Antibiotics

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20 pages, 8830 KiB

Open AccessArticle

Structure–Activity Relationship of Pyrrolidine Pentamine Derivatives as Inhibitors of the Aminoglycoside 6′-N-Acetyltransferase Type Ib

by Jan Sklenicka, Tung Tran, Maria S. Ramirez, Haley M. Donow, Angel J. Magaña, Travis LaVoi, Yasir Mamun, Verónica Jimenez, Prem Chapagain, Radleigh Santos, Clemencia Pinilla, Marc A. Giulianotti and Marcelo E. Tolmasky

Antibiotics 2024, 13(7), 672; https://doi.org/10.3390/antibiotics13070672 - 19 Jul 2024

Cited by 1 | Viewed by 1015

Abstract

Resistance to amikacin and other major aminoglycosides is commonly due to enzymatic acetylation by the aminoglycoside 6′-N-acetyltransferase type I enzyme, of which type Ib [AAC(6′)-Ib] is the most widespread among Gram-negative pathogens. Finding enzymatic inhibitors could be an effective way to [...] Read more.

Resistance to amikacin and other major aminoglycosides is commonly due to enzymatic acetylation by the aminoglycoside 6′-N-acetyltransferase type I enzyme, of which type Ib [AAC(6′)-Ib] is the most widespread among Gram-negative pathogens. Finding enzymatic inhibitors could be an effective way to overcome resistance and extend the useful life of amikacin. Small molecules possess multiple properties that make them attractive for drug development. Mixture-based combinatorial libraries and positional scanning strategy have led to the identification of a chemical scaffold, pyrrolidine pentamine, that, when substituted with the appropriate functionalities at five locations (R1–R5), inhibits AAC(6′)-Ib-mediated inactivation of amikacin. Structure–activity relationship studies have shown that while truncations to the molecule result in loss of inhibitory activity, modifications of functionalities and stereochemistry have different effects on the inhibitory properties. In this study, we show that alterations at position R1 of the two most active compounds, 2700.001 and 2700.003, reduced inhibition levels, demonstrating the essential nature not only of the presence of an S-phenyl moiety at this location but also the distance to the scaffold. On the other hand, modifications on the R3, R4, and R5 positions had varied effects, demonstrating the potential for optimization. A correlation analysis between molecular docking values (ΔG) and the dose required for two-fold potentiation of the compounds described in this and the previous studies showed a significant correlation between ΔG values and inhibitory activity. Full article

(This article belongs to the Special Issue Novel and Traditional Methods to Fight Antibiotic Resistant Bacteria and Biofilm Infections)

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22 pages, 6012 KiB

Open AccessEditor’s ChoiceArticle

Repurposing Farnesol for Combating Drug-Resistant and Persistent Single and Polymicrobial Biofilms

by Li Tan, Rong Ma, Tony Reeves, Adam J. Katz and Nicole Levi

Antibiotics 2024, 13(4), 350; https://doi.org/10.3390/antibiotics13040350 - 11 Apr 2024

Cited by 2 | Viewed by 1602

Abstract

Biofilm-associated infections caused by drug-resistant and persistent bacteria remain a significant clinical challenge. Here we report that farnesol, commercially available as a cosmetic and flavoring agent, shows significant anti-biofilm properties when dissolved in ethanol using a proprietary formulation emulsion technique. Farnesol in the [...] Read more.

Biofilm-associated infections caused by drug-resistant and persistent bacteria remain a significant clinical challenge. Here we report that farnesol, commercially available as a cosmetic and flavoring agent, shows significant anti-biofilm properties when dissolved in ethanol using a proprietary formulation emulsion technique. Farnesol in the new formulation inhibits biofilm formation and disrupts established biofilms for Gram-positive Staphylococcus aureus and Gram-negative Pseudomonas aeruginosa, including their polymicrobial biofilms, and, moreover, kills S. aureus persister cells that have developed tolerance to antibiotics. No resistance to farnesol was observed for S. aureus after twenty continuous passages. Farnesol combats biofilms by direct killing, while also facilitating biofilm detachment. Furthermore, farnesol was safe and effective for preventing and treating biofilm-associated infections of both types of bacteria in an ex vivo burned human skin model. These data suggest that farnesol in the new formulation is an effective broad-spectrum anti-biofilm agent with promising clinical potential. Due to its established safety, low-cost, versatility, and excellent efficacy—including ability to reduce persistent and resistant microbial populations—farnesol in the proprietary formulation represents a compelling transformative, translational, and commercial platform for addressing many unsolved clinical challenges. Full article

