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Antibiotics, Volume 13, Issue 7 (July 2024) – 47 articles

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13 pages, 1803 KiB  
Article
Culex quinquefasciatus Mosquitoes Resist Acquisition of Methicillin-Resistant Staphylococcus aureus: Insights from Field and Laboratory Studies
by Waseema Arif, Gowdham Thangaraj, Pushpa Srinivasan, Srikanth Srirama and Panneer Devaraju
Antibiotics 2024, 13(7), 618; https://doi.org/10.3390/antibiotics13070618 (registering DOI) - 2 Jul 2024
Abstract
The emergence of antimicrobial resistance (AMR) in pathogens and their spillover into the environment have become a global public health menace. Insects can acquire these pathogens from the environment and would serve as mechanical and biological vectors. The current study assessed the ability [...] Read more.
The emergence of antimicrobial resistance (AMR) in pathogens and their spillover into the environment have become a global public health menace. Insects can acquire these pathogens from the environment and would serve as mechanical and biological vectors. The current study assessed the ability of Culex quinquefasciatus mosquitoes to acquire methicillin-resistant Staphylococcus aureus (MRSA) through the exposure of the mosquitoes to the pathogen via rearing water, blood feed, or a feeding membrane under laboratory conditions. In addition, mosquito immatures collected from their habitat in the vicinity of hospitals, veterinary dispensaries, and butcher shops at 15 study sites in Puducherry were screened for MRSA infection. All samples were subjected to the culture-based isolation of S. aureus from the surface and homogenate. The presence of the S. aureus-specific nuc gene and the genes that confer resistance to methicillin (mecA and mecC) were screened using PCR tests. MRSA was not evident either on the external surface or in the homogenate of the mosquitoes emerging from the larvae reared in the MRSA-spiked water or those fed with MRSA through blood or smeared membranes. Furthermore, the presence of MRSA was not evident in any of the field-caught mosquitoes. Hence, we conclude that C. quinquefasciatus mosquitoes are impervious to MRSA colonization. Full article
(This article belongs to the Special Issue Antibiotics Resistance in Animals and the Environment)
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11 pages, 3367 KiB  
Communication
Comparative Antimicrobial Resistance and Prevalence of Methicillin Resistance in Coagulase-Positive Staphylococci from Conventional and Organic Dairy Farms in South Korea
by Therese Ariane N. Neri, Hyunjung Park, Su** Kang, Seung Hee Baek and In Sik Nam
Antibiotics 2024, 13(7), 617; https://doi.org/10.3390/antibiotics13070617 - 2 Jul 2024
Viewed by 139
Abstract
Bovine mastitis (BM) has caused huge economic and financial losses in the dairy industry worldwide, with Staphylococcus aureus as one of its major pathogens. BM treatment still relies on antibiotics and its extensive use often generates methicillin-resistant S. aureus (MRSA) and mupirocin-resistant S. [...] Read more.
Bovine mastitis (BM) has caused huge economic and financial losses in the dairy industry worldwide, with Staphylococcus aureus as one of its major pathogens. BM treatment still relies on antibiotics and its extensive use often generates methicillin-resistant S. aureus (MRSA) and mupirocin-resistant S. aureus (MuRSA). This study compared the antimicrobial resistance trend in coagulase-positive Stapholococci (CoPS) isolated from BM milk in conventional and organic dairy farms and checked prevalence of MRSA and MuRSA. A total of 163 presumptive Staphylococci were isolated, wherein 11 out of 74 from 4 conventional farms (CF1, CF2, CF3, CF4) and 17 out of 89 from 3 organic farms (OF1, OF2, OF3) exhibited coagulase activity. Multiplex-PCR amplification confirmed at least one coagulase-positive isolate from CF1, CF2, CF3, CF4, and OF1 as S. aureus, denoted by the presence of the nuc gene. Three isolates from CF2 contained the mecA gene, indicating MRSA prevalence, while the MuRSA gene marker, mupA, was not detected in any of the isolates. Antimicrobial testing showed that conventional farm isolates were more resistant to antibiotics, especially ampicillin and tetracycline. This suggests a risk of develo** multidrug resistance in dairy farms if antibiotic use is not properly and strictly monitored and regulated. Full article
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13 pages, 911 KiB  
Article
Efficacy and Safety of Ceftazidime–Avibactam Alone versus Ceftazidime–Avibactam Plus Fosfomycin for the Treatment of Hospital-Acquired Pneumonia and Ventilator-Associated Pneumonia: A Multicentric Retrospective Study from the SUSANA Cohort
by Marco Fois, Andrea De Vito, Francesca Cherchi, Elena Ricci, Michela Pontolillo, Katia Falasca, Nicolò Corti, Agnese Comelli, Alessandra Bandera, Chiara Molteni, Stefania Piconi, Francesca Colucci, Paolo Maggi, Vincenzo Boscia, Aakash Fugooah, Sara Benedetti, Giuseppe Vittorio De Socio, Paolo Bonfanti and Giordano Madeddu
Antibiotics 2024, 13(7), 616; https://doi.org/10.3390/antibiotics13070616 - 2 Jul 2024
Viewed by 199
Abstract
Hospital-acquired pneumonia (HAP) and ventilation-associated pneumonia (VAP) are challenging clinical conditions due to the challenging tissue penetrability of the lung. This study aims to evaluate the potential role of fosfomycin (FOS) associated with ceftazidime/avibactam (CZA) in improving the outcome in this setting. We [...] Read more.
Hospital-acquired pneumonia (HAP) and ventilation-associated pneumonia (VAP) are challenging clinical conditions due to the challenging tissue penetrability of the lung. This study aims to evaluate the potential role of fosfomycin (FOS) associated with ceftazidime/avibactam (CZA) in improving the outcome in this setting. We performed a retrospective study including people with HAP or VAP treated with CZA or CZA+FOS for at least 72 h. Clinical data were collected from the SUSANA study, a multicentric cohort to monitor the efficacy and safety of the newer antimicrobial agents. A total of 75 nosocomial pneumonia episodes were included in the analysis. Of these, 34 received CZA alone and 41 in combination with FOS (CZA+FOS). People treated with CZA alone were older, more frequently male, received a prolonged infusion more frequently, and were less frequently affected by carbapenem-resistant infections (p = 0.01, p = 0.06, p < 0.001, p = 0.03, respectively). No difference was found in terms of survival at 28 days from treatment start between CZA and CZA+FOS at the multivariate analysis (HR = 0.32; 95% CI = 0.07–1.39; p = 0.128), while prolonged infusion showed a lower mortality rate at 28 days (HR = 0.34; 95% CI = 0.14–0.96; p = 0.04). Regarding safety, three adverse events (one acute kidney failure, one multiorgan failure, and one urticaria) were reported. Our study found no significant association between combination therapy and mortality. Further investigations, with larger and more homogeneous samples, are needed to evaluate the role of combination therapy in this setting. Full article
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22 pages, 6146 KiB  
Article
The Antimicrobial Peptide Capitellacin: Chemical Synthesis of Analogues to Probe the Role of Disulphide Bridges and Their Replacement with Vinyl Sulphides
by Oscar A. Shepperson, Paul W. R. Harris, Margaret A. Brimble and Alan J. Cameron
Antibiotics 2024, 13(7), 615; https://doi.org/10.3390/antibiotics13070615 - 2 Jul 2024
Viewed by 189
Abstract
Capitellacin (1) is a 20-residue antimicrobial β-hairpin, produced by the marine polychaeta (segmented worms) Capitella teletai. Since its discovery in 2020, only very limited studies have been undertaken to understand capitellacin’s structure–activity relationship (SAR). Using fast-flow Fmoc-SPPS, a focused library [...] Read more.
