Results: Among the compounds tested, 2-methoxynaphthalene-1,4-dione (2-MNQ) demonstrated antifungal activity, with MIC values ranging from 3.12 to 12.5 µg/mL. Checkerboard assays revealed a synergistic interaction between 2-MNQ and AmB, with a fractional inhibitory concentration index (FICI) of 0.27. The combination reduced the MIC of AmB by 4.17-fold. These findings highlight the potential of synthetic naphthoquinones, particularly 2-MNQ, as effective antifungal agents with synergistic properties when combined with AmB. The observed synergy suggests complementary mechanisms, including increased fungal membrane permeability and oxidative stress induction. Conclusions: This study highlights the potential of 2-MNQ and 2,3-DBNQ as antifungal candidates against Cryptococcus spp., with emphasis on the synergistic interaction observed between 2-MNQ and amphotericin B. The findings reinforce the importance of structural modifications in naphthoquinones to enhance antifungal activity and support the need for further preclinical studies investigating combination therapies aimed at improving treatment efficacy in patients with cryptococcosis. Full article

(This article belongs to the Special Issue Fungal Metabolites and Synthetic Derivatives: Antimicrobial Properties Toward Microbial Pathogens)

► Show Figures

Figure 1

18 pages, 1231 KiB

Open AccessArticle

The Genetic Background and Culture Medium Only Marginally Affect the In Vitro Evolution of Pseudomonas aeruginosa Toward Colistin Resistance

by Matteo Cervoni, Antonio Maria Ferriero, Alessandra Lo Sciuto, Francesca Guidi, Naida Babić Jordamović, Silvano Piazza, Olivier Jousson, Alfonso Esposito and Francesco Imperi

Antibiotics 2025, 14(6), 601; https://doi.org/10.3390/antibiotics14060601 - 13 Jun 2025

Abstract

Background/Objectives: Colistin is a last-resort treatment for Pseudomonas aeruginosa multidrug-resistant infections, but resistance to it is emerging. While colistin resistance in P. aeruginosa is typically associated with chromosomal mutations inducing lipopolysaccharide (LPS) aminoarabinosylation, other mutations unrelated to LPS modifications have been proposed to [...] Read more.

Background/Objectives: Colistin is a last-resort treatment for Pseudomonas aeruginosa multidrug-resistant infections, but resistance to it is emerging. While colistin resistance in P. aeruginosa is typically associated with chromosomal mutations inducing lipopolysaccharide (LPS) aminoarabinosylation, other mutations unrelated to LPS modifications have been proposed to influence the extent of colistin resistance. Here, we examined whether the genetic background and culture conditions affect the evolution of high-level colistin resistance in this bacterium. Methods: We performed in vitro evolution experiments in the presence or absence of increasing colistin concentrations with two phylogenetically distant reference strains in a standard laboratory medium and in two media mimicking P. aeruginosa growth during lung or systemic infections. Resistance-associated mutations were identified by comparative genomics, and the role of selected mutated genes was validated by allele replacement, deletion, or conditional mutagenesis. Results: Most colistin-resistant mutants carried mutations in genes belonging to four functional groups: two-component systems controlling LPS aminoarabinosylation (PmrAB, PhoPQ), LPS biosynthesis, the production of the polyamine norspermidine, and fatty acid metabolism. No mutation was exclusively and invariably associated with a specific strain or medium. We demonstrated that norspermidine is detrimental to the acquisition of colistin resistance upon PmrAB activation and that impaired fatty acid biosynthesis can promote colistin resistance, even if it increases susceptibility to other antibiotics. Conclusions: The evolution of colistin resistance in P. aeruginosa appeared to be only marginally affected by the genetic background and culture conditions. Notably, mutations in fatty acid biosynthetic genes represent a newly identified genetic determinant of P. aeruginosa colistin resistance, warranting further investigation in clinical isolates. Full article

(This article belongs to the Special Issue Antibiotic Resistance and Virulence Mechanisms in Gram-Negative Bacteria: An Alliance for Success)

► Show Figures

Figure 1

12 pages, 814 KiB

Open AccessArticle

Pharmacokinetics of Isavuconazole During Extracorporeal Membrane Oxygenation Support in Critically Ill Patients: A Case Series

by Laura Doménech-Moral, Sonia García-García, Alba Pau-Parra, Manuel Sosa, Adrian Puertas Sanjuan, Camilo Bonilla, Elisabeth Gallart, Laura Castellote, Patricia Faixó, Jessica Guevara, Albert Vilanova, María Martínez-Pla, Aldair Conto, Xavier Nuvials, Pilar Lalueza, Ricard Ferrer, Maria Queralt Gorgas and Jordi Riera

Antibiotics 2025, 14(6), 600; https://doi.org/10.3390/antibiotics14060600 - 12 Jun 2025

Viewed by 69

Abstract

Background/Objectives: Extracorporeal membrane oxygenation (ECMO) is increasingly used in critically ill patients, but may significantly alter the pharmacokinetics (PK) of antifungals. Data on plasma concentrations of Isavuconazole (IsaPlasm) in ECMO patients are limited. Our objective is to evaluate Isavuconazole exposure and variability in [...] Read more.

Background/Objectives: Extracorporeal membrane oxygenation (ECMO) is increasingly used in critically ill patients, but may significantly alter the pharmacokinetics (PK) of antifungals. Data on plasma concentrations of Isavuconazole (IsaPlasm) in ECMO patients are limited. Our objective is to evaluate Isavuconazole exposure and variability in critically ill COVID-19 patients receiving ECMO. Methods: We conducted a pharmacokinetic analysis of Isavuconazole in critically ill patients receiving Veno-Venous ECMO for respiratory support. Plasma concentrations were measured using therapeutic drug monitoring (TDM) at multiple time points, including sampling before and after the membrane oxygenator. PK parameters—Area Under Curve (AUC_0–24), Minimum Plasma Concentration (Cmin), Elimination Half-Life (T_1/2), volume of distribution (Vd), and clearance (CL)—were estimated and compared with published data in non-ECMO populations. Results: Five patients were included. The median AUC_0–24 was 227.3 µg·h/mL (IQR 182.4–311.35), higher than reported in non-ECMO patients. The median Vd was 761 L (727–832), suggesting extensive peripheral distribution and potential drug sequestration in the ECMO circuit. CL was increased (1.6 L/h, IQR 1.5–3.4). Two patients with recently replaced ECMO circuits exhibited significant drug loss across the membrane. Obesity and hypoalbuminemia were identified as factors associated with altered drug exposure. Conclusions: Isavuconazole pharmacokinetics show marked variability in critically ill ECMO patients. Increased AUC and Vd, along with reduced clearance, highlight the need for individualized dosing. Full article

(This article belongs to the Special Issue Therapeutic Drug Monitoring of Antimicrobials in Critically Ill Patients)

► Show Figures

Figure 1

11 pages, 644 KiB

Open AccessArticle

Antibiotic Resistance Awareness in Kosovo: Insights from the WHO Antibiotic Resistance: Multi-Country Public Awareness Survey

by Flaka Pasha, Valon Krasniqi, Adelina Ismaili, Shaip Krasniqi, Elton Bahtiri, Hasime Qorraj Bytyqi, Valmira Kolshi Krasniqi and Blana Krasniqi

Antibiotics 2025, 14(6), 599; https://doi.org/10.3390/antibiotics14060599 - 12 Jun 2025

Viewed by 153

Abstract

Background/Objectives: Antimicrobial resistance (AMR) poses a critical global health threat, rendering common bacterial infections increasingly difficult to treat and placing considerable strain on healthcare systems. This study assesses public awareness, perceptions, and behaviors related to antibiotic use and AMR in Kosovo, a country [...] Read more.

