Antibiotics

2 pages, 138 KiB

Open AccessReply

Reply to Canceill et al. Analyzing the Clinical Potential of Cold Atmospheric Plasma in Dentistry as an Alternative to Antibiotic Therapy. Comment on “Gross et al. Guided Plasma Application in Dentistry—An Alternative to Antibiotic Therapy. Antibiotics 2024, 13, 735”

by Tara Gross, Loic Alain Ledernez, Laurent Birrer, Michael Eckhard Bergmann and Markus Jörg Altenburger

Antibiotics 2025, 14(3), 327; https://doi.org/10.3390/antibiotics14030327 - 20 Mar 2025

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Thank you for your interest and your thoughtful comment on our paper “Guided Plasma Application in Dentistry—An Alternative to Antibiotic Therapy” [...] Full article

14 pages, 381 KiB

Open AccessArticle

Unfavorable Outcomes and Their Risk Factors in Hospitalized Patients with Staphylococcus aureus Bacteremia in the US: A Multicenter Retrospective Cohort Study, 2020–2022

by Marya D. Zilberberg, Brian H. Nathanson, Rolf Wagenaar, Jan Posthumus and Andrew F. Shorr

Antibiotics 2025, 14(3), 326; https://doi.org/10.3390/antibiotics14030326 - 20 Mar 2025

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Abstract

Background: In the US, 120,000 cases of Staphylococcus aureus bacteremia (SAB) occur annually. Apart from mortality, little is known about other unfavorable outcomes (UOs). We developed a multifaceted definition for UOs in SAB and examined their incidence and predictors. Methods: We [...] Read more.

Background: In the US, 120,000 cases of Staphylococcus aureus bacteremia (SAB) occur annually. Apart from mortality, little is known about other unfavorable outcomes (UOs). We developed a multifaceted definition for UOs in SAB and examined their incidence and predictors. Methods: We conducted a multicenter (~300 hospitals) retrospective cohort study between 2020 and 2022 of adult hospitalized patients with at least one blood culture (BC) positive for S. aureus. UOs were any of the following: hospital mortality, antibiotic escalation, persistently positive BCs, prolonged post-infection length of stay (LOS), 30-day readmission, and disease worsening. We compared the group with UOs to favorable outcomes (FOs). Regression models identified predictors of UOs. Results: Among 4080 patients with SAB, 2427 (59.5%) experienced a UO, most commonly 30-day readmission (42.0%) and antibiotic escalation (37.7%). Those with UOs more frequently had septic shock at admission (5.7% vs. 1.2%), requiring the ICU (18.8% vs. 14.7%) and dialysis (4.4% vs. 1.9%) prior to SAB onset. Community-onset SAB predominated in both groups, with more complicated SAB in the UO group (39.8% vs. 22.3%). Vancomycin use was similar, while daptomycin was more common in the UO group (8.5% vs. 3.0%). Variables with the highest odds ratios predicting a UO were septic shock on admission (3.498, 95% CI 2.145, 5.704), empiric daptomycin (2.723, 95% CI 1.943, 3.821), and complicated SAB (2.476, 95% CI 2.047, 2.994). Conclusions: UOs occur frequently in the setting of SAB. A broader perspective exploring issues other than mortality demonstrates the substantial implications of SAB both for patients and healthcare systems. Select clinical variables are associated with UOs, some of which may not be modifiable. Full article

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15 pages, 1221 KiB

Open AccessArticle

Effects of Anti-Pseudomonal Agents, Individually and in Combination, With or Without Clarithromycin, on Growth and Biofilm Formation by Antibiotic-Susceptible and -Resistant Strains of Pseudomonas aeruginosa, and the Impact of Exposure to Cigarette Smoke Condensate

by Moloko C. Cholo, Charles Feldman, Ronald Anderson, Lebogang Sekalo, Naledi Moloko and Guy A. Richards

Antibiotics 2025, 14(3), 325; https://doi.org/10.3390/antibiotics14030325 - 19 Mar 2025

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Abstract

Background/Objectives: Pseudomonas aeruginosa (Psa) can circumvent antimicrobial chemotherapy, an ability enhanced by cigarette smoking (CS). This study probed potential benefits of combinations of anti-pseudomonal agents, and potential augmentation by a macrolide, in the absence or presence of cigarette smoke condensate [...] Read more.

Background/Objectives: Pseudomonas aeruginosa (Psa) can circumvent antimicrobial chemotherapy, an ability enhanced by cigarette smoking (CS). This study probed potential benefits of combinations of anti-pseudomonal agents, and potential augmentation by a macrolide, in the absence or presence of cigarette smoke condensate (CSC). Methods: Two susceptible (WT: wild-type and DS: drug-sensitive) and one multidrug-resistant (MDR) strains of Psa were treated with amikacin, cefepime, and ciprofloxacin, individually and in combination, and with and without clarithromycin, followed by the measurement of planktonic growth and biofilm formation by spectrophotometry. Antibiotic interactions were determined using the fractional inhibitory concentration index (FICI) method. Effects on preformed biofilm density were measured following the addition of antibiotics: all procedures were performed in the absence and presence of CSC. Results: The minimal inhibitory concentrations (MICs) of the three agents ranged from 0.125 mg/L to 1 mg/L (WT and DS strains) and 16 mg/L to 64 mg/L (MDR strain), with all resistant to clarithromycin (125 mg/L). MIC values closely correlated with the antibiotic concentrations required to inhibit biofilm formation. FICI revealed synergism between most combinations, with augmentation by clarithromycin. Amikacin had the greatest effect on biofilm density, which was potentiated by combination with the other antibiotics, particularly clarithromycin. Exposure to CSC had variable, albeit modest, effects on bacterial growth and biofilm formation, but low concentrations increased biofilm mass and attenuated synergistic antimicrobial interactions and effects on biofilm density. Conclusions: Amikacin, cefepime, and ciprofloxacin, especially with clarithromycin, exhibit synergistic anti-pseudomonal activity and decrease preformed biofilm density. CSC attenuated these effects, illustrating the pro-infective potential of CS. Full article

(This article belongs to the Special Issue Antibiotics and Infectious Respiratory Diseases, 2nd Edition)

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22 pages, 11518 KiB

Open AccessArticle

Tackling Antimicrobial Resistance: A Sustainable Method for the Removal of Antibiotics from Water

by Lekan Abudu, Rutuja C. Bhosale, Joerg Arnscheidt, Svetlana Tretsiakova-McNally, Barry O’Hagan, David K. Adeyemi, Temilola Oluseyi, Luqman A. Adams and Heather M. Coleman

Antibiotics 2025, 14(3), 324; https://doi.org/10.3390/antibiotics14030324 - 19 Mar 2025

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Abstract

Introduction: The presence of antibiotic residues in the aquatic environment is a likely contributor to the current increase in antibiotic resistance, posing a significant threat to global health. This study investigated the use of a low-cost and sustainable material based on sawdust [...] Read more.

Introduction: The presence of antibiotic residues in the aquatic environment is a likely contributor to the current increase in antibiotic resistance, posing a significant threat to global health. This study investigated the use of a low-cost and sustainable material based on sawdust with the purpose of removing rifampicin residues from water. Methods: The sawdust was pretreated with 2M sulfuric acid and was characterized using Fourier Transform Infrared spectroscopy (FT-IR), a Mastersizer, scanning electron microscopy (SEM), an elemental analyser, and the pH point of zero charge (pH_pzc). The batch adsorption process was conducted using both raw and treated sawdust to determine the effect of contact time, temperature, pH, adsorbent dosage, and the initial concentration of antibiotic dissolved in water. Results and Discussion: The results revealed that the chemical pretreatment of raw sawdust significantly improved its adsorption capacity. The highest removal efficiency of 65% was achieved using an adsorbent dosage of 31.3 g/L. The thermodynamic studies demonstrated that the process was spontaneous and governed by physisorption within the studied temperature range (293.15 K–318.15 K), being more favourable at higher temperatures. The interactions between the functional groups of sawdust and the rifampicin molecules included electrostatic attraction, hydrogen bonding, and π-π interactions. Conclusions: This research highlights the potential of utilizing waste as a valuable and effective adsorbent of residual antibiotics from water, thus contributing to the sustainable practices of solid waste management and water treatment. Full article

(This article belongs to the Special Issue A One Health Approach to Antimicrobial Resistance, 2nd Edition)

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18 pages, 9659 KiB

Open AccessArticle

Whole Genome Analysis of Pediococcus acidilactici XJ-24 and Its Role in Preventing Listeria monocytogenes ATCC^® 19115^TM Infection in C57BL/6 Mice

by Weizhong Hu, Shuxin Zhou, Amel Ibrahim, Guannan Li, Sameh Awad, José Ramos-Vivas, Jianquan Kan and Muying Du

Antibiotics 2025, 14(3), 323; https://doi.org/10.3390/antibiotics14030323 - 19 Mar 2025

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Abstract

Background/Objectives: As probiotics gain prominence in the prevention and treatment of intestinal diseases, their protective effects against pathogens and influence on host health have drawn significant attention. This study investigates the genomic characteristics and functional potential of Pediococcus acidilactici XJ-24 (XJ-24) in the [...] Read more.