Capitellacin (1) is a 20-residue antimicrobial β-hairpin, produced by the marine polychaeta (segmented worms) Capitella teletai. Since its discovery in 2020, only very limited studies have been undertaken to understand capitellacin’s structure–activity relationship (SAR). Using fast-flow Fmoc-SPPS, a focused library of capitellacin analogues was prepared to systematically study the influence of the two disulphide bridges on its structure and activity, and their replacement with a vinyl sulphide as a potential bioisostere. Upon studying the resulting peptides’ antimicrobial activity and secondary structure, the most terminal disulphide emerged as the most critical element for maintaining both bioactivity and the secondary structure, properties which were demonstrated to be closely interlinked. The removal of the innermost disulphide bridge or disulphide replacement with a vinyl sulphide emerged as strategies with which to tune the activity spectrum, producing selectivity towards E. coli. Additionally, an enantiomeric d-capitellacin analogue revealed mechanistic insights, suggesting that chirality may be an inherent property of capitellacin’s bacterial membrane target, or that a hitherto unknown secondary mechanism of action may exist. Additionally, we propose the Alloc protecting group as a more appropriate alternative to the common Dde group during fast-flow Fmoc-SPPS, in particular for short-chain diamino acids. Full article
(This article belongs to the Special Issue Recent Advances in Antimicrobial Drug Discovery, 2nd Edition)
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15 pages, 4406 KiB  
Article
Treating Infected Non-Healing Venous Leg Ulcers with Medical-Grade Honey: A Prospective Case Series
by Georgios E. Papanikolaou, Georgios Gousios, Niels A. J. Cremers and Linsey J. F. Peters
Antibiotics 2024, 13(7), 614; https://doi.org/10.3390/antibiotics13070614 - 2 Jul 2024
Viewed by 205
Abstract
Venous leg ulcers (VLUs) are hard-to-heal wounds and are prone to microbial colonization. Innovative and improved therapies are thus required to resolve local infection and enhance the wound healing process. The objective of this study was to evaluate the effectiveness of medical-grade honey [...] Read more.
Venous leg ulcers (VLUs) are hard-to-heal wounds and are prone to microbial colonization. Innovative and improved therapies are thus required to resolve local infection and enhance the wound healing process. The objective of this study was to evaluate the effectiveness of medical-grade honey (MGH) for the treatment of clinically infected and non-healing VLUs. This prospective case series included nine patients with an average age of 83.4 years (range: 75–91 years) with a total of eleven VLUs, previously ineffectively treated with various products. Major risk factors for the appearance of VLUs were chronic venous insufficiency, advanced age, multiple comorbidities (particularly cardiovascular diseases), and impaired mobility. All wounds presented with local signs of infection. Upon presentation, treatment was commenced with a range of MGH-based products (L-Mesitran®). Clinical signs of infection were eliminated by MGH after 2.2 weeks on average (range: 1–4 weeks), and wounds were completely healed after 7 weeks on average (range: 3–18 weeks). No further complications or recurrences were observed. MGH has a broad-spectrum antimicrobial activity and promotes rapid healing, thus improving patients’ quality of life. Moreover, MGH-based products are safe, easy to use, cost-effective, and can effectively treat VLUs alone or in combination with standard-of-care therapies. Full article
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19 pages, 6392 KiB  
Article
Unveiling the Antimicrobial, Anti-Biofilm, and Anti-Quorum-Sensing Potential of Paederia foetida Linn. Leaf Extract against Staphylococcus aureus: An Integrated In Vitro–In Silico Investigation
by Sirijan Santajit, Witawat Tunyong, Dararat Horpet, Asma Binmut, Thida Kong-Ngoen, Churaibhon Wisessaowapak, Techit Thavorasak, Pornpan Pumirat and Nitaya Indrawattana
Antibiotics 2024, 13(7), 613; https://doi.org/10.3390/antibiotics13070613 - 1 Jul 2024
Viewed by 270
Abstract
Antimicrobial resistance poses a global health threat, with Staphylococcus aureus emerging as a notorious pathogen capable of forming stubborn biofilms and regulating virulence through quorum sensing (QS). In the quest for novel therapeutic strategies, this groundbreaking study unveils the therapeutic potential of Paederia [...] Read more.
Antimicrobial resistance poses a global health threat, with Staphylococcus aureus emerging as a notorious pathogen capable of forming stubborn biofilms and regulating virulence through quorum sensing (QS). In the quest for novel therapeutic strategies, this groundbreaking study unveils the therapeutic potential of Paederia foetida Linn., an Asian medicinal plant containing various bioactive compounds, contributing to its antimicrobial activities, in the battle against S. aureus. Through a comprehensive approach, we investigated the effect of ethanolic P. foetida leaf extract on S. aureus biofilms, QS, and antimicrobial activity. The extract exhibited promising inhibitory effects against S. aureus including the biofilm-forming strain and MRSA. Real-time PCR analysis revealed significant downregulation of key virulence and biofilm genes, suggesting interference with QS. Biofilm assays quantified the extract’s ability to disrupt and prevent biofilm formation. LC-MS/MS analysis identified quercetin and kaempferol glycosides as potential bioactive constituents, while molecular docking studies explored their binding to the QS transcriptional regulator SarA. Computational ADMET predictions highlighted favorable intestinal absorption but potential P-glycoprotein interactions limiting oral bioavailability. While promising anti-virulence effects were demonstrated, the high molecular weights and excessive hydrogen bond donors/acceptors of the flavonoid glycosides raise concerns regarding drug-likeness and permeability. This integrated study offers valuable insights for develo** novel anti-virulence strategies to combat antimicrobial resistance. Full article
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11 pages, 2383 KiB  
Article
Therapeutic Potential of Mangosteen Pericarp Extract-Loaded Liposomes against Superficial Skin Infection Caused by Staphylococcus pseudintermedius in a Murine Model
by Seong-Yeop Kim, Seong-Yong Park, Jung-Hwa Lee, Nayeong Kim, Ha-Na Oh, So-Young Yoo, Dae-Sung Lee and Je-Chul Lee
Antibiotics 2024, 13(7), 612; https://doi.org/10.3390/antibiotics13070612 - 1 Jul 2024
Viewed by 247
Abstract
α-mangostin (α-MG) demonstrates antibacterial activity against Staphylococcus species. Therefore, this study aimed to explore the antibacterial activity of α-MG-rich mangosteen pericarp extract (MPE)-loaded liposomes against Staphylococcus isolates from companion animal skin diseases in vitro and evaluated their therapeutic potential in a murine model [...] Read more.
α-mangostin (α-MG) demonstrates antibacterial activity against Staphylococcus species. Therefore, this study aimed to explore the antibacterial activity of α-MG-rich mangosteen pericarp extract (MPE)-loaded liposomes against Staphylococcus isolates from companion animal skin diseases in vitro and evaluated their therapeutic potential in a murine model of superficial skin infection caused by S. pseudintermedius. α-MG-rich extract was purified from mangosteen pericarp and then complexed with γ-cyclodextrin (γ-CD), forming the inclusion complexes. Nanoliposomes containing MPE and γ-CD complexes were prepared by adding lecithin and casein. Minimum inhibitory concentrations (MICs) and minimum bactericidal concentrations (MBCs) of MPE-loaded liposomes were determined using agar dilution and broth microdilution methods. The therapeutic potential of MPE-loaded liposomes was evaluated in vivo on tape-stripped skin lesions infected with S. pseudintermedius. Purified MPE and MPE-loaded liposomes contained 402.43 mg/g and 18.18 mg/g α-MG, respectively. MPE-loaded liposomes showed antibacterial activity against clinical Staphylococcus isolates in vitro but did not show antibacterial activity against Gram-negative bacterial isolates. MPE-loaded liposomes demonstrated consistent MICs and MBCs against Staphylococcus isolates. These liposomes significantly reduced bacterial numbers and lesional sizes in a superficial skin infection model. Moreover, they reconstructed the epidermal barrier in skin lesions. The therapeutic concentrations of MPE-loaded liposomes did not induce cytotoxicity in canine progenitor epidermal keratinocyte cells. In conclusion, MPE-loaded liposomes hold promise for the development of a prospective topical formulation to treat superficial pyoderma in companion animals. Full article
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13 pages, 466 KiB  
Article
Investigating the Bactericidal Activity of an Ocular Solution Containing EDTA, Tris, and Polysorbate 80 and Its Impact on the In Vitro Efficacy of Neomycin Sulfate against Staphylococcus aureus: A Preliminary Study
by Sophie Amiriantz, Sara Hoummady, Elodie Jarousse, Séverine Roudeix and Thomas Philippon
Antibiotics 2024, 13(7), 611; https://doi.org/10.3390/antibiotics13070611 - 30 Jun 2024
Viewed by 289
Abstract
In the current context of emerging and spreading antimicrobial resistance in human and animal infections, new strategies need to be developed to improve the efficacy of commonly prescribed antibiotics and preserve more critical compounds for multi-drug-resistant infections. This preliminary study aimed at evaluating [...] Read more.
