Antibiotics

13 pages, 655 KiB

Open AccessArticle

Pharmacokinetic Analysis of an Isoniazid Suspension Among Spanish Children Under 6 Years of Age

by Antoni Noguera-Julian, Emma Wilhelmi, Maria Cussó, Rob Aarnoutse, Angela Colbers, Loreto Martorell, Maria Goretti López-Ramos, Joan Vinent, Rosa Farré, Dolors Soy, Sílvia Simó-Nebot and Clàudia Fortuny

Antibiotics 2025, 14(1), 74; https://doi.org/10.3390/antibiotics14010074 (registering DOI) - 12 Jan 2025

Abstract

Background: Isoniazid (INH) remains a first-line drug for the treatment of tuberculosis (TB) in young children. In 2010, the WHO recommended an increase in the daily dose of INH up to 10 (7–15) mg/kg. Currently, there are no INH suspensions available in [...] Read more.

Background: Isoniazid (INH) remains a first-line drug for the treatment of tuberculosis (TB) in young children. In 2010, the WHO recommended an increase in the daily dose of INH up to 10 (7–15) mg/kg. Currently, there are no INH suspensions available in Europe. Methods: We aimed to characterize the pharmacokinetics of a licensed INH suspension (10 mg/mL, Pharmascience Inc., Montreal, QC, Canada) in children receiving INH daily at 10 mg/kg in a single-center, open-label, non-randomized, phase IIa clinical trial (EudraCT Number: 2016-002000-31) in Barcelona (Spain). Samples were analyzed using a validated UPLC-UV assay. The N-acetyltransferase 2 gene was examined to determine the acetylation status. A non-compartmental pharmacokinetic analysis was conducted. Results: Twenty-four patients (12 females) were included (primary chemoprophylaxis, n = 12; TB treatment, n = 9; and TB infection preventive treatment, n = 3). The acetylator statuses were homozygous fast (n = 3), heterozygous intermediate (n = 18), and homozygous slow (n = 2; unavailable in one patient). The INH median (IQR) C_max and AUC_0–24h values were 6.1 (4.5–8.2) mg/L and 23.0 (11.2–35.4) h∙mg/L; adult targets (>3 mg/L and 11.6–26.3 h∙mg/L) were not achieved in three and six cases, respectively. Gender, age at assessment (<2 or >2 years), and INH monotherapy (vs. combined TB treatment) had no impact on pharmacokinetic parameters. Significant differences in C_max (p = 0.030) and AUC_0–24h (p = 0.011) values were observed based on acetylator status. Treatment was well tolerated, and no severe adverse events were observed; three patients developed asymptomatic mildly elevated alanine aminotransferase levels. Conclusions: In infants and children receiving a daily INH suspension at 10 mg/kg, no safety concerns were raised, and the target adult levels were reached in the majority of patients. Full article

(This article belongs to the Special Issue Therapeutic Drug Monitoring: Pharmacodynamics and Pharmacokinetics of Antibiotics in Clinical Care Settings)

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12 pages, 553 KiB

Open AccessArticle

Silent Carriers: The Hidden Threat of Antibiotic-Resistant Staphylococcus aureus in Retail Seafood Across Poland’s Tri-City Area

by Anita Kukułowicz, Izabela Steinka and Aleksandra Szelągowska

Antibiotics 2025, 14(1), 73; https://doi.org/10.3390/antibiotics14010073 (registering DOI) - 12 Jan 2025

Abstract

Background/objectives: Antibiotic-resistant Staphylococcus aureus poses a significant risk to food safety and public health, particularly through the consumption of contaminated seafood. This study aimed to assess the presence and antibiotic resistance of S. aureus in seafood sold in the Tri-City area of [...] Read more.

Background/objectives: Antibiotic-resistant Staphylococcus aureus poses a significant risk to food safety and public health, particularly through the consumption of contaminated seafood. This study aimed to assess the presence and antibiotic resistance of S. aureus in seafood sold in the Tri-City area of Poland, addressing a knowledge gap regarding the region. Methods: Seafood samples (n = 89) were categorized according to their origin: domestic—Poland (PL), European countries (ECs), and Asian countries (ACs). S. aureus was isolated using ISO 6888-1 methods, and antimicrobial susceptibility testing was conducted against three antibiotics: erythromycin, clindamycin, and gentamicin, following CLSI guidelines. Results: Of the 89 samples, 68.5% were contaminated with S. aureus. The highest resistance rates were found for erythromycin (30.5%), with gentamicin showing the lowest resistance (8.3%).No significant correlation (p > 0.05) was found between resistance patterns and fish origin or processing level. Conclusions: The results of this study highlight the widespread occurrence of Staphylococcus aureus in fish sold in the Tri-City area, with a notable prevalence of antibiotic-resistant strains. Full article

(This article belongs to the Special Issue Antibiotic Resistance and Coping Strategies of Methicillin-Resistant Staphylococcus Species)

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18 pages, 3963 KiB

Open AccessArticle

Vismia guianensis Improves Survival of Tenebrio molitor and Mice During Lethal Infection with Candida albicans

by Arthur André Castro Costa, Elizangela Pestana Motta, Aluísio Silva Oliveira, Pamela Gomes Santos, Josivan Regis Farias, Danielle Cristine Gomes Franco, Mayara Cristina Pinto Silva, Nicolle Teixeira Barbosa, Simone Batista Muniz, Luís Douglas Miranda. Silva, Lucilene Amorim Silva, Claudia Quintino Rocha, Flavia Raquel Fernandes Nascimento and Rosane Nassar Meireles Guerra

Antibiotics 2025, 14(1), 72; https://doi.org/10.3390/antibiotics14010072 (registering DOI) - 11 Jan 2025

Abstract

Background/Objectives: Vismia guianensis is a vegetal species popularly used to treat fungal infections. This study evaluated the anti-Candida effect of V. guianensis extract after C. albicans lethal infection in Tenebrio molitor larvae and mice. Methods and Results: The chemical profile [...] Read more.

Background/Objectives: Vismia guianensis is a vegetal species popularly used to treat fungal infections. This study evaluated the anti-Candida effect of V. guianensis extract after C. albicans lethal infection in Tenebrio molitor larvae and mice. Methods and Results: The chemical profile analysis of a hydroethanolic extract of the leaves of V. guianensis (EHVG) identified 14 compounds. Two sets of experiments used T. molitor larvae. To evaluate toxicity, the uninfected larvae were treated with EHVG or anthraquinone. We considered the following groups: the controls received PBS; ANFO B received amphotericin B (600 mg/mL); EHVG received the extract; and ANTQ received anthraquinone. The extract and anthraquinone resulted in low-level toxicity in the T. molitor larvae. Another set of experiments evaluated the EHVG effect during lethal infection with Candida albicans. The T. molitor larvae were treated intracelomically (ic/10 μL). Treatment with EHVG efficiently improved the survival of the larvae after lethal infection (60%), probably due to the reduction in CFUs. In the mice, the antifungal effect of EHVG was determined in three groups of immunosuppressed Swiss mice (cyclophosphamide, 50 mg/kg/ip) infected with C. albicans (1 × 10⁷ CFU/ip). The control animals were infected and untreated; the ANFO B animals were infected and treated with amphotericin B (600 µg/kg/ip); and the EHVG animals were infected and treated with the extract (5 mg/kg/orally). A SHAM group (uninfected and untreated) was also included. Survival was assessed for 5 days. The extract increased the mice’s survival (60%) and life expectancy, reducing the CFU counts in the peritoneum and blood. EHVG also increased the number of blood neutrophils and peritoneal macrophages. These systemic activities are likely associated with the presence of flavonoids in the extract. Conclusions: The beneficial effects of EHVG in lethal sepsis are related to an antifungal effect, with the number of CFUs decreasing in the larvae and the mice. In addition, EHVG showed immunological activity in the mice, considering immune cell distribution and cytokine production. Full article

(This article belongs to the Special Issue Antimicrobial and Anti-Infective Activity of Natural Products, 2nd Edition)

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22 pages, 7293 KiB

Open AccessArticle

Cinnamic Acid Compounds (p-Coumaric, Ferulic, and p-Methoxycinnamic Acid) as Effective Antibacterial Agents Against Colistin-Resistant Acinetobacter baumannii

by Alaaddin Korkut, Serap Özkaya Gül, Esra Aydemir, Hakan Er and Elif Odabaş Köse

Antibiotics 2025, 14(1), 71; https://doi.org/10.3390/antibiotics14010071 (registering DOI) - 11 Jan 2025

Abstract

Colistin-resistant Acinetobacter baumannii (COLR-Ab) is an opportunistic pathogen commonly associated with nosocomial infections, and it is difficult to treat with current antibiotics. Therefore, new antimicrobial agents need to be developed for treatment. Based on this information, we investigated the antimicrobial, antibiofilm, and combination [...] Read more.

