scholarly journals Nano-antibiotics combined with laser irradiation to reduce the development of drug resistance of K. Pneumoniae and accelerate wound healing

2021 ◽  
Author(s):  
Tiansheng Liu ◽  
Guowei Zhong ◽  
Dongying Tang ◽  
Xu Liu ◽  
Xianghua Zhong ◽  
...  
Keyword(s):  
Drug Resistance ◽  
Wound Healing ◽  
Laser Irradiation ◽  
Bacterial Infections ◽  
Bacterial Resistance ◽  
High Efficiency ◽  
Clinical Treatment ◽  
Resistant Bacteria ◽  
Cell Integrity ◽  
Accelerate Wound Healing

Bacterial infections, especially infections caused by multi-drug resistant bacteria, pose a serious threat to human health and bring huge challenges to clinical treatment. The excessive use of antibiotics can easily lead to the emergence of bacterial resistance, which severely limits clinical treatment options. There is an urgent need to develop high-efficiency antibacterial materials and treatment strategies to inhibit infections caused by multidrug-resistant bacteria. In this work, a nanocomposite named Ofloxacin@HMPB@HA(OHH NPs) combined with the laser irradiation was used to reduce the development of drug resistance and accelerate wound healing in a model infected by Klebsiella pneumoniae(K.Pneumoniae). In vitro results showed that compared with OHH NPs or NIR laser irradiation alone, this combination strategy can exert a synergistic effect on anti-K.Pneumoniae by destroying cell integrity with generating ROS and reducing ATP, and also inhibit the development of bacterial resistance. Moreover, in vivo experiments have shown that the system effectively promotes wound healing through killing K.Pneumoniae and promoting the formation of new tissues. In summary, these results indicate that OHH NPs show great potential in the clinical application of bacterial infections.

scholarly journals Treating Bacterial Infections with Bacteriophage-Based Enzybiotics: In Vitro, In Vivo, and Clinical Application

Antibiotics ◽  
2021 ◽  
Vol 10 (12) ◽  
pp. 1497
Author(s):  
Katarzyna M. Danis-Wlodarczyk ◽  
Daniel J. Wozniak ◽  
Stephen T. Abedon
Keyword(s):  
Bacterial Infections ◽  
Bacterial Resistance ◽  
High Efficiency ◽  
Cross Resistance ◽  
Resistant Bacteria ◽  
Drug Classes ◽  
Peptidoglycan Hydrolases ◽  
Bacterial Peptidoglycan

Over the past few decades, we have witnessed a surge around the world in the emergence of antibiotic-resistant bacteria. This global health threat arose mainly due to the overuse and misuse of antibiotics as well as a relative lack of new drug classes in development pipelines. Innovative antibacterial therapeutics and strategies are, therefore, in grave need. For the last twenty years, antimicrobial enzymes encoded by bacteriophages, viruses that can lyse and kill bacteria, have gained tremendous interest. There are two classes of these phage-derived enzymes, referred to also as enzybiotics: peptidoglycan hydrolases (lysins), which degrade the bacterial peptidoglycan layer, and polysaccharide depolymerases, which target extracellular or surface polysaccharides, i.e., bacterial capsules, slime layers, biofilm matrix, or lipopolysaccharides. Their features include distinctive modes of action, high efficiency, pathogen specificity, diversity in structure and activity, low possibility of bacterial resistance development, and no observed cross-resistance with currently used antibiotics. Additionally, and unlike antibiotics, enzybiotics can target metabolically inactive persister cells. These phage-derived enzymes have been tested in various animal models to combat both Gram-positive and Gram-negative bacteria, and in recent years peptidoglycan hydrolases have entered clinical trials. Here, we review the testing and clinical use of these enzymes.

scholarly journals Tackling Virulence of Pseudomonas aeruginosa by the Natural Furanone Sotolon