In the current context of emerging and spreading antimicrobial resistance in human and animal infections, new strategies need to be developed to improve the efficacy of commonly prescribed antibiotics and preserve more critical compounds for multi-drug-resistant infections. This preliminary study aimed at evaluating the benefits of an eye cleaning solution containing 0.1% EDTA, 0.02% Tris, and 0.1% Polysorbate 80 in veterinary ophthalmology. A first in vitro study was performed to assess the bactericidal activity of the test solution against Staphylococcus aureus and Pseudomonas aeruginosa strains. A second in vitro study evaluated the impact of the test solution on the antimicrobial activity of neomycin against Staphylococcus aureus. The test solution alone did not show bactericidal activity against Staphylococcus aureus and Pseudomonas aeruginosa. The test solution seemed to increase the activity of Neomycin Sulfate against Staphylococcus aureus. These findings warrant further research to better characterize the impact on the bactericidal activity of antimicrobials used in veterinary ocular surface infections of the solution containing 0.1% EDTA, 0.02% Tris, and 0.1% Polysorbate 80 as well as of each individual ingredient for a thorough understanding of how this test solution could provide a new strategy to address the growing antimicrobial resistance issue worldwide. Full article
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18 pages, 2803 KiB  
Article
Isolation and Characterization of Novel Bacteriophages to Target Carbapenem-Resistant Acinetobacter baumannii
by Yoon-Jung Choi, Shukho Kim, Minsang Shin and Jungmin Kim
Antibiotics 2024, 13(7), 610; https://doi.org/10.3390/antibiotics13070610 - 29 Jun 2024
Viewed by 281
Abstract
The spread of multidrug-resistant Acinetobacter baumannii in hospitals and nursing homes poses serious healthcare challenges. Therefore, we aimed to isolate and characterize lytic bacteriophages targeting carbapenem-resistant Acinetobacter baumannii (CRAB). Of the 21 isolated A. baumannii phages, 11 exhibited potent lytic activities against clinical [...] Read more.
The spread of multidrug-resistant Acinetobacter baumannii in hospitals and nursing homes poses serious healthcare challenges. Therefore, we aimed to isolate and characterize lytic bacteriophages targeting carbapenem-resistant Acinetobacter baumannii (CRAB). Of the 21 isolated A. baumannii phages, 11 exhibited potent lytic activities against clinical isolates of CRAB. Based on host spectrum and RAPD-PCR results, 11 phages were categorized into four groups. Three phages (vB_AbaP_W8, vB_AbaSi_W9, and vB_AbaSt_W16) were further characterized owing to their antibacterial efficacy, morphology, and whole-genome sequence and were found to lyse 37.93%, 89.66%, and 37.93%, respectively, of the 29 tested CRAB isolates. The lytic spectrum of phages varied depending on the multilocus sequence type (MLST) of the CRAB isolates. The three phages contained linear double-stranded DNA genomes, with sizes of 41,326–166,741 bp and GC contents of 34.4–35.6%. Genome-wide phylogenetic analysis and single gene-based tree construction revealed no correlation among the three phages. Moreover, no genes were associated with lysogeny, antibiotic resistance, or bacterial toxins. Therefore, the three novel phages represent potential candidates for phage therapy against CRAB infections. Full article
11 pages, 1597 KiB  
Article
A New Guanidine-Core Small-Molecule Compound as a Potential Antimicrobial Agent against Resistant Bacterial Strains
by Noelia Morata-Moreno, Ramón Pérez-Tanoira, Almudena del Campo-Balguerias, Fernando Carrillo-Hermosilla, Marcos Hernando-Gozalo, Carlos Rescalvo-Casas, Ana V. Ocana, Pedro Segui, Carlos Alonso-Moreno, Francisco C. Pérez-Martínez and Milagros Molina-Alarcón
Antibiotics 2024, 13(7), 609; https://doi.org/10.3390/antibiotics13070609 - 29 Jun 2024
Viewed by 204
Abstract
The guanidine core has been one of the most studied functional groups in medicinal chemistry, and guanylation reactions are powerful tools for synthesizing this kind of compound. In this study, a series of five guanidine-core small molecules were obtained through guanylation reactions. These [...] Read more.
The guanidine core has been one of the most studied functional groups in medicinal chemistry, and guanylation reactions are powerful tools for synthesizing this kind of compound. In this study, a series of five guanidine-core small molecules were obtained through guanylation reactions. These compounds were then evaluated against three different strains of Escherichia coli, one collection strain from the American Type Culture Collection (ATCC) of E. coli ATCC 35218, and two clinical extended-spectrum beta-lactamase (ESBL)-producing E. coli isolates (ESBL1 and ESBL2). Moreover, three different strains of Pseudomonas aeruginosa were studied, one collection strain of P. aeruginosa ATCC 27853, and two clinical multidrug-resistant isolates (PA24 and PA35). Among Gram-positive strains, three different strains of Staphylococcus aureus, one collection strain of S. aureus ATCC 29213, and two clinical methicillin-resistant S. aureus (MRSA1 and MRSA2) were evaluated. Minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) experiments were reported, and the drop plate (DP) method was used to determine the number of viable suspended bacteria in a known beaker volume. The results from this assessment suggest that guanidine-core small molecules hold promise as therapeutic alternatives for treating infections caused by clinical Gram-negative and Gram-positive bacteria, highlighting the need for further studies to explore their potential. Full article
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26 pages, 1580 KiB  
Article
A Study on the Effect of Quaternization of Polyene Antibiotics’ Structures on Their Activity, Toxicity, and Impact on Membrane Models
by Olga Omelchuk, Anna Tevyashova, Svetlana Efimova, Natalia Grammatikova, Elena Bychkova, George Zatonsky, Lyubov Dezhenkova, Nikita Savin, Svetlana Solovieva, Olga Ostroumova and Andrey Shchekotikhin
Antibiotics 2024, 13(7), 608; https://doi.org/10.3390/antibiotics13070608 - 29 Jun 2024
Viewed by 165
Abstract
Polyene antibiotics have been used in antifungal therapy since the mid-twentieth century. They are highly valued for their broad spectrum of activity and the rarity of pathogen resistance to their action. However, their use in the treatment of systemic mycoses often results in [...] Read more.
Polyene antibiotics have been used in antifungal therapy since the mid-twentieth century. They are highly valued for their broad spectrum of activity and the rarity of pathogen resistance to their action. However, their use in the treatment of systemic mycoses often results in serious side-effects. Recently, there has been a renewed interest in the development of new antifungal drugs based on polyenes, particularly due to the emergence of highly dangerous pathogenic strains of fungi, such as Candida auris, and the increased incidence of mucormycosis. Considerable understanding has been established regarding the structure–biological activity relationships of polyene antifungals. Yet, no previous studies have examined the effect of introducing quaternized fragments into their molecular structure. In this study, we present a series of amides of amphotericin B, nystatin, and natamycin bearing a quaternized group in the side chain, and discuss their biological properties: antifungal activity, cytotoxicity, and effects on lipid bilayers that mimic fungal and mammalian cell membranes. Our research findings suggest that the nature of the introduced quaternized residue plays a more significant role than merely the introduction of a constant positive charge. Among the tested polyenes, derivatives 4b, 5b, and 6b, which contain a fragment of N-methyl-4-(aminomethyl)pyridinium in their structure, are particularly noteworthy due to their biological activity. Full article
(This article belongs to the Section Novel Antimicrobial Agents)
2 pages, 170 KiB  
Editorial
Introduction to the Special Issue on Clostridioides difficile Infection, Second Edition
by Guido Granata
Antibiotics 2024, 13(7), 607; https://doi.org/10.3390/antibiotics13070607 - 29 Jun 2024
Viewed by 201
Abstract
Clostridioides difficile (CD) is a Gram-positive, anaerobic bacterium that is one of the most common causes of infective diarrhoea worldwide [...] Full article
(This article belongs to the Special Issue Clostridioides difficile Infection, 2nd Edition)
11 pages, 921 KiB  
Article
A Cyclic Peptide Based on Pheasant Cathelicidin Inhibits Influenza A H1N1 Virus Infection
by Ya** Pei, Zhihua Chen, Ruihan Zhao, Yanxing An, Haiche Yisihaer, Chaojie Wang, Yaning Bai, Libin Liang, Lin ** and Yongting Hu
Antibiotics 2024, 13(7), 606; https://doi.org/10.3390/antibiotics13070606 - 28 Jun 2024
Viewed by 198
Abstract
Influenza viruses are the leading cause of upper respiratory tract infections, leading to several global pandemics and threats to public health. Due to the continuous mutation of influenza A viruses, there is a constant need for the development of novel antiviral therapeutics. Recently, [...] Read more.