Background/Objectives: As probiotics gain prominence in the prevention and treatment of intestinal diseases, their protective effects against pathogens and influence on host health have drawn significant attention. This study investigates the genomic characteristics and functional potential of Pediococcus acidilactici XJ-24 (XJ-24) in the prevention of Listeria monocytogenes (LM) infection in mice. Methods/Results: Whole-genome analysis confirmed the safety and probiotic properties of XJ-24, including acid and bile salt tolerance, antimicrobial activity, and safety. In vivo, C57BL/6 mice challenges indicated that XJ-24 significantly reduced LM colonization, suppressed pro-inflammatory cytokines (IL-1β, IL-6, TNF-α, IFN-γ), alleviated colon and spleen tissue damage, and maintained intestinal barrier integrity by upregulating tight junction proteins (Occludin, Claudin-1, ZO-1). Moreover, XJ-24 modulated gut microbiota composition by increasing beneficial taxa while reducing harmful bacteria. Correlation analysis highlighted a positive association between Lachnospiraceae and tight junction proteins. Conclusions: These findings demonstrate the potential of XJ-24 as a functional probiotic for preventing LM infection and provide a basis for further clinical exploration. Full article

(This article belongs to the Special Issue Advances in Antimicrobial Strategies to Control Listeria in Food and Clinical Settings)

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18 pages, 449 KiB

Open AccessArticle

Antimicrobial Resistance and Mortality in Carbapenem-Resistant Pseudomonas aeruginosa Infections in Southern Thailand

by Parichart Chotimakorn, Sutthiporn Pattharachayakul, Yongyut Lertsrisatit, Wichai Santimaleeworagun, Pimpimon Tansakul, Mingkwan Yingkajorn, Sureerat Chelae, Rattanaruji Pomwised, Arnon Chukamnerd, Rosesathorn Soontarach and Sarunyou Chusri

Antibiotics 2025, 14(3), 322; https://doi.org/10.3390/antibiotics14030322 - 19 Mar 2025

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Abstract

Background/Objectives: Carbapenem-resistant Pseudomonas aeruginosa (CRPA) is an important pathogen associated with high mortality and treatment failure rates. We aimed to assess the susceptibility of CRPA to antipseudomonal agents, identify its resistance mechanisms, and evaluate clinical outcomes in a sample of CRPA isolates. [...] Read more.

Background/Objectives: Carbapenem-resistant Pseudomonas aeruginosa (CRPA) is an important pathogen associated with high mortality and treatment failure rates. We aimed to assess the susceptibility of CRPA to antipseudomonal agents, identify its resistance mechanisms, and evaluate clinical outcomes in a sample of CRPA isolates. Methods: This was an in vitro study of a clinical isolate of CRPA from hospitalized patients with CRPA infection and a retrospective observational study of these patients, who were diagnosed between 14 February 2021 and 10 August 2023 at Songklanagarind Hospital in Songkhla, Thailand. In vitro experiments were conducted to determine the minimum inhibitory concentrations (MICs) of the antipseudomonal agents using the broth microdilution method. Resistance mechanisms were assessed using the modified carbapenem inactivation method, combined disk tests, and quantitative real-time reverse transcription polymerase chain reaction. Results: A total of 140 CRPA isolates were analyzed. Both traditional and novel β-lactams had high MICs. The most common resistance mechanism was the upregulation of the MexAB-OprM efflux pump (81.3%), followed by the downregulation of the OprD porin (48.9%) and metallo-β-lactamase (MBL) production (45.0%), and the overexpression of bla_AmpC (41.0%). The 30-day all-cause mortality rate was 30.5%. The risk factors associated with 30-day mortality included a Charlson Comorbidity Index of ≥5 (OR: 3.43; 95% CI: 1.07–10.99; p = 0.03), sepsis (OR: 10.62; 95% CI: 1.26–89.44; p = 0.03), and septic shock (OR: 4.39; 95% CI: 1.67–11.55; p < 0.01). In contrast, receiving active documented therapy was significantly associated with reduced mortality (OR: 0.17; 95% CI: 0.04–0.74; p = 0.01). Conclusions: This study revealed higher MIC values of all β-lactams for CRPA, while colistin and amikacin remained effective. The resistance mechanisms included MexAB-OprM overexpression, OprD downregulation, MBL production, and bla_AmpC overexpression, with a higher prevalence of MBL than in other regions of Thailand. High 30-day mortality was associated with comorbidities, sepsis, and septic shock, but active therapy reduced mortality. Full article

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19 pages, 1642 KiB

Open AccessArticle

Antiparasitic and Antifungal Activities of Cetyl-Maritima, a New N-Cetyl-Modified Maritima Derivative

by Ibrahim S. Al Nasr, Jingyi Ma, Tariq A. Khan, Waleed S. Koko, Imen Ben Abdelmalek, Rainer Schobert, Wendy van de Sande and Bernhard Biersack

Antibiotics 2025, 14(3), 321; https://doi.org/10.3390/antibiotics14030321 - 19 Mar 2025

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Abstract

Background/Objectives: New drugs are urgently needed for the treatment of neglected tropical diseases including leishmaniasis and eumycetoma, as well as globally occurring parasitic diseases such as toxoplasmosis. Fragrances, both natural and synthetic, were shown to be a rich source for the development of [...] Read more.

Background/Objectives: New drugs are urgently needed for the treatment of neglected tropical diseases including leishmaniasis and eumycetoma, as well as globally occurring parasitic diseases such as toxoplasmosis. Fragrances, both natural and synthetic, were shown to be a rich source for the development of new anti-infectives and warrant deeper investigations. Exemplarily, we synthetically optimized the fragrance 4-(4,8-dimethyl-3,7-nonadienyl)-pyridine, a.k.a. Maritima, a pyridine derivative with marine odor. Methods: A new cationic N-cetyl-modified derivative of Maritima (dubbed Cetyl-Maritima), obtained by alkylation of Maritima, was tested for its activity against Madurella mycetomatis (M. mycetomatis) fungi, as well as against Toxoplasma gondii (T. gondii) and Leishmania major (L. major) protozoal parasites. Results: Cetyl-Maritima was found to be more strongly antifungal than the parent Maritima and a known antibiotic cetylpyridinium salt. Cetyl-Maritima also showed a similar activity against T. gondii parasites and, most notably, exhibited sub-micromolar activity against L. major amastigotes. Conclusions: The considerable antileishmanial activity of Cetyl-Maritima might lead to the development of a new potent and cost-effective drug candidate for the therapy of leishmaniasis and other infectious diseases caused by kinetoplastid parasites. Full article

(This article belongs to the Collection Synthetic and Natural Products-Based Antimicrobial and Antiparasitic Agents)

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11 pages, 580 KiB

Open AccessArticle

Evaluating Tuberculosis and Drug Resistance in Serbia: A Ten-Year Experience from a Tertiary Center

by Mihailo Stjepanovic, Snjezana Mijatovic, Nikola Nikolic, Nikola Maric, Goran Stevanovic, Ivan Soldatovic and Aleksandra Barac

Antibiotics 2025, 14(3), 320; https://doi.org/10.3390/antibiotics14030320 - 18 Mar 2025

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Abstract

Background: Tuberculosis (TB) remains a leading cause of mortality worldwide, particularly in low- and middle-income countries. The rise of multidrug-resistant TB (MDR-TB) poses significant challenges to global health. This study reviews the experience of the largest pulmonology center in Serbia, a country with [...] Read more.