(This article belongs to the Special Issue Novel and Traditional Methods to Fight Antibiotic Resistant Bacteria and Biofilm Infections)

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13 pages, 1968 KiB

Open AccessArticle

The Antimicrobial Efficacy of Topically Applied Mafenide Acetate, Citric Acid and Wound Irrigation Solutions Lavanox and Prontosan against Pseudomonas aeruginosa

by Mahsa Bagheri, Andreas Zoric, Maria von Kohout, Paul C. Fuchs, Jennifer Lynn. Schiefer and Christian Opländer

Antibiotics 2024, 13(1), 42; https://doi.org/10.3390/antibiotics13010042 - 3 Jan 2024

Viewed by 1903

Abstract

Since burn wound infections caused by Pseudomonas aeruginosa (PA) lead to major complications and sepsis, this study evaluates the antimicrobial efficacy of the wound irrigation solutions Prontosan (PRT), Lavanox (LAV), citric acid (CA) and mafenide acetate (MA) using microbiology assays and an ex [...] Read more.

Since burn wound infections caused by Pseudomonas aeruginosa (PA) lead to major complications and sepsis, this study evaluates the antimicrobial efficacy of the wound irrigation solutions Prontosan (PRT), Lavanox (LAV), citric acid (CA) and mafenide acetate (MA) using microbiology assays and an ex vivo skin wound model. In suspension assays, all the solutions showed significant reductions in bacterial number (log₁₀ reduction: CA 5.77; LAV 4.91; PRT 4.74; MA 1.23). The biofilm assay revealed that PRT and LAV reduced biofilm formation by ~25% after a 15 min treatment, while PRT was most effective after a 24 h treatment (~68%). The number of PA in biofilms measured directly after a 15 min treatment was reduced most effectively with CA and LAV (log₁₀ reductions ~2.5), whereas after a 24 h treatment, all solutions achieved only 1.36–1.65 log₁₀ reductions. In the skin wound model, PRT and LAV provided the highest bacterial reduction after a 15 min treatment (log₁₀ reduction 1.8–1.9), while MA was more effective after a 22 h treatment (log₁₀ reduction 3.6). The results demonstrated the antimicrobial efficacy of all solutions against PA. Further investigation is needed to explore the potential clinical applications of a combination or alternating use of these solutions for infection prophylaxis and treatment of wound infections caused by PA. Full article

(This article belongs to the Special Issue Novel and Traditional Methods to Fight Antibiotic Resistant Bacteria and Biofilm Infections)

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16 pages, 1865 KiB

Open AccessEditor’s ChoiceArticle

Antibiofilm and Antivirulence Properties of 6-Polyaminosteroid Derivatives against Antibiotic-Resistant Bacteria

by Delphine Vergoz, Hung Le, Benoit Bernay, Annick Schaumann, Magalie Barreau, Flore Nilly, Florie Desriac, Ali Tahrioui, Jean-Christophe Giard, Olivier Lesouhaitier, Sylvie Chevalier, Jean Michel Brunel, Cécile Muller and Emmanuelle Dé

Antibiotics 2024, 13(1), 8; https://doi.org/10.3390/antibiotics13010008 - 20 Dec 2023

Viewed by 1877

Abstract

The emergence of multi-drug resistant pathogens is a major public health problem, leading us to rethink and innovate our bacterial control strategies. Here, we explore the antibiofilm and antivirulence activities of nineteen 6-polyaminosterol derivatives (squalamine-based), presenting a modulation of their polyamine side chain [...] Read more.

