Non-antibiotic antimicrobial agents for chronic rhinosinusitis: a narrative review.

OBJECTIVE: This narrative review explores alternative non-antibiotic antimicrobial agents for CRS management in adults. METHODS: Alternative antimicrobial agents using EPOS 2020 guidelines as reference were selected, and articles dated from 2003 to 2022 in English, Portuguese, or Spanish using PubMed and EMBASE databases. The parameters analyzed included study design, evidence level, population characteristics, CRS characteristics, interventions, outcomes, sample size, randomization, blinding, and side effects. Reviews, unrelated contexts,in vitro experiments, and duplicates were excluded. RESULTS: 148 articles were screened; 19 articles were selected for analysis. Randomized controlled trials and cohort studies assessing non-antibiotic antimicrobial treatments for CRS were included. Xylitol demonstrated effectiveness in reducing CRS symptoms, particularly SNOT-22 scores, surpassing saline irrigation benefits. Manuka honey showed potential microbiological benefits in recalcitrant CRS, but symptomatic and endoscopic improvements remained inconclusive. Baby shampoo irrigation improved nasal mucociliary clearance and postoperative outcomes. Colloidal silver nasal irrigation showed limited efficacy in reducing CRS symptoms or endoscopic scores. Povidone-Iodine (PI) nasal irrigation yielded mixed results, with varying effects on culture negativity and SNOT-20 scores. Bacteriophage treatment exhibited promise in decreasing specific bacterial strains and cytokine levels. CONCLUSION: Non-antibiotic antimicrobial therapies, including xylitol, manuka honey, baby shampoo, colloidal silver, PI, bacteriophages, lactoferrin, and carrageenan offer potential alternatives for CRS in adult patients. Xylitol, baby shampoo, and PI presented benefits in improving symptoms and nasal endoscopic scores, however, the number of studies is limited for conclusive recommendations and safety assessments. CRS management should adopt a comprehensive approach, particularly for non-infectious or immune-related cases, moving beyond antibiotics. Antibiotics should be reserved for confirmed bacterial infections. Overall, this review shows the importance of exploring non-antibiotic therapies to enhance the management of CRS.

Elimination of Pathogen Biofilms via Postbiotics from Lactic Acid Bacteria: A Promising Method in Food and Biomedicine.

Pathogenic biofilms provide a naturally favorable barrier for microbial growth and are closely related to the virulence of pathogens. Postbiotics from lactic acid bacteria (LAB) are secondary metabolites and cellular components obtained by inactivation of fermentation broth; they have a certain inhibitory effect on all stages of pathogen biofilms. Postbiotics from LAB have drawn attention because of their high stability, safety dose parameters, and long storage period, which give them a broad application prospect in the fields of food and medicine. The mechanisms of eliminating pathogen biofilms via postbiotics from LAB mainly affect the surface adhesion, self-aggregation, virulence, and QS of pathogens influencing interspecific and intraspecific communication. However, there are some factors (preparation process and lack of target) which can limit the antibiofilm impact of postbiotics. Therefore, by using a delivery carrier and optimizing process parameters, the effect of interfering factors can be eliminated. This review summarizes the concept and characteristics of postbiotics from LAB, focusing on their preparation technology and antibiofilm effect, and the applications and limitations of postbiotics in food processing and clinical treatment are also discussed.

Deciphering the dynamics of methicillin-resistant Staphylococcus aureus biofilm formation: from molecular signaling to nanotherapeutic advances.