Background: Tuberculosis (TB) remains a leading cause of mortality worldwide, particularly in low- and middle-income countries. The rise of multidrug-resistant TB (MDR-TB) poses significant challenges to global health. This study reviews the experience of the largest pulmonology center in Serbia, a country with low MDR-TB incidence, focusing on TB prevalence, resistance detection, and treatment strategies between 2012 and 2021. Methods: We retrospectively analyzed a total of 1239 patients who were diagnosed and treated for TB in the period from 2012 to 2021 at University Clinical Center of Serbia. Results: Drug resistance was identified in 21 patients (1.7%), with the highest resistance to rifampicin (1.4%) and isoniazid (1.3%). Pyrazinamide and streptomycin resistance were detected in only a few cases. Patients with resistant TB were younger on average, though the difference was not statistically significant (46.4 ± 19.1 vs. 53.6 ± 18.4, p = 0.079). Prior TB history was more frequent in the resistant group, almost reaching statistical significance (4 vs. 82, p = 0.052). Conclusions: These findings underscore the critical importance of sustained surveillance, particularly of latent and drug-resistant TB forms, in alignment with the World Health Organization’s (WHO) TB control strategy to preserve Serbia’s low-incidence status. Moreover, given Serbia’s strategic location on a major migration route, there is an elevated risk of new TB cases emerging and potential shifts in TB-drug-resistance patterns developing in the future. Full article

(This article belongs to the Special Issue Antibiotic Use and the Emergence of Antibiotic Resistance in Clinical Settings)

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12 pages, 248 KiB

Open AccessArticle

An Outbreak of Serratia marcescens in a Cardiothoracic Surgery Unit Associated with an Infected Solution of Pre-Prepared Syringes

by Maria Papagianni, Eleni Mylona, Sofia Kostourou, Chrysoula Kolokotroni, Dimitris Kounatidis, Natalia G. Vallianou and Vasileios Papastamopoulos

Antibiotics 2025, 14(3), 319; https://doi.org/10.3390/antibiotics14030319 - 18 Mar 2025

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Abstract

Background/Objectives: The aim of the present study is to report an outbreak of bloodstream infections caused by Serratia marcescens in patients undergoing postoperational procedures in the Cardiothoracic Department and to describe the epidemiological investigations and control measures undertaken. A cluster of bacteremia due [...] Read more.

Background/Objectives: The aim of the present study is to report an outbreak of bloodstream infections caused by Serratia marcescens in patients undergoing postoperational procedures in the Cardiothoracic Department and to describe the epidemiological investigations and control measures undertaken. A cluster of bacteremia due to Serratia marcescens was identified in blood cultures from postoperative patients in the Cardiothoracic Surgery Department in November 2023. Methods: Active surveillance by the hospital’s prevention and control team was initiated. Interviews with nurses and sanitary personnel and reviews of the most common procedures, such as hand washing, bladder catheterization, and intravenous catheter care, were performed. Culturing samples from hospital personnel, postoperative patients, and the environment, including pressure transducers, tap water, soap, therapeutic solutions, antiseptics, respirators, and various intravenous preparations, were drawn up. Overall, 225 samples were collected, including 149 blood cultures, and these were all sent to the Hospital’s Microbiology Laboratory. Results: Twenty-three out of forty-seven postoperative patients had positive blood cultures for Serratia marcescens. All the postoperative patients involved in the outbreak received cefepime according to antimicrobial susceptibility testing. Three pre-prepared flushing syringes were found to be positive for Serratia marcescens as well. The Cardiothoracic Department was kept under surveillance with hand hygiene measures, infusion preparation, medical device use, and cleaning procedures reviewed by the infection’s prevention and control team. Conclusions: Undoubtedly, nosocomial outbreaks represent an important health issue regarding morbidity, mortality, and costs. Timely interventions by the hospital’s infection prevention and control team may be life-saving under these circumstances. Full article

(This article belongs to the Special Issue Epidemiology, Diagnosis and Antimicrobial Treatment of Hospital-Acquired Infections)

20 pages, 3918 KiB

Open AccessArticle

Postbiotic-Based Extracts from Native Probiotic Strains: A Promising Strategy for Food Preservation and Antimicrobial Defense

by Diana Molina, Ioana C. Marinas, Evelyn Angamarca, Anamaria Hanganu, Miruna Stan, Mariana C. Chifiriuc and Gabriela N. Tenea

Antibiotics 2025, 14(3), 318; https://doi.org/10.3390/antibiotics14030318 - 18 Mar 2025

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Abstract

Background/Objectives: The deterioration of food quality and safety is often linked to the presence of pathogenic and spoilage microorganisms. Postbiotics, including organic acids, enzymes, and bacteriocins produced by lactic acid bacteria (LAB), have emerged as promising next-generation food preservatives. This study investigates [...] Read more.

Background/Objectives: The deterioration of food quality and safety is often linked to the presence of pathogenic and spoilage microorganisms. Postbiotics, including organic acids, enzymes, and bacteriocins produced by lactic acid bacteria (LAB), have emerged as promising next-generation food preservatives. This study investigates the biological and physicochemical properties of several postbiotic-based extracts (PBEs) comprising cell-free supernatant (CFS) and exopolysaccharide (EPS) fractions derived from three native probiotic strains: Lactiplantibacillus plantarum UTNGt2, Lactococcus lactis UTNGt28, and Weissella cibaria UTNGt21O. Methods: The antibacterial activity of these PBEs was assessed against multidrug-resistant Escherichia coli L1PEag1. Moreover, the antioxidant capacity and cytotoxicity along with the characterization of these formulations was assessed. Results: FU6 (CFS UTNGt28: EPS UTNGt2) and FU13 (CFS UTNGt21O) were found as the most potent formulations. Transmission electron microscopy (TEM) and scanning electron microscopy (SEM) confirmed dose- and time-dependent damage to the bacterial membrane and cell wall. FU6 exhibited superior antioxidant activity and lacked hemolytic effects, whereas both FU6 and FU13 induced cell-specific responses in HEK293 (human kidney) and HT-29 (intestinal mucus-producing) cell lines. Furthermore, attenuated total reflectance-Fourier transform infrared (ATR-FTIR) spectroscopy identified characteristic absorption bands corresponding to proteins, lipids, carbohydrates, and nucleic acids, while proton nuclear magnetic resonance (¹H-NMR) spectroscopy revealed key monosaccharides, amino acids, and metabolites such as lactate and acetate within the extracts. Conclusions: FU6 and FU13 demonstrate potential as safe and effective postbiotic formulations at non-concentrated doses. However, further research is required to elucidate their molecular composition comprehensively and evaluate their applicability for broader and long-term use in food preservation and pharmaceutical development. Full article

(This article belongs to the Special Issue Microbial Natural Products as a Source of Novel Antimicrobials, 2nd Edition)

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12 pages, 2934 KiB

Open AccessArticle

Nocardia Isolation in People with Cystic Fibrosis and Non-CF Bronchiectasis: A Multicenter Italian Study

by Laura Venditto, Daniela Dolce, Silvia Campana, Pamela Vitullo, Marco Di Maurizio, Cristina Fevola, Francesca Lucca, Giovanni Taccetti and Vito Terlizzi

Antibiotics 2025, 14(3), 317; https://doi.org/10.3390/antibiotics14030317 - 18 Mar 2025

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Abstract

Background: Nocardia species are an emergent pathogen in people with CF (pwCF) or bronchiectasis. Their clinical role and management remain unclear, and their isolation is a challenge. In this paper, we describe four cases of Nocardia detection, in two pwCF and two [...] Read more.

Background: Nocardia species are an emergent pathogen in people with CF (pwCF) or bronchiectasis. Their clinical role and management remain unclear, and their isolation is a challenge. In this paper, we describe four cases of Nocardia detection, in two pwCF and two patients with non-CF bronchiectasis or primary ciliary dyskinesia (PCD). Methods: We conducted a multicenter retrospective study, involving pwCF and non-CF people with bronchiectasis who presented with a Nocardia detection and were followed at three CF Italian centers (Florence, Verona, and Cerignola). Results: Nocardia detection was associated with clinical and radiological respiratory exacerbation and decline in lung function. In one CF patient, Nocardia was not detected in sputum cultures after starting Elexacaftor-Tezacaftor-Ivacaftor therapy. Conclusions: Managing Nocardia detection in patients with underlying lung diseases such as CF, PCD, or bronchiectasis presents significant challenges for clinicians. Full article

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18 pages, 2471 KiB

Open AccessArticle

Kinetic Patterns of Antibiotic Consumption in German Acute Care Hospitals from 2017 to 2023

by Birgitta Schweickert, Niklas Willrich, Marcel Feig, Marc Schneider, Michael Behnke, Luis Alberto Peña Diaz, Christine Geffers, Imke Wieters, Karin Gröschner, Doreen Richter, Alexandra Hoffmann, Tim Eckmanns and Muna Abu Sin

Antibiotics 2025, 14(3), 316; https://doi.org/10.3390/antibiotics14030316 - 18 Mar 2025

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Abstract

Background: Antimicrobial consumption (AMC) patterns, besides prescribing behaviors, reflect the changing epidemiology of infectious diseases. Routine surveillance data have been used to investigate the development of AMC from 2017 to 2023 and the impact of COVID-19 within the context of the framing time [...] Read more.