Colistin-resistant Acinetobacter baumannii (COLR-Ab) is an opportunistic pathogen commonly associated with nosocomial infections, and it is difficult to treat with current antibiotics. Therefore, new antimicrobial agents need to be developed for treatment. Based on this information, we investigated the antimicrobial, antibiofilm, and combination activities of p-coumaric acid (p-CA), ferulic acid (FA), and p-methoxycinnamic acid (p-MCA) against five COLR-Ab isolates. p-CA, FA, and p-MCA exhibited antimicrobial activity against COLR-Ab isolates, with minimum inhibitory concentration (MIC) values in the range of 256–128 µg/mL, 1024–512 µg/mL, and 512–128 µg/mL, respectively. The combination effects of the compounds with colistin (COL) were evaluated using a checkerboard synergy test. The combinations exhibited a synergistic effect and caused a 128- to 16-fold decrease in COL MIC values. In addition, the biofilm production capacities of the COLR-Ab isolates and the antibiofilm activities of the compounds were determined using the microtitre plate-based crystal violet (CV) technique. The compounds showed effective antibiofilm activity against strong and moderate biofilm-producing isolates, inhibiting biofilm formation by 77.5% and 19.7%. Spectrometric measurements were used to examine the effect of compounds on membrane permeability; 1.9-, 1.66-, and 1.34-fold increases in absorbance values were observed at MIC concentrations of p-CA, FA, and p-MCA, respectively. Furthermore, morphological changes caused by the compounds in the isolate were observed using scanning electron microscopy (SEM) micrographs. According to the WST assay, the compounds did not show any statistically significant cytotoxic effect on the cells (p > 0.05). These findings indicate that p-CA, FA, and p-MCA may be potential new alternative candidates against resistant A. baumannii. Full article

(This article belongs to the Special Issue Life Defense in the New Century: Natural Products in the Development of New Antimicrobial Drugs)

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25 pages, 754 KiB

Open AccessArticle

Chemometric Methods—A Valuable Tool for Investigating the Interactions Between Antifungal Drugs (Including Antifungal Antibiotics) and Food

by Agnieszka Wiesner-Kiełczewska, Paweł Zagrodzki, Alicja Gawalska and Paweł Paśko

Antibiotics 2025, 14(1), 70; https://doi.org/10.3390/antibiotics14010070 - 10 Jan 2025

Abstract

Background/Objectives: Developing antifungal drugs with lower potential for interactions with food may help to optimize treatment and reduce the risk of antimicrobial resistance. Chemometrics uses statistical and mathematical methods to analyze multivariate chemical data, enabling the identification of key correlations and simplifying data [...] Read more.

Background/Objectives: Developing antifungal drugs with lower potential for interactions with food may help to optimize treatment and reduce the risk of antimicrobial resistance. Chemometrics uses statistical and mathematical methods to analyze multivariate chemical data, enabling the identification of key correlations and simplifying data interpretation. We used the partial least squares (PLS) approach to explore the correlations between various characteristics of oral antifungal drugs (including antifungal antibiotics) and dietary interventions, aiming to identify patterns that could inform the optimization of antifungal therapy. Methods: We analyzed 15 oral antifungal drugs, including azoles (8), antifungal antibiotics (4), antifungal antimetabolites (1), squalene epoxidase inhibitors (1), and glucan synthase inhibitors (1). The input dataset comprised information from published clinical trials, chemical records, and calculations. We constructed PLS models with changes in the pharmacokinetic parameters (∆AUC, area under the curve; ∆C_max, maximum drug concentration; and ∆T_max, time to reach maximum drug concentration) after dietary intervention as the response parameters and eight groups of molecular descriptors (M1–M8) as the predictor parameters. We performed separate analyses for the different nutritional interventions. Results: In the final PLS model with food as an intervention, we effectively reduced the dimensionality of the dataset while retaining a substantial percentage of the original information (variance), as significant components explained 69.8% and 17.5% of the predictor and response parameter variances, respectively. The PLS model was significant because its components met the cross-validation criteria. We obtained six significant positive and negative correlations between the descriptors related to atoms and the postprandial ∆T_max. Conclusions: The PLS method is valuable for investigating interactions between antifungal drugs (including antifungal antibiotics) and food. The correlations obtained can be used in drug modeling to predict interactions with dietary interventions based on the antifungal drug’s chemical structure. Incorporating chemometric techniques into the early drug development stages could facilitate the design of antifungal antibiotics and other antifungal agents with optimized absorption in the presence of dietary components. Full article

(This article belongs to the Special Issue Antifungal Strategies: Epidemiological Approaches, Mechanisms and Resistance in Fungal Pathogens)

15 pages, 1599 KiB

Open AccessArticle

Monitoring the Spread of Multidrug-Resistant Escherichia coli Throughout the Broiler Production Cycle

by Victor Dellevedove Cruz, Danilo Henrique Rabaçal Alves, Jamile Kellen de Souza, Maísa Fabiana Menck-Costa, Bruno Henrique Dias de Oliva, Ana Angelita Sampaio Baptista, Alexandre Oba, Fabrizio Matté, Kácio Emílio Borges Baierle, Sérgio Paulo Dejato da Rocha, Kelly Cristina Tagliari de Brito, Benito Guimarães de Brito, Gerson Nakazato, Marcio Costa and Renata Katsuko Takayama Kobayashi

Antibiotics 2025, 14(1), 69; https://doi.org/10.3390/antibiotics14010069 - 10 Jan 2025

Abstract

The extensive use of antimicrobials in broiler production is changing the bird microbiota, fostering drug-resistant bacteria, and complicating therapeutic interventions, making the problem of multidrug resistance global. The monitoring of antimicrobial virulence and resistance genes are tools that have come to assist the [...] Read more.

The extensive use of antimicrobials in broiler production is changing the bird microbiota, fostering drug-resistant bacteria, and complicating therapeutic interventions, making the problem of multidrug resistance global. The monitoring of antimicrobial virulence and resistance genes are tools that have come to assist the breeding of these animals, directing possible treatments as already used in human medicine and collecting data to demonstrate possible dissemination of multidrug-resistant strains that may cause damage to industry and public health. This work aimed to monitor broiler farms in southern Brazil, isolating samples of E. coli and classifying them according to the profile of resistance to antimicrobials of interest to human and animal health. We also monitored the profile of virulence genes and conducted an epidemiological survey of possible risk factors that contribute to this selection of multidrug-resistant isolates. Monitoring was carried out on farms in the three southern states of the country, collecting samples of poultry litter, cloacal swabs, and beetles of the species Alphitobius diaperinus, isolating E. coli from each of these samples. These were evaluated by testing their susceptibility to antimicrobials of animal and human interest; detecting whether the samples were extended-spectrum β-lactamase enzyme (ESBL) producers; and when positive, selected for genotypic tests to identify resistant genes (CTX-M, TEM, and SHV) and virulence. Among the antimicrobials tested, enrofloxacin and ciprofloxacin demonstrated some of the highest frequencies of resistance in the isolated strains, with significant statistical results. The use of these antimicrobials increased the likelihood of resistance by over three times and was associated with a 1.5-fold higher probability of multidrug resistance. Of all isolates, 95% were multidrug-resistant, raising concerns for production and public health. Among 231 ESBL-positive samples, the CTX-M1 group predominated. Full article

(This article belongs to the Special Issue Detection of Bacteria and Antibiotics Surveillance in Livestock)

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42 pages, 8074 KiB

Open AccessReview

Antibacterial Activity of Selected Essential Oil Components and Their Derivatives: A Review

by Vuyolwethu Khwaza and Blessing A. Aderibigbe

Antibiotics 2025, 14(1), 68; https://doi.org/10.3390/antibiotics14010068 - 10 Jan 2025

Abstract

Essential oils (EOs) are gaining ground and have been intensively studied due to their widespread use in the pharmaceutical, food, and cosmetics industries. The essential components of EOs have been recognized for diverse therapeutic activities and have gained significant attention for their potential [...] Read more.

