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Antibiotics
Volume 13
Issue 11
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Antibiotics, Volume 13, Issue 11 (November 2024) – 110 articles

Cover Story (view full-size image): In recent decades, bacterial antimicrobial resistance (AMR) has become one of the leading threats to public health. As of 2050, deaths associated with AMR are expected to reach 8.22 million. By this time, global economic losses will total USD 6.1 trillion annually, while also leading to a pronounced increase in extreme poverty, as economies of low-income countries are disproportionally affected. In light of this, there is an urgent need for the widespread availability of newly developed antimicrobial substances, along with well-defined methods and guidelines for laboratories to advise on their use. This study aimed to evaluate and compare the performance of different assays for antimicrobial susceptibility testing for reserve antibiotics in carbapenem-resistant Enterobacterales, Pseudomonas aeruginosa, and Acinetobacter baumannii. View this paper
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20 pages, 1676 KiB  
Article
The Characterisation of Carbapenem-Resistant Acinetobacter baumannii and Klebsiella pneumoniae in a Teaching Hospital in Malaysia
by Min Yi Lau, Sasheela Ponnampalavanar, Chun Wie Chong, Jacky Dwiyanto, Yee Qing Lee, Jia Jie Woon, Zhi Xian Kong, Azmiza Syawani Jasni, Michelle Chin Chin Lee, Unaizah Hanum Obaidellah and Cindy Shuan Ju Teh
Antibiotics 2024, 13(11), 1107; https://doi.org/10.3390/antibiotics13111107 (registering DOI) - 20 Nov 2024
Viewed by 639
Abstract
Background/Objectives: The emergence and dissemination of carbapenem-resistant organisms, particularly Acinetobacter baumannii and Klebsiella pneumoniae, pose a significant threat to healthcare systems worldwide. This retrospective study aims to characterise carbapenem-resistant Acinetobacter baumannii (CRAB) and carbapenem-resistant Klebsiella pneumoniae (CRKP) strains in a teaching [...] Read more.
Background/Objectives: The emergence and dissemination of carbapenem-resistant organisms, particularly Acinetobacter baumannii and Klebsiella pneumoniae, pose a significant threat to healthcare systems worldwide. This retrospective study aims to characterise carbapenem-resistant Acinetobacter baumannii (CRAB) and carbapenem-resistant Klebsiella pneumoniae (CRKP) strains in a teaching hospital and to determine the risk factors associated with patients’ in-hospital mortality. Methods: A total of 90 CRAB and 63 CRKP were included in this study. Carbapenemase genes and MLST types of CRAB and CRKP were determined using specific primers. Risk factors associated with in-hospital mortality were analysed with collected data. Results: All the CRAB strains consisted of OXA carbapenemase genes, with 98% of the strains co-harbouring blaOXA-23-like and blaOXA-51-like carbapenemase genes. Conversely, blaNDM is the predominant carbapenemase gene in CRKP, followed by blaOXA-48-like carbapenemase genes. ST2 and ST20 are the dominant MLST types in CRAB and CRKP, respectively. In CRAB, multivariate analysis identified age, ethnicity, the presence of a mechanical ventilator, and patients who experienced previous exposure to clindamycin in the last 90 days as associated with an increased risk of in-hospital mortality. In contrast, older age, male, ICU admission, and the presence of an indwelling urinary catheter were significantly associated with an increased risk of mortality for patients with CRKP. Conclusions: Both CRAB and CRKP lead to high rates of mortality. The MLST profile showed that the genomic patterns of CRKP were highly diverse, whereas CRAB strains had low genetic diversity. To tackle these challenging pathogens, robust surveillance and an in-depth understanding of molecular epidemiology and genomics studies are needed to tailor infection control strategies and individualise treatment approaches. Full article
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21 pages, 897 KiB  
Review
Therapeutic Potential of Silver Nanoparticles (AgNPs) as an Antimycobacterial Agent: A Comprehensive Review
by Nilakshi Barua and Alak Kumar Buragohain
Antibiotics 2024, 13(11), 1106; https://doi.org/10.3390/antibiotics13111106 - 20 Nov 2024
Viewed by 668
Abstract
The uncontrolled emergence of multidrug-resistant mycobacterial strains presents as the primary determinant of the present crisis in antimycobacterial therapeutics and underscores tuberculosis (TB) as a daunting global health concern. There is an urgent requirement for drug development for the treatment of TB. Numerous [...] Read more.
The uncontrolled emergence of multidrug-resistant mycobacterial strains presents as the primary determinant of the present crisis in antimycobacterial therapeutics and underscores tuberculosis (TB) as a daunting global health concern. There is an urgent requirement for drug development for the treatment of TB. Numerous novel molecules are presently undergoing clinical investigation as part of TB drug development. However, the complex cell wall and the lifecycle of M. tuberculosis within the host pose a significant challenge to the development of new drugs and, therefore, led to a shift in research focus towards alternative antibacterial compounds, notably nanotechnology. A novel approach to TB therapy utilizing silver nanoparticles (AgNPs) holds the potential to address the medical limitations imposed by drug resistance commonly associated with currently available antibiotics. Their broad-spectrum antimicrobial activity presents the utilization of AgNPs as a promising avenue for the development of therapeutics targeting mycobacterial-induced diseases, which can effectively target Mycobacterium tuberculosis, including drug-resistant strains. AgNPs can enhance the effectiveness of traditional antibiotics, potentially leading to better treatment outcomes and a shorter duration of therapy. However, the successful implementation of this complementary strategy is contingent upon addressing several pivotal therapeutic challenges, including suboptimal delivery, variability in intra-macrophagic antimycobacterial effect, and potential toxicity. Future perspectives may involve developing targeted delivery systems that maximize therapeutic effects and minimize side effects, as well as exploring combinations with existing TB medications to enhance treatment outcomes. We have attempted to provide a comprehensive overview of the antimycobacterial activity of AgNPs, and critically analyze the advantages and limitations of employing silver nanoparticles in the treatment of TB. Full article
(This article belongs to the Special Issue Antimicrobial Nanoformulations against Bacterial Infections)
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7 pages, 239 KiB  
Brief Report
Rapid Detection of Carbapenemases Using NG-Test® CARBA 5 in Positive Blood Cultures: A Diagnostic Test Study
by Diana Munguia-Ramos, Luis Fernando Xancal-Salvador, Verónica Esteban-Kenel, Narciso Ortiz-Conchi, Ricardo Antonio Jaimes-Aquino, Miguel Mendoza-Rojas, Axel Cervantes-Sánchez, Steven Méndez-Ramos, Hector Orlando Rivera-Villegas, Sandra Rajme-Lopez, Karla Maria Tamez-Torres, Carla Marina Roman-Montes, Areli Martínez-Gamboa, Miriam Bobadilla del-Valle, Jose Sifuentes-Osornio, Alfredo Ponce-de-Leon, Maria Fernanda Gonzalez-Lara and Bernardo Alfonso Martinez-Guerra
Antibiotics 2024, 13(11), 1105; https://doi.org/10.3390/antibiotics13111105 - 20 Nov 2024
Viewed by 436
Abstract
Background: Infections due to carbapenem-resistant Gram-negative bacteria are emerging as an important challenge in health-care settings and a growing concern worldwide. Lateral flow immunoassay NG-Test® CARBA 5 can detect the five most reported carbapenemases (KPC, OXA-48-like, VIM, IMP, and NDM). Direct testing [...] Read more.
Background: Infections due to carbapenem-resistant Gram-negative bacteria are emerging as an important challenge in health-care settings and a growing concern worldwide. Lateral flow immunoassay NG-Test® CARBA 5 can detect the five most reported carbapenemases (KPC, OXA-48-like, VIM, IMP, and NDM). Direct testing of positive blood cultures could reduce time to detection. This study aims to validate and report on the diagnostic yield of a novel method for carbapenemase detection in positive blood culture vials using NG-Test® CARBA 5. Methods: We implemented an investigator-developed method for the direct testing of positive blood cultures using NG-Test® CARBA 5. We compared results between genotypic, phenotypic, and direct NG-Test® CARBA 5 in blood. Results: A total of 32 isolates were tested (21 Enterobacterales and 11 Pseudomonas aeruginosa). Genotypic testing detected 23 carbapenemases. When comparing the results of NG-Test® CARBA 5 in blood with genotypic testing, agreement was observed in 31/32 (97%) tests. The sensitivity, specificity, positive predictive value, and negative predictive value of the NG-Test® CARBA 5 in blood were 93%, 100%, 100%, and 94%, respectively. Conclusions: Our method using NG-Test® CARBA 5 directly in blood culture samples presented an excellent diagnostic yield when compared to genotypic profiling and permits an accurate detection of carbapenemases. Full article
(This article belongs to the Special Issue Microbial Resistance to Carbapenems: Epidemiology, Detection and Treatment Options)
18 pages, 5476 KiB  
Article
Antibiotic Prescribing Decisions for Upper Respiratory Tract Infections Among Primary Healthcare Physicians in China: A Mixed-Methods Approach Based on the Theory of Planned Behavior
by Muhtar Kadirhaz, Yushan Zhang, Nan Zhao, Iltaf Hussain, Sen Xu, Miaomiao Xu, Chengzhou Tang, Wei Zhao, Yi Dong, Yu Fang and Jie Chang
Antibiotics 2024, 13(11), 1104; https://doi.org/10.3390/antibiotics13111104 - 20 Nov 2024
Viewed by 356
Abstract
Objectives: In China, primary healthcare (PHC) facilities have high antibiotic prescribing rates for upper respiratory tract infections (URTIs), which are primarily viral and self-limited. This study aimed to identify the main factors influencing PHC physicians’ antibiotic decisions for URITs based on the theory [...] Read more.