Background: Antimicrobial consumption (AMC) patterns, besides prescribing behaviors, reflect the changing epidemiology of infectious diseases. Routine surveillance data have been used to investigate the development of AMC from 2017 to 2023 and the impact of COVID-19 within the context of the framing time periods. Methods: Data from 112 hospitals, continuously participating from 2017 to 2023 in the national surveillance system of hospital antimicrobial consumption based at the Robert Koch Institute, were analyzed according to the WHO ATC (Anatomical Therapeutic Chemical)/DDD (Defined Daily Dose) method and categorized according to the WHO AWaRe-classification. AMC was quantified by consumption density (CD) expressed in DDD/100 patient days (PD) and DDD/100 admissions (AD). The time period was subdivided into three phases: pre-pandemic phase (2017–2019), main pandemic phase (2020–2021) and transition phase (2022–2023). Linear regression models have been used to determine the presence of an overall trend, the change in intra-phasic trends and phase-specific mean consumption levels over time. Results: From 2017 to 2023 total antibiotic consumption decreased by 7% from 57.1 to 52.9 DDD/100 PD. Four main kinetic patterns emerged across different antibiotic classes: Pattern 1 displays a decreasing pre-pandemic trend, which slowed down throughout the pandemic and transition phase and was exhibited by second-generation cephalosporins and fluoroquinolones. Pattern 2 reveals a rising pre-pandemic trend, which decelerated in the pandemic phase and accelerated again in the transition phase and was expressed by aminopenicillins/beta-lactamase inhibitors, beta-lactamase sensitive pencillins, azithromycin and first-generation cephalosporins. Pattern 3 shows elevated mean consumption levels in the pandemic phase exhibited by carbapenems, glycopeptides, linezolid and third-generation cephalosporins. Pattern 4 reveals a rising trend throughout the pre-pandemic and pandemic phase, which reversed in the transition phase without achieving pre-pandemic levels and was expressed by beta-lactamase resistant penicillins, daptomycin, fosfomycin (parenteral) and ceftazidime/avibactam. Conclusions: Kinetic consumption patterns across different antibiotic classes might reflect COVID-19-related effects and associated changes in the epidemiology of co-circulating pathogens and health care supply. Broad-spectrum antibiotics with persisting elevated consumption levels throughout the transition phase require special attention and focused antimicrobial stewardship activities. Full article

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

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18 pages, 2597 KiB

Open AccessReview

The Role of PI3k-Gamma Modulation in Bacterial Infection: A Review of the Literature and Selected Experimental Observations

by Daniel Sun, Alexandria Hoffman, Fatemeh Askarian, Elisabet Bjånes, Eric X. Lin, Judith Varner and Victor Nizet

Antibiotics 2025, 14(3), 315; https://doi.org/10.3390/antibiotics14030315 - 18 Mar 2025

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Abstract

Background: Phosphoinositide 3-kinase is a potent target for cancer therapy due to its significant role in the regulation of cellular growth and proliferation. Dysregulation of the PI3k signaling cascade can constitutively activate growth pathways to trigger the progression of cancer, resulting in the [...] Read more.

Background: Phosphoinositide 3-kinase is a potent target for cancer therapy due to its significant role in the regulation of cellular growth and proliferation. Dysregulation of the PI3k signaling cascade can constitutively activate growth pathways to trigger the progression of cancer, resulting in the development of multiple inhibitors as cancer therapeutics. Objectives: The wide array of cells expressing PI3k also include immune cells, and the inhibition of these receptors has shown promise in combating inflammation and infectious disease, a relationship we sought to examine further. Methods: We infected wild-type and PI3kγ knockout murine macrophages as well as PI3kγ inhibitor-treated THP-1 human macrophage-like cells with Staphylococcus aureus and quantified inflammation through gene expression analysis, protein secretion assays, and immunofluorescence imaging. Results: We observed that knockout of PI3kγ in murine macrophages alongside pharmacological inhibition through IPI549 treatment in THP-1 cells led to an NF-κB-driven suppression in transcription and release of inflammatory cytokines upon infection with methicillin-resistant Staphylococcus aureus. We were also able to confirm that this suppression of NF-κB translocation and subsequent decrease in inflammatory cytokine release did not compromise and even slightly boosted the bacterial killing ability. Conclusion: PI3k is primarily targeted for cancer therapies, but further exploration can also be carried out on its potential roles in treating bacterial infection. Full article

(This article belongs to the Special Issue Sepsis Management and Antibiotic Therapy)

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9 pages, 170 KiB

Open AccessTechnical Note

ICD-10 Codes to Identify Adverse Drug Events Associated with Antibiotics in Administrative Data

by Hannah Lishman, Amber Cragg, Erica Chuang, Carl Zou, Fawziah Marra, Jennifer Grant, David M. Patrick and Corinne M. Hohl

Antibiotics 2025, 14(3), 314; https://doi.org/10.3390/antibiotics14030314 - 18 Mar 2025

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Abstract

Antibiotics are among the most used therapeutics in primary care, and while their benefits are clear, the potential harms related to adverse drug events (ADEs) cannot be ignored. We outline the creation of a comprehensive list of diagnostic codes describing antibiotic-associated ADEs resulting [...] Read more.

Antibiotics are among the most used therapeutics in primary care, and while their benefits are clear, the potential harms related to adverse drug events (ADEs) cannot be ignored. We outline the creation of a comprehensive list of diagnostic codes describing antibiotic-associated ADEs resulting in presentations to acute care hospitals. Methods: Previously published ADE codes were used to link BC hospitalizations to prior outpatient antibiotic prescriptions and were restricted based on whether patients received an antibiotic within a month prior to the ADE-related hospitalization. The code list was reviewed by two clinical experts independently for the likelihood of being antibiotic-associated. The inter-rater reliability was calculated using Kappa scores with 95% confidence intervals (CIs). Results: Of the 695 ICD-10 ADE codes with evidence of recent antibiotic administration, 72, 68, and 555 codes were considered likely, possibly, and unlikely antibiotic-associated, respectively. Conclusions: We outline a methodology for developing an ICD-10 code list for antibiotic-associated ADEs severe enough to warrant hospital admission. This will help to improve the use of administrative data to capture antibiotic-associated ADEs. Full article

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

13 pages, 3360 KiB

Open AccessArticle

Impact of Amoxicillin Shortage on Pediatric Antibiotic Prescriptions in Primary Care

by Federica Pagano, Giulio De Marco, Benedetta Trojano, Chiara Amato, Maria Micillo, Gaetano Cecere, Alfredo Guarino and Andrea Lo Vecchio

Antibiotics 2025, 14(3), 313; https://doi.org/10.3390/antibiotics14030313 - 18 Mar 2025

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Abstract

Background/Objectives: A previous study settled in the Campania Region (Southern Italy) has proven the effectiveness of a multifaceted antimicrobial stewardship program in reducing prescription rates and use of broad-spectrum molecules in the Primary Care setting. Since autumn 2022, the amoxicillin shortage has been [...] Read more.

Background/Objectives: A previous study settled in the Campania Region (Southern Italy) has proven the effectiveness of a multifaceted antimicrobial stewardship program in reducing prescription rates and use of broad-spectrum molecules in the Primary Care setting. Since autumn 2022, the amoxicillin shortage has been reported at a national level, and respiratory pathogens resurged in children after the easing of COVID-19 pandemic restrictions. We aimed to assess the impact of amoxicillin shortage on antimicrobial prescription patterns and quality indexes in the same setting as the past AMS campaign. Methods: We conducted a retrospective review of antibiotic prescriptions in a primary care pediatric practice, focusing on amoxicillin, amoxicillin-clavulanate, third-generation cephalosporins, macrolides, and quinolones. To assess drug accessibility, we monitored antibiotic availability in pharmacies within the same healthcare district. We then analyzed monthly prescription rates per 100 consultations in relation to drug availability patterns and calculated the amoxicillin/amoxicillin-clavulanate index and the Access/Watch index as quality indicators. Results: From November 2022 to May 2023, 90% of the surveyed pharmacies reported an amoxicillin shortage lasting 5 to 7 months. Concomitantly, we observed a significant shift in the prescription pattern for amoxicillin-clavulanate (3.53 to 13.82; p = 0.009) and third-generation cephalosporins (2.45 to 4.83; p = 0.026), that resulted in a decline of the amoxicillin/amoxicillin-clavulanate index (1.38 to 0.56; p = 0.009). Conclusions: The lack of amoxicillin could have led to increased prescriptions of second-line antibiotics in Italian regions, reverting the effect of successful stewardship measures. Full article

(This article belongs to the Special Issue Epidemiology, Clinical Microbiology and Antimicrobial Therapy: A Shared Effort against Infectious Diseases)

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20 pages, 2857 KiB

Open AccessArticle

The Cyclic Antimicrobial Peptide C-LR18 Has Enhanced Antibacterial Activity, Improved Stability, and a Longer Half-Life Compared to the Original Peptide

by Zhihua Pei, Qiaoxi Song, Jingqi Xu, Shuang Yu and Hongxia Ma

Antibiotics 2025, 14(3), 312; https://doi.org/10.3390/antibiotics14030312 - 17 Mar 2025

Viewed by 257

Abstract

Background: LR18 is an α₋helical AMP with high antimicrobial activity, low hemolytic activity, and low cytotoxicity. However, the susceptibility to degradation of the peptidase enzyme and a short half-life hinder its application as a therapeutic agent. Improving the stability and prolonging the half-life [...] Read more.