The emergence of multi-drug resistant pathogens is a major public health problem, leading us to rethink and innovate our bacterial control strategies. Here, we explore the antibiofilm and antivirulence activities of nineteen 6-polyaminosterol derivatives (squalamine-based), presenting a modulation of their polyamine side chain on four major pathogens, i.e., carbapenem-resistant A. baumannii (CRAB) and P. aeruginosa (CRPA), methicillin-resistant S. aureus (MRSA), and vancomycin-resistant E. faecium (VRE) strains. We screened the effect of these derivatives on biofilm formation and eradication. Derivatives 4e (for CRAB, VRE, and MRSA) and 4f (for all the strains) were the most potent ones and displayed activities as good as those of conventional antibiotics. We also identified 11 compounds able to decrease by more than 40% the production of pyocyanin, a major virulence factor of P. aeruginosa. We demonstrated that 4f treatment acts against bacterial infections in Galleria mellonella and significantly prolonged larvae survival (from 50% to 80%) after 24 h of CRAB, VRE, and MRSA infections. As shown by proteomic studies, 4f triggered distinct cellular responses depending on the bacterial species but essentially linked to cell envelope. Its interesting antibiofilm and antivirulence properties make it a promising a candidate for use in therapeutics. Full article

(This article belongs to the Special Issue Novel and Traditional Methods to Fight Antibiotic Resistant Bacteria and Biofilm Infections)

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14 pages, 1487 KiB

Open AccessArticle

In Vitro Activities of Oxazolidinone Antibiotics Alone and in Combination with C-TEMPO against Methicillin-Resistant Staphylococcus aureus Biofilms

by Audrey R. N. Ndukwe, Jilong Qin, Sandra Wiedbrauk, Nathan R. B. Boase, Kathryn E. Fairfull-Smith and Makrina Totsika

Antibiotics 2023, 12(12), 1706; https://doi.org/10.3390/antibiotics12121706 - 7 Dec 2023

Viewed by 1540

Abstract

Infections caused by methicillin-resistant Staphylococcus aureus (MRSA) are a global health concern. The propensity of MRSA to form biofilms is a significant contributor to its pathogenicity. Strategies to treat biofilms often involve small molecules that disperse the biofilm into planktonic cells. Linezolid and, [...] Read more.

Infections caused by methicillin-resistant Staphylococcus aureus (MRSA) are a global health concern. The propensity of MRSA to form biofilms is a significant contributor to its pathogenicity. Strategies to treat biofilms often involve small molecules that disperse the biofilm into planktonic cells. Linezolid and, by extension, theoxazolidinones have been developed to treat infections caused by Gram-positive bacteria such as MRSA. However, the clinical development of these antibiotics has mainly assessed the susceptibility of planktonic cells to the drug. Previous studies evaluating the anti-biofilm activity of theoxazolidinones have mainly focused on the biofilm inhibition of Enterococcus faecalis and methicillin-sensitive Staphylococcus aureus, with only a few studies investigating the activity of oxazolidinones for eradicating established biofilms for these species. Very little is known about the ability of oxazolidinones to eradicate MRSA biofilms. In this work, five oxazolidinones were assessed against MRSA biofilms using a minimum biofilm eradication concentration (MBEC) assay. All oxazolidinones had inherent antibiofilm activity. However, only ranbezolid could completely eradicate MRSA biofilms at clinically relevant concentrations. The susceptibility of the MRSA biofilms to ranbezolid was synergistically enhanced by coadministration with the nitroxide biofilm dispersal agent C-TEMPO. We presume that ranbezolid acts as a dual warhead drug, which combines the mechanism of action of the oxazolidinones with a nitric oxide donor or cytotoxic drug. Full article

(This article belongs to the Special Issue Novel and Traditional Methods to Fight Antibiotic Resistant Bacteria and Biofilm Infections)

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14 pages, 2497 KiB

Open AccessArticle

Effect of Camel Peptide on the Biofilm of Staphylococcus epidermidis and Staphylococcus haemolyticus Formed on Orthopedic Implants

by Joanna Nowicka, Adriana Janczura, Magdalena Pajączkowska, Grzegorz Chodaczek, Patrycja Szymczyk-Ziółkowska, Urszula Walczuk and Grażyna Gościniak

Antibiotics 2023, 12(12), 1671; https://doi.org/10.3390/antibiotics12121671 - 28 Nov 2023

Cited by 3 | Viewed by 1521

Abstract

The increasing bacterial drug resistance and the associated challenges in the treatment of infections warrant the search for alternative therapeutic methods. Hope is placed in antimicrobial peptides, which have a broad spectrum of action and are effective against strains which are resistant to [...] Read more.