Background/Objectives: Antimicrobial resistance (AMR) poses a critical global health threat, rendering common bacterial infections increasingly difficult to treat and placing considerable strain on healthcare systems. This study assesses public awareness, perceptions, and behaviors related to antibiotic use and AMR in Kosovo, a country with limited existing data on the topic. Methods: Using a cross-sectional survey design, 568 participants from diverse demographic backgrounds provided insights into their knowledge and practices concerning antibiotic use and antibiotic resistance. Results: The results revealed that although 75% of participants had heard of antibiotic resistance, only a limited proportion understood key terms. Knowledge of appropriate antibiotic use varied, with 67% of respondents correctly recognizing the need to complete a prescribed antibiotic course, while 29% believed it was acceptable to stop treatment once they felt better. Gender and educational level emerged as significant factors, with women and more educated individuals demonstrating greater awareness of proper antibiotic use and the risks of misuse. While 71% of respondents considered it unacceptable to use antibiotics prescribed to others, 41% believed it was acceptable to reuse previously effective antibiotics. Most participants (96%) reported obtaining antibiotics through prescriptions. Public awareness of AMR was generally high, but conceptual understanding remained limited, with misconceptions about the origins of resistance, incorrectly attributing it to the human body rather than bacteria. Conclusions: Targeted public health campaigns, guided by the One Health approach, integrating human, animal, and environmental health, are needed. A multifaceted strategy, including education, policy reforms, and international collaboration, is essential to mitigate AMR and preserve the efficacy of antibiotics for future generations. Full article

(This article belongs to the Special Issue Antibiotic Use in the Communities—2nd Edition)

► Show Figures

Figure 1

26 pages, 2125 KiB

Open AccessReview

Antibiotic Resistance in Aquaculture: Challenges, Trends Analysis, and Alternative Approaches

by Elshafia Ali Hamid Mohammed, Béla Kovács, Ronald Kuunya, Eltayeb Omaima Awad Mustafa, Azza Siddig Hussien Abbo and Károly Pál

Antibiotics 2025, 14(6), 598; https://doi.org/10.3390/antibiotics14060598 - 11 Jun 2025

Viewed by 271

Abstract

Antibiotic resistance in aquaculture has emerged as a global crisis, representing a serious threat to the health of aquatic animals, environment, and human. The extensive use of antibiotics in aquaculture has led to rapid development of resistant bacterial strains, resulting in environmental contamination [...] Read more.

Antibiotic resistance in aquaculture has emerged as a global crisis, representing a serious threat to the health of aquatic animals, environment, and human. The extensive use of antibiotics in aquaculture has led to rapid development of resistant bacterial strains, resulting in environmental contamination and the dissemination of resistant genes. Understanding of the research trends, key contributors, and thematic evolution of this field is essential for guiding future studies and policy interventions. The study aimed to conduct a bibliometric analysis of research on antibiotic resistance development in aquaculture, identifying key areas of research, leading contributors, emerging challenges, and alternative solutions. Data were extracted from the Web of Science (WoS) database covering the period from 2000 to 2025. A systematic search strategy was employed, utilizing terms including “antibiotic resistance” AND “bacteria,” AND “aquaculture”. Relevant publications were extracted from the WoS using these keywords. R-tool was then used to analyze the obtained metadata including keywords, citation patterns, and co-authored country. The analysis revealed a remarkable increase in publications over the past 25 years, with key contributions from China, India, and the USA. The most significant articles focused on the presence of multidrug resistant bacteria in the aquatic environments and, antibiotic-resistant genes, and horizontal gene transfer. Probiotics are the alternative solution to overcome the antibiotic resistance and enhance aquaculture sustainability. Future research should focus on the interdisciplinary collaboration, novel antimicrobial alternatives, and global monitoring approaches. Full article

► Show Figures

Figure 1

12 pages, 1167 KiB

Open AccessArticle

Ability of Linezolid to Combat Staphylococcus aureus and Pseudomonas aeruginosa Isolated from Polymicrobial Wound Infections

by Samar A. Ahmed, Vy T. Luu, Teresa C. Oyono Nsuga, Steven E. Burgos, Eugene Kreys, Jered Arquiette and Justin R. Lenhard

Antibiotics 2025, 14(6), 597; https://doi.org/10.3390/antibiotics14060597 - 11 Jun 2025

Viewed by 173

Abstract

Background/Objectives: The optimal therapy for polymicrobial wound infections is poorly defined. We sought to characterize the ability of linezolid to combat mixed cultures of Staphylococcus aureus and Pseudomonas aeruginosa. Methods: The antistaphylococcal activity of linezolid was assessed in 24-h time-killing [...] Read more.

Background/Objectives: The optimal therapy for polymicrobial wound infections is poorly defined. We sought to characterize the ability of linezolid to combat mixed cultures of Staphylococcus aureus and Pseudomonas aeruginosa. Methods: The antistaphylococcal activity of linezolid was assessed in 24-h time-killing experiments that used S. aureus and P. aeruginosa isolated from polymicrobial wound infections. Clindamycin was also evaluated as a comparator. A Hill-type mathematical model was used to assess the maximum killing of S. aureus (E_max). The ability of linezolid to potentiate the activity of host defense peptides against P. aeruginosa was evaluated using LL-37. Results: In the presence of P. aeruginosa, the E_max of linezolid decreased in 5/9 co-culture experiments and increased in 4/9 co-culture experiments in comparison to linezolid against S. aureus alone. The potency of linezolid was not significantly impacted by the presence of P. aeruginosa. In comparison, the maximal S. aureus killing achieved by clindamycin decreased in eight out of nine experiments, and somewhat paradoxically, the potency increased in nine out of nine experiments. In the host defense peptide assay, the supratherapeutic linezolid concentration of 64 mg/L did not significantly enhance the killing of the LL-37 peptides (p ≥ 0.121), but the concentration of linezolid was significantly associated with the killing of one of three P. aeruginosa isolates (p = 0.005). Conclusions: P. aeruginosa had a minimal impact on the antistaphylococcal activity of linezolid in comparison to clindamycin. Linezolid did not exert a consistent ability to enhance the antipseudomonal activity of host defense peptides. These data may help inform antimicrobial selection during polymicrobial wound infections. Full article

► Show Figures

Figure 1

11 pages, 1844 KiB

Open AccessBrief Report

The Co-Existence of mcr-1.1 and mcr-3.5 in Escherichia coli Isolated from Clinical Samples in Thailand

by Panida Nobthai, Sirigade Ruekit, Dutsadee Peerapongpaisarn, Prawet Sukhchat, Brett E. Swierczewski, Nattaya Ruamsap and Paphavee Lertsethtakarn

Antibiotics 2025, 14(6), 596; https://doi.org/10.3390/antibiotics14060596 - 10 Jun 2025

Viewed by 194

Abstract

The emergence of colistin resistance poses a significant threat to its efficacy as a last-line treatment against multidrug-resistant Gram-negative bacterial infections. In this study, 178 multi-drug resistant (MDR) Escherichia coli isolates collected from clinical samples at Queen Sirikit Naval Hospital, Chonburi, Thailand, were [...] Read more.