Methicillin-resistant Staphylococcus aureus (MRSA) represents a global threat, necessitating the development of effective solutions to combat this emerging superbug. In response to selective pressures within healthcare, community, and livestock settings, MRSA has evolved increased biofilm formation as a multifaceted virulence and defensive mechanism, enabling the bacterium to thrive in harsh conditions. This review discusses the molecular mechanisms contributing to biofilm formation across its developmental stages, hence representing a step forward in developing promising strategies for impeding or eradicating biofilms. During staphylococcal biofilm development, cell wall-anchored proteins attach bacterial cells to biotic or abiotic surfaces; extracellular polymeric substances build scaffolds for biofilm formation; the cidABC operon controls cell lysis within the biofilm, and proteases facilitate dispersal. Beside the three main sequential stages of biofilm formation (attachment, maturation, and dispersal), this review unveils two unique developmental stages in the biofilm formation process for MRSA; multiplication and exodus. We also highlighted the quorum sensing as a cell-to-cell communication process, allowing distant bacterial cells to adapt to the conditions surrounding the bacterial biofilm. In S. aureus, the quorum sensing process is mediated by autoinducing peptides (AIPs) as signaling molecules, with the accessory gene regulator system playing a pivotal role in orchestrating the production of AIPs and various virulence factors. Several quorum inhibitors showed promising anti-virulence and antibiofilm effects that vary in type and function according to the targeted molecule. Disrupting the biofilm architecture and eradicating sessile bacterial cells are crucial steps to prevent colonization on other surfaces or organs. In this context, nanoparticles emerge as efficient carriers for delivering antimicrobial and antibiofilm agents throughout the biofilm architecture. Although metal-based nanoparticles have been previously used in combatting biofilms, its non-degradability and toxicity within the human body presents a real challenge. Therefore, organic nanoparticles in conjunction with quorum inhibitors have been proposed as a promising strategy against biofilms. As nanotherapeutics continue to gain recognition as an antibiofilm strategy, the development of more antibiofilm nanotherapeutics could offer a promising solution to combat biofilm-mediated resistance.

Confronting the Threat: Designing Highly Effective bis-Benzimidazolium Agents to Overcome Biofilm Persistence and Antimicrobial Resistance.

The objective of this study is to take the initial steps toward developing novel antibiotics to counteract the escalating problem of antimicrobial and bacterial persistence, particularly in relation to biofilms. Our approach involves emulating the structural characteristics of cationic antimicrobial peptides. To circumvent resistance development, we have designed a library of bis-benzimidazolium salts that selectively target the microbial membranes in a nonspecific manner. To explore their structure-activity relationship, we conducted experiments using these compounds on various pathogens known for their resistance to conventional antibiotics, including Gram-positive methicillin-resistant Staphylococcus aureus (MRSA), vancomycin-resistant Enterococcus faecium (VRE), and Gram-negative Escherichia coli (E. coli). Notably, two bis-benzimidazolium salts exhibited robust antimicrobial activity while maintaining a high level of selectivity compared with mammalian cells. Our investigations revealed significant antibiofilm activity, as these compounds rapidly acted against established biofilms. In addition, bis-benzimidazolium compounds exhibited consistent results in resistance development and cross-resistance studies. Consequently, amphiphilic bis-benzimidazolium salts hold promise as potential candidates to combat resistance-associated infections.

Antifungal activity of Co(II) and Cu(II) complexes containing 1,3-bis(benzotriazol-1-yl)-propan-2-ol on the growth and virulence traits of fluconazole-resistant Candida species: synthesis, DFT calculations, and biological activity.

Relevant virulence traits in Candida spp. are associated with dimorphic change and biofilm formation, which became an important target to reduce antifungal resistance. In this work, Co(II) complexes containing a benzotriazole derivative ligand showed a promising capacity of reducing these virulence traits. These complexes exhibited higher antifungal activities than the free ligands against all the Candida albicans and non-albicans strains tested, where compounds 2 and 4 showed minimum inhibitory concentration values between 15.62 and 125 µg mL-1. Moreover, four complexes (2-5) of Co(II) and Cu(II) with benzotriazole ligand were synthesized. These compounds were obtained as air-stable solids and characterized by melting point, thermogravimetric analysis, infrared, Raman and ultraviolet/visible spectroscopy. The analysis of the characterization data allowed us to identify that all the complexes had 1:1 (M:L) stoichiometries. Additionally, Density Functional Theory calculations were carried out for 2 and 3 to propose a probable geometry of both compounds. The conformer Da of 2 was the most stable conformer according to the Energy Decomposition Analysis; while the conformers of 3 have a fluxional behavior in this analysis that did not allow us to determine the most probable conformer. These results provide an important platform for the design of new compounds with antifungal activities and the capacity to attack other target of relevance to reduce antimicrobial resistance.

In Vitro Effect of Three-Antibiotic Combinations plus Potential Antibiofilm Agents against Biofilm-Producing Mycobacterium avium and Mycobacterium intracellulare Clinical Isolates.