The increasing bacterial drug resistance and the associated challenges in the treatment of infections warrant the search for alternative therapeutic methods. Hope is placed in antimicrobial peptides, which have a broad spectrum of action and are effective against strains which are resistant to conventional antibiotics. Antimicrobial peptides are also tested for their efficacy in the treatment of infections associated with the formation of biofilm. The aim of the present study was to examine the effect of Camel peptide on S. epidermidis and S. haemolyticus adhesion to and formation of biofilm on steel cortical bone screws and also on the process of reducing mature biofilm in orthopedic implants. The tests were performed on steel implants for osteosynthesis. The MIC value and MBEC values of the peptide were determined using the microdilution method in microtiter plates. The effect of the peptide on adhesion and biofilm formation, as well as on the activity on the preformed biofilm, was evaluated using quantitative methods and confocal microscopy. The presented research results indicate that the peptide exhibits very good antimicrobial properties against the analyzed strains. Concentrations above MIC reduced biofilm in the range of 90–99%. Full article

(This article belongs to the Special Issue Novel and Traditional Methods to Fight Antibiotic Resistant Bacteria and Biofilm Infections)

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15 pages, 1513 KiB

Open AccessArticle

Evaluation of Disinfectant Efficacy against Biofilm-Residing Wild-Type Salmonella from the Porcine Industry

by Ane Mohr Osland, Claire Oastler, Katharina Konrat, Live L. Nesse, Emma Brook, Anja M. Richter, Rebecca J. Gosling, Mardjan Arvand and Lene K. Vestby

Antibiotics 2023, 12(7), 1189; https://doi.org/10.3390/antibiotics12071189 - 14 Jul 2023

Cited by 2 | Viewed by 2124

Abstract

Salmonella enterica is a causative pathogen of Salmonellosis, a zoonosis causing global disease and financial losses every year. Pigs may be carriers of Salmonella and contribute to the spread to humans and food products. Salmonella may persist as biofilms. Biofilms are bacterial aggregates [...] Read more.

Salmonella enterica is a causative pathogen of Salmonellosis, a zoonosis causing global disease and financial losses every year. Pigs may be carriers of Salmonella and contribute to the spread to humans and food products. Salmonella may persist as biofilms. Biofilms are bacterial aggregates embedded in a self-produced matrix and are known to withstand disinfectants. We studied the effect of glutaraldehyde and peracetic acid, two active substances frequently used in disinfectant formulations in the pig industry, on representative biofilm-residing wild-type Salmonella collected from pig housings in the United Kingdom (UK). We screened biofilm production of strains using the microtiter plate (MTP) assay and Congo Red Coomassie Blue (CRCB) agar method. Previously published stainless-steel coupon (SSCA), polyvinylchloride coupon (PCA), and glass bead (GBA) assays were used for disinfection studies. The mean reduction in the tested wild-type strains met the criterion of ≥4 log₁₀ CFU at a disinfectant concentration of 0.05% with SSCA and GBA, and 0.005% with PCA for peracetic acid, along with 0.5% for glutaraldehyde with all three assays on the mean. At these concentrations, both tested disinfectants are suitable for disinfection of pig housings against Salmonella. When evaluating the efficacy of disinfectants, biofilms should be included, as higher disinfectant concentrations are necessary compared to planktonic bacteria. Full article

(This article belongs to the Special Issue Novel and Traditional Methods to Fight Antibiotic Resistant Bacteria and Biofilm Infections)

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17 pages, 6148 KiB

Open AccessFeature PaperArticle

Antibacterial and Antibiofilm Effects of Lactobacilli Strains against Clinical Isolates of Pseudomonas aeruginosa under Conditions Relevant to Cystic Fibrosis

by Giovanna Batoni, Elisa Catelli, Esingül Kaya, Arianna Pompilio, Marta Bianchi, Emilia Ghelardi, Giovanni Di Bonaventura, Semih Esin and Giuseppantonio Maisetta

Antibiotics 2023, 12(7), 1158; https://doi.org/10.3390/antibiotics12071158 - 7 Jul 2023

Cited by 11 | Viewed by 1965

Abstract

Therapy of lung infections sustained by Pseudomonas aeruginosa in cystic fibrosis (CF) patients is challenging due to the presence of a sticky mucus in the airways and the ability of the bacterium to form biofilm, which exhibits increased antibiotic tolerance. A lung-directed bacteriotherapy [...] Read more.