Objectives: In China, primary healthcare (PHC) facilities have high antibiotic prescribing rates for upper respiratory tract infections (URTIs), which are primarily viral and self-limited. This study aimed to identify the main factors influencing PHC physicians’ antibiotic decisions for URITs based on the theory of planned behavior. Methods: A convergent mixed-methods study was conducted at 30 PHC facilities across Shaanxi Province, China. A total of 108 PHC physicians completed a five-point Likert Scale questionnaire focused on behavioral components of antibiotic prescribing, including attitudes, subjective norms, perceived behavioral control, belief in past experiences, and prescribing intentions. Twenty-two physicians participated in semi-structured interviews. Results: Respondents had a good awareness of AMR (Mean = 4.49) and a weak belief regarding the benefit of antibiotics (Mean = 2.34). The mean score for subjective norms was 3.36, and respondents had good control over their prescribing behavior (Mean = 4.00). A reliance on past prescribing experiences was observed (Mean = 3.34), and physicians’ antibiotic prescribing intention was 3.40 on average. Multiple linear regression revealed that physicians showing a more favorable attitude towards antibiotics (p = 0.042) and relying more on their past experiences (p = 0.039) had a higher antibiotic prescribing intention. Qualitative interviews indicated that most physicians would consider prescribing antibiotics when facing diagnostic uncertainty. Low utilization of diagnostic tests, limited effectiveness of training programs, inadequate knowledge of guidelines, and lack of feedback on antibiotic prescriptions all contributed to antibiotic overprescribing. Conclusions: PHC physicians in China demonstrated strong intentions to prescribe antibiotics for URTIs when facing diagnostic uncertainty. Beliefs about antibiotics and previous prescribing behavior were significantly linked to prescribing intentions. Multifaceted interventions that focus on facilitating diagnostic tests, improving the quality of training, effectively implementing clinical guidelines, and providing practical feedback on antibiotic prescriptions may help reduce antibiotic overprescribing in China’s PHC facilities. Full article
(This article belongs to the Section Antibiotics Use and Antimicrobial Stewardship)
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12 pages, 6025 KiB  
Article
Model-Based Dose Identification of Dalbavancin for Long-Term Suppressive Outpatient Treatment of Ventricular Assist Device Infections
by Ute Chiriac, Uwe Liebchen, Otto Roman Frey, Heike Lanzinger, Sabrina Klein, Torsten Hoppe-Tichy, Matthias Karck, Anna Meyer and Benedict Morath
Antibiotics 2024, 13(11), 1103; https://doi.org/10.3390/antibiotics13111103 - 20 Nov 2024
Viewed by 442
Abstract
Increasing evidence suggests that dalbavancin is an effective long-term treatment for ventricular assist device (VAD) infections, with various prolonged dosing regimens currently in use. This retrospective study aimed to assess dalbavancin pharmacokinetics in VAD patients and identify optimal, feasible dosing regimens for long-term [...] Read more.
Increasing evidence suggests that dalbavancin is an effective long-term treatment for ventricular assist device (VAD) infections, with various prolonged dosing regimens currently in use. This retrospective study aimed to assess dalbavancin pharmacokinetics in VAD patients and identify optimal, feasible dosing regimens for long-term suppressive outpatient therapy. Data from Heidelberg University Hospital’s VAD register were analyzed using non-linear mixed-effects modeling for pharmacokinetic analysis and dosing simulations (Lixoft®). The probability of target attainment (PTA) and cumulative fraction of response (CFR) were calculated for different protein-binding scenarios considering the minimum inhibitory concentration (MIC) distribution of Staphylococcus aureus. Using data from 13 patients with 38 blood samples, a two-compartment model best described the dalbavancin pharmacokinetics, with a typical value for clearance of 0.050 L/h, central volume of distribution of 6.5 L, and peripheral volume of 15.4 L. No covariates significantly improved the model fit. The observed protein binding varied between 96 and 98%. Dosing simulations demonstrated that 1500 mg every 3 weeks ensured the target attainment for stasis at MIC values of 0.125 mg/L (PTA ≥ 90%) up to a protein binding of 99%. Considering the CRF, longer dosing intervals up to 5 weeks might be possible. Depending on individual MICs and protein binding, a dalbavancin regimen of 1500 mg every 3 to 5 weeks therefore appears to be a valuable option for outpatient therapy of VAD infections. Therapeutic drug monitoring should be considered to manage inter-individual variability and to support clinicians in long-term treatments of subacute and chronic infections. Full article
(This article belongs to the Section Pharmacokinetics and Pharmacodynamics of Drugs)
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17 pages, 2707 KiB  
Article
Tigecycline Containing Polymethylmethacrylate Cement Against MRSA, VRE, and ESBL—In Vitro Mechanical and Microbiological Investigations
by Michael Abramowicz, Andrej Trampuz and Klaus-Dieter Kühn
Antibiotics 2024, 13(11), 1102; https://doi.org/10.3390/antibiotics13111102 - 19 Nov 2024
Viewed by 428
Abstract
Background: The use of antibiotic-loaded bone cements (ALBCs) in arthroplasty has been well established for the prevention and treatment of infections. Tigecycline (Tig), a broad-spectrum antibiotic, has shown efficacy against various pathogens, including vancomycin-resistant strains. Method: ISO and DIN mechanical and microbiological inhibition [...] Read more.
Background: The use of antibiotic-loaded bone cements (ALBCs) in arthroplasty has been well established for the prevention and treatment of infections. Tigecycline (Tig), a broad-spectrum antibiotic, has shown efficacy against various pathogens, including vancomycin-resistant strains. Method: ISO and DIN mechanical and microbiological inhibition zone tests were performed on PMMA cement with manually added Tigecycline. Results: Manually adding 0.5 and 1.0 g Tigecycline to PMMA always meets the mechanical requirements of ISO and DIN standards. Mixtures containing 0.5 g were microbiologically effective for up to 7 days and those containing 1.0 g were effective for 28–42 days. Conclusion: In revision surgery, manually adding Tigecycline in doses of 0.5–1 g to 40 g of PMMA is effective against MRSA, VRE, and ESBL without negatively affecting the cement’s properties. Full article
(This article belongs to the Special Issue Prevention, Diagnostic and Antibiotic Treatment of Periprosthetic Joint and Fracture Related Infection, 2nd Edition)
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18 pages, 3755 KiB  
Article
Immunomodulatory Effects of the Tobacco Defensin NaD1
by Ekaterina I. Finkina, Ivan V. Bogdanov, Olga V. Shevchenko, Serafima I. Fateeva, Anastasia A. Ignatova, Sergey V. Balandin and Tatiana V. Ovchinnikova
Antibiotics 2024, 13(11), 1101; https://doi.org/10.3390/antibiotics13111101 - 19 Nov 2024
Viewed by 325
Abstract
Background/Objectives: Defensins are important components of the innate plant immune system, exhibiting antimicrobial activity against phytopathogens, as well as against fungi pathogenic to humans. Along with antifungal activity, plant defensins are also capable of influencing various immune processes, but not much is known [...] Read more.
