Type-I Photosensitizer-Triggered Controllable Carbon Monoxide Release for Effective Treatment of Staph Skin Infection.

Staphylococcus aureus (S. aureus) infection is a major infectious skin disease that is highly resistant to conventional antibiotic treatment and host immune defense, leading to recurrence and exacerbation of bacterial infection. Herein, we developed a photoresponsive carbon monoxide (CO)-releasing nanocomposite by integrating anion-π+ type-I photosensitizer (OMeTBP) and organometallic complex (FeCO) for the treatment of planktonic S. aureus and biofilm-associated infections. After optimizing the molar ratio of FeCO and OMeTBP, the prepared nanoparticles, OMeTBP@FeCONPs, not only ensured sufficient loading of CO donors and efficient CO generation but also showed negligible free ROS leakage under light irradiation, which helped to avoid tissue damage caused by excessive ROS. Both in vitro and in vivo results demonstrated that OMeTBP@FeCONPs could effectively inhibit S. aureus methicillin-resistant S. aureus (MRSA), and bacterial biofilm. Our design has the potential to overcome the resistance of conventional antibiotic treatment and provide a more effective option for bacterial infections.

Breaking the Vicious Cycle of Antibiotic Killing and Regrowth of Biofilm-Residing Pseudomonas aeruginosa.

Biofilm-residing bacteria embedded in an extracellular matrix are protected from diverse physicochemical insults. In addition to the general recalcitrance of biofilm bacteria, high bacterial loads in biofilm-associated infections significantly diminish the efficacy of antimicrobials due to a low per-cell antibiotic concentration. Accordingly, present antimicrobial treatment protocols that have been established to serve the eradication of acute infections fail to clear biofilm-associated chronic infections. In the present study, we applied automated confocal microscopy on Pseudomonas aeruginosa to monitor dynamic killing of biofilm-grown bacteria by tobramycin and colistin in real time. We revealed that the time required for surviving bacteria to repopulate the biofilm could be taken as a measure for effectiveness of the antimicrobial treatment. It depends on the (i) nature and concentration of the antibiotic, (ii) duration of antibiotic treatment, (iii) application as monotherapy or combination therapy, and (iv) interval of drug administration. The vicious cycle of killing and repopulation of biofilm bacteria could also be broken in an in vivo model system by applying successive antibiotic dosages at intervals that do not allow full reconstitution of the biofilm communities. Treatment regimens that consider the important aspects of antimicrobial killing kinetics bear the potential to improve control of biofilm regrowth. This is an important and underestimated factor that is bound to ensure sustainable treatment success of chronic infections.

Exposure to artificial daylight or UV irradiation (A, B or C) prior to chemical cleaning: an effective combination for removing phototrophs from granite.

This study evaluated whether exposing samples of granite colonized by a natural biofilm to artificial daylight or UV-A/B/C irradiation for 48 h enhanced removal of the biofilm with a chemical product previously approved for conservation of monuments by the European Biocide Directive. Rodas granite, which is commonly found in stone-built heritage monuments in Galicia (NW Spain), was naturally colonized by a sub-aerial biofilm. The efficacy of the cleaning method was evaluated relative to uncolonized surfaces and colonized control samples without previous irradiation, treated by dry-brushing or with benzalkonium chloride. The effect of UV irradiation in the combined treatment was evident, as comparable cleaning levels were not reached in the controls. Although the biofilm was not totally removed by any of the treatments, UV-B irradiation followed by benzalkonium chloride was potentially useful for cleaning stone, with results comparable to those achieved by UV-C irradiation, which is known to have germicidal effects.

Sustainable treatment scheme for in-situ remediation of contaminated drains using engineered natural systems.