Therapy of lung infections sustained by Pseudomonas aeruginosa in cystic fibrosis (CF) patients is challenging due to the presence of a sticky mucus in the airways and the ability of the bacterium to form biofilm, which exhibits increased antibiotic tolerance. A lung-directed bacteriotherapy through the airway administration of probiotics could represent an alternative approach to probiotic diet supplementation to improve the benefits and clinical outcomes of this kind of intervention in CF patients. This study aims to evaluate the ability of probiotic strains to grow in artificial sputum medium (ASM), mimicking the CF lung microenvironment, and to affect the planktonic and biofilm growth of CF clinical strains of P. aeruginosa in the same conditions. The results demonstrate that Lacticaseibacillus rhamnosus and Lactiplantibacillus plantarum (LP) can grow in ASM. LP inhibited the planktonic growth of P. aeruginosa, while both lactobacilli reduced the pre-formed biofilm of P. aeruginosa. Interestingly, LP was demonstrated to reduce the amount of polysaccharides in the extracellular matrix of P. aeruginosa biofilms and to potentiate the antibiofilm effects of tobramycin. Overall, the results indicated that LP is a promising candidate as an adjuvant in the antimicrobial therapy of P. aeruginosa infections in CF patients. Full article

(This article belongs to the Special Issue Novel and Traditional Methods to Fight Antibiotic Resistant Bacteria and Biofilm Infections)

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13 pages, 1820 KiB

Open AccessArticle

Undesired Effect of Vancomycin Prolonged Treatment: Enhanced Biofilm Production of the Nosocomial Pathogen Candida auris

by Angela Maione, Alessandra La Pietra, Maria Michela Salvatore, Marco Guida, Emilia Galdiero and Elisabetta de Alteriis

Antibiotics 2022, 11(12), 1771; https://doi.org/10.3390/antibiotics11121771 - 8 Dec 2022

Cited by 4 | Viewed by 1874

Abstract

Fungal infections are often consequent to prolonged antibiotic treatments. Vancomycin (Van) is the first-choice antibiotic in the treatment of Staphylococcus aureus infections associated with colonization of catheter surfaces. We demonstrate the direct effect of Van in promoting the formation of the biofilm of [...] Read more.

Fungal infections are often consequent to prolonged antibiotic treatments. Vancomycin (Van) is the first-choice antibiotic in the treatment of Staphylococcus aureus infections associated with colonization of catheter surfaces. We demonstrate the direct effect of Van in promoting the formation of the biofilm of the emergent yeast pathogen Candida auris, developed in the conventional polystyrene microwell plate model, as well as on silicone surfaces (22 and 28% increase in total biomass, respectively) and on an S. aures biofilm, residual after vancomycin treatment, where C. auris achieved 99% of the mixed biofilm population. The effect of Van was assessed also in vivo, in the Galleria mellonella infection model, which showed higher mortality when infected with the yeast pathogen in the presence of the antibiotic. This evidence enhances awareness of the potential risk associated with prolonged antibiotic use in promoting fungal infections. Full article

(This article belongs to the Special Issue Novel and Traditional Methods to Fight Antibiotic Resistant Bacteria and Biofilm Infections)

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13 pages, 1909 KiB

Open AccessArticle

Iron Chelator DIBI Suppresses Formation of Ciprofloxacin-Induced Antibiotic Resistance in Staphylococcus aureus

by David S. Allan and Bruce E. Holbein

Antibiotics 2022, 11(11), 1642; https://doi.org/10.3390/antibiotics11111642 - 17 Nov 2022

Cited by 5 | Viewed by 2012

Abstract

Antibiotic resistance of bacterial pathogens results from their exposure to antibiotics and this has become a serious growing problem that limits effective use of antibiotics. Resistance can arise from mutations induced by antibiotic-mediated damage with these mutants possessing reduced target sensitivity. We have [...] Read more.