Background/Objectives: Defensins are important components of the innate plant immune system, exhibiting antimicrobial activity against phytopathogens, as well as against fungi pathogenic to humans. Along with antifungal activity, plant defensins are also capable of influencing various immune processes, but not much is known about these effects. In this study, we investigated the immunomodulatory effects of the tobacco defensin NaD1, which possesses a pronounced antifungal activity. Methods and Results: We showed that NaD1 could penetrate the Caco-2 polarized monolayer. Using a multiplex assay with a panel of 48 cytokines, chemokines and growth factors, we demonstrated that NaD1 at a concentration of 2 μM had immunomodulatory effects on human dendritic cells and blood monocytes, mainly inhibiting the production of various immune factors. Using the sandwich ELISA method, we demonstrated that NaD1 at the same concentration had a pronounced immunomodulatory effect on unstimulated THP-1-derived macrophages and those stimulated by bacterial LPS or fungal zymosan. NaD1 had a dual effect and induced the production of both pro-inflammatory cytokine IL-1β as well as anti-inflammatory IL-10 on resting and pro-inflammatory THP-1-derived macrophages. We also found that the immunomodulatory effects of the tobacco defensin NaD1 and the pea defensin Psd1 differed from each other, indicating nonuniformity in the modes of action of plant defensins. Conclusions: Thus, our data demonstrated that the tobacco defensin NaD1 exhibits different immunomodulatory effects on various immune cells. We hypothesized that influence on human immune system along with antifungal activity, could determine the effectiveness of this peptide under infection in vivo. Full article
(This article belongs to the Special Issue Antimicrobial Peptides: An Emerging Hope in the Era of New Infections and Resistance)
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15 pages, 3243 KiB  
Article
Proteomic Analysis of Vibrio parahaemolyticus-Stimulated Pinctada martensii Proteins for Antimicrobial Activity, Potential Mechanisms, and Key Components
by Haisheng Lin, Weiqiang Shen, Bei Luo, Wenhong Cao, Xiaoming Qin, Jialong Gao, Zhongqin Chen, Huina Zheng and Bingbing Song
Antibiotics 2024, 13(11), 1100; https://doi.org/10.3390/antibiotics13111100 - 19 Nov 2024
Viewed by 329
Abstract
Background: Bacterial infections are a major challenge in food processing and public health, and there is an urgent need to develop novel antimicrobial agents. Objectives: The purpose of this study is to investigate the potential mechanism and key components of Pinctada martensii antimicrobial [...] Read more.
Background: Bacterial infections are a major challenge in food processing and public health, and there is an urgent need to develop novel antimicrobial agents. Objectives: The purpose of this study is to investigate the potential mechanism and key components of Pinctada martensii antimicrobial proteins (Pm-Aps) to provide a theoretical basis for the development of novel antimicrobial agents. Methods: The researchers used Vibrio parahaemolyticus (VP) to stimulate Pinctada martensii, extracted the antimicrobial proteins, and analyzed their antimicrobial activities, potential mechanisms of action, and key components using proteomics. Results: The results showed that the antimicrobial activity of Pm-Aps, with broad-spectrum antimicrobial effects, was significantly enhanced after VP stimulation. This was associated with the upregulation of LAAO, CHDH, TLR2, ATG16L1, BAK, CLCA4, and CASP8 and the downregulation of MCM3, MCM5, DTYMK, PLK1, FBXO6, LPCAT3, GST, LAMTOR5, CYP17A, CTSA, and RRM1. It is hypothesized that these proteins may inhibit bacterial growth and multiplication by activating immune-related signaling pathways, inhibiting DNA replication and repair, and inducing apoptosis and autophagy. Furthermore, it was found that LAAO may be a key component of the antimicrobial action of Pm-Aps, killing bacteria by catalyzing the oxidation of amino acids to produce hydrogen peroxide (H2O2). Conclusions: These results strongly suggest that Pm-Aps is an effective antimicrobial protein, and it is expected that new LAAO can be obtained from Pm-Aps. Full article
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12 pages, 1221 KiB  
Article
Evaluating the Efficacy of Inhaled Colistin via Two Nebulizer Types in Ventilator-Associated Pneumonia: Prospective Randomized Trial
by Chung-Chi Huang, Tien-Pei Fang, Chieh-Mo Lin, Chien-Ming Chu, Hsuan-Ling Hsiao, Jui-Fang Liu, Hsin-Hsien Li, Li-Chung Chiu, Kuo-Chin Kao, Chin-Hsi Kuo, Shaw-Woei Leu and Hui-Ling Lin
Antibiotics 2024, 13(11), 1099; https://doi.org/10.3390/antibiotics13111099 - 19 Nov 2024
Viewed by 530
Abstract
Backgroud: This prospective randomized trial evaluated the clinical efficacy of inhaled colistin administered through two distinct nebulizer types, a vibrating mesh nebulizer (VMN) and a jet nebulizer (JN), in the treatment of ventilator-associated pneumonia caused by multidrug-resistant bacteria. In addition, an in vitro [...] Read more.
Backgroud: This prospective randomized trial evaluated the clinical efficacy of inhaled colistin administered through two distinct nebulizer types, a vibrating mesh nebulizer (VMN) and a jet nebulizer (JN), in the treatment of ventilator-associated pneumonia caused by multidrug-resistant bacteria. In addition, an in vitro model was used to determine the optimal delivery of colistin. Method: Thirty-two patients prescribed intravenous (IV) colistin inhalation were randomized to receive either a VMN (n = 17) or a JN (n = 15), then compared to the control group (IV alone) over a 7-to 10-day period. The primary endpoint was the clinical pulmonary infection score (CPIS), and the secondary endpoints were the Sequential Organ Failure Assessment (SOFA) score, Acute Physiology and Chronic Health Evaluation (APACE) score, and duration of ventilator use. Results: Results from in vitro testing demonstrated that VMN delivered a significantly higher colistin dose than JN (35.68 ± 3.55% vs. 23.56 ± 3.31%; p < 0.001) when positioned at the humidifier inlet. Compared to the IV alone group, the IV with inhalation group yielded significant improvements in CPIS, SOFA score, and APACHE score on day 7; nevertheless, clinical outcomes between the two nebulizers were statistically indistinguishable. Conclusions: In conclusion, although VMN delivers a higher dose in vitro, both nebulizers yielded comparable clinical outcomes. This study was registered at US Clinical Trial Registration (NCT04633317). Full article
(This article belongs to the Section Antibiotic Therapy in Infectious Diseases)
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28 pages, 386 KiB  
Review
Screening Methods for Antimicrobial Residues in the Dairy Chain—The Past and the Present
by Pavlína Navrátilová, Lenka Vorlová, Sandra Dluhošová, Klára Bartáková, Oto Hanuš and Eva Samková
Antibiotics 2024, 13(11), 1098; https://doi.org/10.3390/antibiotics13111098 - 19 Nov 2024
Viewed by 488
Abstract
The presence of residues of antimicrobial substances in milk has been an important hygienic and technological parameter of raw milk quality since the 1960s. The presented review focuses on screening methods (microbiological inhibition methods and rapid specific tests) that are used in the [...] Read more.
The presence of residues of antimicrobial substances in milk has been an important hygienic and technological parameter of raw milk quality since the 1960s. The presented review focuses on screening methods (microbiological inhibition methods and rapid specific tests) that are used in the control of antimicrobial residues in milk in the context of their historical development up to the present. We briefly explain the principles of the methods and discuss their pros and cons. The aim was to provide both the historical perspective on this topic and provide useful information on screening methods that are currently routinely used for the detection of residues of antimicrobials at farms, in the dairy industry, and in milk quality control laboratories. Full article
(This article belongs to the Special Issue Emerging Challenges in Food Safety: Addressing Antimicrobial Resistance, Virulence Factors, and Biofilm Formation in Food-Borne Pathogens)
12 pages, 279 KiB  
Article
Ciprofloxacin Concentrations in Food Could Select for Quinolone Resistance in Klebsiella pneumoniae: An In Vivo Study in Galleria mellonella
by Nele Panis, Zina Gestels, Dorien Van Den Bossche, Irith De Baetselier, Said Abdellati, Thibaut Vanbaelen, Tessa de Block, Sheeba Santhini Manoharan-Basil and Chris Kenyon
Antibiotics 2024, 13(11), 1097; https://doi.org/10.3390/antibiotics13111097 - 18 Nov 2024
Viewed by 501
Abstract
Background: The use of antimicrobials to treat food animals leaves antimicrobial residues in foodstuffs. The World Health Organization (WHO) defines the acceptable daily intakes (ADIs) of these residues as the dose of these antimicrobials that is safe for an average human to [...] Read more.
Background: The use of antimicrobials to treat food animals leaves antimicrobial residues in foodstuffs. The World Health Organization (WHO) defines the acceptable daily intakes (ADIs) of these residues as the dose of these antimicrobials that is safe for an average human to consume on a daily basis. We hypothesized that the lowest dose of ciprofloxacin classified as safe by the WHO could select for ciprofloxacin-resistant strains of Klebsiella pneumoniae in a Galleria mellonella model. Objectives: We aimed to evaluate if the consumption of peri-ADI doses of ciprofloxacin could select for ciprofloxacin-resistant (Ser464Phe, GyrB, ciprofloxacin MIC of 4 µg/mL) compared to -susceptible (isogenic, ciprofloxacin MIC of 0.047 µg/mL) strains of K. pneumoniae in a Galleria mellonella model. Results: A significant increase was seen in the proportion of resistance for the 1× ADI and 1/10th ADI concentrations on day 2 compared to the positive control. Methods: A model of K. pneumoniae infection in G. mellonella larvae was used for the experiment. The larvae were inoculated with K. pneumoniae followed by 10× ADI, 1× ADI, 1/10th ADI, 1/100th ADI, and 1/1000th ADI doses of ciprofloxacin. The isolation of K. pneumoniae colonies was then performed on selective agar plates with and without ciprofloxacin (1 µg/mL). The proportion of colonies with ciprofloxacin resistance was then calculated for each group at 24 and 48 h. Conclusions: We found that, at 48 h, there was an enrichment of K. pneumoniae colonies with ciprofloxacin resistance in the larvae receiving 1× ADI and 1/10th ADI concentrations of ciprofloxacin. These results suggest that the ciprofloxacin MSCselect for K. pneumoniae in this model is 1/10th of the acceptable daily concentration (ADI) dose of ciprofloxacin, which is equivalent to 0.239 ng/µL. Full article
18 pages, 1954 KiB  
Review
Structural Equation Modelling as a Proof-of-Concept Tool for Mediation Mechanisms Between Topical Antibiotic Prophylaxis and Six Types of Blood Stream Infection Among ICU Patients
by James Hurley
Antibiotics 2024, 13(11), 1096; https://doi.org/10.3390/antibiotics13111096 - 18 Nov 2024
Viewed by 532
Abstract
Whether exposing the microbiome to antibiotics decreases or increases the risk of blood stream infection with Pseudomonas aeruginosa, Staphylococcus aureus, Acinetobacter, and Candida among ICU patients, and how this altered risk might be mediated, are critical research questions. Addressing these [...] Read more.