Essential oils (EOs) are gaining ground and have been intensively studied due to their widespread use in the pharmaceutical, food, and cosmetics industries. The essential components of EOs have been recognized for diverse therapeutic activities and have gained significant attention for their potential antibacterial activities. Despite the popularity of EOs and potent biological properties, their bioactive components and their derivatives are still not comprehensively characterized. This review explores the antibacterial efficacy of selected EO components and their derivatives, focusing on monoterpenes chosen (i.e., carvacrol, menthol, and thymol) and phenylpropanoids (i.e., cinnamaldehyde and eugenol). Furthermore, this review highlights recent advancements in developing derivatives of these EO components, which have shown improved antibacterial activity with reduced toxicity. By summarizing recent studies, this review reveals the potential of these natural compounds and their derivatives as promising candidates for pharmaceuticals, food preservation, and as alternatives to synthetic antibiotics in combating bacterial resistance. Full article

(This article belongs to the Special Issue The Search for Antimicrobial Agents from Natural Products)

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14 pages, 901 KiB

Open AccessArticle

Mapping Antimicrobial Resistance in Staphylococcus epidermidis Isolates from Subclinical Mastitis in Danish Dairy Cows

by Desiree Corvera Kløve, Mikael Lenz Strube, Peter M. H. Heegaard and Lærke Boye Astrup

Antibiotics 2025, 14(1), 67; https://doi.org/10.3390/antibiotics14010067 - 10 Jan 2025

Abstract

Background/Objectives: Although Staphylococcus epidermidis is a key cause of subclinical mastitis in Danish dairy cows, its sensitivity to antimicrobials remains unexplored. Here, we analyzed sixty S. epidermidis isolates derived from 42 dairy cows across six conventional dairy herds in Denmark. Methods: Phenotypic resistance [...] Read more.

Background/Objectives: Although Staphylococcus epidermidis is a key cause of subclinical mastitis in Danish dairy cows, its sensitivity to antimicrobials remains unexplored. Here, we analyzed sixty S. epidermidis isolates derived from 42 dairy cows across six conventional dairy herds in Denmark. Methods: Phenotypic resistance was measured by antimicrobial susceptibility testing and minimum inhibitory concentration (MIC) analysis, and genotypic resistance was examined through whole-genome sequencing and identification of antimicrobial resistance genes (ARGs). Correspondence between phenotypic and genotypic resistance was then evaluated by Cohen’s kappa statistics. Furthermore, the presence of plasmid replicon genes and the strain diversity among the S. epidermidis isolates was investigated to associate these findings with the observed AMR patterns. Results: Results showed that 30/60 isolates (50.0%) were resistant to penicillin phenotypically, while 35/60 (58.3%) were positive for a corresponding blaZ gene (κ = 0.83, p < 0.01). A fosB gene, encoding fosfomycin resistance, was detected in all 60/60 isolates (100.0%), but fosfomycin resistance was not analyzed phenotypically. Based on MIC analysis, 3/60 isolates (5.0%) were multi-drug resistant, showing resistance towards penicillin, erythromycin, and tetracycline. However, in 11/60 genomes (18.3%), ARGs encoding resistance towards ≥3 antimicrobial classes (e.g., beta-lactams, phosphonic acid, tetracyclines, aminoglycosides, macrolides, lincosamides, and fusidane) were detected. Eleven different ARGs were detected among the 60 isolates in total. No methicillin-resistant Staphylococcus epidermidis (MRSE) were recorded. Results further showed that each herd had one primary sequence type (ST) and resistance profile associated with it, and plasmid-mediated horizontal gene transfer of ARGs was indicated This study underscores the importance of routine resistance surveillance and species-specific diagnoses to improve treatment outcomes and ensure prudent use of antimicrobials. Full article

(This article belongs to the Special Issue Antimicrobial Resistance of Pathogens Isolated from Bovine Mastitis)

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21 pages, 4434 KiB

Open AccessArticle

Comparative Structural and Biophysical Investigation of Lycosa erythrognatha Toxin I (LyeTx I) and Its Analog LyeTx I-b

by Amanda Neves de Souza, Gabriele de Azevedo Cardoso, Lúcio Otávio Nunes, Christopher Aisenbrey, Evgeniy Salnikov, Kelton Rodrigues de Souza, Ahmad Saad, Maria Elena de Lima, Jarbas Magalhães Resende, Burkhard Bechinger and Rodrigo Moreira Verly

Antibiotics 2025, 14(1), 66; https://doi.org/10.3390/antibiotics14010066 - 10 Jan 2025

Abstract

Background/Objectives: This study investigates the structural and biophysical properties of the wild-type antimicrobial peptide LyeTx I, isolated from the venom of the spider Lycosa erythrognatha, and its analog LyeTx I-b, designed to enhance antibacterial activity, selectivity, and membrane interactions by the acetylation [...] Read more.

Background/Objectives: This study investigates the structural and biophysical properties of the wild-type antimicrobial peptide LyeTx I, isolated from the venom of the spider Lycosa erythrognatha, and its analog LyeTx I-b, designed to enhance antibacterial activity, selectivity, and membrane interactions by the acetylation and increased amphipathicty. Methods: To understand the mechanisms behind these enhanced properties, comparative analyses of the structural, topological, biophysical, and thermodynamic aspects of the interactions between each peptide and phospholipid bilayers were evaluated. Both peptides were isotopically labeled with ²H₃-Ala and ¹⁵N-Leu to facilitate structural studies via NMR spectroscopy. Results: Circular dichroism and solid-state NMR analyses revealed that, while both peptides adopt α-helical conformations in membrane mimetic environments, LyeTx I-b exhibits a more amphipathic and extended helical structure, which correlates with its enhanced membrane interaction. The thermodynamic properties of the peptide–membrane interactions were quantitatively evaluated in the presence of phospholipid bilayers using ITC and DSC, highlighting a greater propensity of LyeTx I-b to disrupt lipid vesicles. Calcein release studies reveal that both peptides cause vesicle disruption, although DLS measurements and TEM imaging indicate distinct effects on phospholipid vesicle organization. While LyeTx I-b permeabilizes anionic membrane retaining the vesicle integrity, LyeTx I promotes significant vesicle agglutination. Furthermore, DSC and calcein release assays indicate that LyeTx I-b exhibits significantly lower cytotoxicity toward eukaryotic membranes compared to LyeTx I, suggesting greater selectivity for bacterial membranes. Conclusions: Our findings provide insights into the structural and functional modifications that enhance the antimicrobial and therapeutic potential of LyeTx I-b, offering valuable guidance for the design of novel peptides targeting resistant bacterial infections and cancer. Full article

(This article belongs to the Special Issue Mechanisms of Antimicrobial Peptides on Pathogens, 2nd Edition)