Patients with chronic pulmonary diseases infected by Mycobacterium avium complex (MAC) often develop complications and suffer from treatment failure due to biofilm formation. There is a lack of correlation between in vitro susceptibility tests and the treatment of clinical isolates producing biofilm. We performed susceptibility tests of 10 different three-drug combinations, including two recommended in the guidelines, in biofilm forms of eight MAC clinical isolates. Biofilm developed in the eight isolates following incubation of the inoculum for 3 weeks. Then, the biofilm was treated with three-drug combinations with and without the addition of potential antibiofilm agents (PAAs). Biofilm bactericidal concentrations (BBCs) were determined using the Vizion lector system. All selected drug combinations showed synergistic activity, reducing BBC values compared to those treated with single drugs, but BBC values remained high enough to treat patients. However, with the addition of PAAs, the BBCs steadily decreased, achieving similar values to the combinations in planktonic forms and showing synergistic activity in all the combinations and in both species. In conclusion, three-drug combinations with PAAs showed synergistic activity in biofilm forms of MAC isolates. Our results suggest the need for clinical studies introducing PAAs combined with antibiotics for the treatment of patients with pulmonary diseases infected by MAC.

Harnessing the Potential of Biosurfactants for Biomedical and Pharmaceutical Applications.

Biosurfactants (BSs) are microbial compounds that have emerged as potential alternatives to chemical surfactants due to their multifunctional properties, sustainability and biodegradability. Owing to their amphipathic nature and distinctive structural arrangement, biosurfactants exhibit a range of physicochemical properties, including excellent surface activity, efficient critical micelle concentration, humectant properties, foaming and cleaning abilities and the capacity to form microemulsions. Furthermore, numerous biosurfactants display additional biological characteristics, such as antibacterial, antifungal and antiviral effects, and antioxidant, anticancer and immunomodulatory activities. Over the past two decades, numerous studies have explored their potential applications, including pharmaceuticals, cosmetics, antimicrobial and antibiofilm agents, wound healing, anticancer treatments, immune system modulators and drug/gene carriers. These applications are particularly important in addressing challenges such as antimicrobial resistance and biofilm formations in clinical, hygiene and therapeutic settings. They can also serve as coating agents for surfaces, enabling antiadhesive, suppression, or eradication strategies. Not least importantly, biosurfactants have shown compatibility with various drug formulations, including nanoparticles, liposomes, micro- and nanoemulsions and hydrogels, improving drug solubility, stability and bioavailability, and enabling a targeted and controlled drug release. These qualities make biosurfactants promising candidates for the development of next-generation antimicrobial, antibiofilm, anticancer, wound-healing, immunomodulating, drug or gene delivery agents, as well as adjuvants to other antibiotics. Analysing the most recent literature, this review aims to update the present understanding, highlight emerging trends, and identify promising directions and advancements in the utilization of biosurfactants within the pharmaceutical and biomedical fields.

Evaluation of the polyphenolic profile of native Ecuadorian stingless bee honeys (Tribe: Meliponini) and their antibiofilm activity on susceptible and multidrug-resistant pathogens: An exploratory analysis.