Influenza viruses are the leading cause of upper respiratory tract infections, leading to several global pandemics and threats to public health. Due to the continuous mutation of influenza A viruses, there is a constant need for the development of novel antiviral therapeutics. Recently, natural antimicrobial peptides have provided an opportunity for the discovery of anti-influenza molecules. Here, we designed several peptides based on pheasant cathelicidin and tested their antiviral activities and mechanisms against the H1N1 virus. Of note, the designed peptides Pc-4 and Pc-5 were found to inhibit replication of the H1N1 virus with an IC50 = 8.14 ± 3.94 µM and 2.47 ± 1.95 µM, respectively. In addition, the cyclic peptide Pc-5 was found to induce type I interferons and the expression of interferon-induced genes. An animal study showed that the cyclic peptide Pc-5 effectively inhibited H1N1 virus infection in a mouse model. Taken together, our work reveals a strategy for designing cyclic peptides and provides novel molecules with therapeutic potential against influenza A virus infection. Full article
(This article belongs to the Special Issue Antimicrobial Activity of Bioactive Peptides and Their Derivatives)
18 pages, 4197 KiB  
Article
Essential Oils from Southern Italian Aromatic Plants Synergize with Antibiotics against Escherichia coli, Pseudomonas aeruginosa and Enterococcus faecalis Cell Growth and Biofilm Formation
by Giada Sena, Elisabetta De Rose, Michele Crudo, Gianfranco Filippelli, Giuseppe Passarino, Dina Bellizzi and Patrizia D’Aquila
Antibiotics 2024, 13(7), 605; https://doi.org/10.3390/antibiotics13070605 - 28 Jun 2024
Viewed by 276
Abstract
The spread of antibiotic-resistant pathogens has prompted the development of novel approaches to identify molecules that synergize with antibiotics to enhance their efficacy. This study aimed to investigate the effects of ten Essential Oils (EOs) on the activity of nine antibiotics in influencing [...] Read more.
The spread of antibiotic-resistant pathogens has prompted the development of novel approaches to identify molecules that synergize with antibiotics to enhance their efficacy. This study aimed to investigate the effects of ten Essential Oils (EOs) on the activity of nine antibiotics in influencing growth and biofilm formation in Escherichia coli, Pseudomonas aeruginosa, and Enterococcus faecalis. The effects of the EOs alone and in combination with antibiotics on both bacterial growth and biofilm formation were analyzed by measuring the MIC values through the broth microdilution method and the crystal violet assay, respectively. All EOs inhibited the growth of E. coli (1.25 ≤ MIC ≤ 5 mg/mL) while the growth of P. aeruginosa and E. faecalis was only affected by EOs from Origanum vulgare, (MIC = 5 mg/mL) and O. vulgare (MIC = 1.25 mg/mL) and Salvia rosmarinus (MIC = 5 mg/mL), respectively. In E. coli, most EOs induced a four- to sixteen-fold reduction in the MIC values of ampicillin, ciprofloxacin, ceftriaxone, gentamicin, and streptomycin, while in E. faecalis such a reduction is observed in combinations of ciprofloxacin with C. nepeta, C. bergamia, C. limon, C. reticulata, and F. vulgare, of gentamicin with O. vulgare, and of tetracycline with C. limon and O. vulgare. A smaller effect was observed in P. aeruginosa, in which only C. bergamia reduced the concentration of tetracycline four-fold. EO-antibiotic combinations also inhibit the biofilm formation. More precisely, all EOs with ciprofloxacin in E. coli, tetracycline in P. aeruginosa, and gentamicin in E. faecalis showed the highest percentage of inhibition. Combinations induce up- and down-methylation of cytosines and adenines compared to EO or antibiotics alone. The study provides evidence about the role of EOs in enhancing the action of antibiotics by influencing key processes involved in resistance mechanisms such as biofilm formation and epigenetic changes. Synergistic interactions should be effectively considered in dealing with pathogenic microorganisms. Full article
(This article belongs to the Special Issue Molecular Mechanism of Antibiotic Resistance in Microbial Biofilms)
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21 pages, 4710 KiB  
Article
Exploring Weissella confusa W1 and W2 Strains Isolated from Khao-Mahk as Probiotic Candidates: From Phenotypic Traits to Genomic Insights
by Ei Phway Thant, Komwit Surachat, Sarunyou Chusri, Chonticha Romyasamit, Rattanaruji Pomwised, Monwadee Wonglapsuwan, Thunchanok Yaikhan, Sirikan Suwannasin and Kamonnut Singkhamanan
Antibiotics 2024, 13(7), 604; https://doi.org/10.3390/antibiotics13070604 - 28 Jun 2024
Viewed by 358
Abstract
Growing interest in probiotics has spurred research into their health benefits for hosts. This study aimed to evaluate the probiotic properties, especially antibacterial activities and the safety of two Weissella confusa strains, W1 and W2, isolated from Khao-Mahk by describing their phenotypes and [...] Read more.
Growing interest in probiotics has spurred research into their health benefits for hosts. This study aimed to evaluate the probiotic properties, especially antibacterial activities and the safety of two Weissella confusa strains, W1 and W2, isolated from Khao-Mahk by describing their phenotypes and genotypes through phenotypic assays and whole genome sequencing. In vitro experiments demonstrated that both strains exhibited robust survival under gastric and intestinal conditions, such as in the presence of low pH, bile salt, pepsin, and pancreatin, indicating their favorable gut colonization traits. Additionally, both strains showed auto-aggregation and strong adherence to Caco2 cells, with adhesion rates of 86.86 ± 1.94% for W1 and 94.74 ± 2.29% for W2. These high adherence rates may be attributed to the significant exopolysaccharide (EPS) production observed in both strains. Moreover, they exerted remarkable antimicrobial activities against Stenotrophomonas maltophilia, Salmonella enterica serotype Typhi, Vibrio cholerae, and Acinetobacter baumannii, along with an absence of hemolytic activities and antibiotic resistance, underscoring their safety for probiotic application. Genomic analysis corroborated these findings, revealing genes related to probiotic traits, including EPS clusters, stress responses, adaptive immunity, and antimicrobial activity. Importantly, no transferable antibiotic-resistance genes or virulence genes were detected. This comprehensive characterization supports the candidacy of W1 and W2 as probiotics, offering substantial potential for promoting health and combating bacterial infections. Full article
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17 pages, 1586 KiB  
Review
Current View on Major Natural Compounds Endowed with Antibacterial and Antiviral Effects
by Roberto Arrigoni, Andrea Ballini, Emilio Jirillo and Luigi Santacroce
Antibiotics 2024, 13(7), 603; https://doi.org/10.3390/antibiotics13070603 - 28 Jun 2024
Viewed by 665
Abstract
Nowadays, infectious diseases of bacterial and viral origins represent a serious medical problem worldwide. In fact, the development of antibiotic resistance is responsible for the emergence of bacterial strains that are refractory even to new classes of antibiotics. Furthermore, the recent COVID-19 pandemic [...] Read more.