Background: LR18 is an α₋helical AMP with high antimicrobial activity, low hemolytic activity, and low cytotoxicity. However, the susceptibility to degradation of the peptidase enzyme and a short half-life hinder its application as a therapeutic agent. Improving the stability and prolonging the half-life of LR18 are crucial to accelerate its application in the treatment of infectious diseases. Methods: A new cyclic peptide, C-LR18, was designed and synthesized through end-to-end cyclization of LR18 via disulfide bonds. The biological activity, half-life, and therapeutic effect of C-LR18 on Escherichia coli₋infected mice were studied. Results: C-LR18 maintained the characteristics of low cytotoxicity and low hemolytic activity of the original LR18 peptide and had higher antibacterial activity and significantly improved stability. After treatment with 1 mg/mL of trypsin, carboxypeptidase, and papain for 1 h, the MIC of C-LR18 against E. coli ATCC25922 was 4 μM, while that of LR18 had increased to 128 μM. After exposure to 50% serum or artificial gut solution for 30 min, the MIC of C-LR18 against E. coli ATCC25922 increased 4-fold, while that of LR18 increased 16-fold. The half-life of C-LR18 in plasma and in rats was extended to 3.37-fold and 4.46-fold, respectively, that of LR18. The acute toxicity of C-LR18 in mice is lower than many AMPs reported so far (LD50 = 37.8 mg/kg). C-LR18 has a therapeutic effect on E.coli-infected mice. Conclusions: The cyclic peptide C-LR18 has higher antibacterial activity and stability and a longer half-life than LR18 in rats in vitro and in vivo. C-LR18 also has a therapeutic effect on KM mice infected with E. coli and is expected to become a therapeutic drug for bacterial diseases and applied to the treatment of human and veterinary diseases. Full article

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13 pages, 1986 KiB

Open AccessArticle

Antibacterial Effects of Synthetic Plantaricins Against Staphylococcus aureus

by Seung-Eun Oh, Sojeong Heo, Gawon Lee, Jina Kim, Mi-Sun Kwak and Do-Won Jeong

Antibiotics 2025, 14(3), 311; https://doi.org/10.3390/antibiotics14030311 - 17 Mar 2025

Viewed by 352

Abstract

Background/Objectives: Plantaricins without a signal sequence were synthesized based on bacteriocins, plantaricins A, E, F, J, and K, of Lactiplantibacillus plantarum KM2. The antibacterial activities of four combinations of synthetic plantaricins—spPlnA, E&F, E&J, and J&K—were identified against Staphylococcus aureus ATCC 12692. And in [...] Read more.

Background/Objectives: Plantaricins without a signal sequence were synthesized based on bacteriocins, plantaricins A, E, F, J, and K, of Lactiplantibacillus plantarum KM2. The antibacterial activities of four combinations of synthetic plantaricins—spPlnA, E&F, E&J, and J&K—were identified against Staphylococcus aureus ATCC 12692. And in this experiment, we aimed to identify the antimicrobial mechanism of the synthesized plantaricin sample against S. aureus. Methods/Results: The minimal inhibitory concentrations for each combination were 1.4 μg/mL, 1.8 μg/mL, 1.6 μg/mL, and 1.6 μg/mL, respectively. Raman spectra changed after treating S. aureus ATCC 12692 with synthetic plantaricins. Furthermore, transmission electron microscopy results revealed that the four synthetic plantaricin combinations could induce the cell lysis of S. aureus ATCC 12692. Finally, the four synthetic plantaricin combinations maintained their antibacterial effect at temperatures below 40 °C, and at pH levels of pH = (4–7). Except for spPlnJ&K, they are stable against the action of α–amylase and lysozyme. Overall, these results indicate that, excepting spPlnJ&K, the three synthetic plantaricin combinations exhibit similar antibacterial activity. Conclusions: Through this study, we confirmed that synthetic plantaricin exhibited antimicrobial activity against S. aureus, demonstrating its potential as a direct antimicrobial agent. However, since the antimicrobial activity decreased due to protease, it was confirmed that its use is limited in environments where protease is present. Full article

(This article belongs to the Collection Synthetic and Natural Products-Based Antimicrobial and Antiparasitic Agents)

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13 pages, 1527 KiB

Open AccessArticle

Antibiotic Usage for Treatment of Acute Upper Respiratory Tract Infections in Children in Lithuania from 2018 to 2022

by Tadas Alčauskas, Kristina Garuolienė and Sigita Burokienė

Antibiotics 2025, 14(3), 310; https://doi.org/10.3390/antibiotics14030310 - 17 Mar 2025

Viewed by 327

Abstract

Background/Objectives: Acute upper respiratory tract infections (URIs) are defined as inflammatory diseases of the nose, sinuses, pharynx, larynx, or trachea. They are common in children. The prescription of antibiotics for the treatment of URIs became a relevant theme in the scientific literature [...] Read more.

Background/Objectives: Acute upper respiratory tract infections (URIs) are defined as inflammatory diseases of the nose, sinuses, pharynx, larynx, or trachea. They are common in children. The prescription of antibiotics for the treatment of URIs became a relevant theme in the scientific literature in recent decades. One of the most important ways to deal with increasing antimicrobial resistance is rational antibiotic therapy. This study aimed to evaluate the tendencies of antibiotic prescribing practices for Lithuanian children with URIs from 2018 to 2022. We describe how many children with URIs were prescribed antibiotics, which antibiotics were used, and whether prescribing practices meet national guidelines. Methods: Secondary data, which were used in this observational study, were collected from the Lithuanian Compulsory Health Insurance Fund (CHIF) electronic records. The study population consisted of children aged between 0 and 18 years who visited their primary care doctors (pediatricians or family doctors) between January 2018 and December 2022 and were prescribed antibiotics for the treatment of URIs. Results: Between 2018 and 2022, there were 445,328 visits reported when antibiotics, which belong to the J01 group according to the Anatomical Therapeutic Chemical Classification (ATC), were prescribed to children aged 0–18. In more than half of the visits (51.70%), children aged 0–5 were consulted. Penicillins were mostly prescribed for the treatment of acute nasopharyngitis. Macrolides were mostly used to treat acute laryngitis and tracheitis. Of all penicillin-class antibiotics, the most popular choice was amoxycillin. The primary choice of cephalosporin was cefadroxil, and the primary choice of macrolide was clarithromycin. Conclusions: During the period of 2018–2022, the number of prescriptions for antibiotics for URTIs decreased, but prescriptions for penicillin-class antibiotics increased in a relative manner. The most common diagnoses during these visits were acute tonsillitis and acute pharyngitis, and most antibiotic prescriptions were for children in the 0–5 age group. If Lithuania’s National Recommendations on the Rational Use of Antibiotics were implemented during the analyzed period, the prescribing tendencies would not meet them. Full article

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

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15 pages, 1160 KiB

Open AccessArticle

Increase in Antibiotic Utilisation in Primary Care Post COVID-19 Pandemic

by Sky Wei Chee Koh, Si Hui Low, Jun Cong Goh and Li Yang Hsu

Antibiotics 2025, 14(3), 309; https://doi.org/10.3390/antibiotics14030309 - 17 Mar 2025

Viewed by 473

Abstract

Introduction: The COVID-19 pandemic has disrupted antibiotic use; easing public health measures may alter infection presentations and antibiotic prescribing in primary care. The study investigated post-pandemic antibiotic utilisation trends in primary care. Methods: A multi-centre, retrospective cohort study was conducted across [...] Read more.