Biofilms are associated with infections that are resistant to conventional therapies, contributing to the antimicrobial resistance crisis. The need for alternative approaches against biofilms is well-known. Although natural products like stingless bee honeys (tribe: Meliponini) constitute an alternative treatment, much is still unknown. Our main goal was to evaluate the antibiofilm activity of stingless bee honey samples against multidrug-resistant (MDR) pathogens through biomass assays, fluorescence (cell count and viability), and scanning electron (structural composition) microscopy. We analyzed thirty-five honey samples at 15% (v/v) produced by ten different stingless bee species (Cephalotrigona sp., Melipona sp., M. cramptoni, M. fuscopilosa, M. grandis, M. indecisa, M. mimetica, M. nigrifacies, Scaptotrigona problanca, and Tetragonisca angustula) from five provinces of Ecuador (Tungurahua, Pastaza, El Oro, Los Ríos, and Loja) against 24-h biofilms of Staphylococcus aureus, Klebsiella pneumoniae, Candida albicans, and Candida tropicalis. The present honey set belonged to our previous study, where the samples were collected in 2018-2019 and their physicochemical parameters, chemical composition, mineral elements, and minimal inhibitory concentration (MIC) were screened. However, the polyphenolic profile and their antibiofilm activity on susceptible and multidrug-resistant pathogens were still unknown. According to polyphenolic profile of the honey samples, significant differences were observed according to their geographical origin in terms of the qualitative profiles. The five best honey samples (OR24.1, LR34, LO40, LO48, and LO53) belonging to S. problanca, Melipona sp., and M. indecisa were selected for further analysis due to their high biomass reduction values, identification of the stingless bee specimens, and previously reported physicochemical parameters. This subset of honey samples showed a range of 63-80% biofilm inhibition through biomass assays. Fluorescence microscopy (FM) analysis evidenced statistical log reduction in the cell count of honey-treated samples in all pathogens (P <0.05), except for S. aureus ATCC 25923. Concerning cell viability, C. tropicalis, K. pneumoniae ATCC 33495, and K. pneumoniae KPC significantly decreased (P <0.01) by 21.67, 25.69, and 45.62%, respectively. Finally, scanning electron microscopy (SEM) analysis demonstrated structural biofilm disruption through cell morphological parameters (such as area, size, and form). In relation to their polyphenolic profile, medioresinol was only found in the honey of Loja, while scopoletin, kaempferol, and quercetin were only identified in honey of Los Rios, and dihydrocaffeic and dihydroxyphenylacetic acids were only detected in honey of El Oro. All the five honey samples showed dihydrocoumaroylhexose, luteolin, and kaempferol rutinoside. To the authors' best knowledge, this is the first study to analyze stingless bees honey-treated biofilms of susceptible and/or MDR strains of S. aureus, K. pneumoniae, and Candida species.

In-silico and in-vitro assessment of the antibiofilm potential of azo dye, carmoisine against Pseudomonas aeruginosa.

Biofilm is a community of microorganisms attached to the substrate and plays a significant role in microbial pathogenesis and medical device-related infection. Pseudomonas aeruginosa (PA) is a highly infectious gram-negative opportunistic biofilm-forming bacterium with high antibiotic resistance. Several reports underscore the antimicrobial activity of natural and synthetic food coloring agents, including carmoisine, turmeric dye, red amaranth dye, and phloxine B. However, their ability to suppress the PA biofilm is not clearly understood. Carmoisine is a red-colored synthetic azo dye containing naphthalene subunits and sulfonic groups and is widely used as a food coloring agent. This study investigated the antibiofilm potential and possible mechanism of biofilm inhibition by carmoisine against PA. Computational studies through molecular docking revealed that carmoisine strongly binds to QS regulator LasR (-12.7) and relatively less strongly but significantly with WspR (-6.9). Further analysis of the docked LasR-carmoisine complex using 100 ns MD simulation (Desmond, Schrödinger) validated the bonding strength and stability. Crystal violet assay, triphenyl tetrazolium chloride salt assay, and confocal microscopic studies were adopted for biofilm quantification, and the results indicated the dose-dependent antibiofilm activity of carmoisine against PA. We hypothesise that the carmoisine-mediated reduction of biofilm in PA is due to its interaction with LasR and interference with the QS system. The computational and biochemical analysis of another compound, 1,2-naphthoquinone-4-sulphonic acid, reiterated the role of the naphthalene ring in biofilm inhibition. Hence, this work will pave the way for the future discovery of antibiofilm drugs based on naphthalene ring-based lead compounds.Communicated by Ramaswamy H. Sarma.

Combating Bacterial Biofilms: Current and Emerging Antibiofilm Strategies for Treating Persistent Infections.