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CD spectra of (A,C,E) LyeTx I and (B,D,F) LyeTx I-b in the presence of (A,B) POPC/POPG (3:1, mol/mol) and (C,D) POPC/POPG (3:1, mol/mol) + 1% PEGylated POPE (pH 8.0, 20 mM Tris buffer) phospholipid vesicles, as well as in (E,F) in the presence of SDS micelles. Full article ">Figure 2
Graphical representation of NOE correlations indicative of helical structures in the NOESY spectra of (A) LyeTx I and (B) LyeTx I-b in SDS-d25 micelles. Full article ">Figure 3
NMR three-dimensional structures of (A–C) LyeTx I and (D–F) LyeTx I-b in the presence of 200 mM SDS-d25 micelles. (A,D) Superposition of the 10 lowest-energy structures. (B,E) Horizontal and (C,F) frontal perspectives of the most stable peptide structure. (C) LyeTx I and (F) LyeTx I-b structure with the front view of the helix. In (B,C,E,F), the hydrophilic residues are shown in green, hydrophobic residues in dark blue, and the Trp residue in orange. The N-terminals are shown in the front in (E,F) and on the left in (B,E). Full article ">Figure 4
Solid-state NMR spectra of the selectively labeled (A–D) LyeTx I and (E–H) LyeTx I-b at 1.0 mol % in uniaxially oriented POPC/POPG (3:1, mol/mol) bilayers. (A,C,E,G) Proton-decoupled 15N and (B,D,F,H) 2H solid-state NMR. All spectra were recorded for alignments with the membrane normal parallel to the magnetic field of the spectrometer. Full article ">Figure 5
Isothermal titration calorimetric curves obtained from the titration of 20 mM POPC/POPG (3:1, mol/mol) vesicles into Tris-HCl buffer pH 8.0 peptide solutions at 25 °C: (A) 50 μM LyeTx I; (B) 50 μM LyeTx I-b; (C) 100 μM LyeTx I; and (D) 100 μM LyeTx I-b. In the panels, the blue shading highlights the molar ratio, while the red line on the curves represents the fitting. Full article ">Figure 6
Isothermal calorimetric titration of pH 8.0 Tris-HCl buffered solutions of (A,C) LyeTx I and (B,D) LyeTx I-b with 20 mM POPC/POPG (3:1, mol/mol) LUVs: (A) 25 μM LyeTx I; (B) 25 μM LyeTx I-b; (C) 50 μM LyeTx I; and (D) 50 μM LyeTx I-b. Experiments were performed at 30 °C. In the panels, the blue shading highlights the molar ratio, while the red line on the curves represents the fitting. Full article ">Figure 7
(A) Hydrodynamic diameter (Dh) and (B) normalized zeta potential (ζ) of POPC/POPG (3:1, mol/mol) LUVs measured at different concentrations of LyeTx I (squares) or LyeTx I-b (circles). LUVs (500 μM) were suspended in 10 mM Tris-HCl buffer (pH 8.0) and 25 °C. Error bars indicate standard deviation from three independent experiments. Full article ">Figure 8
Kinetics of calcein release from (A,B) POPC/POPG (3:1, mol/mol) and (C,D) POPC/Chol LUVs induced by different concentrations of (A,C) LyeTx I and (B,D) LyeTx I-b. Full article ">Figure 9
DSC profile of the gel-to-liquid-crystalline phase transition of 3.0 mM (A,B) DMPC/DMPG and (C,D) DMPC/Chol in the presence of (A,C) LyeTx I and (B,D) LyeTx I-b at different concentrations. Dash grey lines indicate the Tm of the LUVs in the absence of peptides. Full article ">

10 pages, 463 KiB

Open AccessReview

Tetracyclines in Rheumatoid Arthritis: Dual Anti-Inflammatory and Immunomodulatory Roles, Effectiveness, and Safety Insights

by Mislav Radić, Andrej Belančić, Hana Đogaš, Marijana Vučković, Andrea Gelemanović, Andrea Faour, Ivan Vlak and Josipa Radić

Antibiotics 2025, 14(1), 65; https://doi.org/10.3390/antibiotics14010065 - 10 Jan 2025

Abstract

Rheumatoid arthritis (RA) is a chronic autoimmune disease characterized by persistent inflammation, joint pain, and progressive cartilage and bone erosion. Despite advancements in RA management with disease-modifying antirheumatic drugs (DMARDs) and biologics, some patients remain refractory to conventional treatments. Tetracyclines, such as minocycline [...] Read more.

Rheumatoid arthritis (RA) is a chronic autoimmune disease characterized by persistent inflammation, joint pain, and progressive cartilage and bone erosion. Despite advancements in RA management with disease-modifying antirheumatic drugs (DMARDs) and biologics, some patients remain refractory to conventional treatments. Tetracyclines, such as minocycline and doxycycline, exhibit anti-inflammatory and immunomodulatory properties, making them potential supplementary treatments. This narrative review explores their effectiveness, mechanisms of action, safety profiles, and current challenges in RA care. Tetracyclines have demonstrated significant immunomodulatory effects, including the inhibition of pro-inflammatory cytokines and matrix metalloproteinases (MMPs), which are critical in RA pathology. Clinical trials, including double-blind, placebo-controlled studies, have shown efficacy in reducing RA symptoms, particularly in early and refractory cases. However, their use remains limited by inconsistent evidence, small sample sizes, and concerns about antimicrobial resistance. Current guidelines for RA management do not explicitly recommend tetracyclines due to these limitations, although off-label use may be considered in specific cases. The use of tetracycline for RA is restricted by drug interactions causing bacterial resistance alongside unpredictable patient responses, hence the necessity for prudence in its prescription within a clinical setting. To overcome these limitations, the development of safer compounds, in-depth in silico analyses, and integration with personalized medicine approaches are needed. Overall, tetracyclines show promise as adjunct therapies in RA management due to their dual anti-inflammatory and immunomodulatory actions. This review highlights the need for further research to address gaps in evidence, including the development of modified tetracyclines with reduced antimicrobial effects and improved safety profiles, as well as the integration of personalized medicine approaches to optimize patient outcomes. Full article

(This article belongs to the Special Issue Clinical Guidelines and Real Practice of Antimicrobial Pharmacotherapy)

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18 pages, 1528 KiB

Open AccessArticle

Evaluation of the Bacterial Infections and Antibiotic Prescribing Practices in the Intensive Care Unit of a Clinical Hospital in Romania

by Sándor Szabó, Bogdan Feier, Alina Mărginean, Andra-Elena Dumitrana, Simona Ligia Costin, Cecilia Cristea and Sorana D. Bolboacă

Antibiotics 2025, 14(1), 64; https://doi.org/10.3390/antibiotics14010064 - 9 Jan 2025

Abstract

Introduction: Healthcare-associated infections (HAIs) are associated with increased mortality, antimicrobial resistance, and high antibiotic use. Methods: The characteristics of bacterial resistance and antibiotic consumption in the intensive care unit (ICU) of a clinical hospital in Romania were evaluated. Demographic data of patients, [...] Read more.