Nowadays, infectious diseases of bacterial and viral origins represent a serious medical problem worldwide. In fact, the development of antibiotic resistance is responsible for the emergence of bacterial strains that are refractory even to new classes of antibiotics. Furthermore, the recent COVID-19 pandemic suggests that new viruses can emerge and spread all over the world. The increase in infectious diseases depends on multiple factors, including malnutrition, massive migration of population from develo** to industrialized areas, and alteration of the human microbiota. Alternative treatments to conventional antibiotics and antiviral drugs have intensively been explored. In this regard, plants and marine organisms represent an immense source of products, such as polyphenols, alkaloids, lanthipeptides, and terpenoids, which possess antibacterial and antiviral activities. Their main mechanisms of action involve modifications of bacterial cell membranes, with the formation of pores, the release of cellular content, and the inhibition of bacterial adherence to host cells, as well as of the efflux pump. Natural antivirals can interfere with viral replication and spreading, protecting the host with the enhanced production of interferon. Of note, these antivirals are not free of side effects, and their administration to humans needs more research in terms of safety. Preclinical research with natural antibacterial and antiviral compounds confirms their effects against bacteria and viruses, but there are still only a few clinical trials. Therefore, their full exploitation and more intensive clinical studies represent the next steps to be pursued in this area of medicine. Full article
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17 pages, 4087 KiB  
Article
Unraveling the Microbial Symphony: Impact of Antibiotics and Probiotics on Infant Gut Ecology and Antibiotic Resistance in the First Six Months of Life
by Qi Qi, Liang Wang, Yingze Zhu, Shaoru Li, Mitslal Abrha Gebremedhin, Baozhu Wang, Zhonghai Zhu and Lingxia Zeng
Antibiotics 2024, 13(7), 602; https://doi.org/10.3390/antibiotics13070602 - 27 Jun 2024
Viewed by 352
Abstract
We aimed to examine the effects of antibiotic and probiotic usage on the gut microbiota structure and the presence of antibiotic-resistance genes (ARGs) in infants during the first six months of life. Questionnaires and fecal samples were collected within three days of birth, [...] Read more.
We aimed to examine the effects of antibiotic and probiotic usage on the gut microbiota structure and the presence of antibiotic-resistance genes (ARGs) in infants during the first six months of life. Questionnaires and fecal samples were collected within three days of birth, two months, and six months to assess antibiotic and probiotic exposure. Gut microbiotas were sequenced via 16S rRNA, and ARGs were conducted by qPCR, including beta-lactam (mecA, blaTEM), tetracycline (tetM), fluoroquinolone (qnrS), aminoglycoside (aac(6′)-Ib), and macrolide (ermB). Infants were categorized by antibiotic and probiotic usage and stratified by delivery mode, microbial composition, and ARG abundances were compared, and potential correlations were explored. A total of 189 fecal samples were analyzed in this study. The gut microbiota diversity (Chao1 index) was significantly lower in the “only probiotics” (PRO) group compared to the “neither antibiotics nor probiotics” (CON) group at six months for the CS stratification (p = 0.029). Compositionally, the abundance of core genus Bifidobacterium_pseudocatenulatum was less abundant for the antibiotic during delivery (IAP) group than that in the CON group within the first three days (p = 0.009), while core genus Enterococcus_faecium was more abundant in the PRO than that in the CON group (p = 0.021) at two months. ARGs were highly detected, with Enterococcus hosting tetM and Escherichia associated with blaTEM within three days of birth, though no correlation was found between Bifidobacterium and ARGs. These findings emphasized the critical importance of carefully managing antibiotic and probiotic exposures in early life, with implications for promoting lifelong health through preserving a healthy infant gut ecosystem. Full article
(This article belongs to the Special Issue Antibiotics and Probiotics: What Is the Effect on the Gut?)
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12 pages, 754 KiB  
Article
Risk Factors for 30-Day Mortality in Nosocomial Enterococcal Bloodstream Infections
by Verena Zerbato, Riccardo Pol, Gianfranco Sanson, Daniel Alexandru Suru, Eugenio Pin, Vanessa Tabolli, Jacopo Monticelli, Marina Busetti, Dan Alexandru Toc, Lory Saveria Crocè, Roberto Luzzati and Stefano Di Bella
Antibiotics 2024, 13(7), 601; https://doi.org/10.3390/antibiotics13070601 - 27 Jun 2024
Viewed by 283
Abstract
Enterococci commonly cause nosocomial bloodstream infections (BSIs), and the global incidence of vancomycin-resistant enterococci (VRE) BSIs is rising. This study aimed to assess the risk factors for enterococcal BSIs and 30-day mortality, stratified by Enterococcus species, vancomycin resistance, and treatment appropriateness. We conducted [...] Read more.
Enterococci commonly cause nosocomial bloodstream infections (BSIs), and the global incidence of vancomycin-resistant enterococci (VRE) BSIs is rising. This study aimed to assess the risk factors for enterococcal BSIs and 30-day mortality, stratified by Enterococcus species, vancomycin resistance, and treatment appropriateness. We conducted a retrospective cohort study (2014–2021) including all hospitalized adult patients with at least one blood culture positive for Enterococcus faecalis or Enterococcus faecium. We included 584 patients with enterococcal BSI: 93 were attributed to vancomycin-resistant E. faecium. The overall 30-day mortality was 27.5%; higher in cases of BSI due to vancomycin-resistant E. faecium (36.6%) and vancomycin-sensitive E. faecium (31.8%) compared to E. faecalis BSIs (23.2%) (p = 0.016). This result was confirmed by multivariable Cox analysis. Independent predictors of increased mortality included the PITT score, complicated bacteremia, and age (HR = 1.269, p < 0.001; HR = 1.818, p < 0.001; HR = 1.022, p = 0.005, respectively). Conversely, male gender, consultation with infectious disease (ID) specialists, and appropriate treatment were associated with reduced mortality (HR = 0.666, p = 0.014; HR = 0.504, p < 0.001; HR = 0.682, p = 0.026, respectively). In conclusion, vancomycin-resistant E. faecium bacteremia is independently associated with a higher risk of 30-day mortality. Full article
(This article belongs to the Special Issue Antimicrobial Stewardship and Use in Healthcare Setting)
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15 pages, 2145 KiB  
Article
Development and ELISA Characterization of Antibodies against the Colistin, Vancomycin, Daptomycin, and Meropenem: A Therapeutic Drug Monitoring Approach
by Vivian Garzon, J.-Pablo Salvador, M.-Pilar Marco, Daniel G.-Pinacho and Rosa-Helena Bustos
Antibiotics 2024, 13(7), 600; https://doi.org/10.3390/antibiotics13070600 - 27 Jun 2024
Viewed by 322
Abstract
More than 70% of bacteria are resistant to all or nearly all known antimicrobials, creating the need for the development of new types of antimicrobials or the use of “last-line” antimicrobial therapies for the treatment of multi-resistant bacteria. These antibiotics include Glycopeptide (Vancomycin), [...] Read more.
More than 70% of bacteria are resistant to all or nearly all known antimicrobials, creating the need for the development of new types of antimicrobials or the use of “last-line” antimicrobial therapies for the treatment of multi-resistant bacteria. These antibiotics include Glycopeptide (Vancomycin), Polymyxin (Colistin), Lipopeptide (Daptomycin), and Carbapenem (Meropenem). However, due to the toxicity of these types of molecules, it is necessary to develop new rapid methodologies to be used in Therapeutic Drug Monitoring (TDM). TDM could improve patient outcomes and reduce healthcare costs by enabling a favorable clinical outcome. In this way, personalized antibiotic therapy emerges as a viable option, offering optimal dosing for each patient according to pharmacokinetic (PK) and pharmacodynamic (PD) parameters. Various techniques are used for this monitoring, including high-performance liquid chromatography (HPLC), gas chromatography-mass spectrometry (GC-MS), and immunoassays. The objective of this study is the development and characterization by ELISA of specific polyclonal antibodies for the recognition of the antibiotics Vancomycin (glycopeptide), Colistin (polymyxin), Daptomycin (lipopeptide), and Meropenem (carbapenem) for future applications in the monitoring of these antibiotics in different fluids, such as human plasma. The developed antibodies are capable of recognizing the antibiotic molecules with good detectability, showing an IC50 of 0.05 nM for Vancomycin, 7.56 nM for Colistin, 183.6 nM for Meropenem, and 13.82 nM for Daptomycin. These antibodies offer a promising tool for the precise and effective therapeutic monitoring of these critical antibiotics, potentially enhancing treatment efficacy and patient safety. Full article
(This article belongs to the Special Issue Challenges for Therapeutic Drug Monitoring of Antimicrobials)
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9 pages, 422 KiB  
Article
Bacterial Profile and Antimicrobial Resistance Patterns of Diabetic Foot Infections in a Major Research Hospital of Turkey
by Belgin Coşkun, Müge Ayhan, Serap Ulusoy and Rahmet Guner
Antibiotics 2024, 13(7), 599; https://doi.org/10.3390/antibiotics13070599 - 27 Jun 2024
Viewed by 255
Abstract
Background/Aim: Diabetic foot infection (DFI) occurs frequently in patients, followed up with diabetic foot ulcers (DFU). For this reason, antibiotic treatment is often used in patients followed with DFU. Inappropriate use of antibiotics and increasing antibiotic resistance threaten public health. We aimed to [...] Read more.