Whether exposing the microbiome to antibiotics decreases or increases the risk of blood stream infection with Pseudomonas aeruginosa, Staphylococcus aureus, Acinetobacter, and Candida among ICU patients, and how this altered risk might be mediated, are critical research questions. Addressing these questions through the direct study of specific constituents within the microbiome would be difficult. An alternative tool for addressing these research questions is structural equation modelling (SEM). SEM enables competing theoretical causation networks to be tested ‘en bloc’ by confrontation with data derived from the literature. These causation models have three conceptual steps: exposure to specific antimicrobials are the key drivers, clinically relevant infection end points are the measurable observables, and the activity of key microbiome constituents on microbial invasion serve as mediators. These mediators, whether serving to promote, to impede, or neither, are typically unobservable and appear as latent variables in each model. SEM methods enable comparisons through confronting the three competing models, each versus clinically derived data with the various exposures, such as topical or parenteral antibiotic prophylaxis, factorized in each model. Candida colonization, represented as a latent variable, and concurrency are consistent promoters of all types of blood stream infection, and emerge as harmful mediators. 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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14 pages, 1958 KiB  
Review
Cinnamaldehyde in Focus: Antimicrobial Properties, Biosynthetic Pathway, and Industrial Applications
by Brandon Armando Jaramillo Jimenez, Fatima Awwad and Isabel Desgagné-Penix
Antibiotics 2024, 13(11), 1095; https://doi.org/10.3390/antibiotics13111095 - 18 Nov 2024
Viewed by 769
Abstract
Trans-cinnamaldehyde (TCA), a major bioactive compound derived from cinnamon (Cinnamomum spp.), has garnered significant attention for its diverse therapeutic properties. Its broad-spectrum antimicrobial activity, targeting both Gram-positive and Gram-negative bacteria as well as various fungi, positions TCA as a potent natural [...] Read more.
Trans-cinnamaldehyde (TCA), a major bioactive compound derived from cinnamon (Cinnamomum spp.), has garnered significant attention for its diverse therapeutic properties. Its broad-spectrum antimicrobial activity, targeting both Gram-positive and Gram-negative bacteria as well as various fungi, positions TCA as a potent natural antimicrobial agent. Beyond its antimicrobial effects, TCA demonstrates promising antidiabetic and anti-inflammatory activities, making it a valuable compound in medicinal and cosmetic applications. Recent studies have highlighted its role in disrupting microbial membranes, inhibiting biofilm formation, and modulating key metabolic pathways in pathogens. Furthermore, TCA has gained popularity in cosmetics due to its antimicrobial activity, antioxidant properties, and skin-friendly profile. This review provides a comprehensive overview of TCA’s antimicrobial potential, focusing on its mechanisms of action and its market and industrial applications. We also discuss the biosynthetic pathway of TCA, exploring both its natural production in cinnamon and advances in biotechnological production methods. As the demand for sustainable and natural antimicrobial agents grows, TCA emerges as a promising candidate for diverse applications. Finally, this review explores future directions for optimizing TCA production through metabolic engineering and synthetic biology approaches to meet industrial-scale demands. Full article
(This article belongs to the Special Issue Antimicrobial Activity of Secondary Metabolites Produced in Nature)
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9 pages, 869 KiB  
Article
Improving Turnaround Times for Routine Antimicrobial Sensitivity Testing Following European Committee on Antimicrobial Susceptibility Testing Methodology in Patients with Bacteraemia
by Raewyn Edmondson, Kordo Saeed, Steve Green and Matthew O’Dwyer
Antibiotics 2024, 13(11), 1094; https://doi.org/10.3390/antibiotics13111094 - 17 Nov 2024
Viewed by 540
Abstract
Background/Objectives: Bacteraemia can be fatal without antibiotic intervention. Antibiotic Susceptibility Testing (AST) provides the necessary information for targeted antibiotic therapy; however, the traditional method using disc diffusion can take over two days from a positive blood culture. Inappropriate empiric therapy is associated [...] Read more.
Background/Objectives: Bacteraemia can be fatal without antibiotic intervention. Antibiotic Susceptibility Testing (AST) provides the necessary information for targeted antibiotic therapy; however, the traditional method using disc diffusion can take over two days from a positive blood culture. Inappropriate empiric therapy is associated with increased mortality and increased antibiotic resistance, highlighting the need for more rapid turnaround times for AST. By making changes to an established method, turnaround times can be reduced. Methods: Eighty-two patient positive blood culture samples were collected from January to April 2022, representing the range of common bacteria causing sepsis. This followed the normal methodology in the laboratory of inoculating agar from positive blood cultures in preparation for European Committee on Antimicrobial Susceptibility Testing (EUCAST) disc diffusion AST method. EUCAST methodology outlines that disc diffusion should be performed on isolates from an overnight culture of 16–24 h. This study looked at comparing disc diffusion results from cultures with 6 h of incubation to those with incubation times of 24 h, after organism identification by MALDI-ToF. Results from 6-h and 24-h cultures were compared by disc zone sizes and by interpreted susceptibility reading following EUCAST guidelines of sensitive, resistant, susceptible with increased exposure, or an area of technical uncertainty. Results: A total of 99.65% interpreted susceptibility readings matched across all organisms to all relevant antibiotics, with an average zone size difference of 1.08 mm between results from 6 h versus 24 h cultures. Conclusions: This method offers a non-automated way of using the traditional disc diffusion method, reducing turnaround times while still producing reliable and accurate results. This would mean validated ASTs can be set up in the same day as a blood culture flags positive rather than waiting for a longer culture. As this method is widely used within the laboratory already, it would mean that additional training is not required, as the process is the same, and only incubation time varies. This would positively impact patient outlook due to the shorter use of empiric therapy, and benefit antimicrobial stewardship (AMS). Full article
(This article belongs to the Special Issue Clinical Guidelines and Real Practice of Antimicrobial Pharmacotherapy)
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14 pages, 1331 KiB  
Article
Risk Assessment and Recommended Approaches to Optimize Infection Control and Antibiotic Stewardship to Reduce External Ventricular Drain Infection: A Single-Center Study
by Jozsef Kelemen, Marton Sztermen, Eva Dakos, Gergely Agocs, Jozsef Budai, Jozsef Katona, Zsuzsanna Szekeressy, Laszlo Sipos, Zoltan Papp, Mate Bata, Janos Karczub, Mate Korompai, Zsuzsanna A. Dunai, Bela Kocsis, Dora Szabo and Lorand Eross
Antibiotics 2024, 13(11), 1093; https://doi.org/10.3390/antibiotics13111093 - 17 Nov 2024
Viewed by 494
Abstract
Background: An external ventricular drain (EVD) is used to release elevated intracranial pressure by draining cerebrospinal fluid (CSF) from the brain’s ventricles. The establishment of an EVD is one of the most commonly performed neurosurgical procedures to treat intracranial pressure in patients. Nevertheless, [...] Read more.