Introduction: Healthcare-associated infections (HAIs) are associated with increased mortality, antimicrobial resistance, and high antibiotic use. Methods: The characteristics of bacterial resistance and antibiotic consumption in the intensive care unit (ICU) of a clinical hospital in Romania were evaluated. Demographic data of patients, identified bacteria, antibiotics administered, and their sensitivity profiles were collected and analyzed. Results: One hundred and twenty-five patients, with a median age of 68 years, mostly male (60%), were included in the study. More than one-third of the patients died. The deceased patients were older (median age of 74 years), had longer hospitalization (median of 9 days) and bacteria detected (55.3%), and had higher antibiotic consumption than the discharged patients. The most frequent bacteria identified in our cohort were Acinetobacter baumannii, Klebsiella pneumoniae, and Pseudomonas aeruginosa in deceased patients and Klebsiella pneumoniae, Escherichia coli, Staphylococcus hemolyticus, and Enterococcus faecalis in the survived group. The top three antibiotics used were ceftriaxone, metronidazole, and meropenem. Resistance to antibiotics was observed in 44.3% of the deceased group and 37.5% of patients who were discharged (χ² = 5.5, p = 0.0628). Discussion: A positive monotonic association was observed between the number of hospitalization days and the number of antibiotic doses, with a higher correlation coefficient for deceased patients (0.6327, p < 0.0001) than in survived group (0.4749, p < 0.0001). Conclusions and Future Trends: This study provides a real picture of HAIs, the characteristics of bacteria, and the consumption of antibiotics in an ICU of a clinical hospital in Romania. The data obtained are similar to those from other international studies, but further studies are needed to reflect the real situation in Romania. Full article

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(a) Distribution of collected biological samples (38 deceased patients and 87 who survived); (b) distribution of bacteria per group expressed as the number of positive cases per number of eligible cases, considering that the same patient can have more than one bacterium). Full article ">Figure 2
Distribution of number of hospitalization days by number of biological samples (post hoc analysis: 0 vs. 3 p = 0.0007, 0 vs. 4 p < 0.0001, 1 vs. 4 p = 0.0069). Dots represent the raw data, the box middle line is the median, the boxes are the first, and the third quartile and the wickers are the minimum and maximum (excluding the outliers). Colors represent the distribution of the length of hospital stay for each number of biological samples. Full article ">Figure 3
Distribution of hospitalization length and number of identified bacteria by groups: (a) deceased, (b) survived. Dots represent the raw data, the box middle line is the median, the boxes are the first, and the third quartile and the wickers are the minimum and maximum (excluding the outliers). Colors represent the distribution of the length of hospital stay for each number of identified bacteria. Full article ">Figure 4
Distribution of number of antibiotic doses and number of identified bacteria by groups: (a) deceased and (b) survived. Dots represent the raw data, the box middle line is the median, the boxes are the first, and the third quartile and the wickers are the minimum and maximum (excluding the outliers). Colors represent the distribution of antibiotic doses for each number of biological sample. Full article ">Figure 5
Distribution of number of antibiotics doses and number of biological samples by groups: (a) deceased and (b) survived. Dots represent the raw data, the box middle line is the median, the boxes are the first, and the third quartile and the wickers are the minimum and maximum (excluding the outliers). Colors represent the distribution of antibiotic doses for each number of biological sample. Full article ">Figure 6
The matrix of bacteria by antibiotic resistance. A specific color was used for a specific number of antibiotic resistances. Grey background indicates the absence of resistance. Full article ">

43 pages, 4242 KiB

Open AccessReview

Unseen Enemy: Mechanisms of Multidrug Antimicrobial Resistance in Gram-Negative ESKAPE Pathogens

by Giedrė Valdonė Sakalauskienė, Lina Malcienė, Edgaras Stankevičius and Aurelija Radzevičienė

Antibiotics 2025, 14(1), 63; https://doi.org/10.3390/antibiotics14010063 - 9 Jan 2025

Abstract

Multidrug antimicrobial resistance (AMR) represents a formidable challenge in the therapy of infectious diseases, triggered by the particularly concerning gram-negative Enterococcus faecium, Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa, and Enterobacter spp. (ESKAPE) pathogens. Designated as a [...] Read more.

Multidrug antimicrobial resistance (AMR) represents a formidable challenge in the therapy of infectious diseases, triggered by the particularly concerning gram-negative Enterococcus faecium, Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa, and Enterobacter spp. (ESKAPE) pathogens. Designated as a “priority” in 2017, these bacteria continue to pose a significant threat in 2024, particularly during the worldwide SARS-CoV-2 pandemic, where coinfections with ESKAPE members contributed to worsened patient outcomes. The declining effectiveness of current treatments against these pathogens has led to an increased disease burden and an increase in mortality rates globally. This review explores the sophisticated mechanisms driving AMR in gram-negative ESKAPE bacteria, focusing on Acinetobacter baumannii, Klebsiella pneumoniae, Pseudomonas aeruginosa, and Enterobacter spp. Key bacterial mechanisms contributing to resistance include limitations in drug uptake, production of antibiotic-degrading enzymes, alterations in drug target sites, and enhanced drug efflux systems. Comprehending these pathways is vital for formulating innovative therapeutic strategies and tackling the ongoing threat posed by these resistant pathogens. Full article

(This article belongs to the Topic Challenges and Future Prospects of Antibacterial Therapy)

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14 pages, 2557 KiB

Open AccessArticle

Detection of Delafloxacin Resistance Mechanisms in Multidrug-Resistant Klebsiella pneumoniae

by András Kubicskó, János Juhász, Katalin Kamotsay, Dora Szabo and Béla Kocsis

Antibiotics 2025, 14(1), 62; https://doi.org/10.3390/antibiotics14010062 - 9 Jan 2025

Abstract

Background: In this study, the mechanisms implicated in delafloxacin resistance in Klebsiella pneumoniae strains were investigated. Delafloxacin is a novel, broad-spectrum fluoroquinolone that has been approved for clinical application. Methods: In our study, 43 K. pneumoniae strains were assessed, antimicrobial susceptibility testing was [...] Read more.

Background: In this study, the mechanisms implicated in delafloxacin resistance in Klebsiella pneumoniae strains were investigated. Delafloxacin is a novel, broad-spectrum fluoroquinolone that has been approved for clinical application. Methods: In our study, 43 K. pneumoniae strains were assessed, antimicrobial susceptibility testing was performed via the broth microdilution method, and the minimum inhibitory concentration (MIC) values for ciprofloxacin, delafloxacin, levofloxacin, moxifloxacin, ceftazidime, cefotaxime, and imipenem were determined. Four delafloxacin-resistant K. pneumoniae strains were selected for whole-genome sequencing (WGS). Results: The MIC50 values for the 43 K. pneumoniae strains were as follows: ciprofloxacin 0.5 mg/L, levofloxacin 0.25 mg/L, moxifloxacin 0.5 mg/L, and delafloxacin 0.25 mg/L. All four selected delafloxacin-resistant K. pneumoniae strains showed extended-spectrum beta-lactamase production, and one strain exhibited carbapenem resistance. WGS enabled us to determine the sequence types (STs) of these strains, namely, ST307 (two strains), ST377, and ST147. Multiple mutations in quinolone-resistance-determining regions (QRDRs) were detected in all the delafloxacin-resistant K. pneumoniae strains; specifically, gyrA Ser83Ile and parC Ser80Ile were uniformly present in the strains of ST307 and ST147. However, in the ST377 strain, gyrA Ser83Tyr, Asp87Ala, and parC Ser80Ile, amino acid substitutions were detected. We also identified OqxAB and AcrAB efflux pumps in all delafloxacin-resistant K. pneumoniae strains. The association between beta-lactamase production and delafloxacin resistance was determined; specifically, CTX-M-15 production was detected in the ST147, ST307, and ST377 strains. Moreover, NDM-1 was detected in ST147. Conclusions: We conclude that multiple mutations in QRDRs, in combination with OqxAB and AcrAB efflux pumps, achieved delafloxacin resistance in K. pneumoniae. In our study, we report on NDM-1-producing K. pneumoniae ST147 in Hungary. Full article

(This article belongs to the Special Issue Antimicrobial Resistance Genes: Spread and Evolution)