Ensuring water security in resource-constrained, densely populated regions is a significant challenge globally. Due to insufficient treatment infrastructure, untreated sewage discharge into drainage channels is prevalent, especially in developing countries. This leads to the pollution of already dwindling water bodies and threatens future water availability. In this context, in-situ treatment within drains using nature-based systems is an attractive option. This study evaluates microbial bioremediation and phytoremediation as engineered natural solutions for in-stream treatment of municipal wastewater. A three-stage treatment system consisting of anoxic biofilm, aerobic biofilm, and hydroponic floating wetlands was adopted. Each stage was optimized for operational parameters through batch and continuous flow studies. The anoxic biofilm system using autoclaved aerated concrete (AAC) as the attachment media, at an optimized hydraulic retention time (HRT) of 2 h, showed the best performance with respect to COD removal. Comparable COD removal was observed in both externally aerated and non-aerated aerobic biofilm systems with coir fibre at 6 h HRT. However, aerated system outperformed non-aerated system at low HRTs. The hydroponic system with Canna indica effectively removed residual ammonia-N with an HRT of 2 h. The sequential continuous flow studies employing the optimized conditions showed significant removals of COD (86%) and ammonia-N (97.6%). The results highlight that locally available materials having a high specific surface area can be used as biofilm supports for COD removal, and floating wetlands employing indigenous macrophytes can be an ideal choice for in-situ nutrient removal. The Life Cycle Assessment (LCA) showed that the developed system did not have direct significant impacts on freshwater eco-toxicity and eutrophication. The proposed hybrid treatment system can be implemented as modular units without major drainage modifications or energy-intensive operations. The study, therefore, finds potential application in densely populated settlements in low-income countries where systematic sewage treatment options remain inadequate.

Development and Evaluation of Microencapsulated Oregano Essential Oil as an Alternative Treatment for Candida albicans Infections.

Vulvovaginal candidiasis (VVC) is characterized as a very common fungal infection that significantly affects women's health worldwide. Essential oils (EOs) are currently being evaluated as an alternative therapy. The development of efficient techniques such as micro- or nanoencapsulation for protecting and controlling release is essential to overcome the limitations of EO applications. Therefore, the aim of this study was to develop and characterize oregano EO-loaded keratin microparticles (OEO-KMPs) as a potential treatment for VVC. OEO-KMPs were produced using high-intensity ultrasonic cycles and characterized in terms of morphological and physicochemical parameters. In vitro evaluation included assessing the toxicity of the OEO-KMPs and their effect against Candida albicans using microdilution and agar diffusion, while the activity against biofilm was quantified using colony forming units (CFU). The efficacy of the OEO-KMPs in an in vivo VVC mouse model was also studied. Female BALB/c mice were intravaginally infected with C. albicans, 24 h postinfection animals were treated intravaginally with 15 µL of OEO-KMPs and 24 h later vaginal fluid was analyzed for C. albicans and Lactobacillus growth (CFU mL-1). The results showed the stability of the OEO-KMPs over time, with high encapsulation efficiency and controlled release. This nanoparticle size facilitated penetration and completely inhibited the planktonic growth of C. albicans. In addition, an in vitro application of 2.5% of the OEO-KMPs eradicated mature C. albicans biofilms while preserving Lactobacillus species. In in vivo, a single intravaginal application of OEO-KMPs induced a reduction in C. albicans growth, while maintaining Lactobacillus species. In conclusion, this therapeutic approach with OEO-KMPs is promising as a potential alternative or complementary therapy for VVC while preserving vaginal microflora.

A review of recent advances in the use of complex metal nanostructures for biomedical applications from diagnosis to treatment.

Complex metal nanostructures represent an exceptional category of materials characterized by distinct morphologies and physicochemical properties. Nanostructures with shape anisotropies, such as nanorods, nanostars, nanocages, and nanoprisms, are particularly appealing due to their tunable surface plasmon resonances, controllable surface chemistries, and effective targeting capabilities. These complex nanostructures can absorb light in the near-infrared, enabling noteworthy applications in nanomedicine, molecular imaging, and biology. The engineering of targeting abilities through surface modifications involving ligands, antibodies, peptides, and other agents potentiates their effects. Recent years have witnessed the development of innovative structures with diverse compositions, expanding their applications in biomedicine. These applications encompass targeted imaging, surface-enhanced Raman spectroscopy, near-infrared II imaging, catalytic therapy, photothermal therapy, and cancer treatment. This review seeks to provide the nanomedicine community with a thorough and informative overview of the evolving landscape of complex metal nanoparticle research, with a specific emphasis on their roles in imaging, cancer therapy, infectious diseases, and biofilm treatment. This article is categorized under: Diagnostic Tools > In Vivo Nanodiagnostics and Imaging Therapeutic Approaches and Drug Discovery > Nanomedicine for Infectious Disease Diagnostic Tools > Diagnostic Nanodevices.

Ultrasound-Enhanced Antibacterial Activity of Polymeric Nanoparticles for Eradicating Bacterial Biofilms.