Background: An external ventricular drain (EVD) is used to release elevated intracranial pressure by draining cerebrospinal fluid (CSF) from the brain’s ventricles. The establishment of an EVD is one of the most commonly performed neurosurgical procedures to treat intracranial pressure in patients. Nevertheless, infections are very frequent complications. Identifying the risk factors for EVD-related infections is a key to improving patient safety and outcomes. Methods: We conducted a retrospective, single-center study of patients who underwent EVD implantation between January 2022 and March 2024. Patients were classified into infected and non-infected groups based on their clinical symptoms, as well as laboratory and microbiological results. Patient characteristics and possible risk factors for infection were compared between the two groups. Results: In total, 123 patients treated with 156 EVDs were included in this study, with a mean age of 55.8 (range: 25–84) years. EVD-associated infections were observed in 37 patients (30%). We found no significant association between infection risk and patient characteristics, including gender, primary diagnosis, craniotomy, or immunosuppression. There was no significant difference in terms of EVD insertion, i.e., whether the insertion took place in the operating room (OR) with antibiotic prophylaxis or outside the OR with no periprocedural antibiotic treatment. However, within the intensive care unit (ICU), EVD infection was much lower (13%) if EVD insertion took place in a single-bed room compared to multiple-bed room insertions (34%). Furthermore, there were significant differences in terms of the duration of first EVD (both single and multiple catheterizations) (p < 0.0001) and the total catheterization time (p = 0.0001). Additionally, there was a significant association with patient days in the ICU and EVD catheterization. Conclusions: Revisiting infection control measures is necessary, with special attention to the replacement of EVDs in single-bed ICU rooms, to introduce antibiotic prophylaxis in the ICU. Minimizing unnecessary EVD manipulation during catheterization is crucial in order to decrease the risk of EVD infection. Full article
(This article belongs to the Special Issue Antimicrobial Treatment and Management of Central Nervous System Infections)
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23 pages, 6586 KiB  
Article
Studies Regarding Antimicrobial Properties of Some Microbial Polyketides Derived from Monascus Strains
by Daniela Albisoru, Nicoleta Radu, Lucia Camelia Pirvu, Amalia Stefaniu, Narcisa Băbeanu, Rusandica Stoica and Dragos Paul Mihai
Antibiotics 2024, 13(11), 1092; https://doi.org/10.3390/antibiotics13111092 - 16 Nov 2024
Viewed by 664
Abstract
Finding new molecules to prevent the growth of antimicrobial resistance is a hot topic for scientists worldwide. It has been reported that some raw bioproducts containing Monascus polyketides have antimicrobial activities, but extensive studies on this effect have not been conducted. In this [...] Read more.
Finding new molecules to prevent the growth of antimicrobial resistance is a hot topic for scientists worldwide. It has been reported that some raw bioproducts containing Monascus polyketides have antimicrobial activities, but extensive studies on this effect have not been conducted. In this context, our studies aimed to evaluate the antimicrobial properties of six raw bioproducts containing three classes of microbial polyketides biosynthesized by three Monascus strains through solid-state biosynthesis. As a methodology, we performed in silico predictions using programs such as PyMOL v3.0.4 and employed ESI-MS techniques to provide evidence of the presence of the six studied compounds in our bioproducts. The results obtained in silico were validated through in vitro studies using the Kirby-Bauer diffusion method on bacteria and fungi. The test performed in silico showed that Monascorubramine has the highest affinity for both Gram-positive and Gram-negative bacteria, followed by yellow polyketides such as Ankaflavin and Monascin. The estimated pharmacokinetic parameters indicated high gastrointestinal absorption and the potential to cross the blood-brain barrier for all studied compounds. However, the compounds also inhibit most enzymes involved in drug metabolism, presenting some level of toxicity. The best in vitro results were obtained for S. aureus, with an extract containing yellow Monascus polyketides. Predictions made for E. coli were validated in vitro for P. aeruginosa, S. enterica, and S. marcescens, as well as for fungi. Significant antibacterial properties were observed during this study for C. albicans, S. aureus, and fungal dermatophytes for crude bioproducts containing Monascus polyketides. In conclusion, the antimicrobial properties of Monascus polyketides were validated both in silico and in vitro. However, due to their potential toxicity, these bioproducts would be safer to use as topical formulations. Full article
(This article belongs to the Special Issue Antimicrobial and Anti-infective Activity of Natural Products, 2nd Edition)
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21 pages, 1602 KiB  
Review
A Comprehensive Review on the Antibacterial, Antifungal, Antiviral, and Antiparasitic Potential of Silybin
by José Lima Pereira-Filho, Amanda Graziela Gonçalves Mendes, Carmem Duarte Lima Campos, Israel Viegas Moreira, Cinara Regina Aragão Vieira Monteiro, Suzany Hellen da Silva Soczek, Elizabeth Soares Fernandes, Rafael Cardoso Carvalho and Valério Monteiro-Neto
Antibiotics 2024, 13(11), 1091; https://doi.org/10.3390/antibiotics13111091 - 15 Nov 2024
Viewed by 766
Abstract
Silybin, a flavonolignan extracted from the seeds of the plant species Silybum marianum (L.) Gaertn., has a variety of pharmacological activities, including antimicrobial activity against several microorganisms of clinical interest. This review analyzes the existing studies on silybin’s antimicrobial activity and possible mechanisms [...] Read more.
Silybin, a flavonolignan extracted from the seeds of the plant species Silybum marianum (L.) Gaertn., has a variety of pharmacological activities, including antimicrobial activity against several microorganisms of clinical interest. This review analyzes the existing studies on silybin’s antimicrobial activity and possible mechanisms of action. Silybin has been shown to inhibit the growth of Gram-positive and Gram-negative bacteria, as well as some fungi, viruses, and protozoa. In general, possible mechanisms of antimicrobial action include the inhibition of efflux pumps, prevention of biofilm formation, reduction of the expression of virulence factors, induction of apoptosis-like effects, and plasma membrane damage, as well as the inhibition of nucleic acid and protein synthesis. Silybin has been shown to have synergistic effects when combined with conventional antibiotics against both drug-sensitive and drug-resistant microorganisms. However, the low bioavailability observed for this flavonolignan has been a challenge to its clinical use. In this context, nanotechnology has been used to increase silybin’s bioavailability while enhancing its antimicrobial activity. Furthermore, certain structural modifications have been able to enhance its antimicrobial activity in comparison to that of the natural molecule. Overall, this review provides insights into the scientific understanding of the mechanism of action of silybin and its desired properties for the effective treatment of infections. Full article
(This article belongs to the Special Issue Antimicrobial and Anti-infective Activity of Natural Products, 2nd Edition)
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10 pages, 564 KiB  
Article
Methicillin-Resistant S. aureus Carrying the PVL and Toxic Shock Syndrome Toxin in Healthy Dogs in Algeria
by Fares Khermouche, Nouzha Heleili, Manel Merradi, Amina Hachemi, Antoine Drapeau, Séverine Murri, Jean-Yves Madec and Marisa Haenni
Antibiotics 2024, 13(11), 1090; https://doi.org/10.3390/antibiotics13111090 - 15 Nov 2024
Viewed by 582
Abstract
Background/Objectives: Staphylococcus aureus and Staphylococcus pseudintermedius are major opportunistic pathogens in both humans and dogs. In pets, the dissemination of methicillin-resistant isolates (MRSA or MRSP) is problematic for the treatment of animals and is a public health issue due to their zoonotic [...] Read more.
Background/Objectives: Staphylococcus aureus and Staphylococcus pseudintermedius are major opportunistic pathogens in both humans and dogs. In pets, the dissemination of methicillin-resistant isolates (MRSA or MRSP) is problematic for the treatment of animals and is a public health issue due to their zoonotic potential. MRSA and MRSP may also harbor virulent genes that increase their dangerousness. This study aimed to assess the prevalence of (MR)SA and (MR)SP in healthy dogs and their owners in Algeria. Methods: Swabs were collected from various body sites of healthy dogs (n = 88) and from the nose of their owners (n = 38). Antimicrobial susceptibility testing was performed by antibiograms according to the disc diffusion method, and clonality was assessed using Pulsed-Field Gel Electrophoresis (PFGE). All methicillin-resistant isolates were short-read whole-genome sequenced using the Illumina technology. Results: 26 S. aureus and 17 S. pseudintermedius isolates were respectively collected from 13 dogs (13/88, 14.8%). No MRSP isolate was detected, while MRSA was found in six dogs (6.8%). Isolates belonged to ST1 (n = 3), ST 80 (n = 1), and ST 22 (n = 2, including the single-locus variant ST7118). All MRSA displayed the immune evasion cluster (IEC) type E. The ST80 isolate presented the Panton–Valentine toxin, and the ST22/ST7118 isolates carried the tst gene coding for the toxic shock syndrome toxin. Conclusions: The epidemiology of MRSA in healthy Algerian dogs mirrors the one in Algerian people. This poses a zoonotic and public health concern due to the virulence and resistance genes displayed by these isolates. Our results indicate the need for developing One Health strategies to avoid a large-scale dissemination of MRSA in Algerian dogs. Full article
(This article belongs to the Special Issue Epidemiology of Zoonotic Pathogens and Antimicrobial Resistance)
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20 pages, 2961 KiB  
Article
The Impact of Urban Pollution on Plasmid-Mediated Resistance Acquisition in Enterobacteria from a Tropical River
by Bradd Mendoza-Guido, Kenia Barrantes, César Rodríguez, Keilor Rojas-Jimenez and Maria Arias-Andres
Antibiotics 2024, 13(11), 1089; https://doi.org/10.3390/antibiotics13111089 - 14 Nov 2024
Viewed by 896
Abstract
Background: The exposure of environmental bacteria to contaminants in aquatic ecosystems accelerates the dissemination of antibiotic-resistance genes (ARGs) through horizontal gene transfer (HGT). Methods: In this study, we sampled three locations along a contamination gradient of a polluted river, focusing on isolating Enterobacteria [...] Read more.