Introduction: The COVID-19 pandemic has disrupted antibiotic use; easing public health measures may alter infection presentations and antibiotic prescribing in primary care. The study investigated post-pandemic antibiotic utilisation trends in primary care. Methods: A multi-centre, retrospective cohort study was conducted across seven public primary care clinics in Western Singapore, which included all patients prescribed oral antibiotics between 2022 and 2023. Descriptive statistics were used to visualise the prevalence and conditions of the prescribed antibiotics. Antibiotic quality was evaluated using the WHO’s AWaRe (access, watch, reserve) classification. Antibiotic use was quantified using the number of items dispensed per 1000 inhabitants (NTI), defined daily doses (DDD) per 1000 inhabitants per day (DID), and DDD per 100 visits. Segmented regression analysis was applied to monthly prescriptions to assess the utilisation trends. Results: Antibiotic prescription rates increased significantly, from 3.5% in 2022 to 4.0% in 2023 (p = 0.001), with a 9.5% relative increase (38,920 prescriptions for 1,112,574 visits to 42,613 prescriptions for 1,063,646 visits). Respiratory conditions drove the increase in antibiotics use, with a 68.3% rise in prescriptions, with upper respiratory tract infections being the most common diagnosis for antibiotic prescriptions (n = 9296 prescriptions in 2023), with a steady monthly upward trend. Access group antibiotics accounted for >90% of prescriptions. The most antibiotics were prescribed for acne, with 36,304 DDD per 100 visits in 2023. Both NTI and DID significantly increased in 2022, largely contributed by a >100% increase in Watch group antibiotic use. Total antibiotic NTI dipped slightly in 2023, with a stable trend in both NTI and DID for all antibiotics. Conclusions: The post-COVID-19 pandemic surge in the antibiotic prescription rate for respiratory conditions and Watch group antibiotic use highlight the need for targeted stewardship interventions. Optimising acne treatment and diagnosis coding are key strategies to further reduce unnecessary prescriptions. Full article

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19 pages, 731 KiB

Open AccessReview

Anacardiaceae Family: Effect of Isolated Compounds and Other Identified Phytochemicals Against Clinically Relevant Candida Species—A Short Review

by Rosane Nassar Meireles Guerra, Aluísio Silva Oliveira, Josivan Regis Farias, Danielle Cristine Gomes Franco, Pamela Gomes Santos, Nicolle Teixeira Barbosa, Simone Batista Muniz, Afonso Gomes Abreu and Flavia Raquel Fernandes Nascimento

Antibiotics 2025, 14(3), 308; https://doi.org/10.3390/antibiotics14030308 - 17 Mar 2025

Viewed by 382

Abstract

Background: The increased rates of common fungal diseases are a constant challenge. Therefore, the search for plant-based compounds with antifungal activity, particularly ones against Candida species, is always relevant in the medical context. However, most of the studies have focused on screening the [...] Read more.

Background: The increased rates of common fungal diseases are a constant challenge. Therefore, the search for plant-based compounds with antifungal activity, particularly ones against Candida species, is always relevant in the medical context. However, most of the studies have focused on screening the antifungal activity of extracts rather than isolated compounds. Based on this, we aimed to analyze and organize a comprehensive overview of the antifungal and other biological activities of isolated compounds found in Anacardiaceae family vegetal species, covering mechanisms of action and potential therapeutic applications. Results: The extracts, essential oils, and compounds are frequently assayed for anti-Candida activity using the in vitro minimum inhibitory concentration (MIC), minimum fungicide concentration (MFC), and halo inhibition assays. Candida albicans, C. tropicalis, C. parapsilosis, C. glabrata, C. krusei, and C. guilliermondii were the most tested fungus species. Essential oils were the most used form (37% of the studies). The isolated compounds included shikimic acid, 2-hydroxy-1,8-cineole β-D-glucopyranoside, myricitrin, cardanol, estragole, trans-anethole, β-caryophyllene, myrcene, catechin-3-O-rhamnoside, β-sitosterol-3-O-glucoside, 24Z-isomasticadienolic acid, oleanolic acid, pistagremic acid, apigenin, sakuranetin, oleanolic aldehyde, and integriside. Conclusions: Our data indicate that the compounds isolated from Anacardiaceae species show promise for developing new therapeutic antifungal drugs, mainly if we consider their other biological activities, including anti-inflammatory, antioxidant, and apoptotic effects. In this context, they may be candidates for future treatments of fungal infections, especially in combination with conventional antifungals or when used in nanostructured formulations, which may result in a new avenue of using plant extracts and isolated compounds. Full article

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

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12 pages, 1319 KiB

Open AccessArticle

Antibacterial and Antifungal Properties of New Synthetic Tricyclic Flavonoids

by Laura Gabriela Sarbu, Irina Rosca and Mihail Lucian Birsa

Antibiotics 2025, 14(3), 307; https://doi.org/10.3390/antibiotics14030307 - 16 Mar 2025

Viewed by 329

Abstract

Background/Objectives: The discovery of new molecules to which bacteria have not yet developed resistance is a significant medical priority. Synthetic flavonoids are good candidates for developing new antimicrobials. Our study investigates a series of newly synthesized tricyclic flavonoids with several different substituents on [...] Read more.

Background/Objectives: The discovery of new molecules to which bacteria have not yet developed resistance is a significant medical priority. Synthetic flavonoids are good candidates for developing new antimicrobials. Our study investigates a series of newly synthesized tricyclic flavonoids with several different substituents on the flavonoid core. Methods: By varying the nature of the substituents on rings A and B, a structure–activity relationship study using different microbial strains has been performed. The antibacterial and antifungal properties of these compounds have been investigated against Gram-positive and Gram-negative bacteria and several Candida strains. Results: All seven tested compounds have been found to exhibit the highest antimicrobial activity against S. aureus, with an inhibition zone of up to 23 mm. The tricyclic flavonoids 5c, 5e, and 5f showed good antifungal properties against C. parapsilosis, with an inhibition zone of around 17 mm. Conclusions: All the data support the idea that flavonoids 5 are reliable candidates for developing effective antimicrobial agents. Full article

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31 pages, 4512 KiB

Open AccessReview

Rare or Unusual Non-Fermenting Gram-Negative Bacteria: Therapeutic Approach and Antibiotic Treatment Options

by Nicholas Geremia, Andrea Marino, Andrea De Vito, Federico Giovagnorio, Stefano Stracquadanio, Agnese Colpani, Stefano Di Bella, Giordano Madeddu, Saverio Giuseppe Parisi, Stefania Stefani and Giuseppe Nunnari

Antibiotics 2025, 14(3), 306; https://doi.org/10.3390/antibiotics14030306 - 16 Mar 2025

Viewed by 815

Abstract

Non-fermenting Gram-negative bacteria (NFGNB) are a heterogeneous group of opportunistic pathogens increasingly associated with healthcare-associated infections. While Pseudomonas aeruginosa, Acinetobacter baumannii, and Stenotrophomonas maltophilia are well known, rarer species such as Burkholderia cepacia complex, Achromobacter spp., Chryseobacterium spp., Elizabethkingia spp., Ralstonia spp., [...] Read more.

Non-fermenting Gram-negative bacteria (NFGNB) are a heterogeneous group of opportunistic pathogens increasingly associated with healthcare-associated infections. While Pseudomonas aeruginosa, Acinetobacter baumannii, and Stenotrophomonas maltophilia are well known, rarer species such as Burkholderia cepacia complex, Achromobacter spp., Chryseobacterium spp., Elizabethkingia spp., Ralstonia spp., and others pose emerging therapeutic challenges. Their intrinsic and acquired resistance mechanisms limit effective treatment options, making targeted therapy essential. Objectives: This narrative review summarizes the current understanding of rare and unusual NFGNB, their clinical significance, resistance profiles, and evidence-based therapeutic strategies. Methods: A literature review was conducted using PubMed, Scopus, and Web of Science to identify relevant studies on the epidemiology, antimicrobial resistance, and treatment approaches to rare NFGNB. Results: Rare NFGNB exhibits diverse resistance mechanisms, including β-lactamase production, efflux pumps, and porin modifications. Treatment selection depends on species-specific susceptibility patterns, but some cornerstones can be individuated. Novel β-lactam/β-lactamase inhibitors and combination therapy approaches are being explored for multidrug-resistant isolates. However, clinical data remain limited. Conclusions: The increasing incidence of rare NFGNB requires heightened awareness and a tailored therapeutic approach. Given the paucity of clinical guidelines, antimicrobial stewardship and susceptibility-guided treatment are crucial in optimizing patient outcomes. Full article

(This article belongs to the Special Issue Emerging Treatment Options for Multidrug-Resistant Bacterial and Fungal Infections, 2nd Edition)

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18 pages, 3290 KiB

Open AccessArticle

Antimicrobial Susceptibility Profiles of Commensal Escherichia coli Isolates from Turkeys in Hungarian Poultry Farms Between 2022 and 2023

by Ákos Jerzsele, Ádám Kerek, Franciska Barnácz, Bence Csirmaz, Ábel Szabó and László Kovács

Antibiotics 2025, 14(3), 305; https://doi.org/10.3390/antibiotics14030305 - 16 Mar 2025

Viewed by 409

Abstract

Background: The global spread of antimicrobial resistance (AMR) has prompted the critical importance of regular monitoring. Escherichia coli, a widely distributed facultative anaerobic pathogen, is significant both in terms of the clinical diseases that it causes and as a reservoir of [...] Read more.