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Distribution of MIC values for ciprofloxacin, levofloxacin, moxifloxacin, and delafloxacin among the 43 K. pneumoniae strains. Breakpoints are shown for ciprofloxacin (C), levofloxacin (L), moxifloxacin (M), and delafloxacin (D). EUCAST breakpoints were used for ciprofloxacin, levofloxacin, and moxifloxacin. In the case of delafloxacin, the FDA breakpoint was applied. Full article ">Figure 2
Distribution of MIC values for cefotaxime, ceftazidime, and imipenem among the 43 K. pneumoniae strains. Breakpoints are shown for cefotaxime (Ctx), ceftazidime (Caz), and imipenem (Imi). EUCAST breakpoints were used for cefotaxime, ceftazidime, and imipenem. Full article ">Figure 3
Genome characteristics of the NDM-1-producing K. pneumoniae ST147 strain. Major resistance genes are indicated in the figure. The circos plot shows the GC content skew in the inner circle histograms, the contigs (with grey arrows), and the positions of the detected resistance genes. Full article ">Figure 4
The wgMLST of four delafloxacin-resistant K. pneumoniae strains. Each circle indicates a K. pneumoniae strain. Lines between the circles denote differences in the allelic variant between the clones. Each clone is shown in a different color. Full article ">Figure 5
Role of amino acid substitutions in gyrase and topoisomerase enzymes in correlation with the action of delafloxacin. This figure illustrates the substitution of serine to isoleucine (a), the substitution of aspartate to alanine (b), and the substitution of serine to tyrosine (c) in correlation with the action of delafloxacin. Full article ">Figure 5 Cont.
Role of amino acid substitutions in gyrase and topoisomerase enzymes in correlation with the action of delafloxacin. This figure illustrates the substitution of serine to isoleucine (a), the substitution of aspartate to alanine (b), and the substitution of serine to tyrosine (c) in correlation with the action of delafloxacin. Full article ">

25 pages, 2475 KiB

Open AccessArticle

Green Tea Extract (Theaceae; Camellia sinensis L.): A Promising Antimicrobial, Anti-Quorum Sensing and Antibiofilm Candidate Against Multidrug-Resistant Campylobacter Species

by Mona S. Emara, Ahmed M. Ammar, Ashraf M.O. Abdelwahab, Attia A. Elgdawy, Adel Abdelkhalek, Elena Pet, Gabi Dumitrescu, Mirela Ahmadi and Norhan K. Abd El-Aziz

Antibiotics 2025, 14(1), 61; https://doi.org/10.3390/antibiotics14010061 - 9 Jan 2025

Abstract

Background: Thermophilic Campylobacter species are among the main culprits behind bacterial gastroenteritis globally and have grown progressively resistant to clinically important antimicrobials. Many studies have been carried out to explore innovative and alternative strategies to control antibiotic-resistant campylobacters in animal reservoirs and human [...] Read more.

Background: Thermophilic Campylobacter species are among the main culprits behind bacterial gastroenteritis globally and have grown progressively resistant to clinically important antimicrobials. Many studies have been carried out to explore innovative and alternative strategies to control antibiotic-resistant campylobacters in animal reservoirs and human hosts; however, limited studies have been performed to develop efficient control schemes against Campylobacter biofilms. Methods: This study investigated the antimicrobial and antibiofilm activities of some herbal extracts against multidrug-resistant (MDR) Campylobacter species recovered from different sources using phenotypic and molecular techniques. Results: The overall Campylobacter species prevalence was 21.5%, representing 15.25% and 6.25% for C. jejuni and C. coli, respectively. Regarding C. jejuni, the highest resistance rate was observed for amoxicillin–clavulanic acid and colistin (85.25% each), followed by cefotaxime (83.61%) and tetracycline (81.97%), whereas C. coli isolates showed absolute resistance to cefotaxime followed by erythromycin (92%) and colistin (88%). Remarkably, all Campylobacter isolates were MDR with elevated multiple antimicrobial resistance (MAR) indices (0.54–1). The antimicrobial potentials of green tea (Camellia sinensis), rosemary (Rosmarinus officinalis) and ginger (Zingiber officinale) extracts against MDR Campylobacter isolates were assessed by the disk diffusion assay and broth microdilution technique. Green tea extract showed a marked inhibitory effect against tested isolates, exhibiting growth inhibition zone diameters of 8 to 38 mm and a minimum inhibitory concentration (MIC) range of 1.56–3.12 mg/mL, unlike the rosemary and ginger extracts. Our findings reveal a respectable antibiofilm activity (>50% biofilm formation inhibition) of green tea against the preformed biofilms of Campylobacter isolates. Furthermore, real-time quantitative polymerase chain reaction (RT-qPCR) results showed a significant decrease (p < 0.05) in the expression levels of biofilm biosynthesis gene and its regulator (FlaA and LuxS, respectively) in Campylobacter isolates treated with the green tea extract in comparison with untreated ones. Conclusion: This is the first in vitro approach that has documented the inhibitory activity of green tea extract against MDR-biofilm-producing Campylobacter species isolated from different sources. Further in vivo studies in animals’ models should be performed to provide evidence of concept for the implementation of this alternative candidate for the mitigation of MDR Campylobacter infections in the future. Full article

(This article belongs to the Special Issue Antimicrobial and Antibiofilm Activity by Natural Compounds)

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The heatmap illustrates the antimicrobial resistance of Campylobacter species recovered from different sources. Dark colors refer to the antimicrobials displaying high resistance levels and light colors refers to the antimicrobials displaying low resistance. Color bar on the right side indicates color intensity. AMA, antimicrobial agent; P, penicillin; SAM, ampicillin–sulbactam; AMC, amoxicillin–clavulanic acid; E, erythromycin; TL, tylosin; CT, colistin; C, chloramphenicol; CTX, cefotaxime; TE, tetracycline; CN, gentamycin; CIP, ciprofloxacin; NOR, norfloxacin; SXT, sulfamethoxazole–trimethoprim. *** indicate significant differences at p < 0.05. Full article ">Figure 2
LC-ESI-MS/MS multiple reaction monitoring (MRM) chromatogram of the standard sample (a) and green tea extract sample (b). Different colours indicate extract constituents, and each analyte has two fragments generated at the same extension time. The scientific notation (i.e., 1.0e+6 is equal to 1 × 106) could be converted into decimal notation using the following website: <a href="https://converthere.com/numbers/2.3e+7-written-out" target="_blank">https://converthere.com/numbers/2.3e+7-written-out</a> (accessed on 2 December 2024). Full article ">Figure 3
Catechins (a) and epigallocatechin gallate [M-H2O-H]- (EGCG) (b) identified in the green tea extract by LC-ESI-MS/MS in negative mode. The scientific notation (i.e., 1.0e6 is equal to 1 × 106) could be converted into decimal notation using the following website: <a href="https://converthere.com/numbers/2.3e+7-written-out" target="_blank">https://converthere.com/numbers/2.3e+7-written-out</a> (accessed on 2 December 2024). Full article ">Figure 4
Epicatechin–gallate (ECG) (a) and epigallocatechine (EGC) (b) identified in the green tea extract by LC-ESI-MS/MS in positive mode. The scientific notation (i.e., 1e4 is equal to 1 × 104) could be converted into decimal notation using the following website: <a href="https://converthere.com/numbers/2.3e+7-written-out" target="_blank">https://converthere.com/numbers/2.3e+7-written-out</a> (accessed on 2 December 2024). Full article ">Figure 5
Fold changes in the expression levels of examined biofilm genes after treatment of Campylobacter isolates with sub-inhibitory concentrations of green tea extract. a–c Values of the same row with different superscripts are significantly different (p < 0.05). Full article ">

20 pages, 1567 KiB

Open AccessReview

The Role of ChatGPT and AI Chatbots in Optimizing Antibiotic Therapy: A Comprehensive Narrative Review

by Ninel Iacobus Antonie, Gina Gheorghe, Vlad Alexandru Ionescu, Loredana-Crista Tiucă and Camelia Cristina Diaconu

Antibiotics 2025, 14(1), 60; https://doi.org/10.3390/antibiotics14010060 - 9 Jan 2025

Abstract

Background/Objectives: Antimicrobial resistance represents a growing global health crisis, demanding innovative approaches to improve antibiotic stewardship. Artificial intelligence (AI) chatbots based on large language models have shown potential as tools to support clinicians, especially non-specialists, in optimizing antibiotic therapy. This review aims to [...] Read more.