Biofilms are intricate multicellular structures created by microorganisms on living (biotic) or nonliving (abiotic) surfaces. Medically, biofilms often lead to persistent infections, increased antibiotic resistance, and recurrence of infections. In this review, we highlighted the clinical problem associated with biofilm infections and focused on current and emerging antibiofilm strategies. These strategies are often directed at disrupting quorum sensing, which is crucial for biofilm formation, preventing bacterial adhesion to surfaces, impeding bacterial aggregation in viscous mucus layers, degrading the extracellular polymeric matrix, and developing nanoparticle-based antimicrobial drug complexes which target persistent cells within the biofilm core. It is important to acknowledge, however, that the use of antibiofilm agents faces obstacles, such as limited effectiveness in vivo, potential cytotoxicity to host cells, and propensity to elicit resistance in targeted biofilm-forming microbes. Emerging next generation antibiofilm strategies, which rely on multipronged approaches, were highlighted, and these benefit from current advances in nanotechnology, synthetic biology, and antimicrobial drug discovery. The assessment of current antibiofilm mitigation approaches, as presented here, could guide future initiatives toward innovative antibiofilm therapeutic strategies. Enhancing the efficacy and specificity of some emerging antibiofilm strategies via careful investigations, under conditions that closely mimic biofilm characteristics within the human body, could bridge the gap between laboratory research and practical application.

pH-activated antibiofilm strategies for controlling dental caries.

Dental biofilms are highly assembled microbial communities surrounded by an extracellular matrix, which protects the resident microbes. The microbes, including commensal bacteria and opportunistic pathogens, coexist with each other to maintain relative balance under healthy conditions. However, under hostile conditions such as sugar intake and poor oral care, biofilms can generate excessive acids. Prolonged low pH in biofilm increases proportions of acidogenic and aciduric microbes, which breaks the ecological equilibrium and finally causes dental caries. Given the complexity of oral microenvironment, controlling the acidic biofilms using antimicrobials that are activated at low pH could be a desirable approach to control dental caries. Therefore, recent researches have focused on designing novel kinds of pH-activated strategies, including pH-responsive antimicrobial agents and pH-sensitive drug delivery systems. These agents exert antibacterial properties only under low pH conditions, so they are able to disrupt acidic biofilms without breaking the neutral microenvironment and biodiversity in the mouth. The mechanisms of low pH activation are mainly based on protonation and deprotonation reactions, acids labile linkages, and H+-triggered reactive oxygen species production. This review summarized pH-activated antibiofilm strategies to control dental caries, concentrating on their effect, mechanisms of action, and biocompatibility, as well as the limitation of current research and the prospects for future study.

Antibiofilm Activity of LL-37 Peptide and D-Amino Acids Associated with Antibiotics Used in Regenerative Endodontics on an Ex Vivo Multispecies Biofilm Model.

The antimicrobial peptide LL-37 and D-amino acids (D-AAs) have been proposed as antibiofilm agents. Therefore, this study aimed to test the antimicrobial effect of antibiofilm agents associated with antibiotics used in regenerative endodontic procedures (the triple antibiotic paste­TAP: ciprofloxacin + metronidazole + minocycline). An endodontic-like biofilm model grown on bovine dentin discs was used in this study. After 21-day growth, the biofilms were treated with 1 mg/mL TAP, 10 µM LL-37, an association of LL-37 + TAP, 40 mM D-AAs solution, an association of D-AAs + TAP, and phosphate-buffered saline (negative control). Colony forming unit (CFU) data were analyzed by two-way ANOVA and Tukey's multiple comparison test (p < 0.05). LL-37 + TAP showed the best antibacterial activity (7-log10 CFU/mL ± 0.5), reaching a 1 log reduction of cells in relation to the negative control (8-log10 CFU/mL ± 0.7) (p < 0.05). In turn, no significant reduction in bacterial cells was observed with TAP, LL-37, D-AAs, and D-AAs + TAP compared to the negative control. In conclusion, the combination of antibiotics and LL-37 peptide showed mild antibacterial activity, while the combination of antibiotics and D-AAs showed no activity against complex biofilms.

Prevention and Eradication of Biofilm by Dendrimers: A Possibility Still Little Explored.