The emergence of colistin resistance poses a significant threat to its efficacy as a last-line treatment against multidrug-resistant Gram-negative bacterial infections. In this study, 178 multi-drug resistant (MDR) Escherichia coli isolates collected from clinical samples at Queen Sirikit Naval Hospital, Chonburi, Thailand, were evaluated for colistin resistance. Of these, six were identified as mcr gene carriers, mediating colistin resistance. Specifically, mcr-1 was detected in three E. coli isolates, mcr-3 was detected in one E. coli isolate, and mcr-1 and mcr-3 were detected in two E. coli isolates, designated AMR-0220 and AMR-0361. Whole-genome sequencing and bioinformatics analysis revealed that AMR-0220 and AMR-0361 belonged to ST410 and ST617 lineages, respectively. Both isolates carried multiple plasmids, with mcr-1.1 located on an IncX4-type plasmid that is closely related to previously reported mcr-1.1-carrying IncX4 plasmids. In contrast, mcr-3.5 was identified on distinct plasmid backbones: an IncFIB-type plasmid in AMR-0220 and an IncFII-type plasmid in AMR-0361. Overall, our findings demonstrate that the mcr genes found in E. coli isolates in this region are located on different mobile genetic elements, indicating the potential for a widespread dissemination of colistin resistance among Gram-negative bacteria throughout Thailand’s healthcare system. Full article

► Show Figures

Figure 1

24 pages, 4082 KiB

Open AccessArticle

Epoxy-Functionalized Isatin Derivative: Synthesis, Computational Evaluation, and Antibacterial Analysis

by Deepanjali Shukla, Iqbal Azad, Mohd Arsh Khan, Ziaul Husain, Azhar Kamal, Sabahat Yasmeen Sheikh, Ibrahim Alotibi, Varish Ahmad and Firoj Hassan

Antibiotics 2025, 14(6), 595; https://doi.org/10.3390/antibiotics14060595 - 9 Jun 2025

Viewed by 314

Abstract

Background/Objectives: The current need for new antibacterial compounds that target non-classical pathways is highlighted by the emergence of multidrug-resistant Klebsiella pneumoniae. In the development of antibiotics, DNA adenine methyltransferase (Dam), a key regulator of bacterial gene expression and pathogenicity, is still underutilized. [...] Read more.

Background/Objectives: The current need for new antibacterial compounds that target non-classical pathways is highlighted by the emergence of multidrug-resistant Klebsiella pneumoniae. In the development of antibiotics, DNA adenine methyltransferase (Dam), a key regulator of bacterial gene expression and pathogenicity, is still underutilized. Epoxy-functionalized analogues of isatin derivatives have not been adequately investigated for their antibacterial activity, particularly as Dam inhibitors. In the pursuit of antimicrobial agents, this study synthesized an epoxy-functionalized isatin derivative (L3) using a one-pot reaction. The compound was characterized using FT-IR, ¹H-NMR, ¹³C-NMR, HR-MS, and UV–Vis spectroscopy. Methods: In silico evaluation performed by using ADMETlab3 and SwissADME. While molecular docking studies were achieved by AutoDock and Vina to find L3’s interaction with potential antibacterial target (Dam protein in K. pneumoniae). In addition, the antibacterial potential of L3 was evaluated using minimum inhibitory concentration (MIC) assays against Bacillus cereus, Bacillus pumilus, Escherichia coli, and K. pneumoniae. Results: Among these, L3 exhibited potential inhibitory activity against K. pneumoniae, with a MIC value of 93.75 μg/mL. In silico evaluations confirmed L3’s favorable drug-like properties, including potential oral bioavailability, blood–brain barrier (BBB) permeability, and low plasma protein binding (PPB). The compound satisfied Lipinski’s and other drug-likeness rules as well as getting a quantitative estimate of drug-likeness (QED) score of 0.52. Here, a homology model of Dam protein in K. pneumoniae was generated using the SWISS-MODEL server and validated using computational tools. Targeted docking analysis revealed that L3 exhibited significant potential binding affinity against Dam protein, with binding energies of −6.4 kcal/mol and −4.85 kcal/mol, as determined by Vina and AutoDock, respectively. The associated inhibition constant was calculated as 280.35 µM. Further interaction analysis identified the formation of hydrogen bonds with TRP7 and PHE32, along with Van der Waals’ interactions involving GLY9, ASP51, and ASP179. Conclusions: These findings highlight L3 as a promising scaffold for antimicrobial drug development, particularly in targeting Dam protein in K. pneumoniae. Furthermore, the ADMET profiling and physicochemical properties of L3 support its potential as a drug-like candidate. Full article

(This article belongs to the Special Issue Discovery and Synthesis of Antimicrobial Compounds Against Multidrug Resistance)

► Show Figures

Figure 1

20 pages, 3977 KiB

Open AccessArticle

Does Empirical Antibiotic Use Improve Outcomes in Ventilated Patients with Pandemic Viral Infection? A Multicentre Retrospective Study

by Elisabeth Papiol, Julen Berrueta, Juan Carlos Ruíz-Rodríguez, Ricard Ferrer, Sara Manrique, Laura Claverias, Alejandro García-Martínez, Pau Orts, Emili Díaz, Rafael Zaragoza, Marco Marotta, María Bodí, Sandra Trefler, Josep Gómez, Ignacio Martín-Loeches and Alejandro Rodríguez

Antibiotics 2025, 14(6), 594; https://doi.org/10.3390/antibiotics14060594 - 8 Jun 2025

Viewed by 221

Abstract

Background: During the influenza A(H1N1) and COVID-19 pandemics, empirical antibiotic treatment (EAT) was widely administered to critically ill patients despite low rates of confirmed bacterial co-infection (COI). The clinical benefit of this practice remains uncertain and may contradict antimicrobial stewardship principles. Objective: To [...] Read more.

Background: During the influenza A(H1N1) and COVID-19 pandemics, empirical antibiotic treatment (EAT) was widely administered to critically ill patients despite low rates of confirmed bacterial co-infection (COI). The clinical benefit of this practice remains uncertain and may contradict antimicrobial stewardship principles. Objective: To evaluate whether EAT at ICU admission reduces ventilator-associated pneumonia (VAP) incidence or ICU mortality in critically ill patients with pandemic viral pneumonia, stratified by presence of COI. Methods: This retrospective analysis combined two national multicentre ICU registries in Spain, including 4197 adult patients requiring invasive mechanical ventilation for influenza A(H1N1) or COVID-19 between 2009 and 2021. Primary outcomes were ICU mortality and VAP incidence. Analyses were stratified by microbiologically confirmed bacterial COI. Propensity score matching, Cox regression, General Linear (GLM), and random forest models were applied. Results: Among patients without COI (n = 3543), EAT was not associated with lower ICU mortality (OR = 1.02, 95%CI 0.81–1.28, p = 0.87) or VAP (OR = 1.02, 95%CI 0.79–1.39, p = 0.89). In patients with confirmed COI (n = 654), appropriate EAT was associated with reduced VAP (17.4% vs. 36.3%, p < 0.001) and ICU mortality (38.4% vs. 49.6%, OR = 1.89, 95%CI 1.13–3.14, p = 0.03) compared to inappropriate EAT. Conclusions: EAT was not associated with a lower incidence of VAP or higher survival rates and could be harmful if administered incorrectly. These findings support a more targeted approach to antibiotic use, guided by microbiology, biomarkers and stewardship principles. Full article

