Antibiotics

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, 8908 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

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 with [...] 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. Conclusion 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)

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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Graphical abstract

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

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 Special Issue 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

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

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

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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