Antibiotic resistance of bacterial pathogens results from their exposure to antibiotics and this has become a serious growing problem that limits effective use of antibiotics. Resistance can arise from mutations induced by antibiotic-mediated damage with these mutants possessing reduced target sensitivity. We have studied ciprofloxacin (CIP)-mediated killing of Staphylococcus aureus and the influence of the Reactive Oxygen Species (ROS) inactivator, thiourea and the iron chelator DIBI, on initial killing by CIP and their effects on survival and outgrowth upon prolonged exposure to CIP. CIP at 2× MIC caused a rapid initial killing which was not influenced by initial bacterial iron status and which was followed by robust recovery growth over 96 h exposure. Thiourea and DIBI did slow the initial rate of CIP killing but the overall extent of kill by 24 h exposure was like CIP alone. Thiourea permitted recovery growth whereas this was strongly suppressed by DIBI. Small Colony Variant (SCV) survivors were progressively enriched in the survivor population during CIP exposure, and these were found to have stable slow-growth phenotype and acquired resistance to CIP and moxifloxacin but not to other non-related antibiotics. DIBI totally suppressed SCV formation with all survivors remaining sensitive to CIP and to DIBI. DIBI exposure did not promote resistance to DIBI. Our evidence indicates a high potential for DIBI as an adjunct to CIP and other antibiotics to both improve antibiotic efficacy and to thwart antibiotic resistance development. Full article

(This article belongs to the Special Issue Novel and Traditional Methods to Fight Antibiotic Resistant Bacteria and Biofilm Infections)

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19 pages, 2846 KiB

Open AccessArticle

Development and Characterization of Azithromycin-Loaded Microemulsions: A Promising Tool for the Treatment of Bacterial Skin Infections

by Angela Abruzzo, Carola Parolin, Martina Rossi, Beatrice Vitali, Concettina Cappadone and Federica Bigucci

Antibiotics 2022, 11(8), 1040; https://doi.org/10.3390/antibiotics11081040 - 2 Aug 2022

Cited by 11 | Viewed by 2991

Abstract

In recent years, the treatment of bacterial skin infections has been considered a major healthcare issue due to the growing emergence of antibiotic-resistant strains of Staphylococcus aureus. The incorporation of antibiotics in appropriate nanosystems could represent a promising strategy, able to overcome [...] Read more.

In recent years, the treatment of bacterial skin infections has been considered a major healthcare issue due to the growing emergence of antibiotic-resistant strains of Staphylococcus aureus. The incorporation of antibiotics in appropriate nanosystems could represent a promising strategy, able to overcome several drawbacks of the topical treatment of infections, including poor drug retention within the skin. The present work aims to develop microemulsions containing azithromycin (AZT), a broad-spectrum macrolide antibiotic. Firstly, AZT solubility in various oils, surfactants and co-surfactants was assessed to select the main components. Subsequently, microemulsions composed of vitamin E acetate, Labrasol^® and Transcutol^® P were prepared and characterized for their pH, viscosity, droplet size, zeta potential and ability to release the drug and to promote its retention inside porcine skin. Antimicrobial activity against S. aureus methicillin-resistant strains (MRSA) and the biocompatibility of microemulsions were evaluated. Microemulsions showed an acceptable pH and were characterized by different droplet sizes and viscosities depending on their composition. Interestingly, they provided a prolonged release of AZT and promoted its accumulation inside the skin. Finally, microemulsions retained AZT efficacy on MRSA and were not cytotoxic. Hence, the developed AZT-loaded microemulsions could be considered as useful nanocarriers for the treatment of antibiotic-resistant infections of the skin. Full article

(This article belongs to the Special Issue Novel and Traditional Methods to Fight Antibiotic Resistant Bacteria and Biofilm Infections)

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Review

Jump to: Research

11 pages, 270 KiB

Open AccessReview

Efficacy and Experience of Bacteriophages in Biofilm-Related Infections

by Monica Gordon and Paula Ramirez

Antibiotics 2024, 13(2), 125; https://doi.org/10.3390/antibiotics13020125 - 26 Jan 2024

Cited by 3 | Viewed by 2889

Abstract

Bacterial infection has always accompanied human beings, causing suffering and death while also contributing to the advancement of medical science. However, the treatment of infections has become more complex in recent times. The increasing resistance of bacterial strains to antibiotics has diminished the [...] Read more.