Background: The exposure of environmental bacteria to contaminants in aquatic ecosystems accelerates the dissemination of antibiotic-resistance genes (ARGs) through horizontal gene transfer (HGT). Methods: In this study, we sampled three locations along a contamination gradient of a polluted river, focusing on isolating Enterobacteria from the surface waters to investigate the relationship between urban pollution and antibiotic resistance. The genomes of 15 isolates (5 per site) were sequenced to identify plasmid-borne ARGs and their association with resistance phenotypes. Results: Isolates from the site with the highest contamination (Site 3) showeda larger number of ARGs, plasmids, and resistance phenotypes. Notably, one of the isolates analyzed, E. coli A231-12, exhibited phenotypic resistance to seven antibiotics, presumably conferred by a single plasmid carrying 12 ARGs. Comparative analysis of this plasmid revealed its close evolutionary relationship with another IncH plasmid hosted by Salmonella enterica, underscoring its high ARG burden in the aquatic environment. Other plasmids identified in our isolates carried sul and dfrA genes, conferring resistance to trimethoprim/sulfamethoxazole, a commonly prescribed antibiotic combination in clinical settings. Conclusions: These results highlight the critical need to expand research on the link between pollution and plasmid-mediated antimicrobial resistance in aquatic ecosystems, which can act as reservoirs of ARGs. Full article
(This article belongs to the Special Issue The Spread of Antibiotic Resistance in Natural Environments)
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13 pages, 3660 KiB  
Article
Phytogenic Synthesis of Cuprous and Cupric Oxide Nanoparticles Using Black jack Leaf Extract: Antibacterial Effects and Their Computational Docking Insights
by Sutha Paramasivam, Sathishkumar Chidambaram, Palanisamy Karumalaiyan, Gurunathan Velayutham, Muthusamy Chinnasamy, Ramar Pitchaipillai and K. J. Senthil Kumar
Antibiotics 2024, 13(11), 1088; https://doi.org/10.3390/antibiotics13111088 - 14 Nov 2024
Viewed by 481
Abstract
Background: Green synthesized nanoparticles (NPs) have gained increasing popularity in recent times due to their broad spectrum of antimicrobial properties. This study aimed to develop a phytofabrication approach for producing cuprous (Cu2O) and cupric oxide (CuO) NPs using a simple, non-hazardous [...] Read more.
Background: Green synthesized nanoparticles (NPs) have gained increasing popularity in recent times due to their broad spectrum of antimicrobial properties. This study aimed to develop a phytofabrication approach for producing cuprous (Cu2O) and cupric oxide (CuO) NPs using a simple, non-hazardous process and to examine their antimicrobial properties. Methods: The synthesis employed Bidens pilosa plant extract as a natural reducing and stabilizing agent, alongside copper chloride dihydrate as the precursor. The biosynthesized NPs were characterized through various techniques, including X-ray diffraction (XRD), transmission electron microscopy (TEM), Fourier-transform infrared (FT-IR) spectroscopy, ultraviolet–visible (UV-Vis) spectroscopy, scanning electron microscopy (SEM), and energy-dispersive X-ray spectroscopy (EDS). Results: XRD analysis confirmed that the synthesized CuO and Cu2O NPs exhibited a high degree of crystallinity, with crystal structures corresponding to monoclinic and face-centered cubic systems. SEM images revealed that the NPs displayed distinct spherical and sponge-like morphologies. EDS analysis further validated the purity of the synthesized CuO NPs. The antimicrobial activity of the CuO and Cu2O NPs was tested against various pathogenic bacterial strains, including Staphylococcus aureus, Pseudomonas aeruginosa, Escherichia coli, and Bacillus cereus, with the minimum inhibitory concentration (MIC) used to gauge their effectiveness. Conclusions: The results showed that the phytosynthesized NPs had promising antibacterial properties, particularly the Cu2O NPs, which, with a larger crystal size of 68.19 nm, demonstrated significant inhibitory effects across all tested bacterial species. These findings suggest the potential of CuO and Cu2O NPs as effective antimicrobial agents produced via green synthesis. Full article
(This article belongs to the Special Issue Discovery of Novel Antimicrobial Peptides Using Machine Learning and Molecular Dynamic Simulations)
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40 pages, 1037 KiB  
Review
Environmental Antimicrobial Resistance: Implications for Food Safety and Public Health
by Onyinye Victoria Ifedinezi, Nnabueze Darlington Nnaji, Christian Kosisochukwu Anumudu, Chiemerie Theresa Ekwueme, Chijioke Christopher Uhegwu, Francis Chukwuebuka Ihenetu, Promiselynda Obioha, Blessing Oteta Simon, Precious Somtochukwu Ezechukwu and Helen Onyeaka
Antibiotics 2024, 13(11), 1087; https://doi.org/10.3390/antibiotics13111087 - 14 Nov 2024
Viewed by 1034
Abstract
Antimicrobial resistance (AMR) is a serious global health issue, aggravated by antibiotic overuse and misuse in human medicine, animal care, and agriculture. This study looks at the different mechanisms that drive AMR, such as environmental contamination, horizontal gene transfer, and selective pressure, as [...] Read more.
Antimicrobial resistance (AMR) is a serious global health issue, aggravated by antibiotic overuse and misuse in human medicine, animal care, and agriculture. This study looks at the different mechanisms that drive AMR, such as environmental contamination, horizontal gene transfer, and selective pressure, as well as the severe implications of AMR for human and animal health. This study demonstrates the need for concerted efforts across the scientific, healthcare, agricultural, and policy sectors to control the emergence of AMR. Some crucial strategies discussed include developing antimicrobial stewardship (AMS) programs, encouraging targeted narrow-spectrum antibiotic use, and emphasizing the significance of strict regulatory frameworks and surveillance systems, like the Global Antimicrobial Resistance and Use Surveillance System (GLASS) and the Access, Watch, and Reserve (AWaRe) classification. This study also emphasizes the need for national and international action plans in combating AMR and promotes the One Health strategy, which unifies environmental, animal, and human health. This study concludes that preventing the spread of AMR and maintaining the effectiveness of antibiotics for future generations requires a comprehensive, multidisciplinary, and internationally coordinated strategy. Full article
(This article belongs to the Special Issue The Spread of Antibiotic Resistance in Natural Environments)
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30 pages, 3795 KiB  
Article
Isolation and Characterization of Infection of Four New Bacteriophages Infecting a Vibrio parahaemolyticus Strain
by João Duarte, David Trindade, Vanessa Oliveira, Newton C. M. Gomes, Ricardo Calado, Carla Pereira and Adelaide Almeida
Antibiotics 2024, 13(11), 1086; https://doi.org/10.3390/antibiotics13111086 - 14 Nov 2024
Viewed by 536
Abstract
Bacteria from genus Vibrio continue to be one of the most common threats to aquaculture sustainability. Vibrio spp. have been associated with infectious outbreaks in fish, shrimp, bivalves and even algae farms worldwide. Moreover, several Vibrio spp. are also pathogens that impact human [...] Read more.
Bacteria from genus Vibrio continue to be one of the most common threats to aquaculture sustainability. Vibrio spp. have been associated with infectious outbreaks in fish, shrimp, bivalves and even algae farms worldwide. Moreover, several Vibrio spp. are also pathogens that impact human health and are a threat to public health when transferred to consumers through contaminated seafood products. The use of bacteriophages is an evolving technology that could be applied in the treatment of Vibrio spp. either to protect aquaculture farms or to decontaminate seafood, namely bivalves during their depuration. In the present study, bacteriophages vB_VpS_LMAVpS1 (S1) vB_VpS_LMAVpVPP (VPP), vB_VpS_LMAVpSH (SH) and vB_VpS_LMAVpH (H) infecting V. parahaemolyticus were isolated and characterized. All phages presented fast adsorption rates and were able to control V. parahaemolyticus at all multiplicity of infections (MOIs) tested (MOI of 1, 10 and 100), with reductions of more than 4 log CFU/mL being recorded, but only in the presence of divalent cation calcium. The rate of emergence of phage-resistant mutants was very low (1.8 × 10−6 to 3.1 × 10−6). Bacterial phage resistance was not permanent and led to a loss of bacterial fitness. All four phages presented with lysins encoded in their genomes. The results presented provide valuable insights for future studies in the application of these bacteriophages in different scenarios to control, decontaminate or treat bacterial infections or contaminations of V. parahaemolyticus. Full article
(This article belongs to the Section Bacteriophages)
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11 pages, 276 KiB  
Article
Efficacy of Copper Ion Treatment on Bacteria and Antibiotic Residues Contained in Bovine Waste Milk
by Fernando Ulloa, Martina Penati, Constanza Naegel, Carlos Tejeda, Miguel Hernández-Agudelo, Pamela Steuer and Miguel Salgado
Antibiotics 2024, 13(11), 1085; https://doi.org/10.3390/antibiotics13111085 - 14 Nov 2024
Viewed by 525
Abstract
Background/Objectives: Waste milk harbors many bacteria and antibiotic residues. Calves fed with untreated waste milk have a higher incidence of scours and an increased risk of developing antimicrobial-resistant bacteria. This study aimed to evaluate the efficacy of treatment with copper ions on [...] Read more.