Multidrug resistance (MDR) among pathogens and the associated infections represent an escalating global public health problem that translates into raised mortality and healthcare costs. MDR bacteria, with both intrinsic abilities to resist antibiotics treatments and capabilities to transmit genetic material coding for further resistance to other bacteria, dramatically decrease the number of available effective antibiotics, especially in nosocomial environments. Moreover, the capability of several bacterial species to form biofilms (BFs) is an added alarming mechanism through which resistance develops. BF, made of bacterial communities organized and incorporated into an extracellular polymeric matrix, self-produced by bacteria, provides protection from the antibiotics' action, resulting in the antibiotic being ineffective. By adhering to living or abiotic surfaces present both in the environment and in the healthcare setting, BF causes the onset of difficult-to-eradicate infections, since it is difficult to prevent its formation and even more difficult to promote its disintegration. Inspired by natural antimicrobial peptides (NAMPs) acting as membrane disruptors, with a low tendency to develop resistance and demonstrated antibiofilm potentialities, cationic polymers and dendrimers, with similar or even higher potency than NAMPs and with low toxicity, have been developed, some of which have shown in vitro antibiofilm activity. Here, aiming to incite further development of new antibacterial agents capable of inhibiting BF formation and dispersing mature BF, we review all dendrimers developed to this end in the last fifteen years. The extension of the knowledge about these still little-explored materials could be a successful approach to find effective weapons for treating chronic infections and biomaterial-associated infections (BAIs) sustained by BF-producing MDR bacteria.

An Overview of Biofilm Formation-Combating Strategies and Mechanisms of Action of Antibiofilm Agents.

Biofilm formation on surfaces via microbial colonization causes infections and has become a major health issue globally. The biofilm lifestyle provides resistance to environmental stresses and antimicrobial therapies. Biofilms can cause several chronic conditions, and effective treatment has become a challenge due to increased antimicrobial resistance. Antibiotics available for treating biofilm-associated infections are generally not very effective and require high doses that may cause toxicity in the host. Therefore, it is essential to study and develop efficient anti-biofilm strategies that can significantly reduce the rate of biofilm-associated healthcare problems. In this context, some effective combating strategies with potential anti-biofilm agents, including plant extracts, peptides, enzymes, lantibiotics, chelating agents, biosurfactants, polysaccharides, organic, inorganic, and metal nanoparticles, etc., have been reviewed to overcome biofilm-associated healthcare problems. From their extensive literature survey, it can be concluded that these molecules with considerable structural alterations might be applied to the treatment of biofilm-associated infections, by evaluating their significant delivery to the target site of the host. To design effective anti-biofilm molecules, it must be assured that the minimum inhibitory concentrations of these anti-biofilm compounds can eradicate biofilm-associated infections without causing toxic effects at a significant rate.

Distinct Agents Induce Streptococcus mutans Cells with Altered Biofilm Formation Capacity.

Dental caries is a multifactorial biofilm- and sugar-dependent disease. This study investigated the influence of different agents on the induction of surviving Streptococcus mutans cells after successive treatment cycles and characterized the biofilms formed by these cells recovered posttreatment. The agents (with their main targets listed in parentheses) were compound 1771 (lipoteichoic acids), 4' hydroxychalcone (exopolysaccharides), myricetin (exopolysaccharides), tt-farnesol (cytoplasmatic membrane), sodium fluoride (enolase-glycolysis), chlorhexidine (antimicrobial), and vehicle. Recovered cells from biofilms were generated from exposure to each agent during 10 cycles of consecutive treatments (modeled on a polystyrene plate bottom). The recovered cell counting was different for each agent. The recovered cells from each group were grown as biofilms on saliva-coated hydroxyapatite discs (culture medium with sucrose/starch). In S. mutans biofilms formed by cells recovered from biofilms previously exposed to compound 1771, 4' hydroxychalcone, or myricetin, cells presented higher expression of the 16S rRNA, gyrA (DNA replication and transcription), gtfB (insoluble exopolysaccharides), and eno (enolase-glycolysis) genes and lower quantities of insoluble dry weight and insoluble exopolysaccharides than those derived from other agents. These findings were confirmed by the smaller biovolume of bacteria and/or exopolysaccharides and the biofilm distribution (coverage area). Moreover, preexposure to chlorhexidine increased exopolysaccharide production. Therefore, agents with different targets induce cells with distinct biofilm formation capacities, which is critical for developing formulations for biofilm control. IMPORTANCE This article addresses the effect of distinct agents with distinct targets in the bacterial cell (cytoplasmatic membrane and glycolysis), the cell's extracellular synthesis of exopolysaccharides that are important for cariogenic extracellular matrix construction and biofilm buildup in the generation of cells that persisted after treatment, and how these cells form biofilms in vitro. For example, if preexposure to an agent augments the production of virulence determinants, such as exopolysaccharides, its clinical value may be inadequate. Modification of biofilm formation capacity after exposure to agents is critical for the development of formulations for biofilm control to prevent caries, a ubiquitous disease associated with biofilm and diet.