Antibiotics ◽  
2021 ◽  
Vol 10 (7) ◽  
pp. 871
Author(s):  
Mohammed F. Aldawsari ◽  
El-Sayed Khafagy ◽  
Ahmed Al Saqr ◽  
Ahmed Alalaiwe ◽  
Hisham A. Abbas ◽  
...  
Keyword(s):  
Pseudomonas Aeruginosa ◽  
Virulence Factors ◽  
Bacterial Infections ◽  
Therapeutic Agent ◽  
Bacterial Resistance ◽  
Inhibitory Concentration ◽  
Bacterial Biofilm ◽  
Resistant Bacteria ◽  
Resistance Development

The bacterial resistance development due to the incessant administration of antibiotics has led to difficulty in their treatment. Natural adjuvant compounds can be co-administered to hinder the pathogenesis of resistant bacteria. Sotolon is the prevailing aromatic compound that gives fenugreek its typical smell. In the current work, the anti-virulence activities of sotolon on Pseudomonas aeruginosa have been evaluated. P. aeruginosa has been treated with sotolon at sub-minimum inhibitory concentration (MIC), and production of biofilm and other virulence factors were assessed. Moreover, the anti-quorum sensing (QS) activity of sotolon was in-silico evaluated by evaluating the affinity of sotolon to bind to QS receptors, and the expression of QS genes was measured in the presence of sotolon sub-MIC. Furthermore, the sotolon in-vivo capability to protect mice against P. aeruginosa was assessed. Significantly, sotolon decreased the production of bacterial biofilm and virulence factors, the expression of QS genes, and protected mice from P. aeruginosa. Conclusively, the plant natural substance sotolon attenuated the pathogenicity of P. aeruginosa, locating it as a plausible potential therapeutic agent for the treatment of its infections. Sotolon can be used in the treatment of bacterial infections as an alternative or adjuvant to antibiotics to combat their high resistance to antibiotics.

scholarly journals Better living through chemistry: Addressing emerging antibiotic resistance

2018 ◽  
Vol 243 (6) ◽  
pp. 538-553 ◽  
Author(s):  
Nathan P Coussens ◽  
Ashley L Molinaro ◽  
Kayla J Culbertson ◽  
Tyler Peryea ◽  
Gergely Zahoránszky-Köhalmi ◽  
...  
Keyword(s):  
Drug Resistance ◽  
Human Health ◽  
Small Molecule ◽  
Bacterial Infections ◽  
Public Investment ◽  
Antibiotic Use ◽  
Unintended Consequences ◽  
Resistant Bacteria ◽  
Antibiotic Resistant ◽  
Small Molecule Drugs

The increasing emergence of multidrug-resistant bacteria is recognized as a major threat to human health worldwide. While the use of small molecule antibiotics has enabled many modern medical advances, it has also facilitated the development of resistant organisms. This minireview provides an overview of current small molecule drugs approved by the US Food and Drug Administration (FDA) for use in humans, the unintended consequences of antibiotic use, and the mechanisms that underlie the development of drug resistance. Promising new approaches and strategies to counter antibiotic-resistant bacteria with small molecules are highlighted. However, continued public investment in this area is critical to maintain an edge in our evolutionary “arms race” against antibiotic-resistant microorganisms. Impact statement The alarming increase in antibiotic-resistant microorganisms is a rapidly emerging threat to human health throughout the world. Historically, small molecule drugs have played a major role in controlling bacterial infections and they continue to offer tremendous potential in countering resistant organisms. This minireview provides a broad overview of the relevant issues, including the diversity of FDA-approved small molecule drugs and mechanisms of drug resistance, unintended consequences of antibiotic use, the current state of development for small molecule antibacterials and financial challenges that impact progress towards novel therapies. The content will be informative to diverse stakeholders, including clinicians, basic scientists, translational scientists and policy makers, and may be used as a bridge between these key players to advance the development of much-needed therapeutics.