Background/Aim: Diabetic foot infection (DFI) occurs frequently in patients, followed up with diabetic foot ulcers (DFU). For this reason, antibiotic treatment is often used in patients followed with DFU. Inappropriate use of antibiotics and increasing antibiotic resistance threaten public health. We aimed to investigate the microbial spectrum and antimicrobial resistance patterns isolated from diabetic foot infections in Turkey and help clinicians to choose optimal antibiotics empirically. Materials and Methods: This study was planned as a retrospective, single-center, cross-sectional study. Two hundred sixty-two patients whose causative microorganism was isolated in culture of tissue between 1 January 2021 and 31 December 2022 were included in this study. Bacterial profile and antimicrobial resistance patterns were analyzed. Results: Four hundred thirty two isolates from 262 patients isolated in culture of tissue were evaluated. Of these microorganisms, 57.60% were Gram-negative, 41.20% were Gram-positive bacteria, and 1.2% were Candida spp. The most frequently detected Gram-positive microorganism was Staphylococcus spp. Gram-negative microorganisms were Escherichia coli (E. coli) and Pseudomonas aeruginosa (P. aeruginosa). Polymicrobial infections were observed in 40.5% of the patients. Methicillin-resistant Staphylococcus spp. rate was 51.3%, while extended-spectrum beta-lactamase (ESBL) resistance for E. coli was 66.7%. Conclusions: Due to increasing antibiotic resistance rates, treatment of common infections becomes more difficult. Knowledge of the microbiological profile and antibiotic resistance patterns of patients with DFIs is useful to guide empirical therapy. Full article
(This article belongs to the Special Issue Feature Papers in Therapy of Diabetic Foot Infections)
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13 pages, 267 KiB  
Article
Ceftazidime–Avibactam Use in a Case Series of Difficult-to-Treat or Recurrent Infections in Pediatric Patients with Complex Chronic Conditions: Effectiveness and Absence of Resistance Development
by Miguel García-Boyano, María Alós Díez, Lorena Fernández Tomé, Luis Escosa-García, Francisco Moreno Ramos, Cristina Schuffelmann-Gutiérrez, Emilio Cendejas Bueno, Cristina Calvo, Fernando Baquero-Artigao and Esteban Frauca Remacha
Antibiotics 2024, 13(7), 598; https://doi.org/10.3390/antibiotics13070598 - 27 Jun 2024
Viewed by 250
Abstract
The prevalence of multidrug-resistant Gram-negative infections, particularly carbapenem-resistant strains, has become a significant global health concern. Ceftazidime–avibactam (CZA) has emerged as a promising treatment option. However, data on its efficacy and safety in children are scarce, necessitating further investigation. We conducted a descriptive [...] Read more.
The prevalence of multidrug-resistant Gram-negative infections, particularly carbapenem-resistant strains, has become a significant global health concern. Ceftazidime–avibactam (CZA) has emerged as a promising treatment option. However, data on its efficacy and safety in children are scarce, necessitating further investigation. We conducted a descriptive case series at a tertiary hospital in Spain from February 2019 to January 2022. Pediatric patients (<16 years) treated with CZA for confirmed or suspected multidrug-resistant Gram-negative infections were included. The clinical and microbiological characteristics, treatment approaches, and outcomes were examined. Eighteen children received CZA treatment. All had complex chronic conditions, with the most frequent underlying main diseases being liver transplantation (n = 8) and biliary atresia (n = 4). The predominant type of infection for which they received CZA was intra-abdominal infection caused or suspected to be caused by OXA-48-producing Klebsiella pneumoniae. CZA was generally well tolerated. Within the first month of starting CZA therapy, two patients died, with one case directly linked to the infection’s fatal outcome. Some patients needed repeated courses of therapy due to recurrent infections, yet no resistance development was noted. In summary, the use of CZA showed effectiveness and safety, while the lack of resistance development highlights CZA’s potential as a primary treatment option against OXA-48-producing infections. Full article
26 pages, 1599 KiB  
Review
New Insights into Pseudomonas spp.-Produced Antibiotics: Genetic Regulation of Biosynthesis and Implementation in Biotechnology
by Alexandra Baukova, Alexander Bogun, Svetlana Sushkova, Tatiana Minkina, Saglara Mandzhieva, Ilya Alliluev, Hanuman Singh Jatav, Valery Kalinitchenko, Vishnu D. Rajput and Yanina Delegan
Antibiotics 2024, 13(7), 597; https://doi.org/10.3390/antibiotics13070597 - 27 Jun 2024
Viewed by 261
Abstract
Pseudomonas bacteria are renowned for their remarkable capacity to synthesize antibiotics, namely mupirocin, gluconic acid, pyrrolnitrin, and 2,4-diacetylphloroglucinol (DAPG). While these substances are extensively employed in agricultural biotechnology to safeguard plants against harmful bacteria and fungi, their potential for human medicine and healthcare [...] Read more.
Pseudomonas bacteria are renowned for their remarkable capacity to synthesize antibiotics, namely mupirocin, gluconic acid, pyrrolnitrin, and 2,4-diacetylphloroglucinol (DAPG). While these substances are extensively employed in agricultural biotechnology to safeguard plants against harmful bacteria and fungi, their potential for human medicine and healthcare remains highly promising for common science. However, the challenge of obtaining stable producers that yield higher quantities of these antibiotics continues to be a pertinent concern in modern biotechnology. Although the interest in antibiotics of Pseudomonas bacteria has persisted over the past century, many uncertainties still surround the regulation of the biosynthetic pathways of these compounds. Thus, the present review comprehensively studies the genetic organization and regulation of the biosynthesis of these antibiotics and provides a comprehensive summary of the genetic organization of antibiotic biosynthesis pathways in pseudomonas strains, appealing to both molecular biologists and biotechnologists. In addition, attention is also paid to the application of antibiotics in plant protection. Full article
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14 pages, 300 KiB  
Review
Native Joint Septic Arthritis
by Kevin A. Wu, David N. Kugelman, Jessica L. Seidelman and Thorsten M. Seyler
Antibiotics 2024, 13(7), 596; https://doi.org/10.3390/antibiotics13070596 - 27 Jun 2024
Viewed by 334
Abstract
Native joint septic arthritis (NJSA) is a severe and rapidly progressing joint infection, predominantly bacterial but also potentially fungal or viral, characterized by synovial membrane inflammation and joint damage, necessitating urgent and multidisciplinary management to prevent permanent joint damage and systemic sepsis. Common [...] Read more.