(This article belongs to the Section Antibiotics Use and Antimicrobial Stewardship)

► Show Figures

Figure 1

24 pages, 1219 KiB

Open AccessArticle

Antibacterial and Synergistic Effects of Terminalia citrina Leaf Extracts Against Gastrointestinal Pathogens: Insights from Metabolomic Analysis

by Sze-Tieng Ang, Tak Hyun Kim, Matthew James Cheesman and Ian Edwin Cock

Antibiotics 2025, 14(6), 593; https://doi.org/10.3390/antibiotics14060593 - 8 Jun 2025

Viewed by 330

Abstract

Background/Objectives: Bacterial contamination leads to foodborne illnesses, and new antibiotics are required to combat these pathogens. Interest has increased in medicinal plants as targets for new antibiotics. Methods: This study evaluated the antibacterial activity of leaf extracts from Terminalia citrina (Gaertn.) [...] Read more.

Background/Objectives: Bacterial contamination leads to foodborne illnesses, and new antibiotics are required to combat these pathogens. Interest has increased in medicinal plants as targets for new antibiotics. Methods: This study evaluated the antibacterial activity of leaf extracts from Terminalia citrina (Gaertn.) Roxb. ex Fleming against four bacterial pathogens (including a methicillin-resistant Staphylococcus aureus (MRSA) strain) using disc diffusion and liquid microdilution assays. The phytochemical composition of the extracts were determined using ultra-high-performance liquid chromatography–mass spectrometry (UPLC-MS). Results: Both the aqueous and methanol extracts demonstrated noteworthy antibacterial activity against Bacillus cereus (MICs of 468.8 µg/mL and 562.5 µg/mL, respectively). Additionally, the extracts were effective against MRSA (MICs = 625 µg/mL). Strong antibacterial effects were also observed against S. aureus, with MICs of 625 µg/mL (aqueous extract) and 833.3 µg/mL (methanol extract). Twelve combinations of extracts and conventional antibiotics were synergistic against B. cereus and S. flexneri. UPLC-MS analysis revealed two flavonoids, orientin 2″-O-gallate and astragalin, exclusive to the aqueous extract, whilst pinocembrin and gallic acid were only detected in the methanol extract. Both extracts contained vitexin 2″-O-p-coumarate, ellagic acid, orientin, rutin, chebulic acid, terminalin, and quercetin-3β-D-glucoside. Both extracts were determined to be nontoxic. Conclusions: The abundance and diversity of polyphenols in the extracts may contribute to their strong antibacterial properties. Further research is required to investigate the antibacterial effects of the individual extract compounds, including their effects when combined with conventional antibiotics, and the potential mechanisms of action against foodborne pathogens. Full article

(This article belongs to the Special Issue New Natural Products as Candidates for the Discovery of Antimicrobial Drugs)

► Show Figures

Graphical abstract

27 pages, 3028 KiB

Open AccessArticle

Integrated Assessment of Antibacterial Activity, Polyphenol Composition, Molecular Docking, and ADME Properties of Romanian Oak and Fir Honeydew Honeys

by Calin Hulea, Diana Obistioiu, Anca Hulea, Mukhtar Adeiza Suleiman, Doris Floares (Oarga), Ersilia Alexa, Ilinca Merima Imbrea, Alina-Georgeta Neacșu, Marius Pentea, Cosmin Alin Popescu and Florin Imbrea

Antibiotics 2025, 14(6), 592; https://doi.org/10.3390/antibiotics14060592 - 8 Jun 2025

Viewed by 300

Abstract

Background: This study evaluated the polyphenolic composition, antibacterial activity, molecular docking interactions, and pharmacokinetic properties of Romanian oak and fir honeydew honeys. Methods: Spectrophotometric methods quantified total phenolic, flavonoid contents and antioxidant activity, and individual polyphenols were identified via HPLC-MS. Antibacterial efficacy against [...] Read more.

Background: This study evaluated the polyphenolic composition, antibacterial activity, molecular docking interactions, and pharmacokinetic properties of Romanian oak and fir honeydew honeys. Methods: Spectrophotometric methods quantified total phenolic, flavonoid contents and antioxidant activity, and individual polyphenols were identified via HPLC-MS. Antibacterial efficacy against Gram-positive and Gram-negative bacteria was evaluated by determining the bacterial inhibition percentage and minimum inhibitory concentrations. The bioactive compounds identified via LC-MS analysis were used to further delineate the possible antibacterial activities in silico. Molecular docking was carried out to predict the binding interactions and complex formation of the identified compounds against protein crystal structures of the bacteria used in this study. Additionally, the pharmacokinetic profile of compounds with high inhibitory potential was assessed via ADMET (absorption, Distribution, Metabolism, Excretion, toxicity) predictors to ascertain their value. Results: Fir honeydew honey showed higher total phenolic (844.5 mg GAE/kg) and flavonoid contents (489.01 mg QUE/kg) compared to oak honeydew honey, correlating with more potent antioxidant activity (IC50 = 5.16 mg/mL). In vitro antimicrobial tests indicated a stronger inhibitory effect of fir honeydew honey, especially against Gram-positive strains like S. aureus, S. pyogenes, and L. monocytogenes, alongside certain Gram-negative strains such as E. coli and H. influenzae. Oak honeydew honey displayed selective antimicrobial action, particularly against P. aeruginosa and S. typhimurium. The docking outcomes showed rutin, rosmarinic acid, beta resorcylic acid, quercetin, ferulic acid, and p-coumaric acid have high inhibitory activities characterised by binding affinities and binding interactions against shiga toxin, riboflavin synthase, ATP-binding sugar transporter-like protein, undecaprenyl diphosphate synthase, putative lipoprotein, sortase A, and immunity protein, making them key contributors to the honey’s antimicrobial activity. Moreover, beta-resorcylic acid, quercetin, ferulic acid, and p-coumaric acid revealed interesting ADMET scores that qualify honey to serve as a good antimicrobial agent. Conclusions: These findings support their potential use as natural antibacterial agents and emphasise the value of integrating chemical, biological, and computational approaches for multidisciplinary characterisations. Full article

(This article belongs to the Special Issue Antimicrobial Activities of Bioactive Components from Honeybee Products)

► Show Figures

Figure 1

15 pages, 7806 KiB

Open AccessArticle

Novel p-Hydroxybenzoic Acid Derivative Isolated from Bacopa procumbens and Its Antibacterial Activity

by Elizabeth Vargas-Anaya, Alejandro Zamilpa, Manasés González-Cortazar, Blanca Eda Domínguez-Mendoza, Ma. Dolores Pérez-García, Minerva Rosas Morales, Ada María Ríos Cortés and Valentin López Gayou

Antibiotics 2025, 14(6), 591; https://doi.org/10.3390/antibiotics14060591 - 7 Jun 2025

Viewed by 298

Abstract

Background/Objectives: Antimicrobial resistance represents a critical global health challenge that has been exacerbated by the significant decline in antibiotic development. Natural product-based drugs, particularly plant-derived phenolic compounds, offer promising alternatives to conventional antibiotics. This study aimed to isolate and characterize a novel phenolic [...] Read more.