Background/Objectives: Antimicrobial resistance represents a growing global health crisis, demanding innovative approaches to improve antibiotic stewardship. Artificial intelligence (AI) chatbots based on large language models have shown potential as tools to support clinicians, especially non-specialists, in optimizing antibiotic therapy. This review aims to synthesize current evidence on the capabilities, limitations, and future directions for AI chatbots in enhancing antibiotic selection and patient outcomes. Methods: A narrative review was conducted by analyzing studies published in the last five years across databases such as PubMed, SCOPUS, Web of Science, and Google Scholar. The review focused on research discussing AI-based chatbots, antibiotic stewardship, and clinical decision support systems. Studies were evaluated for methodological soundness and significance, and the findings were synthesized narratively. Results: Current evidence highlights the ability of AI chatbots to assist in guideline-based antibiotic recommendations, improve medical education, and enhance clinical decision-making. Promising results include satisfactory accuracy in preliminary diagnostic and prescriptive tasks. However, challenges such as inconsistent handling of clinical nuances, susceptibility to unsafe advice, algorithmic biases, data privacy concerns, and limited clinical validation underscore the importance of human oversight and refinement. Conclusions: AI chatbots have the potential to complement antibiotic stewardship efforts by promoting appropriate antibiotic use and improving patient outcomes. Realizing this potential will require rigorous clinical trials, interdisciplinary collaboration, regulatory clarity, and tailored algorithmic improvements to ensure their safe and effective integration into clinical practice. Full article

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Conceptual Framework of AI Chatbot Integration into Antibiotic Therapy Decision-Making. This schematic illustrates how AI-driven chatbots, integrated with clinical data sources and supported by human expertise, can guide antibiotic prescribing. Starting from the patient’s presentation of acute infection, non-specialist clinicians access the chatbot to receive evidence-based recommendations derived from patient records, local resistance patterns, and established guidelines. Infectious disease specialists and pharmacists review the chatbot’s suggestions, providing necessary oversight to refine treatment plans and ensure adherence to stewardship principles. Feedback loops, including outcome monitoring and expert input, continuously inform algorithm refinement. In this way, AI chatbots serve as adjunct decision-support tools, working in tandem with human judgment to optimize antibiotic therapy and improve patient outcomes. Full article ">Figure 2
Comparison of AMR-Attributable Death Rates per 100,000 in 2021 and 2050 by region. This figure compares AMR-attributable death rates per 100,000 population across global regions for the years 2021 (yellow) and 2050 (orange), highlighting significant regional disparities and projected trends The data was adapted from [<a href="#B21-antibiotics-14-00060" class="html-bibr">21</a>]. Full article ">Figure 3
Privacy and Compliance Measures in Federated Learning for AI Models. The data flow diagram illustrates how patient data is securely processed and integrated into an AI model using federated learning, ensuring compliance with privacy regulations like GDPR and HIPAA. It highlights each step in the data pipeline, ensuring transparency and accountability in data handling. Full article ">

18 pages, 5416 KiB

Open AccessArticle

Bacteria-Inspired Synthesis of Silver-Doped Zinc Oxide Nanocomposites: A Novel Synergistic Approach in Controlling Biofilm and Quorum-Sensing-Regulated Virulence Factors in Pseudomonas aeruginosa

by Abirami Karthikeyan, Manoj Kumar Thirugnanasambantham, Fazlurrahman Khan and Arun Kumar Mani

Antibiotics 2025, 14(1), 59; https://doi.org/10.3390/antibiotics14010059 - 9 Jan 2025

Abstract

Multidrug-resistant Pseudomonas aeruginosa infections pose a critical challenge to healthcare systems, particularly in nosocomial settings. This drug-resistant bacterium forms biofilms and produces an array of virulent factors regulated by quorum sensing. In this study, metal-tolerant bacteria were isolated from a metal-contaminated site and [...] Read more.

Multidrug-resistant Pseudomonas aeruginosa infections pose a critical challenge to healthcare systems, particularly in nosocomial settings. This drug-resistant bacterium forms biofilms and produces an array of virulent factors regulated by quorum sensing. In this study, metal-tolerant bacteria were isolated from a metal-contaminated site and screened for their ability to synthesize multifunctional nanocomposites (NCs). Rapid color changes in the reaction solution evidenced the biotransformation process. The potent isolated Bacillus cereus SASAK, identified via 16S rRNA sequencing and deposited in GenBank under accession number MH885570, facilitated the microbial-mediated synthesis of ZnO nanoparticles and silver-doped ZnO NCs. These biogenic nanocomposites were characterized using UV-VIS-NIR spectroscopy, FTIR, XRD, zeta potential, HRTEM, FESEM, and EDX analyses. At a sub-MIC concentration of 100 µg/mL, 2% Ag-ZnO NCs effectively inhibited virulent factor production and biofilm formation in P. aeruginosa without affecting bacterial growth. Notably, there was a significant reduction in violacein pigment (96.25%), swarming motility, and pyocyanin concentration (1.87 µg/mL). Additionally, biofilm formation (81.1%) and EPS production (83.9%) using P. aeruginosa were substantially hindered, along with reduced extracellular protease activity, as indicated by zone formation (from 2.3 to 1.8 cm). This study underscores the potential of Ag-ZnO NCs as promising agents for combating quorum sensing-mediated virulence in chronic infections caused by multidrug-resistant P. aeruginosa. Full article

(This article belongs to the Special Issue Antimicrobial Resistance in Biofilm-Associated Infections)

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Screening and molecular identification of potent bacterial strain for the synthesis of Ag-ZnO NCs. (A) Screening of isolated bacteria (SASAK) for the synthesis of Ag-ZnO NCs and bacterial-inspired synthesis of Ag-ZnO NCs, (B) initial color change, (C) final color change, and (D) phylogenetic tree of isolated bacteria (Bacillus cereus SASAK). Full article ">Figure 2
UV-vis NIR spectrum of undoped ZnO NPs and Ag-ZnO NCs. (A) Bandgap spectra and (B) UV-vis absorption spectra. Full article ">Figure 3
Characterization of NCs (A). Histogram showing the particle size analysis of 2% Ag-ZnO NCs, (B) the zeta potential distributions of 2% Ag-ZnO NCs, (C) the XRD spectra of undoped ZnO NPs and Ag-ZnO NCs, and (D) the FTIR spectrum of undoped ZnO NPs and Ag-ZnO NCs. Full article ">Figure 4
Morphological and elemental composition of 2% Ag-ZnO NCs (A). FESEM analysis (B) and (C) size analysis of NCs using HRTEM, and (D) EDX analysis of NCs. Full article ">Figure 5
(A) Antibiotic susceptibility test against the hospital-acquired test pathogen P. aeruginosa; (B) the effect of pure and Ag-ZnO NCs on the cell viability of P. aeruginosa; and (C) the determination of the MIC and sub-MIC of 2% Ag-ZnO NCs, including the positive control (without NCs) and negative control (0.5 µg/mL of colistin). Full article ">Figure 6
Antiquorum sensing activity of NCs. (A) The inhibition of the violacein pigment in bioreporter strain C. violaceum using 2% Ag-ZnO NCs, (B) the pyocyanin inhibition assay, and (C) the inhibition of biofilm formation using undoped ZnO NPs and 2% Ag-ZnO NCs using the Congo red assay and tube assay, and (D) the inhibition of EPSs using undoped ZnO NPs and 2% Ag-ZnO NCs. Full article ">Figure 7
(A) The inhibition of swarming motility and (B) protease inhibition assay. Full article ">

14 pages, 3295 KiB

Open AccessArticle

Use of Antibiotics in Companion Animals from 133 German Practices from 2018 to 2023

by Roswitha Merle, Leonie Feuer, Katharina Frenzer, Jan-Lukas Plenio, Astrid Bethe, Nunzio Sarnino, Antina Lübke-Becker and Wolfgang Bäumer

Antibiotics 2025, 14(1), 58; https://doi.org/10.3390/antibiotics14010058 - 9 Jan 2025

Abstract

Background/Objectives: While antibiotic usage in farm animals has been systematically monitored and reduced in many countries, including Germany, data on companion animals such as dogs and cats remain scarce. To address this gap, a study was conducted in Germany to analyze patterns [...] Read more.