Bacterial biofilms are a major healthcare concern resulting in refractory conditions such as chronic wounds, implant infections and failure, and multidrug-resistant infections. Aggressive and invasive strategies are employed to cure biofilm infections but are prone to long and expensive treatments, adverse side-effects, and low patient compliance. Recent strategies such as ultrasound-based therapies and antimicrobial nanomaterials have shown some promise in the effective eradication of biofilms. However, maximizing therapeutic effect while minimizing healthy tissue damage is a key challenge that needs to be addressed. Here a combination treatment involving ultrasound and antimicrobial polymeric nanoparticles (PNPs) that synergistically eradicate bacterial biofilms is reported. Ultrasound treatment rapidly disrupts biofilms and increases penetration of antimicrobial PNPs thereby enhancing their antimicrobial activity. This results in superior biofilm toxicity, while allowing for a two- to sixfold reduction in both the concentration of PNPs as well as the duration of ultrasound. Furthermore, that this reduction minimizes cytotoxicity toward fibroblast cells, while resulting in a 100- to 1000-fold reduction in bacterial concentration, is demonstrated.

Physical Approaches to Prevent and Treat Bacterial Biofilm.

Prosthetic joint infection (PJI) presents several clinical challenges. This is in large part due to the formation of biofilm which can make infection eradication exceedingly difficult. Following an extensive literature search, this review surveys a variety of non-pharmacological methods of preventing and/or treating biofilm within the body and how they could be utilized in the treatment of PJI. Special attention has been paid to physical strategies such as heat, light, sound, and electromagnetic energy, and their uses in biofilm treatment. Though these methods are still under study, they offer a potential means to reduce the morbidity and financial burden related to multiple stage revisions and prolonged systemic antibiotic courses that make up the current gold standard in PJI treatment. Given that these options are still in the early stages of development and offer their own strengths and weaknesses, this review offers an assessment of each method, the progress made on each, and allows for comparison of methods with discussion of future challenges to their implementation in a clinical setting.

Updates in the Use of Antibiotics, Biofilms.

Guidelines for the rational use of antibiotics are evolving as new understanding of the mechanisms and development of antimicrobial resistance develops. The goals of antibiotic use are to follow the tenets of good antimicrobial stewardship while preventing or treating infection to reduce the risk of developing resistance in bacteria. Biofilm infections also infer microbial resistance and are the cause of recalcitrant infections in humans and animals. Current antibiofilm treatment strategies include the use of antibiotics that can penetrate the biofilm, debridement when possible, dispersal agents, and antibiofilm agents. New and exciting antibiofilm treatment strategies are in various stages of development.

Pulse Dosing of Antibiotic Enhances Killing of a Staphylococcus aureus Biofilm.

Biofilms are highly tolerant to antibiotics and underlie the recalcitrance of many chronic infections. We demonstrate that mature Staphylococcus aureus biofilms can be substantially sensitized to the treatment by pulse dosing of an antibiotic - in this case, oxacillin. Pulse (periodic) dosing was compared to continuous application of antibiotic and was studied in a novel in vitro flow system which allowed for robust biofilm growth and tractable pharmacokinetics of dosing regimens. Our results highlight that a subpopulation of the biofilm survives antibiotic without becoming resistant, a population we refer to as persister bacteria. When oxacillin was continuously present the persister level did not decline, but, importantly, providing correctly timed periodic breaks decreased the surviving population. We found that the length of the periodic break impacted efficacy, and there was an optimal length that sensitized the biofilm to repeat treatment without allowing resistance expansion. Periodic dosing provides a potential simple solution to a complicated problem.

Treatment of late bacterial infections resulting from soft-tissue filler injections.

PURPOSE: Late bacterial infections (LBIs) after esthetic facial augmentation using hyaluronic acid (HA) fillers are relatively rare yet severe complications that are difficult to treat. No adequate treatment standards have hitherto been formulated. We have bridged this gap by formulating a treatment scheme based on the principles of treating foreign-body implantation-related infections and treating bacterial growth in the form of biofilm. The objective of this study was to evaluate the efficacy of a comprehensive scheme for treating LBI complications after facial augmentation using cross-linked HA fillers. METHODS: A total of 22 patients with LBI symptoms at a site of cross-linked HA injection underwent treatment and observation. The comprehensive treatment scheme formulated by Marusza and Netsvyetayeva (M&N scheme) comprised draining the lesion, dissolution of cross-linked HA with hyaluronidase, broad-spectrum antibiotic combination therapy, and use of probiotics. While 17 patients underwent the M&N scheme, the remaining five were treated with other schemes. Statistical analysis of the data was performed using Mann-Whitney U and χ2 nonparametric tests with SAS 9.4 software. RESULTS: All 17 patients who underwent the M&N scheme experienced resolution of symptoms, with no recurrence of infection at the HA-injection sites. CONCLUSION: To treat LBI at a site of cross-linked HA administration, the principles applicable to infections resulting from implantation of a foreign body must be followed. The treatment period should be sufficiently long for complete resolution of symptoms. The efficacy of treatment is considered proven if 2 months have elapsed without recurrence since the symptoms resolved. The M&N scheme is recommended for use as the first therapeutic option for treating LBI related to soft-tissue fillers.