Background/Objectives: Antimicrobial resistance represents a critical global health challenge that has been exacerbated by the significant decline in antibiotic development. Natural product-based drugs, particularly plant-derived phenolic compounds, offer promising alternatives to conventional antibiotics. This study aimed to isolate and characterize a novel phenolic compound from Bacopa procumbens, a Mexican perennial repent plant that is widespread in the Mexican valley and produces a variety of saponins, gastrodin derivatives, and phenolic acids, and to evaluate its antibacterial potential against clinically relevant pathogens. Methods: The hydroalcoholic extraction of B. procumbens was followed by liquid–liquid partitioning with ethyl acetate. The resulting fraction underwent chromatographic separation and purification. The structural elucidation of the isolated compound was performed using thin-layer chromatography (TLC), high-performance liquid chromatography (HPLC), mass spectrometry (MS-EI), and nuclear magnetic resonance (NMR) techniques. Antimicrobial activity was assessed via a microdilution assay against five bacterial strains, including drug-resistant Staphylococcus species and Gram-negative pathogens. Results: A novel phenolic compound, 5-(p-hydroxybenzoyl) shikimic acid (5pHSA), was isolated and characterized. The compound demonstrated moderate antibacterial activity against methicillin-resistant Staphylococcus haemolyticus and Escherichia coli (minimum inhibitory concentration (MIC) = 100 μg/mL) but showed limited efficacy against Staphylococcus aureus, MRSA, and Klebsiella pneumoniae (MIC > 100 μg/mL). Comparative analysis with the previously isolated compound ProcumGastrodin A revealed structure–activity relationships where the higher lipophilicity of PG-A was correlated with enhanced antimicrobial activity. Conclusions: This study establishes 5pHSA as a novel phenolic compound with moderate antibacterial properties. The findings highlight the importance of molecular polarity and structural complexity in determining antimicrobial efficacy, offering valuable insights into the development of phenolic, acid-based antimicrobial agents to address the growing challenge of antimicrobial resistance. Full article

(This article belongs to the Special Issue Antimicrobial Activity of Plants Against Emerging or Drug-Resistant Human Pathogens)

► Show Figures

Figure 1

14 pages, 1495 KiB

Open AccessArticle

Assessment of Oral Microbial Viability by 2,6-Dichlorophenolindophenol a Redox Agent

by Prem K. Sreenivasan and Violet I. Haraszthy

Antibiotics 2025, 14(6), 590; https://doi.org/10.3390/antibiotics14060590 - 7 Jun 2025

Viewed by 272

Abstract

Background/Objectives: This investigation evaluated 2,6-Dichlorophenolindophenol (DCIP), a redox dye, as a colorimetric reagent for rapid quantification of oral bacteria and examined the antimicrobial effects of oral hygiene formulations. Methods/Results: Viable microbial cells reduce DCIP, resulting in a loss of its blue color which [...] Read more.

Background/Objectives: This investigation evaluated 2,6-Dichlorophenolindophenol (DCIP), a redox dye, as a colorimetric reagent for rapid quantification of oral bacteria and examined the antimicrobial effects of oral hygiene formulations. Methods/Results: Viable microbial cells reduce DCIP, resulting in a loss of its blue color which can be measured spectrophotometrically. Strains of Actinomyces viscosus, Veillonella atypica, Aggregatibacter actinomycetemcomitans, Streptococcus mutans and Candida albicans grown in the laboratory reduced DCIP. Significant correlations between increasing viable plate counts and DCIP reduction were noted for strains of oral organisms. Intact microbial cells reduced DCIP, with insignificant reductions observed by spent microbial media or bacteria free culture media. Organisms inactivated by either heat or cold demonstrated significantly lower DCIP reduction in comparison to metabolically intact organisms grown under optimal conditions. Conclusions: DCIP reduction provided a rapid and accurate method to evaluate antimicrobial effects of clinical proven mouthwashes formulated with cetylpyridinium chloride or chlorhexidine and toothpastes for a range of oral bacteria. Together, these results identify a rapid, low-cost method using common laboratory equipment to enumerate oral organisms with a visual outcome. Full article

(This article belongs to the Special Issue Antibacterial Treatment in Periodontal and Endodontic Therapy, 3rd Edition)

► Show Figures

Figure 1

11 pages, 239 KiB

Open AccessBrief Report

Resistance Patterns of Neisseria gonorrhoeae in PLHIV: A Cross-Sectional Study from the Republic of Cyprus, 2015–2023

by Michaela Takos, George Siakallis, Annalisa Quattrocchi, Maria Alexandrou, Panagiota Papadamou, Loukia Panagiotou and Danny Alon-Ellenbogen

Antibiotics 2025, 14(6), 589; https://doi.org/10.3390/antibiotics14060589 - 7 Jun 2025

Viewed by 258

Abstract

Background: The rise in antimicrobial-resistant (AMR) strains of Neisseria gonorrhoeae is internationally recognised as a critical public health concern, with limited treatment options available. The urgency of this issue prompted the European Centre for Disease Prevention and Control to establish ‘EURO-GASP’ to monitor [...] Read more.

Background: The rise in antimicrobial-resistant (AMR) strains of Neisseria gonorrhoeae is internationally recognised as a critical public health concern, with limited treatment options available. The urgency of this issue prompted the European Centre for Disease Prevention and Control to establish ‘EURO-GASP’ to monitor trends in resistance and address developments. Comprehensive data on AMR strains in people living with HIV (PLHIV) is limited, especially in Cyprus. Objectives: To analyse trends in rates of resistant N. gonorrhoeae infections and identify any correlations between patient factors that may contribute to such in PLHIV in The Republic of Cyprus. Methods: We conducted a retrospective chart review study on N. gonorrhoea resistance among PLHIV from the Gregorios HIV reference clinic in Larnaca, Cyprus, between 2015 and 2023. Antimicrobial susceptibility was assessed via disc diffusion or gradient strip method on GC II agar against a non-homogenous panel of antibiotic preparations, based on standard laboratory practice variation. Demographic and clinical data, including antibiograms, treatments and test of cure, were recorded. Statistical analysis was performed using Stata v16, with significance set at p < 0.05. The study received approval from the Cyprus National Bioethics Committee. Results: A total of 45 isolates from 39 patients were analysed, with 62% of these demonstrating resistance to at least one antibiotic. Resistance rates were not shown to change over time. We identified a statistically significant linear association between a person having a history of an STI and the number of antibiotics which the isolate is resistant to (β = 1.2; p: 0.004). Notably, a single isolate demonstrated resistance to ceftriaxone, the first-line treatment currently recommended in both Europe and the United States. This finding is particularly alarming given the critical role of ceftriaxone in the management of gonorrhoea. Conclusions: Whilst there has been no increase in resistance rates over time, the detection of ceftriaxone-resistant N. gonorrhoeae is a significant public health concern. Given that having a history of an STI makes a person more likely to develop a resistant infection, PLHIV or those who engage in risky sexual behaviours are particularly vulnerable. There is a pressing need to enhance surveillance and implement routine susceptibility testing in Cyprus, given the country’s role as a major international hub for travel and migration. Molecular analysis can further improve our understanding. Additionally, the global public health community must urgently prioritise the development of novel therapeutic agents for the treatment of gonorrhoea. Full article