Background/Objectives: Waste milk harbors many bacteria and antibiotic residues. Calves fed with untreated waste milk have a higher incidence of scours and an increased risk of developing antimicrobial-resistant bacteria. This study aimed to evaluate the efficacy of treatment with copper ions on bacteria and antibiotics contained in bovine waste milk. Methods: Waste milk samples were collected from a dairy farm for seven weeks and were subjected to treatment with copper ions. Total bacterial counts, coliforms, Streptococcus, and Staphylococcus were assessed before and after treatment. Additionally, metagenomic analysis was performed to determine microbial diversity. Results: Before treatment, the total bacterial count average was 4.0 × 106 CFU/mL, 1.7 × 104 CFU/mL for coliforms, 2.6 × 106 CFU/mL for Streptococcus, and 5.4 × 102 CFU/mL for Staphylococcus Copper treatment significantly reduced bacterial counts within 15 min. Total bacteria decreased from 4.0 × 106 CFU/mL to 1.1 × 102 CFU/mL after 30 min; meanwhile, other groups were not detected. The most abundant groups were Lactococcus (29.94%), Pseudomonas (28.89%), and Enterobacteriaceae (21.19%). Beta-lactams were detected in five-sevenths samples, and in one sample they were detected before and at 15 min of treatment but not after 30 min. Conclusions: The effect of treatment with copper ions on the different bacterial groups was significantly effective but showed limited effect on the detection of antibiotics. Full article
12 pages, 1913 KiB  
Article
Diversity, Distribution, and Resistance Profiles of Bacterial Bloodstream Infections in Three Tertiary Referral Hospitals in Rwanda Between 2020 and 2022
by Misbah Gashegu, Vedaste Ndahindwa, Edson Rwagasore, Albert Tuyishime, Clarisse Musanabaganwa, Noel Gahamanyi, Isabelle Mukagatare, Djibril Mbarushimana, Christopher Aird Green, Tafadzwa Dzinamarira, Ayman Ahmed and Claude Mambo Muvunyi
Antibiotics 2024, 13(11), 1084; https://doi.org/10.3390/antibiotics13111084 - 14 Nov 2024
Viewed by 667
Abstract
Background: The burden of bacterial bloodstream infections (BSIs) is rapidly increasing in Africa including Rwanda. Methods: This is a retrospective study that investigates the diversity, distribution, and antimicrobial susceptibility profiles of BSI bacteria in three tertiary referral hospitals in Rwanda between [...] Read more.
Background: The burden of bacterial bloodstream infections (BSIs) is rapidly increasing in Africa including Rwanda. Methods: This is a retrospective study that investigates the diversity, distribution, and antimicrobial susceptibility profiles of BSI bacteria in three tertiary referral hospitals in Rwanda between 2020 and 2022. Results: A total of 1532 blood culture tests were performed for visiting patients. Overall, the proportions of Gram-negative and Gram-positive bacteria were 48.2% and 51.8, respectively. Staphylococcus aureus was the predominant species accounting for 25% of all Gram-positive BSI species, and Klebsiella species represented 41% of all Gram-negative BSI species. Antimicrobial susceptibility testing revealed that Amikacin exhibited the highest activity against Enterobacter spp., Serratia spp., and Escherichia coli in >92% of cases and Klebsiella spp. in 75.7%. Meropenem and Imipenem were highly efficacious to Salmonella spp. (100% susceptibility), Enterobacter spp. (96.2% and 91.7%, respectively), and Escherichia coli (94.7% and 95.5%, respectively). The susceptibility of Enterococcus spp., S. aureus, and Streptococcus spp. to Vancomycin was 100%, 99.5%, and 97.1%, respectively. Klebsiella spp. was highly sensitive to Colistin (98.7%), Polymyxin B (85.6%), Imipenem (84.9%), and Meropenem (78.5%). Conclusions: We recommend strengthening the implementation of integrated transdisciplinary and multisectoral One Health including AMR stewardship for the surveillance, prevention, and control of AMR in Rwanda. Full article
(This article belongs to the Special Issue The Epidemiology of Antimicrobial Resistance in Bloodstream Infections: Focus on Activity of New Antibiotics)
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19 pages, 5938 KiB  
Article
Isolation and Characterization of a Novel Escherichia Bacteriophage with Potential to Control Multidrug-Resistant Avian Pathogenic Escherichia coli and Biofilms
by Phitchayapak Wintachai, Fahsai Thaion, Martha R. J. Clokie and Thotsapol Thomrongsuwannakij
Antibiotics 2024, 13(11), 1083; https://doi.org/10.3390/antibiotics13111083 - 13 Nov 2024
Viewed by 701
Abstract
Background/Objectives: Avian pathogenic Escherichia coli (APEC) infection is a significant problem for the global chicken industry, as it decreases animal welfare and is associated with substantial economic losses. Traditionally, APEC infections have been controlled through the use of antibiotics, which has led to [...] Read more.
Background/Objectives: Avian pathogenic Escherichia coli (APEC) infection is a significant problem for the global chicken industry, as it decreases animal welfare and is associated with substantial economic losses. Traditionally, APEC infections have been controlled through the use of antibiotics, which has led to an increased prevalence of antibiotic-resistant E. coli. Therefore, developing alternative treatments for APEC infection is crucial. Methods: In this study, an Escherichia phage specific to multidrug-resistant (MDR) APEC, designated as phage vB_EcoP_PW8 (phage vECPW8), was isolated. The morphology, phage adsorption to host cells, one-step growth curve, thermal stability, pH stability, whole-genome sequencing, antibacterial ability, and antibiofilm efficacy of phage vECPW8 were evaluated. Results: The results demonstrated that phage vECPW8 has a Podoviridae morphology and is effective at lysing bacteria. Phage vECPW8 exhibited a high absorption rate to bacterial cells (more than 85% within 10 min) and had a latent period of 20 min, with a burst size of 143 plaque-forming units per cell. Additionally, phage vECPW8 showed good temperature and pH stability. The phage displayed strong antibacterial activity in vitro, and its efficacy in controlling bacteria was confirmed through scanning electron microscopy. Whole-genome sequencing revealed that the phage has a linear genome with 69,579 base pairs. The genome analysis supported the safety of the phage, as no toxin, virulence, or resistance-related genes were detected. Phage vECPW8 was identified as a novel lytic phage in the Gamaleyavirus genus and Schitoviridae family. The phage also demonstrated antibiofilm efficacy by reducing and preventing biofilm formation, as evidenced by biofilm biomass and bacterial cell viability measurements. Conclusions: These results indicate that phage vECPW8 is a promising candidate for the effective treatment of MDR APEC infections in poultry. Full article
(This article belongs to the Special Issue Phage Applications from Diagnostics to Treatment of Bacterial Infections in a One Health World)
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13 pages, 795 KiB  
Article
The Effect of a Care Bundle on the Rate of Blood Culture Contamination in a General Intensive Care Unit
by Fani Veini, Michael Samarkos, Pantazis-Michael Voutsinas and Anastasia Kotanidou
Antibiotics 2024, 13(11), 1082; https://doi.org/10.3390/antibiotics13111082 - 13 Nov 2024
Viewed by 551
Abstract
Background/objectives: Blood culture (BC) contamination is a frequent problem which leads to increased laboratory workload, inappropriate use of antibiotics and the associated adverse events, and increased healthcare costs. This study prospectively examined the effect of a care bundle on BC contamination rates [...] Read more.
Background/objectives: Blood culture (BC) contamination is a frequent problem which leads to increased laboratory workload, inappropriate use of antibiotics and the associated adverse events, and increased healthcare costs. This study prospectively examined the effect of a care bundle on BC contamination rates in a high workload ICU. Results: During the study, in total, 4236 BC vials were collected. After the intervention, the BC contamination rate decreased significantly from 6.2% to 1.3%. The incidence rate of contaminated BC sets was significantly lower following the intervention: 0.461 vs. 0.154 BC sets per 100 ICU bed-days. Overall compliance with the BC care bundle increased dramatically from 3.4% to 96.9%. Methods: We performed a before–after study in a general ICU from January 2018 to May 2019, with the intervention starting on November 2018. Blood culture sets were classified as positive, contaminated, indeterminate, and negative. We used bivariate and interrupted time series analysis to assess the effect of the intervention on BC contamination rates and other BC quality indicators. Conclusions: The BC care bundle was effective in reducing BC contamination rates and improving several quality indicators in our setting. The indeterminate BC rate is an important but understudied problem, and we suggest that it should be included in BC quality indicators as well. A significant limitation of the study was that the long-term effect of the intervention was not assessed. Full article
(This article belongs to the Special Issue Nosocomial Infections and Complications in ICU Settings)
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13 pages, 1626 KiB  
Article
Enhancing Antibacterial Efficacy: Combining Novel Bacterial Topoisomerase Inhibitors with Efflux Pump Inhibitors and Other Agents Against Gram-Negative Bacteria
by Maša Zorman, Maja Kokot, Irena Zdovc, Lidija Senerovic, Mina Mandic, Nace Zidar, Andrej Emanuel Cotman, Martina Durcik, Lucija Peterlin Mašič, Nikola Minovski, Marko Anderluh and Martina Hrast Rambaher
Antibiotics 2024, 13(11), 1081; https://doi.org/10.3390/antibiotics13111081 - 13 Nov 2024
Viewed by 604
Abstract
Background: The novel bacterial topoisomerase inhibitors (NBTIs) developed in our laboratory show potent on-target enzyme inhibition but suffer from low activity against Gram-negative bacteria. Methods: With the aim of improving the antibacterial activity of our compounds against Gram-negative bacteria, we tested them in [...] Read more.