Bacterial infection has always accompanied human beings, causing suffering and death while also contributing to the advancement of medical science. However, the treatment of infections has become more complex in recent times. The increasing resistance of bacterial strains to antibiotics has diminished the effectiveness of the therapeutic arsenal, making it less likely to find the appropriate empiric antibiotic option. Additionally, the development and persistence of bacterial biofilms have become more prevalent, attributed to the greater use of invasive devices that facilitate biofilm formation and the enhanced survival of chronic infection models where biofilm plays a crucial role. Bacteria within biofilms are less susceptible to antibiotics due to physical, chemical, and genetic factors. Bacteriophages, as biological weapons, can overcome both antimicrobial resistance and biofilm protection. In this review, we will analyze the scientific progress achieved in vitro to justify their clinical application. In the absence of scientific evidence, we will compile publications of clinical cases where phages have been used to treat infections related to biofilm. The scientific basis obtained in vitro and the success rate and safety observed in clinical practice should motivate the medical community to conduct clinical trials establishing a protocol for the proper use of bacteriophages. Full article

(This article belongs to the Special Issue Novel and Traditional Methods to Fight Antibiotic Resistant Bacteria and Biofilm Infections)

15 pages, 1337 KiB

Open AccessReview

Antibiotic Resistance: Do We Need Only Cutting-Edge Methods, or Can New Visions Such as One Health Be More Useful for Learning from Nature?

by Maria Vitale

Antibiotics 2023, 12(12), 1694; https://doi.org/10.3390/antibiotics12121694 - 3 Dec 2023

Cited by 2 | Viewed by 2696

Abstract

Antibiotic resistance is an increasing global problem for public health, and focusing on biofilms has provided further insights into resistance evolution in bacteria. Resistance is innate in many bacterial species, and many antibiotics are derived from natural molecules of soil microorganisms. Is it [...] Read more.

Antibiotic resistance is an increasing global problem for public health, and focusing on biofilms has provided further insights into resistance evolution in bacteria. Resistance is innate in many bacterial species, and many antibiotics are derived from natural molecules of soil microorganisms. Is it possible that nature can help control AMR diffusion? In this review, an analysis of resistance mechanisms is summarized, and an excursus of the different approaches to challenging resistance spread based on natural processes is presented as “lessons from Nature”. On the “host side”, immunotherapy strategies for bacterial infections have a long history before antibiotics, but continuous new inputs through biotechnology advances are enlarging their applications, efficacy, and safety. Antimicrobial peptides and monoclonal antibodies are considered for controlling antibiotic resistance. Understanding the biology of natural predators is providing new, effective, and safe ways to combat resistant bacteria. As natural enemies, bacteriophages were used to treat severe infections before the discovery of antibiotics, marginalized during the antibiotic era, and revitalized upon the diffusion of multi-resistance. Finally, sociopolitical aspects such as education, global action, and climate change are also considered as important tools for tackling antibiotic resistance from the One Health perspective. Full article

(This article belongs to the Special Issue Novel and Traditional Methods to Fight Antibiotic Resistant Bacteria and Biofilm Infections)

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15 pages, 1895 KiB

Open AccessReview

Inhibitors of ATP Synthase as New Antibacterial Candidates

by Rawan Mackieh, Nadia Al-Bakkar, Milena Kfoury, Rabih Roufayel, Jean-Marc Sabatier and Ziad Fajloun

Antibiotics 2023, 12(4), 650; https://doi.org/10.3390/antibiotics12040650 - 24 Mar 2023

Cited by 10 | Viewed by 4695

Abstract

ATP, the power of all cellular functions, is constantly used and produced by cells. The enzyme called ATP synthase is the energy factory in all cells, which produces ATP by adding inorganic phosphate (Pi) to ADP. It is found in the inner, thylakoid [...] Read more.

ATP, the power of all cellular functions, is constantly used and produced by cells. The enzyme called ATP synthase is the energy factory in all cells, which produces ATP by adding inorganic phosphate (Pi) to ADP. It is found in the inner, thylakoid and plasma membranes of mitochondria, chloroplasts and bacteria, respectively. Bacterial ATP synthases have been the subject of multiple studies for decades, since they can be genetically manipulated. With the emergence of antibiotic resistance, many combinations of antibiotics with other compounds that enhance the effect of these antibiotics have been proposed as approaches to limit the spread of antibiotic-resistant bacteria. ATP synthase inhibitors, such as resveratrol, venturicidin A, bedaquiline, tomatidine, piceatannol, oligomycin A and N,N-dicyclohexylcarbodiimide were the starting point of these combinations. However, each of these inhibitors target ATP synthase differently, and their co-administration with antibiotics increases the susceptibility of pathogenic bacteria. After a brief description of the structure and function of ATP synthase, we aim in this review to highlight therapeutic applications of the major bacterial ATP synthase inhibitors, including animal’s venoms, and to emphasize their importance in decreasing the activity of this enzyme and subsequently eradicating resistant bacteria as ATP synthase is their source of energy. Full article