Native joint septic arthritis (NJSA) is a severe and rapidly progressing joint infection, predominantly bacterial but also potentially fungal or viral, characterized by synovial membrane inflammation and joint damage, necessitating urgent and multidisciplinary management to prevent permanent joint damage and systemic sepsis. Common in large joints like knees, hips, shoulders, and elbows, NJSA's incidence is elevated in individuals with conditions like rheumatoid arthritis, diabetes, immunosuppression, joint replacement history, or intravenous drug use. This review provides a comprehensive overview of NJSA, encompassing its diagnosis, treatment, antibiotic therapy duration, and surgical interventions, as well as the comparison between arthroscopic and open debridement approaches. Additionally, it explores the unique challenges of managing NJSA in patients who have undergone graft anterior cruciate ligament (ACL) reconstruction. The epidemiology, risk factors, pathogenesis, microbiology, clinical manifestations, diagnosis, differential diagnosis, antibiotic treatment, surgical intervention, prevention, and prophylaxis of NJSA are discussed, highlighting the need for prompt diagnosis, aggressive treatment, and ongoing research to enhance patient outcomes. Full article
(This article belongs to the Special Issue Diagnosis and Antimicrobial Therapy of Osteoarticular Infection)
11 pages, 2408 KiB  
Article
High Biofilm-Forming Multidrug-Resistant Salmonella Infantis Strains from the Poultry Production Chain
by Laura Musa, Valeria Toppi, Valentina Stefanetti, Noah Spata, Maria Cristina Rapi, Guido Grilli, Maria Filippa Addis, Giacomo Di Giacinto, Maria Pia Franciosini and Patrizia Casagrande Proietti
Antibiotics 2024, 13(7), 595; https://doi.org/10.3390/antibiotics13070595 - 27 Jun 2024
Viewed by 311
Abstract
The ability of Salmonella species to adhere to surfaces and form biofilms, leading to persistent environmental reservoirs, might represent a direct link between environmental contamination and food processing contamination. The purpose of this study was to investigate the biofilm-forming ability of 80 multidrug-resistant [...] Read more.
The ability of Salmonella species to adhere to surfaces and form biofilms, leading to persistent environmental reservoirs, might represent a direct link between environmental contamination and food processing contamination. The purpose of this study was to investigate the biofilm-forming ability of 80 multidrug-resistant (MDR) and extended-spectrum beta-lactamase (ESBL) producing Salmonella enterica serovar Infantis strains isolated from the broiler food chain production through whole genome sequencing (WGS), PCR, and morphotype association assays. Biofilm formation was quantified by testing the strains at two different temperatures, using 96-well polystyrene plates. The rough and dry colony (rdar) morphotype was assessed visually on Congo red agar (CRA) plates. Based on our results, all tested S. Infantis strains produced biofilm at 22 °C with an rdar morphotype, while at 37 °C, all the isolates tested negative, except one positive. Most isolates (58.75%) exhibited strong biofilm production, while 36.25% showed moderate production. Only 5 out of 80 (6.25%) were weak biofilm producers. WGS analysis showed the presence of the fim cluster (fimADF) and the csg cluster (csgBAC and csgDEFG), also described in S. Typhimurium, which are responsible for fimbriae production. PCR demonstrated the presence of csgD, csgB, and fimA in all 80 S. Infantis strains. To our knowledge, this is the first study comparing the effects of two different temperatures on the biofilm formation capacity of ESBL producing S. Infantis from the broiler production chain. This study highlights that the initial biofilm components, such as curli and cellulose, are specifically expressed at lower temperatures. It is important to emphasize that within the broiler farm, the environmental temperature ranges between 18–22 °C, which is the optimum temperature for in vitro biofilm formation by Salmonella spp. This temperature range facilitates the expression of biofilm-associated genes, contributing to the persistence of S. Infantis in the environment. This complicates biosecurity measures and makes disinfection protocols on the farm and in the production chain more difficult, posing serious public health concerns. Full article
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10 pages, 398 KiB  
Article
Staphylococcus aureus is the Predominant Pathogen in Hospitalised Patients with Diabetes-Related Foot Infections: An Australian Perspective
by Kate E. Morton and Sarah H. Coghill
Antibiotics 2024, 13(7), 594; https://doi.org/10.3390/antibiotics13070594 - 26 Jun 2024
Viewed by 407
Abstract
Diabetes prevalence continues to increase worldwide, which has led to a rising incidence of diabetes-related foot infections (DFIs). There is significant local variation in the microbiology of DFIs, and Pseudomonas spp. is suggested to be more prevalent in subtropical climates. The aim of [...] Read more.
Diabetes prevalence continues to increase worldwide, which has led to a rising incidence of diabetes-related foot infections (DFIs). There is significant local variation in the microbiology of DFIs, and Pseudomonas spp. is suggested to be more prevalent in subtropical climates. The aim of this study was to investigate the local microbiological findings in patients admitted to the hospital with DFIs. This retrospective study analysed data from all adult patients diagnosed with diabetes and admitted to the hospital for the treatment of a DFI between 1 January 2021 and 31 December 2022. Both superficial wound swabs and tissue cultures were included. The Infectious Diseases Society of America classification system was used to categorise the severity of the DFI. Patient characteristics and demographics were analysed using descriptive statistics. One hundred fifty-one episodes of care were included. Most of the DFIs were classified as moderate infections 101/151 (67%). The most commonly isolated microorganism was Staphylococcus aureus (33%) followed by normal skin flora (11%) and β-haemolytic streptococci (7%). P. aeruginosa was isolated more commonly in those with chronic DFIs (10%) compared to those with acute DFIs (2%). Despite the frequent identification of S. aureus, 83% of patients received an antipseudomonal antibiotic. The introduction of multidisciplinary DFI rounds should be considered. Full article
(This article belongs to the Special Issue Feature Papers in Therapy of Diabetic Foot Infections)
20 pages, 1948 KiB  
Review
The Molecular Mechanisms and Therapeutic Potential of Cranberry, D-Mannose, and Flavonoids against Infectious Diseases: The Example of Urinary Tract Infections
by Petros Ioannou and Stella Baliou
Antibiotics 2024, 13(7), 593; https://doi.org/10.3390/antibiotics13070593 - 26 Jun 2024
Viewed by 473
Abstract
The treatment of infectious diseases typically includes the administration of anti-infectives; however, the increasing rates of antimicrobial resistance (AMR) have led to attempts to develop other modalities, such as antimicrobial peptides, nanotechnology, bacteriophages, and natural products. Natural products offer a viable alternative due [...] Read more.
The treatment of infectious diseases typically includes the administration of anti-infectives; however, the increasing rates of antimicrobial resistance (AMR) have led to attempts to develop other modalities, such as antimicrobial peptides, nanotechnology, bacteriophages, and natural products. Natural products offer a viable alternative due to their potential affordability, ease of access, and diverse biological activities. Flavonoids, a class of natural polyphenols, demonstrate broad anti-infective properties against viruses, bacteria, fungi, and parasites. Their mechanisms of action include disruption of microbial membranes, inhibition of nucleic acid synthesis, and interference with bacterial enzymes. This review explores the potential of natural compounds, such as flavonoids, as an alternative therapeutic approach to combat infectious diseases. Moreover, it discusses some commonly used natural products, such as cranberry and D-mannose, to manage urinary tract infections (UTIs). Cranberry products and D-mannose both, yet differently, inhibit the adhesion of uropathogenic bacteria to the urothelium, thus reducing the likelihood of UTI occurrence. Some studies, with methodological limitations and small patient samples, provide some encouraging results suggesting the use of these substances in the prevention of recurrent UTIs. While further research is needed to determine optimal dosages, bioavailability, and potential side effects, natural compounds hold promise as a complementary or alternative therapeutic strategy in the fight against infectious diseases. Full article
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16 pages, 2632 KiB  
Article
Genomic Study of High-Risk Clones of Enterobacter hormaechei Collected from Tertiary Hospitals in the United Arab Emirates
by Akela Ghazawi, Febin Anes, Shaimaa Mouftah, Mohammed Elbediwi, Awase Baig, Muna Alketbi, Fatema Almazrouei, Mariam Alhashmi, Norah Alzarooni, Ashrat Manzoor, Ihab Habib, Nikolaos Strepis, Anju Nabi and Mushtaq Khan
Antibiotics 2024, 13(7), 592; https://doi.org/10.3390/antibiotics13070592 - 26 Jun 2024
Viewed by 697
Abstract
Enterobacter hormaechei has emerged as a significant pathogen within healthcare settings due to its ability to develop multidrug resistance (MDR) and survive in hospital environments. This study presents a genome-based analysis of carbapenem-resistant Enterobacter hormaechei isolates from two major hospitals in the United [...] Read more.