(This article belongs to the Special Issue Therapy of Infectious Diseases Among Children and Adults: The Role of Antibiotics in Daily Practice)

15 pages, 6378 KiB

Open AccessArticle

Development of an Effective and Cost-Saving Synergistic-Antibacterial Therapy for Prevention of Endophthalmitis

by Huy Dong, Phat Tran, Keaton Luth, Dana Thalman, Coby Ray, Pamela Lin, Staci Moss, Abdul Hamood, David McCartney and Ted W. Reid

Antibiotics 2025, 14(6), 588; https://doi.org/10.3390/antibiotics14060588 - 7 Jun 2025

Viewed by 240

Abstract

Background: Endophthalmitis, associated with intraocular procedures, is an infection of the eye that can rapidly result in substantial irreversible loss of vision and may even lead to removal of the eye. Prevention strategies vary globally and often include antibiotic use—often consisting of a [...] Read more.

Background: Endophthalmitis, associated with intraocular procedures, is an infection of the eye that can rapidly result in substantial irreversible loss of vision and may even lead to removal of the eye. Prevention strategies vary globally and often include antibiotic use—often consisting of a broad-spectrum mono-therapeutic agent. The purpose of this study is to test the efficacy and value of combinations of cefuroxime (cefu), cefazolin (cefa), azithromycin (azith), and/or tobramycin (tob) as alternatives to the use of moxifloxacin. We looked for synergism since these antimicrobials used different mechanisms of inhibition. Methods: Initially, we examined individual antimicrobials to determine the minimal bactericidal concentrations (MBC) of each individual treatment against Klebsiella pneumonia, Pseudomonas aeruginosa, Staphylococcus aureus, two clinical isolates of MRSA, and Staphylococcus epidermidis, by both the Zone of Inhibition (ZOI) and the Colony Forming Unit (CFU) assays. We then used these data in a combinatorial study. Results: We found combinations that were synergistic against all the bacteria tested, resulting in total eradication [8 logs] of all bacteria. We found that the ZOI assay provided less consistent results than the CFU assays. Conclusions: We have found combinations of these antimicrobials that were synergistic in the total eradication (8 logs) of all bacteria tested. These three combinations were: cefuroxime/azithromycin; azithromycin/tobramycin; and cefuroxime/tobramycin. Moxifloxacin (Vigamox) did not completely eradicate Staphylococcus epidermidis. These combinations can then be used as eye drops to serve as a prophylactic for endophthalmitis after eye injections and eye surgery. Full article

(This article belongs to the Section The Global Need for Effective Antibiotics)

► Show Figures

Figure 1

14 pages, 1086 KiB

Open AccessReview

Challenges of Carbapenem-Resistant Enterobacteriaceae in the Development of New β-Lactamase Inhibitors and Antibiotics

by Pierre Leroux, Charleric Bornet, Jean-Michel Bolla and Anita Cohen

Antibiotics 2025, 14(6), 587; https://doi.org/10.3390/antibiotics14060587 - 7 Jun 2025

Viewed by 290

Abstract

Nowadays, antimicrobial resistance (AMR) is a growing global health threat, with carbapenem-resistant Enterobacteriaceae (CRE) posing particular concern due to limited treatment options. In fact, CRE have been classified as a critical priority by the World Health Organization (WHO). Carbapenem resistance results from complex [...] Read more.

Nowadays, antimicrobial resistance (AMR) is a growing global health threat, with carbapenem-resistant Enterobacteriaceae (CRE) posing particular concern due to limited treatment options. In fact, CRE have been classified as a critical priority by the World Health Organization (WHO). Carbapenem resistance results from complex mechanisms, often combining the production of hydrolytic enzymes such as β-lactamases with reduced membrane permeability and efflux system induction. The Ambler classification is an effective tool for differentiating the characteristics of serine-β-lactamases (SβLs) and metallo-β-lactamases (MβLs), including ESβLs (different from carbapenemases), KPC, NDM, VIM, IMP, AmpC (different from carbapenemases), and OXA-48. Recently approved inhibitor drugs, such as diazabicyclooctanones and boronic acid derivatives, only partially address this problem, not least because of their ineffectiveness against MβLs. However, compared with taniborbactam, xeruborbactam is the first bicyclic boronate in clinical development with a pan-β-lactamase inhibition spectrum, including the IMP subfamily. Recent studies explore strategies such as chemical optimization of β-lactamase inhibitor scaffolds, novel β-lactam/β-lactamase inhibitor combinations, and siderophore–antibiotic conjugates to enhance bacterial uptake. A deeper understanding of the mechanistic properties of the active sites enables rational drug design principles to be established for inhibitors targeting both SβLs and MβLs. This review aims to provide a comprehensive overview of current therapeutic strategies and future perspectives for the development of carbapenemase inhibitor drug candidates. Full article

(This article belongs to the Special Issue Discovery and Synthesis of Antimicrobial Compounds Against Multidrug Resistance)

► Show Figures

Figure 1

12 pages, 861 KiB

Open AccessArticle

Impact of Cooking Procedures on Coccidiostats in Poultry Muscle

by Rui R. Martins, André M. P. T. Pereira, Liliana J. G. Silva, Sofia C. Duarte, Andreia Freitas and Angelina Pena

Antibiotics 2025, 14(6), 586; https://doi.org/10.3390/antibiotics14060586 - 7 Jun 2025

Viewed by 289

Abstract

Background/Objectives: Poultry meat is a popular and nutritious food, valued for its high protein content and healthy fat profile. However, like other animal products, it can contain pharmaceutical residues, including coccidiostats, antimicrobials commonly used to prevent parasitic infections caused by Eimeria species. While [...] Read more.

Background/Objectives: Poultry meat is a popular and nutritious food, valued for its high protein content and healthy fat profile. However, like other animal products, it can contain pharmaceutical residues, including coccidiostats, antimicrobials commonly used to prevent parasitic infections caused by Eimeria species. While most monitoring focuses on raw meat, it is important to understand how these compounds behave during cooking to assess potential health risks better and ensure food safety. Methods: This study examined how five different cooking methods (roasting, grilling, and microwaving, beer and wine marinating) affect the levels of eight coccidiostat residues in 45 samples of poultry muscle collected from a supermarket located in the center of mainland Portugal from May to July 2024. After applying different cooking procedures, ionophore and synthetic coccidiostat residue levels were measured using solid–liquid extraction followed by ultrahigh-performance liquid chromatography with tandem mass spectrometry (UHPLC-MS/MS). Results are expressed as percentages of the original concentrations: 100% indicates stability, values above 100% suggest a relative increase (often due to moisture loss), and values below 100% reflect a decrease, likely from heat degradation. Results: Roasting, grilling, and microwaving all increased residue concentrations—up to 198.5%, 180.1%, and 158.4%, respectively. In contrast, marinating meat in wine or beer before cooking reduced residues to 73.1% and 72.0%, suggesting a mitigating effect. The initial concentration also influenced the outcome: samples fortified at the maximum residue limit (MRL) had an overall higher mean concentration after cooking (148.3%,) than those fortified at twice the MRL (2 MRL), which averaged 124.5%. Conclusions: These results show that cooking can significantly alter coccidiostat residue levels depending on the cooking procedures and initial concentration. Ongoing monitoring and further research are essential to better understand how cooking affects these residues and their by-products. This knowledge is key to improving food safety practices and refining consumer health risk assessments. Full article