Background: The novel bacterial topoisomerase inhibitors (NBTIs) developed in our laboratory show potent on-target enzyme inhibition but suffer from low activity against Gram-negative bacteria. Methods: With the aim of improving the antibacterial activity of our compounds against Gram-negative bacteria, we tested them in combination with different efflux pump inhibitors (EPIs), a strategy that showed promise in several other classes of antimicrobials. We also investigated the combined effect of NBTIs with ATP-competitive inhibitors of bacterial type II topoisomerases (ACIs), as well as the antibiofilm properties of our compounds and the combination with EPIs against early and mature Acietobacter baumannii biofilm. Results: Our results demonstrate that combinations of NBTIs with EPI Phenylalanine-arginyl-β-naphthylamide significantly reduce the corresponding NBTIs’ minimal inhibitory concentration values and show potentiation of A. baumannii biofilm inhibition as compared to NBTIs alone. Although combinations of NBITs and ACIs did not show synergistic effects, the FIC index value calculations revealed additive effects for all the combinations of a selected NBTI in combination with three ACIs in all the assayed Gram-negative bacteria from the ESKAPE group. Conclusions: These results show for the first time that combinations of NBTIs with either EPIs or a different class of the topoisomerase inhibitors may be a beneficial strategy to combat difficult-to-treat bacterial infections. Full article
(This article belongs to the Special Issue Multitalented Synthetic Antimicrobial Compounds: From Design to Effect)
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12 pages, 4961 KiB  
Article
Identification of 2,4-Di-tert-Butylphenol as an Antimicrobial Agent Against Cutibacterium acnes Bacteria from Rwandan Propolis
by Florent Rouvier, Lydia Abou, Emmanuel Wafo, Perrine Andre, Julien Cheyrol, Mohamed-Mohsen Khacef, Claude Nappez, Hubert Lepidi and Jean Michel Brunel
Antibiotics 2024, 13(11), 1080; https://doi.org/10.3390/antibiotics13111080 - 13 Nov 2024
Viewed by 572
Abstract
Background/Objectives: Acne is the most prevalent dermatological condition among humans, affecting approximately 80% of adolescents during puberty. To date, numerous compounds have been used for acne treatment, including erythromycin ointments and antiseptics, with varying degrees of success. The emergence of erythromycin-resistant C. acnes [...] Read more.
Background/Objectives: Acne is the most prevalent dermatological condition among humans, affecting approximately 80% of adolescents during puberty. To date, numerous compounds have been used for acne treatment, including erythromycin ointments and antiseptics, with varying degrees of success. The emergence of erythromycin-resistant C. acnes strains has spurred the search for new antimicrobial agents, particularly from natural sources. Methods: Propolis collected in Rwanda was extracted and fractionated by flash chromatography and tested against C. acnes growth by using NCLSI recommendations. Results: In our research, we identified a molecule, 2,4-Di-tert-butylphenol (2,4-DTBP) which inhivbited the C. acnes growth at a concentration of 16 µg/mL. Based on these results, we formulated an ointment (1%) using OFAP18 and petroleum jelly for the potential treatment of acne using a mouse model. Conclusions: In vitro and in vivo evidence suggests that 2,4-DTBP has anti-inflammatory properties and could effectively manage the overgrowth of C. acnes as well as serve as a potent alternative for the formulation of an active propolis ointment for acne treatment. Full article
(This article belongs to the Special Issue Exploring Antimicrobial Properties and Bioactive Compounds of Edible and Medicinal Plants)
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11 pages, 751 KiB  
Article
Genetic Characterization of Multidrug-Resistant Acinetobacter baumannii and Synergy Assessment of Antimicrobial Combinations
by Aurora Luna-De-Alba, Samantha Flores-Treviño, Adrián Camacho-Ortiz, Juan Francisco Contreras-Cordero and Paola Bocanegra-Ibarias
Antibiotics 2024, 13(11), 1079; https://doi.org/10.3390/antibiotics13111079 - 13 Nov 2024
Viewed by 548
Abstract
Background/Objectives: A. baumannii is a prominent nosocomial pathogen due to its drug-resistant phenotype, representing a public health problem. In this study, the aim was to determine the effect of different antimicrobial combinations against selected multidrug-resistant (MDR) or extensive drug-resistant (XDR) isolates of [...] Read more.
Background/Objectives: A. baumannii is a prominent nosocomial pathogen due to its drug-resistant phenotype, representing a public health problem. In this study, the aim was to determine the effect of different antimicrobial combinations against selected multidrug-resistant (MDR) or extensive drug-resistant (XDR) isolates of A. baumannii. Methods: MDR or XDR A. baumannii isolates were characterized by assessing genes associated with drug resistance, efflux pumps, porin expression, and biofilm formation. The activities of antimicrobial combinations including tigecycline, ampicillin/sulbactam, meropenem, levofloxacin, and colistin were evaluated using checkerboard and time-to-kill assays on isolates with different susceptibility profiles and genetic characteristics. Results: Genetic characterization of MDR/XDR strains (n = 100) included analysis of OXA-24/40 gene carbapenemase (98%), genes encoding aminoglycoside-modifying enzymes (44%), and parC gene mutations (10%). AdeIJK, AdeABC, and AdeFGH efflux pumps were overexpressed in 17–34% of isolates. Omp33-36, OmpA, and CarO membrane porins were under-expressed in 50–76% of isolates; CarO was overexpressed in 22% of isolates. Isolates showed low biofilm production (11%). Synergistic activity was observed with levofloxacin-ampicillin/sulbactam and meropenem-colistin, which were able to inhibit bacterial growth. Conclusions: Genetic characteristics of A. baumannii were highly variable among the strains. Synergistic activity was observed with meropenem-colistin and levofloxacin-ampicillin/sulbactam combinations in the checkerboard method, but not in the time-to-kill assays. These discrepancies among both methods indicate that further studies are needed to determine the best therapeutic combination for treating infections by A. baumannii. Full article
(This article belongs to the Special Issue Antimicrobial Resistance and Hospital- and Community-Associated Infections)
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26 pages, 1655 KiB  
Review
Duration of Antimicrobial Treatment in Adult Patients with Pneumonia: A Narrative Review
by Dimitra Dimopoulou, Charalampos D. Moschopoulos, Konstantina Dimopoulou, Anastasia Dimopoulou, Maria M. Berikopoulou, Ilias Andrianakis, Sotirios Tsiodras, Anastasia Kotanidou and Paraskevi C. Fragkou
Antibiotics 2024, 13(11), 1078; https://doi.org/10.3390/antibiotics13111078 - 12 Nov 2024
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Abstract
Pneumonia remains a major global health concern, causing significant morbidity and mortality among adults. This narrative review assesses the optimal duration of antimicrobial treatment in adults with community-acquired pneumonia (CAP), hospital-acquired pneumonia (HAP), and ventilator-associated pneumonia (VAP). Current evidence about the impact of [...] Read more.
Pneumonia remains a major global health concern, causing significant morbidity and mortality among adults. This narrative review assesses the optimal duration of antimicrobial treatment in adults with community-acquired pneumonia (CAP), hospital-acquired pneumonia (HAP), and ventilator-associated pneumonia (VAP). Current evidence about the impact of treatment duration on clinical outcomes demonstrates that shorter antibiotic courses are non-inferior, regarding safety and efficacy, compared to longer courses, particularly in patients with mild to moderate CAP, which is in line with the recommendations of international guidelines. Data are limited regarding the optimal antimicrobial duration in HAP patients, and it should be individually tailored to each patient, taking into account the causative pathogen and the clinical response. Shorter courses are found to be as effective as longer courses in the management of VAP, except for pneumonia caused by non-fermenting Gram-negative bacteria; however, duration should be balanced between the possibility of higher recurrence rates and the documented benefits with shorter courses. Additionally, the validation of reliable biomarkers or clinical predictors that identify patients who would benefit from shorter therapy is crucial. Insights from this review may lead to future research on personalized antimicrobial therapies in pneumonia, in order to improve patient outcomes. Full article
(This article belongs to the Special Issue Antimicrobial Treatment of Lower Respiratory Tract Infections)
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