Enterobacter hormaechei has emerged as a significant pathogen within healthcare settings due to its ability to develop multidrug resistance (MDR) and survive in hospital environments. This study presents a genome-based analysis of carbapenem-resistant Enterobacter hormaechei isolates from two major hospitals in the United Arab Emirates. Eight isolates were subjected to whole-genome sequencing (WGS), revealing extensive resistance profiles including the blaNDM-1, blaOXA-48, and blaVIM-4 genes. Notably, one isolate belonging to ST171 harbored dual carbapenemase genes, while five isolates exhibited colistin resistance without mcr genes. The presence of the type VI secretion system (T6SS), various adhesins, and virulence genes contributes to the virulence and competitive advantage of the pathogen. Additionally, our isolates (87.5%) possessed ampC β-lactamase genes, predominantly blaACT genes. The genomic context of blaNDM-1, surrounded by other resistance genes and mobile genetic elements, highlights the role of horizontal gene transfer (HGT) in the spread of resistance. Our findings highlight the need for rigorous surveillance, strategic antibiotic stewardship, and hospital-based WGS to manage and mitigate the spread of these highly resistant and virulent pathogens. Accurate identification and monitoring of Enterobacter cloacae complex (ECC) species and their resistance mechanisms are crucial for effective infection control and treatment strategies. Full article
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10 pages, 843 KiB  
Case Report
Isolation of Multidrug-Resistant Mycobacterium Avium Subsp. Avium from a Wild Eurasian Otter (Lutra Lutra)
by Irena Reil, Sanja Duvnjak, Silvio Špičić, Gordan Kompes, Antonela Bagarić, Martina Đuras, Andrea Gudan Kurilj, Maja Lukač, Mišel Jelić and Maja Zdelar-Tuk
Antibiotics 2024, 13(7), 591; https://doi.org/10.3390/antibiotics13070591 - 26 Jun 2024
Viewed by 544
Abstract
Mycobacterium avium subsp. avium is pathogenic mainly to birds, although cases of mycobacteriosis caused by these bacteria have also been reported in other animals and humans. Not much is known about the effects of this pathogen on otters. The aim of this study [...] Read more.
Mycobacterium avium subsp. avium is pathogenic mainly to birds, although cases of mycobacteriosis caused by these bacteria have also been reported in other animals and humans. Not much is known about the effects of this pathogen on otters. The aim of this study was to report for the first time the isolation of M. avium subsp. avium in wild otter and to describe its multidrug resistance profile. A female otter injured in a car accident was found dead and subjected to postmortem examination. Apart from the trauma changes, no other macroscopic pathological changes were detected. Bacteriologic examination revealed the presence of acid-fast bacilli in the lymph nodes, which were confirmed by molecular methods as M. avium subsp. avium. Antimicrobial susceptibility testing revealed susceptibility to clarithromycin and amikacin, but resistance to linezolid, moxifloxacin, streptomycin, isoniazid, trimethoprim/sulfamethoxazole, ciprofloxacin, doxycycline, and ethionamide. This is unusual for wild species, which generally should not come into contact with antimicrobials, and may suggest that multidrug-resistant MAC strains are circulating between wild and domestic animals. These results emphasise the need for additional epidemiological studies on non-tuberculous mycobacteria in wildlife and their implications for one health. Full article
(This article belongs to the Section Antibiotics in Animal Health)
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13 pages, 1754 KiB  
Article
Improvement in Diagnosis and Management of Nosocomial Pneumonias in a Cardiovascular Surgery Intensive Care Unit: A Multidisciplinary Approach
by Kirstin J. Kooda, Alejandra A. Zambrano, Dylan L. Kosaski, Leah Higbe, William Brian B. Beam, J. Kyle K. Bohman, Erica D. Wittwer, Steven D. Brady, Allison M. LeMahieu, Madiha Fida and Aditya Shah
Antibiotics 2024, 13(7), 590; https://doi.org/10.3390/antibiotics13070590 - 26 Jun 2024
Viewed by 433
Abstract
Abstract: Background: While criteria for the diagnosis of nosocomial pneumonias exist, objective definitions are a challenge and there is no gold standard for diagnosis. We analyzed the impact of the implementation of a logical, consensus-based diagnostic and treatment protocol for managing nosocomial [...] Read more.
Abstract: Background: While criteria for the diagnosis of nosocomial pneumonias exist, objective definitions are a challenge and there is no gold standard for diagnosis. We analyzed the impact of the implementation of a logical, consensus-based diagnostic and treatment protocol for managing nosocomial pneumonias in the cardiovascular surgery intensive care unit (CVS-ICU). Methods: We conducted a quasi-experimental, interrupted time series analysis to evaluate the impact of a diagnostic and treatment protocol for nosocomial pneumonias in the CVS-ICU. Impacts were measured relative to patient outcomes, diagnostic processes, and antimicrobial stewardship improvement. Descriptive statistics were used to analyze results. Results: Overall, 35 pre-protocol and 39 post-protocol patients were included. Primary clinical variables suggesting pneumonia in pre- and post-protocol patients were new lung consolidation (50% vs. 71%), new leukocytosis (59% vs. 64%), and positive culture (32% vs. 55%). Appropriate diagnostic testing improved (23% vs. 54%, p = 0.008) after protocol implementation. The proportion of patients meeting the criteria for nosocomial pneumonia (77% vs. 87%) was not statistically significant, though more patients in the post-protocol group met probable diagnostic criteria (51% vs. 77%). Duration of therapy was not significantly different (6 days [IQR = 5.0, 10.0] vs. 7 days [IQR = 6.0, 9.0]). Conclusions: The implementation of a diagnostic and treatment protocol for management of nosocomial pneumonias in the CVS-ICU resulted in improved diagnostic accuracy, advanced antimicrobial and diagnostic stewardship efforts, and laboratory cost savings without an adverse impact on patient-centered outcomes. Full article
(This article belongs to the Special Issue Pulmonary Infections: Pathogenesis and Antimicrobial Treatment)
16 pages, 323 KiB  
Review
Yokenella regensburgei—Past, Present and Future
by Dan Alexandru Toc, Carmen Costache, Vlad Sever Neculicioiu, Irina-Maria Rusu, Bogdan-Valentin Roznovan, Alexandru Botan, Adelina Georgiana Toc, Pavel Șchiopu, Paul-Stefan Panaitescu, Adrian Gabriel Pană and Ioana Alina Colosi
Antibiotics 2024, 13(7), 589; https://doi.org/10.3390/antibiotics13070589 - 26 Jun 2024
Viewed by 439
Abstract
Yokenella regensburgei is a Gram-negative rod part of the Enterobacteriaceae family (order Enterobacterales) and a rare cause of human infections. Although improved diagnostic methods have led to an increase in reports of this elusive pathogen, information remains limited. In order to provide [...] Read more.
Yokenella regensburgei is a Gram-negative rod part of the Enterobacteriaceae family (order Enterobacterales) and a rare cause of human infections. Although improved diagnostic methods have led to an increase in reports of this elusive pathogen, information remains limited. In order to provide a better understanding of this bacterium, we developed the first comprehensive review of its biology, biochemical profile, antimicrobial resistance pattern, virulence factors, natural reservoir and involvement in various veterinary and human infections. Human infections with this bacterium are scarcely reported, most probably due to constraints regarding its identification and biochemical similarities to Hafnia alvei. Multiple systematic searches revealed 23 cases of human infection, with a seemingly worldwide distribution, mostly in middle-aged or elderly male patients, often associated with immunosuppression. To date, Y. regensburgei has been reported in skin and soft tissue infections, bacteremia and sepsis, osteoarticular infections and in others such as urinary tract and digestive infections. The unique ability of Y. regensburgei to degrade polystyrene presents a novel and promising avenue for addressing plastic pollution in the near future. However, large-scale applications of this bacterium will undoubtedly increase human exposure, highlighting the necessity for comprehensive research into its role in human and veterinary infections, pathogenicity and antibiotic resistance. Full article
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