(This article belongs to the Special Issue Research Advances in Antimicrobial Stewardship, Residues and Resistance in Veterinary and Environmental Science)

► Show Figures

Figure 1

8 pages, 213 KiB

Open AccessArticle

Periprosthetic Joint Infection in Unicompartmental vs. Total Knee Arthroplasty: Microbiological Spectrum and Management Outcomes

by Ali Said Nazlıgül, Şahan Güven, Yasin Erdoğan, Ahmet Fırat, Metin Doğan and Mustafa Akkaya

Antibiotics 2025, 14(6), 585; https://doi.org/10.3390/antibiotics14060585 - 6 Jun 2025

Viewed by 242

Abstract

Background/Objectives: Periprosthetic joint infection (PJI) is a severe complication following both total knee arthroplasty (TKA) and unicompartmental knee arthroplasty (UKA). While the microbiological profile of TKA PJI has been well characterized, limited data exist regarding UKA PJIs. This study aimed to compare [...] Read more.

Background/Objectives: Periprosthetic joint infection (PJI) is a severe complication following both total knee arthroplasty (TKA) and unicompartmental knee arthroplasty (UKA). While the microbiological profile of TKA PJI has been well characterized, limited data exist regarding UKA PJIs. This study aimed to compare the causative microorganisms and surgical treatment outcomes in PJI cases following UKA and TKA. Methods: This retrospective cohort study included 82 patients (71 TKA and 11 UKA) who underwent surgical treatment for PJI between January 2017 and May 2024. PJI was diagnosed based on the Musculoskeletal Infection Society (MSIS) criteria. Treatment strategies included debridement, antibiotics, and implant retention (DAIR) or two-stage revision arthroplasty. Microbiological data were extracted from intraoperative cultures. Fisher’s exact test and the Mann–Whitney U test were used for statistical comparisons. Results: Gram-positive organisms, primarily Staphylococcus aureus and coagulase-negative staphylococci, were isolated in all UKA PJIs. In contrast, the TKA group demonstrated greater microbial diversity, including Gram-negative bacilli, polymicrobial infections, and a higher rate of culture-negative cases (33.8% vs. 18.2%). DAIR was performed more frequently in UKA cases (72.7% vs. 28.2%, p = 0.002). Recurrence rates following DAIR were similar in both groups (12.5% in UKA, 20.0% in TKA, p = 1.000). Two-stage revision resulted in no recurrence in UKA and a 9.8% recurrence rate in TKA patients. Conclusions: UKA PJIs appear to be microbiologically less complex than TKA PJI cases, with Gram-positive organisms predominating. Despite these differences, the outcomes of surgical treatment—both DAIR and two-stage revision—were comparable between groups. Standard PJI treatment principles may be applicable to both arthroplasty types; however, larger prospective studies are needed to confirm these findings. Full article

(This article belongs to the Special Issue Periprosthetic Joint Infection: Understanding the Epidemiology, Pathogenesis, Diagnosis and Treatment Options)

14 pages, 1347 KiB

Open AccessArticle

Genomic Characterization of Carbapenem-Resistant Acinetobacter baumannii (OXA-23) and Klebsiella pneumoniae (KPC-2) Causing Hospital-Acquired Infections in Dogs

by Isabela Pádua Zanon, João Victor Ferreira Campos, Yasmin Gonçalves de Castro, Isadora Maria Soares de Melo, Flávia Figueira Aburjaile, Bertram Brenig, Vasco Azevedo and Rodrigo Otávio Silveira Silva

Antibiotics 2025, 14(6), 584; https://doi.org/10.3390/antibiotics14060584 - 6 Jun 2025

Viewed by 374

Abstract

Background/Objectives: Antimicrobial resistance is a major global health threat. Among the most problematic pathogens are carbapenem-resistant Acinetobacter baumannii and Klebsiella pneumoniae, which are significant causes of mortality in humans, particularly in the context of nosocomial infections. In companion animals, these bacteria have [...] Read more.

Background/Objectives: Antimicrobial resistance is a major global health threat. Among the most problematic pathogens are carbapenem-resistant Acinetobacter baumannii and Klebsiella pneumoniae, which are significant causes of mortality in humans, particularly in the context of nosocomial infections. In companion animals, these bacteria have been reported mainly as colonizers of healthy animals or, less frequently, in community-acquired infections. However, no confirmed cases of healthcare-associated infections caused by these species have been documented in this population. This study reports the first confirmed fatal cases of infection with carbapenem-resistant A. baumannii and KPC-producing K. pneumoniae in dogs. Methods: Three hospitalized dogs developed infections associated with distinct anatomical devices, including a venous catheter, an endotracheal tube, and a Penrose drain. Bacterial isolation followed by antimicrobial susceptibility testing identified carbapenem-resistant A. baumannii and K. pneumoniae. The isolates were subsequently subjected to additional antimicrobial resistance tests and whole-genome sequencing (WGS). Results: WGS confirmed the presence of the OXA-23 carbapenemase gene in both A. baumannii isolates and the KPC-2 carbapenemase gene was detected in the K. pneumoniae strain. All three strains exhibited resistance to multiple antimicrobial classes, including β-lactams (amoxicillin-clavulanic acid, ampicillin, cephalotin, piperacillin-tazobactam, cefoxitin, ceftiofur, cefotaxime, ertapenem, imipenem and meropenem), aminoglycosides (gentamicin, neomycin), tetracyclines (doxycycline, tetracycline and oxytetracycline), fluoroquinolones (ciprofloxacin, enrofloxacin), and folate pathway antagonists (trimethoprim-sulfamethoxazole). Multilocus sequence typing identified two high-risk clones: K. pneumoniae ST340 (CC258) and A. baumannii ST15 (CC15). Single nucleotide polymorphism analysis confirmed a high degree of genetic similarity between these isolates and strains previously associated with human infections in Brazil. Conclusions: These findings provide the first evidence of fatal, healthcare-associated infections caused by these multidrug-resistant pathogens in dogs and underscore the need to strengthen surveillance and infection control practices in veterinary hospitals. Furthermore, the results raise concerns about the potential of companion animals to act as reservoirs for multidrug-resistant organisms of public health relevance. Full article

(This article belongs to the Special Issue Antimicrobial Resistance: Epidemiology and Implications for Veterinary Medicine)

► Show Figures

Figure 1

17 pages, 623 KiB

Open AccessArticle

Landscape of Post-Marketing Requirements Under the Pediatric Research Equity Act for Antibiotics from 2009–2024

by Daniel Selig, Funmi Aminu, Sue Cammarata, Ting Chen, Lauren Dolak, Stephen Duprez, Stephanie Ecker, Lisa Gault, Sandra George, Margaret Harkins, Clayton Litchmore, Michael Serenko, William Waverczak and Doug Girgenti

Antibiotics 2025, 14(6), 583; https://doi.org/10.3390/antibiotics14060583 - 6 Jun 2025

Viewed by 350

Abstract

Background/Objectives: We reviewed Post-Marketing Requirements (PMRs) under the Pediatric Research Equity Act (PREA) for antibiotics approved in adults from 2009 to 2024 to better understand factors associated with PMR study completion. Methods: Initial PMRs, including study design and completion timelines were extracted [...] Read more.