An Ag-loaded photoactive nano-metal organic framework as a promising biofilm treatment.

Surface biofilm inhibition is still currently a considerable challenge. Among other organisms, Staphylococcus aureus is notable for its ability to form a strong biofilm with proved resistance to chemotherapy. Contamination of high-touch surfaces with S. aureus biofilm not only promotes disease spread but also generates tremendous health-associated costs. Therefore, development of new bactericidal and antiadhesive surface coatings is a priority. Considering that metal-organic frameworks (MOFs) have recently emerged as promising antibacterial agents, we originally report here the synthesis of a multi-active silver-containing nanoscaled MOF composite as a potential surface coating against S. aureus biofilm owing to a triple effect: intrinsic bactericide activity of the MOF, biocidal character of silver nanoparticles (AgNPs), and photoactivity after UVA irradiation. AgNPs were successfully entrapped within the benchmarked nanoscaled porous photoactive titanium(IV) aminoterephthalate MIL-125(Ti)NH2 using a simple and efficient impregnation-reduction method. After complete characterization of the composite thin film, its antibacterial and anti-adherent properties were fully evaluated. After UVA irradiation, the composite coating exhibited relevant bacterial inhibition and detachment, improved ligand-to-cluster charge transfer, and steady controlled delivery of Ag+. These promising results establish the potential of this composite as an active coating for biofilm treatment on high-touch surfaces (e.g., surgical devices, door knobs, and rail bars). STATEMENT OF SIGNIFICANCE: Surface contamination due to bacterial biofilm formation is still a demanding issue, as it causes severe disease spread. One possible solution is the development of antifouling and antibacterial surface coatings. In this work, we originally propose the use of photoactive metal-organic frameworks (MOFs) for biofilm treatment. The novelty of this work relies on the following: i) the treatment of strongly contaminated surfaces, as previous studies with MOFs have exclusively addressed biofilm prevention; ii) this pioneering work reports both antiadherent effect, which removes the biofilm, and bacterial inhibition; iii) our original successful strategy has never been proposed thus far, involving the multi-active combination of 1) intrinsic antibacterial effect of a photoactive titanium-based nanoMOF, 2) immobilization of biocide silver nanoparticles, and 3) improved anti-bioadherent effect upon irradiation of the composite coating.

ESCMID guideline for the diagnosis and treatment of biofilm infections 2014.

Biofilms cause chronic infections in tissues or by developing on the surfaces of medical devices. Biofilm infections persist despite both antibiotic therapy and the innate and adaptive defence mechanisms of the patient. Biofilm infections are characterized by persisting and progressive pathology due primarily to the inflammatory response surrounding the biofilm. For this reason, many biofilm infections may be difficult to diagnose and treat efficiently. It is the purpose of the guideline to bring the current knowledge of biofilm diagnosis and therapy to the attention of clinical microbiologists and infectious disease specialists. Selected hallmark biofilm infections in tissues (e.g. cystic fibrosis with chronic lung infection, patients with chronic wound infections) or associated with devices (e.g. orthopaedic alloplastic devices, endotracheal tubes, intravenous catheters, indwelling urinary catheters, tissue fillers) are the main focus of the guideline, but experience gained from the biofilm infections included in the guideline may inspire similar work in other biofilm infections. The clinical and laboratory parameters for diagnosing biofilm infections are outlined based on the patient's history, signs and symptoms, microscopic findings, culture-based or culture-independent diagnostic techniques and specific immune responses to identify microorganisms known to cause biofilm infections. First, recommendations are given for the collection of appropriate clinical samples, for reliable methods to specifically detect biofilms, for the evaluation of antibody responses to biofilms, for antibiotic susceptibility testing and for improvement of laboratory reports of biofilm findings in the clinical microbiology laboratory. Second, recommendations are given for the prevention and treatment of biofilm infections and for monitoring treatment effectiveness. Finally, suggestions for future research are given to improve diagnosis and treatment of biofilm infections.