Novel Antimicrobial Strategies to Prevent Biofilm Infections in Catheters after Radical Cystectomy: A Pilot Study.

Catheter-associated infections in bladder cancer patients, following radical cystectomy or ureterocutaneostomy, are very frequent, and the development of antibiotic resistance poses great challenges for treating biofilm-based infections. Here, we characterized bacterial communities from catheters of patients who had undergone radical cystectomy for muscle-invasive bladder cancer. We evaluated the efficacy of conventional antibiotics, alone or combined with the human ApoB-derived antimicrobial peptide r(P)ApoBLAla, to treat ureteral catheter-colonizing bacterial communities on clinically isolated bacteria. Microbial communities adhering to indwelling catheters were collected during the patients' regular catheter change schedules (28 days) and extracted within 48 h. Living bacteria were characterized using selective media and biochemical assays. Biofilm growth and novel antimicrobial strategies were analyzed using confocal laser scanning microscopy. Statistical analyses confirmed the relevance of the biofilm reduction induced by conventional antibiotics (fosfomycin, ceftriaxone, ciprofloxacin, gentamicin, and tetracycline) and a well-characterized human antimicrobial peptide r(P)ApoBLAla (1:20 ratio, respectively). Catheters showed polymicrobial communities, with Enterobactericiae and Proteus isolates predominating. In all samples, we recorded a meaningful reduction in biofilms, in both biomass and thickness, upon treatment with the antimicrobial peptide r(P)ApoBLAla in combination with low concentrations of conventional antibiotics. The results suggest that combinations of conventional antibiotics and human antimicrobial peptides might synergistically counteract biofilm growth on ureteral catheters, suggesting novel avenues for preventing catheter-associated infections in patients who have undergone radical cystectomy and ureterocutaneostomy.

Marine natural products and their synthetic analogs as promising antibiofilm agents for antibiotics discovery and development.

Biofilm is a complex microbial consortium that are embedded in a membrane structure of the extracellular polymeric substances (EPS). As a major form of microorganisms in nature, biofilm has evolved complex and diverse resistance mechanisms to numerous known antibiotics, posing a major threat to human health. The biofilm formation of pathogens including Pseudomonas aeruginosa, Staphylococcus aureus and Candida albicans, etc. has become the most commonly reasons for clinically chronic and incurable infectious diseases, which urges the development of effective antibiofilm agents. The adaptation of marine organisms and microorganisms to their unique habitats has led to the formation of natural products with charming chemical diversity and biological activity, providing a rich reservoir for the development of antibiofilm agents. According to chemical classification, 129 marine-derived natural products and their synthetic analogs with antibiofilm activity were systematically reviewed, and the related mechanisms and efficacy were discussed as well, aiming to find and develop new and effective antibiofilm agents.

Topical Antibiofilm Agents With Potential Utility in the Treatment of Chronic Rhinosinusitis: A Narrative Review.

The role of bacterial biofilms in chronic and recalcitrant diseases is widely appreciated, and the treatment of biofilm infection is an increasingly important area of research. Chronic rhinosinusitis (CRS) is a complex disease associated with sinonasal dysbiosis and the presence of bacterial biofilms. While most biofilm-related diseases are associated with highly persistent but relatively less severe inflammation, the presence of biofilms in CRS is associated with greater severity of inflammation and recalcitrance despite appropriate treatment. Oral antibiotics are commonly used to treat CRS but they are often ineffective, due to poor penetration of the sinonasal mucosa and the inherently antibiotic resistant nature of bacteria in biofilms. Topical non-antibiotic antibiofilm agents may prove more effective, but few such agents are available for sinonasal application. We review compounds with antibiofilm activity that may be useful for treating biofilm-associated CRS, including halogen-based compounds, quaternary ammonium compounds and derivatives, biguanides, antimicrobial peptides, chelating agents and natural products. These include preparations that are currently available and those still in development. For each compound, antibiofilm efficacy, mechanism of action, and toxicity as it relates to sinonasal application are summarised. We highlight the antibiofilm agents that we believe hold the greatest promise for the treatment of biofilm-associated CRS in order to inform future research on the management of this difficult condition.