Background: The global spread of antimicrobial resistance (AMR) has prompted the critical importance of regular monitoring. Escherichia coli, a widely distributed facultative anaerobic pathogen, is significant both in terms of the clinical diseases that it causes and as a reservoir of antimicrobial resistance, with notable implications for both animal and public health. Within the poultry industry, the turkey sector is an emerging and internationally significant branch. Methods: Our objective was to assess the antimicrobial resistance profile of commensal Escherichia coli strains isolated from large-scale turkey flocks in Hungary using minimum inhibitory concentration (MIC) determination. Results: A total of 470 isolates were analyzed, revealing that 61.5% of the strains were resistant to amoxicillin, while 18.5% were resistant to amoxicillin–clavulanic acid. The resistance observed against enrofloxacin (62.8%) and ceftriaxone (24%) is concerning. Comparison with human resistance data showed a similar resistance rate for amoxicillin and ampicillin, as well as amoxicillin–clavulanic acid and cephalosporins. However, for other active substances, the situation was significantly worse in veterinary medicine. Conclusions: The lower resistance to amoxicillin–clavulanic acid indicates that most strains are β-lactamase producers. Our findings underscore the necessity of regular and comprehensive surveillance, which can establish temporal trends over time. Incorporating data on antibiotic usage into future studies could facilitate the exploration of relevant correlations. Additionally, the next-generation sequencing of multidrug-resistant strains could help elucidate the genetic basis of resistance. Full article

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

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12 pages, 573 KiB

Open AccessArticle

Vancomycin-Resistant Enterococci: Screening Efficacy and the Risk of Bloodstream Infections in a Specialized Healthcare Setting

by Assunta Navarra, Stefania Cicalini, Silvia D’Arezzo, Francesca Pica, Marina Selleri, Carla Nisii, Carolina Venditti, Angela Cannas, Antonio Mazzarelli, Antonella Vulcano, Stefania Carrara, Donatella Vincenti, Barbara Bartolini, Paolo Giacomini, Maria Grazia Bocci and Carla Fontana

Antibiotics 2025, 14(3), 304; https://doi.org/10.3390/antibiotics14030304 - 16 Mar 2025

Viewed by 688

Abstract

Background: Vancomycin-resistant enterococci (VRE) rectal colonization represents a critical risk factor for subsequent bloodstream infections (BSIs), posing a serious concern in healthcare settings. This study aims to investigate the association between the presence of VRE in rectal swabs and the occurrence of [...] Read more.

Background: Vancomycin-resistant enterococci (VRE) rectal colonization represents a critical risk factor for subsequent bloodstream infections (BSIs), posing a serious concern in healthcare settings. This study aims to investigate the association between the presence of VRE in rectal swabs and the occurrence of BSIs, highlighting the challenges of rapid detection and patient care implications in an infectious disease hospital setting. Methods: We performed a retrospective analysis of cultural rectal swab screening and molecular assays (MAs) for VRE detection between January 2020 and December 2023. All adult patients admitted with at least one rectal swab screening performed during hospitalization were included. All blood cultures that yielded VRE were identified, and the first Enterococcus-positive blood sample for each patient with at least one prior rectal swab per year was analyzed. Results: The results showed a 15.4% positivity rate for VRE in cultural screening, predominantly Enterococcus faecium. MA showed a higher prevalence of 49.4%, with a significant discordance between MA rectal swab screening and cultural testing. Patients with VRE intestinal colonization by E. faecium were significantly more likely to develop E. faecium BSI, with a risk ratio of 9.78 (p < 0.001). Conclusions: The study identified a strong correlation between VRE rectal colonization and the risk of developing BSI, emphasizing the need for effective screening and infection control measures. The results support the inclusion of molecular testing in VRE detection protocols and highlight the importance of ongoing surveillance for antimicrobial resistance. Full article

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12 pages, 234 KiB

Open AccessArticle

Antibiotic Usage and Healthcare-Associated Clostridioides difficile in Patients with and Without COVID-19: A Tertiary Hospital Experience

by Darko Zdravkovic, Ljiljana Markovic-Denic, Vladimir Nikolic, Zoran Todorovic, Marija Brankovic, Aleksandra Radojevic, Dusan Radovanovic and Borislav Toskovic

Antibiotics 2025, 14(3), 303; https://doi.org/10.3390/antibiotics14030303 - 15 Mar 2025

Cited by 1 | Viewed by 416

Abstract

Background/Objectives: Data about the relationship between COVID-19 and healthcare-associated Clostridioides difficile infection (HA-CDI) occurrence are still controversial. This study examines antibiotics associated with CDI in patients with and without COVID-19 infection. Methods: A prospective cohort study was conducted at the University [...] Read more.

Background/Objectives: Data about the relationship between COVID-19 and healthcare-associated Clostridioides difficile infection (HA-CDI) occurrence are still controversial. This study examines antibiotics associated with CDI in patients with and without COVID-19 infection. Methods: A prospective cohort study was conducted at the University Clinical Center Belgrade, Serbia, from January 2019 to December 2021. Patients with the first episode of HA-CDI without and with COVID-19 were included. Results of bacteriology analyses, demographic and clinical data, and data on antibiotic usage and daily defined doses (DDD) were collected by the hospital Infection Control Team. Results: Out of 547 HA-CDI cases, 341 (62.3%) had COVID-19 infection. HA-CDI patients with COVID-19 were significantly younger (p = 0.017) with fewer comorbidities (<0.001). Two or more antibiotics in therapy were more frequently used by those patients (p = 0.03). COVID-19 patients were treated significantly more by third- and fourth-generation cephalosporins, fluoroquinolones (p < 0.001) and macrolides (p = 0.01). Ceftriaxone had a higher median DDD in COVID-19 patients (6.00, range 1.00–20.00) compared to non-COVID-19 patients (4.00, range 1.00–14.00), (p = 0.007). Conversely, meropenem showed a lower median DDD in COVID-19 patients. Multivariate analysis identified the use of fourth-generation cephalosporins and fluoroquinolones as independent risk factors for HA-CDI in COVID-19 patients. Conclusions: Patients with HA-CDI and COVID-19 more frequently received two or more antibiotics before the onset of HAI-CDI. The third and fourth generations of cephalosporins, fluoroquinolones and macrolides were administered significantly more often in these patients. More frequent administration of ceftriaxone was observed, but the lower DDD associated with meropenem needed additional analysis. Full article

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

13 pages, 538 KiB

Open AccessArticle

Resistance of Pseudomonas aeruginosa to Antibiotics During Long-Term Persistence in Patients with Cystic Fibrosis

by Natalia Belkova, Uliana Nemchenko, Elizaveta Klimenko, Nadezhda Smurova, Raisa Zugeeva, Marina Sukhoreva, Viacheslav Sinkov and Evgenij Savilov

Antibiotics 2025, 14(3), 302; https://doi.org/10.3390/antibiotics14030302 - 14 Mar 2025

Viewed by 569

Abstract

Pseudomonas aeruginosa is one of the leading causes of nosocomial respiratory tract infections, significantly affecting morbidity and mortality. It can persist in the lungs of patients with cystic fibrosis (CF) for extended periods because of its adaptive capacity. The main aim of this [...] Read more.

Pseudomonas aeruginosa is one of the leading causes of nosocomial respiratory tract infections, significantly affecting morbidity and mortality. It can persist in the lungs of patients with cystic fibrosis (CF) for extended periods because of its adaptive capacity. The main aim of this study was to determine the phenotypic and genotypic resistance to antibiotics of clinical isolates of P. aeruginosa that persist in patients with CF receiving long-term antimicrobial therapy. The study included nine strains of P. aeruginosa isolated from the sputum of patients with CF admitted to the hospital. Susceptibility to antibiotics was determined using the European Committee on Antimicrobial Susceptibility Testing (EUCAST) criteria. Whole-genome sequencing was performed for phylogeny, sequence typing, and to identify antibiotic-resistant genes. The study showed that during long-term persistence in the lungs of patients receiving antibacterial therapy, the restoration of susceptibility to antibiotics occurred in some cases. Multilocus sequence typing and phylogeny revealed six sequence types. Functional annotation identified 72 genes responsible for resistance to antibacterial and chemical substances, with either chromosomal or plasmid localisation. Full article

(This article belongs to the Special Issue Genomic Characterization of Antimicrobial Resistance and Evolution Mechanism of Bacteria)

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48 pages, 2599 KiB

Open AccessReview

Antibiotics and Opportunities of Their Alternatives in Pig Production: Mechanisms Through Modulating Intestinal Microbiota on Intestinal Health and Growth

by Jung Yeol Sung, Zixiao Deng and Sung Woo Kim

Antibiotics 2025, 14(3), 301; https://doi.org/10.3390/antibiotics14030301 - 14 Mar 2025

Viewed by 732

Abstract

Antibiotics at subtherapeutic levels have been used in pig diets as antimicrobial growth promoters. However, concerns about antibiotic resistance have increased the demand for alternatives to these antimicrobial growth promoters. This review paper explores the mechanisms through which antimicrobial growth promoters and their [...] Read more.