(This article belongs to the Special Issue Novel and Traditional Methods to Fight Antibiotic Resistant Bacteria and Biofilm Infections)

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14 pages, 313 KiB

Open AccessReview

Antibiotic Resistance and Biofilm Infections in the NICUs and Methods to Combat It

by Maria Baltogianni, Vasileios Giapros and Chrysoula Kosmeri

Antibiotics 2023, 12(2), 352; https://doi.org/10.3390/antibiotics12020352 - 8 Feb 2023

Cited by 4 | Viewed by 2113

Abstract

Neonatal sepsis is an important cause of neonatal morbidity and mortality. A significant proportion of bacteria causing neonatal sepsis is resistant to multiple antibiotics, not only to the usual empirical first-line regimens, but also to second- and third-line antibiotics in many neonatal intensive [...] Read more.

Neonatal sepsis is an important cause of neonatal morbidity and mortality. A significant proportion of bacteria causing neonatal sepsis is resistant to multiple antibiotics, not only to the usual empirical first-line regimens, but also to second- and third-line antibiotics in many neonatal intensive care units (NICUs). NICUs have unique antimicrobial stewardship goals. Apart from antimicrobial resistance, NICUs have to deal with another problem, namely biofilm infections, since neonates often have central and peripheral lines, tracheal tubes and other foreign bodies for a prolonged duration. The aim of this review is to describe traditional and novel ways to fight antibiotic-resistant bacteria and biofilm infections in NICUs. The topics discussed will include prevention and control of the spread of infection in NICUs, as well as the wise use of antimicrobial therapy and ways to fight biofilm infections. Full article

(This article belongs to the Special Issue Novel and Traditional Methods to Fight Antibiotic Resistant Bacteria and Biofilm Infections)

13 pages, 561 KiB

Open AccessReview

Antibiotic Resistance in Patients with Cystic Fibrosis: Past, Present, and Future

by Evanthia P. Perikleous, Despoina Gkentzi, Aris Bertzouanis, Emmanouil Paraskakis, Aleksandar Sovtic and Sotirios Fouzas

Antibiotics 2023, 12(2), 217; https://doi.org/10.3390/antibiotics12020217 - 20 Jan 2023

Cited by 24 | Viewed by 3373

Abstract

Patients with cystic fibrosis (CF) are repeatedly exposed to antibiotics, especially during the pulmonary exacerbations of the disease. However, the available therapeutic strategies are frequently inadequate to eradicate the involved pathogens and most importantly, facilitate the development of antimicrobial resistance (AMR). The evaluation [...] Read more.

Patients with cystic fibrosis (CF) are repeatedly exposed to antibiotics, especially during the pulmonary exacerbations of the disease. However, the available therapeutic strategies are frequently inadequate to eradicate the involved pathogens and most importantly, facilitate the development of antimicrobial resistance (AMR). The evaluation of AMR is demanding; conventional culture-based susceptibility-testing techniques cannot account for the lung microenvironment and/or the adaptive mechanisms developed by the pathogens, such as biofilm formation. Moreover, features linked to modified pharmaco-kinetics and pulmonary parenchyma penetration make the dosing of antibiotics even more challenging. In this review, we present the existing knowledge regarding AMR in CF, we shortly review the existing therapeutic strategies, and we discuss the future directions of antimicrobial stewardship. Due to the increasing difficulty in eradicating strains that develop AMR, the appropriate management should rely on targeting the underlying resistance mechanisms; thus, the interest in novel, molecular-based diagnostic tools, such as metagenomic sequencing and next-generation transcriptomics, has increased exponentially. Moreover, since the development of new antibiotics has a slow pace, the design of effective treatment strategies to eradicate persistent infections represents an urgency that requires consorted work. In this regard, both the management and monitoring of antibiotics usage are obligatory and more relevant than ever. Full article

(This article belongs to the Special Issue Novel and Traditional Methods to Fight Antibiotic Resistant Bacteria and Biofilm Infections)

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