Background/Objectives: We reviewed Post-Marketing Requirements (PMRs) under the Pediatric Research Equity Act (PREA) for antibiotics approved in adults from 2009 to 2024 to better understand factors associated with PMR study completion. Methods: Initial PMRs, including study design and completion timelines were extracted from Food and Drug Administration (FDA) approval letters. Studies were cross-referenced at clinicaltrials.gov, with follow-up from adult approval to study completion or through 31 December 2024. Results: Eighteen antibiotics were approved in adults from 2009 to 2024, with 53 associated PREA PMRs. A total of nine PMRs were excluded from analysis (six exclusions for projected study completion dates on or after 12/31/2024, one exclusion due to lack of information, and two exclusions because the study type was not categorizable as Phase 1 or Phase 2). Of the 44 remaining PMRs in the analysis set, the median pediatric study follow-up time from adult approval was 5.3 years (range 0.94 to 11.5 years), with a study completion rate of 54.5% (N = 24). Small- and medium-sized companies had a study completion rate of 10% (N = 2/20) over a median of 6.44 years of follow-up, with no pediatric approvals. Large pharmaceutical corporations had a significantly higher study completion rate of 91.6% (N = 22/24; adjusted hazard ratio 20.3 95%CI, 5.02 to 82.4) over a median follow-up time of 4.7 years and achieved pediatric approval with labelling updates for 75% of antibiotics (N = 6/8). Conclusions: Compared to larger organizations, smaller pharmaceutical companies have experienced difficulty in PREA PMR antibiotic study completion, which may be related to financial difficulties in the challenging market for antibiotics. To improve PMR study completion, smaller companies require continued financial support and innovation in study design. For pediatric antibiotic development, the FDA accepts the extrapolation of efficacy from well-conducted randomized adult trials (i.e., pharmacokinetics (PK) and the safety approach). Therefore, sponsors should consider the use of single-arm, non-comparative PK and safety study designs to reduce the size and scope of trials. Sponsors should also assess whether the evaluation of an antibiotic is necessary in adolescents, or if data in a surrogate population of adults (e.g., low-weight adults) may serve as adequate evidence for adolescent approval. Full article

(This article belongs to the Special Issue New Drugs, Innovative Antimicrobial Approaches, and Optimized Dosages: Bridging Research and Clinical Practice)

► Show Figures

Figure 1

23 pages, 506 KiB

Open AccessArticle

Design and Synthesis of Hybrid Compounds for Potential Treatment of Bacterial Co-Infections: In Vitro Antibacterial and In Silico Studies

by Vuyolwethu Khwaza, Opeoluwa O. Oyedeji, Eric Morifi, Mutshinyalo Nwamadi, Thierry Youmbi Fonkui, Derek Tantoh Ndinteh and Blessing A. Aderibigbe

Antibiotics 2025, 14(6), 582; https://doi.org/10.3390/antibiotics14060582 - 6 Jun 2025

Viewed by 298

Abstract

Background: The need for innovative therapeutic strategies to enhance patient outcomes has increased due to the rise in bacterial co-infections associated with COVID-19. Methods: In this study, ten hybrid compounds were synthesized by combining two known pharmaceutical scaffolds to enhance antibacterial activity and [...] Read more.

Background: The need for innovative therapeutic strategies to enhance patient outcomes has increased due to the rise in bacterial co-infections associated with COVID-19. Methods: In this study, ten hybrid compounds were synthesized by combining two known pharmaceutical scaffolds to enhance antibacterial activity and overcome resistance mechanisms. The synthesized compounds were evaluated for their antibacterial activity against five Gram-negative and seven Gram-positive bacterial strains. In silico pharmacokinetic and drug-likeness properties of selected active compounds (12–16, 19, 21, and 23) were predicted using the SwissADME web tool. Results: Compounds 12–16, 19, 21, and 23 demonstrated significant antibacterial activity, with compound 16 (a ciprofloxacin-containing hybrid) exhibiting the most potent effect, showing a minimum inhibitory concentration (MIC) of 7.8125 µg/mL against all tested bacterial strains. The in silico analysis revealed favorable pharmacokinetic profiles, drug-likeness, lipophilicity, and water solubility of most hybrid compounds. Discussion: The synthesized hybrid compounds exhibited enhanced antibacterial activity and desirable pharmacokinetic properties, particularly compound 16. These findings suggest the potential of these molecules in combating bacterial pathogens, especially those implicated in co-infections in COVID-19 infections. Conclusions: The study presents promising hybrid antibacterial agents with potential application as adjunct therapies for treating COVID-19-associated bacterial co-infections. Further investigation is needed, which may lead to effective treatments for managing secondary bacterial infections in viral disease contexts. Full article

(This article belongs to the Special Issue Strategies for the Design of Hybrid-Based Antimicrobial Compounds)

► Show Figures

Figure 1

15 pages, 264 KiB

Open AccessReview

Current Applications and the Future of Phage Therapy for Periprosthetic Joint Infections

by Arian Ocean Abedi, Armita Armina Abedi, Tristan Ferry and Mustafa Citak

Antibiotics 2025, 14(6), 581; https://doi.org/10.3390/antibiotics14060581 - 6 Jun 2025

Viewed by 367

Abstract

Periprosthetic joint infections (PJI) present significant challenges in orthopedic surgery, largely due to the complexity of treating antibiotic-resistant infections. Phage therapy, which utilizes bacteriophages to target bacterial pathogens, offers a promising supplement to traditional antimicrobial methods. This review discusses the current applications of [...] Read more.

Periprosthetic joint infections (PJI) present significant challenges in orthopedic surgery, largely due to the complexity of treating antibiotic-resistant infections. Phage therapy, which utilizes bacteriophages to target bacterial pathogens, offers a promising supplement to traditional antimicrobial methods. This review discusses the current applications of phage therapy in the management of PJI, exploring its underlying mechanisms, clinical outcomes, and practical considerations. We also explore advances in phage therapy technology, including the development of phage cocktails, bioengineered phages, and combination therapies with antibiotics, which enhance the specificity and effectiveness of treatments. Furthermore, we address the future potential of phage therapy to be integrated into standard treatment protocols, focusing on ongoing innovations and research areas.The regulatory and ethical aspects of phage therapy in clinical settings are also discussed. By offering a comprehensive evaluation of both the current state and prospects of phage therapy, this review aims to inform clinical practice and stimulate further research into this innovative treatment modality for PJI management. Full article

(This article belongs to the Special Issue Bacteriophage Therapy a Renaissance Weapon Recent Developments and Application, 2nd Edition)

Journal Menu

Journal Browser

Antibiotics, Volume 14, Issue 6 (June 2025) – 82 articles

Further Information

Guidelines

MDPI Initiatives

Follow MDPI