Antibiotics at subtherapeutic levels have been used in pig diets as antimicrobial growth promoters. However, concerns about antibiotic resistance have increased the demand for alternatives to these antimicrobial growth promoters. This review paper explores the mechanisms through which antimicrobial growth promoters and their alternatives exert their antimicrobial effects. Additionally, this systemic review also covers how modulation of intestinal microbiota by antimicrobial growth promoters or their alternatives affects intestinal health and, subsequently, growth of pigs. The mechanisms and effects of antimicrobial growth promoters and their alternatives on intestinal microbiota, intestinal health, and growth are diverse and inconsistent. Therefore, pig producers should carefully assess which alternative is the most effective for optimizing both profitability and the health status of pigs in their production system. Full article

(This article belongs to the Section Antibiotics in Animal Health)

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13 pages, 1051 KiB

Open AccessArticle

Community Pharmacists’ Responses Toward Antimicrobial Prescriptions in Jordan: A Cross-Sectional Survey

by Ma’en Al-Odat, Shadi Mustafa, Yousef Al-Hajaya, Anwar Kandari, Amane Alaroud, Ahmad Alenezi, Haitham Qaralleh and Yasmeen Hazaimeh

Antibiotics 2025, 14(3), 300; https://doi.org/10.3390/antibiotics14030300 - 14 Mar 2025

Viewed by 541

Abstract

Background: Globally, community pharmacists worldwide have prescribed more over-the-counter systemic antibiotics, posing significant issues for international organizations tackling antibiotic-resistant bacteria, a major global threat, due to the accessibility in pharmacies. Objectives: This study aimed to examine the Jordanian pharmacists’ antibiotic selection and over-the-counter [...] Read more.

Background: Globally, community pharmacists worldwide have prescribed more over-the-counter systemic antibiotics, posing significant issues for international organizations tackling antibiotic-resistant bacteria, a major global threat, due to the accessibility in pharmacies. Objectives: This study aimed to examine the Jordanian pharmacists’ antibiotic selection and over-the-counter antibiotic prescriptions. Methods: A total of 244 community pharmacists participated in an online standardized survey, which examined five essential domains including sources and trust of pharmacy antibiotic prescription information, category and frequency of permitted antimicrobials, prescription-free antimicrobials, interactions, antimicrobial prescription issues for pharmacists, and pharmacy staff’s knowledge of non-prescription antimicrobial questions and answers. Results: This study found that 1—pharmacists are confident in prescribing antibiotics and they use various tools to improve their skills. 2—Antibiotics were the most sought antimicrobials without a prescription, followed by antifungals and antivirals. 3—Throat, urinary tract, chest, and otitis media are the most common infections that require antibiotics. Pharmacists prescribe penicillin for 75% of throat infections, Fluoroquinolones for 48.2% of urinary tract infections, and cephalosporins for 35.9%. Macrolides are the most prevalent otitis media treatment (43.2%). 4—Some people obtain antimicrobial prescriptions without a valid reason or diagnosis. 5—Many pharmacists (171/244, 70%) agree or strongly believe that antibiotic prescription information is difficult to obtain. 6—Many pharmacists (183/200, 91.5%) aimed to educate patients on the risks and correct use of antimicrobials without prescriptions. Conclusions: These results show that Jordanian community pharmacists follow clinical antibiotic prescribing guidelines and conduct antimicrobial stewardship, yet they demand antimicrobials without prescriptions and lack decision support tools. Antibiotic classes address most diseases, and pharmacists emphasize antimicrobial misuse. Full article

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

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24 pages, 7266 KiB

Open AccessArticle

A Simple In Vitro Method to Determine Bactericidal Activity Against Mycobacterium abscessus Under Hypoxic Conditions

by Ruth Feilcke, Robert Eckenstaler, Markus Lang, Adrian Richter and Peter Imming

Antibiotics 2025, 14(3), 299; https://doi.org/10.3390/antibiotics14030299 - 13 Mar 2025

Viewed by 518

Abstract

Background/Objectives: Non-replicating persisters (NRPs) of Mycobacterium abscessus are a bacterial subpopulation that can survive in the host under unfavorable conditions, such as hypoxia or nutrient starvation. The eradication of these bacteria is difficult, which is one reason for the long treatment duration [...] Read more.

Background/Objectives: Non-replicating persisters (NRPs) of Mycobacterium abscessus are a bacterial subpopulation that can survive in the host under unfavorable conditions, such as hypoxia or nutrient starvation. The eradication of these bacteria is difficult, which is one reason for the long treatment duration and treatment failure. The drug discovery process should therefore contain methods to screen activity against NRPs. Methods: A hypoxic environment is used to generate NRPs of M. abscessus that are termed low-oxygen persisters (LOPs). For this, an oxidation process is used to transition a replicating culture of M. abscessus distributed in microtiter plates within a sealable box into LOPs. Colony counting, automated object counting, bactericidal activity determination of known agents, and confocal laser scanning microscopy are used to study the obtained culture. Results: The obtained culture shows typical attributes of non-replicating cells, such as significantly reduced replication, the reversibility of the LOP state under aerobic conditions, delayed regrowth on solid medium, altered morphological patterns on a single-cell level, and phenotypical resistance against a variety of clinically relevant antimycobacterial compounds. The study reveals metronidazole and niclosamide as bactericidal against M. abscessus LOPs. These compounds can be used as LOP verification compounds within the described model. Conclusions: Our model is easily implemented and quickly identifies compounds that are inactive under hypoxic conditions. It can therefore accelerate the identification of clinically effective antimycobacterial drug substances, and can be a helpful tool during the drug development process. Full article

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

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21 pages, 488 KiB

Open AccessArticle

Rosaceae Honey: Antimicrobial Activity and Prebiotic Properties

by Francesca Coppola, Manar Abdalrazeq, Florinda Fratianni, Maria Neve Ombra, Bruno Testa, Gokhan Zengin, Jesus Fernando Ayala Zavala and Filomena Nazzaro

Antibiotics 2025, 14(3), 298; https://doi.org/10.3390/antibiotics14030298 - 13 Mar 2025

Cited by 1 | Viewed by 1231

Abstract

Background: Flowering members of the globally diffused Rosaceae family include popular plants, such as apple, almond, and cherry, which play a fundamental role as honeybee nectariferous and polleniferous agents. Through the production of honey, these plants can also play an indirect role in [...] Read more.

Background: Flowering members of the globally diffused Rosaceae family include popular plants, such as apple, almond, and cherry, which play a fundamental role as honeybee nectariferous and polleniferous agents. Through the production of honey, these plants can also play an indirect role in the prevention and treatment of many diseases, including infections, fighting the occurrence of resistant microorganisms, and concurrently stimulating the growth of beneficial bacteria. Objectives: This study focused on the effect of some Rosaceae plants’ honey, including hawthorn, cherry, raspberry, almond, and apple, against the pathogens Acinetobacter baumannii, Escherichia coli, Klebsiella pneumoniae, Listeria monocytogenes, Pseudomonas aeruginosa, and Staphylococcus aureus. Results: Results demonstrated the honey’s ability to impair swimming motility. A crystal violet test indicated that honey could inhibit the formation and stabilization of biofilms, with inhibition rates up to 59.43% for immature biofilms (showed by apple honey against A. baumannii) and 39.95% for sessile bacterial cells in mature biofilms (when we used cherry honey against S. aureus). In the test with 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide, cherry and apple honey were the most effective in inhibiting sessile cell metabolism honey in both immature (56.47% cherry honey vs. K. pneumoniae) and mature biofilms (54.36% apple honey vs. A. baumannii). Honey stimulated the growth of Lactobacillus bulgaricus, Lacticaseibacillus casei Shirota, Lactobacillus gasseri, Lacticaseibacillus plantarum, and Lacticaseibacillus rhamnosus; hawthorn, raspberry, and almond honey significantly increased the in vitro adhesion capacity of L. bulgaricus and L. casei Shirota. Tests with probiotic supernatants demonstrated honey’s ability to inhibit the biofilm formation and metabolism of the pathogens. Conclusions: Our results encourage further studies to assess the potential application of Rosaceae honey for food preservation and in the health field, as it could fight the antimicrobial resistance of food and clinical pathogens, and potentially enhance the host’s gut wellness. The use of honey for nanotechnological and biotechnological approaches could be suggested too. Full article

(This article belongs to the Special Issue Honey: Antimicrobial and Anti-infective Function)

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Antibiotics, Volume 14, Issue 3 (March 2025) – 115 articles

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