Antibiotics

13 pages, 1591 KiB

Open AccessArticle

Antimicrobial Performance of a Novel Drug-Eluting Bioenvelope

by Zerelda Esquer Garrigos, Sunil Kapur, Michelle LeRoux Williams and M. Rizwan Sohail

Antibiotics 2025, 14(4), 330; https://doi.org/10.3390/antibiotics14040330 (registering DOI) - 21 Mar 2025

Background: Preventing infections associated with cardiac implantable electronic devices (CIED) and neurostimulators is essential to optimizing patient outcomes. This study aimed to evaluate the antimicrobial performance of a biologic CIED envelope incorporating a bioabsorbable disc infused with rifampin and minocycline. Methods: The [...] Read more.

Background: Preventing infections associated with cardiac implantable electronic devices (CIED) and neurostimulators is essential to optimizing patient outcomes. This study aimed to evaluate the antimicrobial performance of a biologic CIED envelope incorporating a bioabsorbable disc infused with rifampin and minocycline. Methods: The antimicrobial activity was evaluated in a rabbit model and in vitro elution tests. Based on in vivo–in vitro correlation studies, a modified AATCC-100 method was used to quantitatively assess antibacterial activity across seven bacterial strains relevant to CIED infections. Results: Pharmacokinetic analysis showed a biphasic elution profile, with rapid initial release followed by more gradual elution over 14 days. The AATCC results showed no bacterial recovery for any tested species, with complete eradication in all replicates. Conclusions: These results support the use of antibiotic-eluting bioenvelopes as an effective strategy for preventing bacterial infections associated with CIED. The modified AATCC-100 test and in vivo–in vitro correlation studies provide new tools for the evaluation of the antibiotic activity of implantable biomaterials. Full article

(This article belongs to the Section Antimicrobial Materials and Surfaces)

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17 pages, 1622 KiB

Open AccessArticle

Molecular Characterization of Extended-Spectrum ß-Lactamases-Producing Escherichia coli Isolated from a Greek Food Testing Laboratory

by Aikaterini Dikaiou, Nikolaos Tzimotoudis, Daniel Sergelidis, Emmanouil Papadogiannakis and Panagiota Giakkoupi

Antibiotics 2025, 14(4), 329; https://doi.org/10.3390/antibiotics14040329 (registering DOI) - 21 Mar 2025

Abstract

Background/Objectives: Over the past decade, extended-spectrum beta-lactamase (ESBL)-producing Escherichia coli have emerged as a significant public health concern due to their potential to spread beyond clinical settings and healthy carriers, in various environments, including in animal source foods. This study seeks to investigate [...] Read more.

Background/Objectives: Over the past decade, extended-spectrum beta-lactamase (ESBL)-producing Escherichia coli have emerged as a significant public health concern due to their potential to spread beyond clinical settings and healthy carriers, in various environments, including in animal source foods. This study seeks to investigate the molecular characteristics of ESBL-producing E. coli strains isolated from food of animal origin, with a focus on chromosomal typing, plasmid typing, and the description of the associated resistance genes’ genetic environment. Methods: Ninety-seven food of animal origin samples were tested for E. coli isolates resistant to cefotaxime. The resulting isolates were then subjected to antimicrobial susceptibility testing and PCR analysis to detect beta-lactamase genes. Additional assays, encompassing mating-out procedures, molecular typing utilizing Pulsed-Field Gel Electrophoresis, Multilocus Sequence Typing Analysis, and Oxford Nanopore Technology Lite whole plasmid sequencing, were also conducted. Results: E. coli was detected in 26 raw food specimens, generating a percentage of 27%. Fourteen of the current isolates (14%) were resistant to third generation cephalosporins, producing CTX-M-1, CTX-M-15, CTX-M-55, and SHV-12 beta-lactamases. The respective genes were accompanied by Insertion Sequences ISEcp1 and IS26, facilitating their transfer. Among plasmids harboring ESBL genes, representatives belonging to incI1 incompatibility group prevailed (5/8), followed by IncY and IncX3. Most plasmids proved conjugative. Diversity of molecular fingerprints of ESBL producing E. coli was revealed. Conclusions: To the best our knowledge, this study is the first to describe the molecular characteristics of E. coli isolates producing ESBLs sourced from foods of animal origin in Greece. The prevalence of ESBLs in our confined food collection is primarily associated with the very successful IncI1 plasmids, which were not linked to a specific E. coli genetic background. This lack of association confirms that horizontal plasmid transfer plays a more significant role than clonal dissemination in the spread of ESBL-mediated cephalosporin resistance. Full article

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14 pages, 3299 KiB

Open AccessArticle

Trends in Antimicrobial Resistance of Canine Otitis Pathogens in the Iberian Peninsula (2010–2021)

by Biel Garcias, Mar Batalla, Anna Vidal, Inma Durán and Laila Darwich

Antibiotics 2025, 14(4), 328; https://doi.org/10.3390/antibiotics14040328 (registering DOI) - 21 Mar 2025

Abstract

Background: The close relationship between humans and petsraises health concerns due to the potential transmission of antimicrobial-resistant (AMR) bacteria and genes. Bacterial otitis is an emerging health problem in dogs, given its widespread prevalence and impact on animal welfare. Early detection of [...] Read more.

Background: The close relationship between humans and petsraises health concerns due to the potential transmission of antimicrobial-resistant (AMR) bacteria and genes. Bacterial otitis is an emerging health problem in dogs, given its widespread prevalence and impact on animal welfare. Early detection of resistance is vital in veterinary medicine to anticipate future treatment challenges. Objective: This study aimed to determine the prevalence of AMR bacteria involved in 12,498 cases of otitis in dogs from the Iberian Peninsula and the evolution of AMR patterns over an 11-year period. Methods: Data was provided by the Veterinary Medicine Department of a large private diagnostic laboratory in Barcelona. Antimicrobial susceptibility testing was performed using the standard disk diffusion method and minimum inhibitory concentration (MIC) testing. Results: The frequency of the principal bacterial agents was 35% Staphylococcus spp. (principally S. pseudointermedius), 20% Pseudomonas spp. (P. aeruginosa), 13% Streptococcus spp. (S. canis), and 11% Enterobacterales (Escherichia coli and Proteus mirabilis). Antimicrobial susceptibility testing revealed P. aeruginosa (among Gram-negatives) and Enterococcus faecalis (among Gram-positives) as the species with the highest AMR to multiple antimicrobial classes throughout the years. According to the frequency and time evolution of multidrug resistance (MDR), Gram-negative bacteria like P. mirabilis (33%) and E. coli (25%) presented higher MDR rates compared to Gram-positive strains like Corynebacterium (7%) and Enterococcus (5%). The AMR evolution also showed an increase in resistance patterns in Proteus spp. to doxycycline and Streptococcus spp. to amikacin. Conclusions: This information can be useful for clinicians, particularly in this region, to make rational antimicrobial use decisions, especially when empirical treatment is common in companion animal veterinary medicine. In summary, improving treatment guidelines is a key strategy for safeguarding both animal and human health, reinforcing the One Health approach. Full article

(This article belongs to the Special Issue Companion Animals: Antimicrobial Resistance in Bacterial and Fungal Pathogens Associated with Skin and Ear Infections)

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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

Abstract

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

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

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 (registering DOI) - 19 Mar 2025

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

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

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

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 Special Issue 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

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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13 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

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

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

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

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

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

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

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

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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