Background/Objectives: While antibiotic usage in farm animals has been systematically monitored and reduced in many countries, including Germany, data on companion animals such as dogs and cats remain scarce. To address this gap, a study was conducted in Germany to analyze patterns of antibiotic use in dogs and cats. Methods: Antibiotic usage data were obtained from debevet, a cloud-based veterinary practice management software based in Berlin, Germany. Practices with fewer than 100 patients were excluded, and data from 2018 to 2022 were analyzed. Results: The analysis included 477,310 consultations of 78,381 dogs and 241,532 consultations of 55,729 cats across 133 veterinary practices. Antibiotics were used in 12.9% of dog consultations and 22.5% of cat consultations, with substantial variation across practices. Aminopenicillins, particularly amoxicillin, were the most commonly used antibiotics, while the highest-priority critically important antibiotics (HPCIAs) accounted for 12.4% of treatments. Follow-up treatments led to changes in antibiotic substances in 9.3% of cases, often within the first two days. Indications varied by species, with respiratory issues more frequent in cats and orthopedic problems in dogs. Body weight and breed characteristics influenced the likelihood of antibiotic treatment, with short-nosed breeds showing higher odds. Conclusions: The routine data analysis provided valuable insights into antibiotic use in dogs and cats, enabling tracking trends across species and indications over time. While some specific information was missing, the invoicing data’s completeness, the cost-effectiveness of their use, and their unbiased nature make them a robust tool for monitoring and informing legislative changes. Full article

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

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Percentage of consultations with antibiotic treatment per veterinary practice. The ● represents an outlier outside the range of 1.5 standard deviations. Full article ">Figure 2
Histogram of time to follow-up consultations for dogs and cats, categorized by consultations with or without treatment with antibiotics. Full article ">Figure 3
Percentage of consultations with antibiotic treatment per substance class in dogs and cats (145,846 applications or deliveries). Highlighted are substance groups that belong to the highest priority critically important antibiotics. Full article ">Figure 4
Percentage of consultations per indication group in cats and dogs. Full article ">Figure 5
Percentage of consultations with antibiotic treatment per indication group in cats and dogs. Full article ">Figure 6
Percentage of visits with antibiotic treatment in cats and dogs over age. Displayed are the estimates of a non-linear regression model with natural splines, 4 degrees of freedom, and a 95% confidence interval; n = 610,854 consultations. Full article ">Figure 7
Influence of body weight on the probability of being treated with antibiotics in dogs (n = 477,310 consultations). Displayed are the estimates of a non-linear regression model with natural splines, 4 degrees of freedom, and a 95% confidence interval. Full article ">

30 pages, 2107 KiB

Open AccessReview

Harnessing Non-Antibiotic Strategies to Counter Multidrug-Resistant Clinical Pathogens with Special Reference to Antimicrobial Peptides and Their Coatings

by Shyam Kumar Mishra, Tanzina Akter, Umme Laila Urmi, George Enninful, Manjulatha Sara, Jiawei Shen, Dittu Suresh, Liangjun Zheng, Elias Shiferaw Mekonen, Binod Rayamajhee, Francesco M. Labricciosa, Massimo Sartelli and Mark Willcox

Antibiotics 2025, 14(1), 57; https://doi.org/10.3390/antibiotics14010057 - 9 Jan 2025

Abstract

Antimicrobial resistance is a critical global challenge in the 21st century, validating Sir Alexander Fleming’s warning about the misuse of antibiotics leading to resistant microbes. With a dwindling arsenal of effective antibiotics, it is imperative to concentrate on alternative antimicrobial strategies. Previous studies [...] Read more.

Antimicrobial resistance is a critical global challenge in the 21st century, validating Sir Alexander Fleming’s warning about the misuse of antibiotics leading to resistant microbes. With a dwindling arsenal of effective antibiotics, it is imperative to concentrate on alternative antimicrobial strategies. Previous studies have not comprehensively discussed the advantages and limitations of various strategies, including bacteriophage therapy, probiotics, immunotherapies, photodynamic therapy, essential oils, nanoparticles and antimicrobial peptides (AMPs) within a single review. This review addresses that gap by providing an overview of these various non-antibiotic antimicrobial strategies, highlighting their pros and cons, with a particular emphasis on antimicrobial peptides (AMPs). We explore the mechanism of action of AMPs against bacteria, viruses, fungi and parasites. While these peptides hold significant promise, their application in mainstream drug development is hindered by challenges such as low bioavailability and potential toxicity. However, advancements in peptide engineering and chemical modifications offer solutions to enhance their clinical utility. Additionally, this review presents updates on strategies aimed at improving the cost, stability and selective toxicity of AMPs through the development of peptidomimetics. These molecules have demonstrated effective activity against a broad range of pathogens, making them valuable candidates for integration into surface coatings to prevent device-associated infections. Furthermore, we discuss various approaches for attaching and functionalising these peptides on surfaces. Finally, we recommend comprehensive in vivo studies to evaluate the efficacy of AMPs and their mimetics, investigate their synergistic combinations with other molecules and assess their potential as coatings for medical devices. Full article

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12 pages, 1140 KiB

Open AccessArticle

Plasma Concentrations of Benzylpenicillin and Cloxacillin in Infective Endocarditis—With Special Reference to Delayed Hypersensitivity Reactions

by Malin Hägglund, Ulrika Snygg-Martin, Lars Olaison, Michael Stofkoper, Bert Ove Larsson and Magnus Brink

Antibiotics 2025, 14(1), 56; https://doi.org/10.3390/antibiotics14010056 (registering DOI) - 9 Jan 2025

Abstract

Background: Current antibiotic regimens for infective endocarditis (IE) are effective but pose a high risk of delayed hypersensitivity reactions (DHR). Dose adjustments guided by therapeutic drug monitoring (TDM) could mitigate these risks while maintaining treatment efficacy. This study aimed to investigate the plasma [...] Read more.

Background: Current antibiotic regimens for infective endocarditis (IE) are effective but pose a high risk of delayed hypersensitivity reactions (DHR). Dose adjustments guided by therapeutic drug monitoring (TDM) could mitigate these risks while maintaining treatment efficacy. This study aimed to investigate the plasma concentration of benzylpenicillin and cloxacillin in patients with IE and explore associations between antibiotic concentrations and DHR. Methods: Plasma concentrations of benzylpenicillin and cloxacillin were measured as centre (midpoint concentrations between consecutive doses) and trough values during the first and third weeks of treatment in patients with IE. Patient characteristics and outcomes, including DHR, were documented. Results: A total of 55 patients were included, with 37 patients (67%) receiving benzylpenicillin and 18 (33%) receiving cloxacillin. The 90-day mortality rate was 3%. Both centre and trough concentration exhibited substantial interpatient variation for the two antibiotics, while intra-patient variability between weeks 1 and 3 remained low for most patients. Kidney function could explain, at best, 54% of the variation, and a multiple regression model including kidney function, body mass index, age, and albumin explained up to 68% of the variation for benzylpenicillin. There was no relation between high plasma concentration and the prevalence of DHR; conversely, we observed a tendency of low plasma concentrations in these patients. Conclusions: This study revealed significant interindividual variation in plasma concentrations for both studied penicillins. TDM might be useful in situations where concentrations are hard to predict, such as severe obesity or kidney failure. Additionally, we found no indication that high plasma concentrations are related to the prevalence of DHR. Full article

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