Bacteriophage Therapy of Chronic Nonhealing Wound: Clinical Study

2019 ◽  
Vol 18 (2) ◽  
pp. 171-175 ◽  
Author(s):  
Pooja Gupta ◽  
Hari Shankar Singh ◽  
Vijay K. Shukla ◽  
Gopal Nath ◽  
Satyanam Kumar Bhartiya
Keyword(s):  
Wound Healing ◽  
Biofilm Formation ◽  
Bacterial Infections ◽  
Chronic Wounds ◽  
Bacterial Count ◽  
Complete Healing ◽  
Resistant Bacteria ◽  
Bacteriophage Therapy ◽  
Inflammatory Phase ◽  
Drug Resistant Bacteria

Background: A chronic wound usually results due to halt in the inflammatory phase of wound healing. Bacterial infections and biofilm formation are considered to be the basic cause of it. Chronic wounds significantly impair the quality of life. Antibiotics are now failing due to biofilm formation emergence of drug-resistant bacteria. Objective: This study aims to see the effect of bacteriophage therapy in chronic nonhealing wound infected with the following bacteria: Escherichia coli, Staphylococcus aureus, and Pseudomonas aeruginosa. Subject: Patients with chronic nonhealing wound not responding to conventional local debridement and antibiotic therapy were included in the study. The age of patients ranged between 12 and 60 years. Method: A total of 20 patients selected and tissue biopsies and wound swabs were taken for isolation of the bacteria. After confirmation of organism, a cocktail of customized bacteriophages was topically applied over the wound on alternate days till the wound surface became microbiologically sterile. Mean bacterial count and clinical assessment were done and compared at the time of presentation and after 3 and 5 doses of application. Results: A significant improvement was observed in the wound healing, and there were no signs of infection clinically and microbiologically after 3 to 5 doses of topical bacteriophage therapy. Seven patients achieved complete healing on day21 during follow up while in others healthy margins and healthy granulation tissue were observed. Conclusion: Topical bacteriophage application may be quite effective therapy for the treatment of chronic nonhealing wounds.

scholarly journals Dual functional β-peptide polymer-modified resin beads for bacterial killing and endotoxin adsorption

BMC Materials ◽  
2019 ◽  
Vol 1 (1) ◽  
Author(s):  
Yuxin Qian ◽  
Yue Shen ◽  
Shuai Deng ◽  
Tingyan Liu ◽  
Fan Qi ◽  
...  
Keyword(s):  
Bacterial Infections ◽  
Bacterial Resistance ◽  
Resistant Bacteria ◽  
High Concentration ◽  
Major Step ◽  
Bacterial Killing ◽  
Host Defense Peptides ◽  
Dual Functional ◽  
Resin Beads ◽  
Bacteria Killing

Abstract Background Bacterial infections and endotoxin contaminations are serious problems in the production/manufacture of food, water, drinks, and injections. The development of effective materials to kill bacteria and adsorb endotoxins, particularly those caused by gram-negative bacteria, represents a major step toward improved safety. As synthetic mimic of host defense peptides, β-peptide polymers are not susceptible to bacterial resistance and exhibit potent bacteria-killing abilities upon antibiotic-resistant bacteria. This study investigated the potential of synthetic β-peptide polymer-modified polyacrylate (PA) beads to kill bacteria and remove endotoxin, i.e. lipopolysaccharide (LPS), produced by these bacteria. Results Synthetic β-peptide polymer-modified PA beads displayed strong antimicrobial activity against Escherichia coli and methicillin-resistant Staphylococcus aureus, as well as excellent biocompatibility. In addition, these β-peptide polymer-modified beads removed around 90% of the endotoxins, even at 200 EU/mL of LPS, a very high concentration of LPS. Conclusions β-peptide polymer-modified PA beads are efficient in bacterial killing and endotoxin adsorption. Hence, these modified beads demonstrate the potential application in the production/manufacture of food, water, drinks, and injections.

scholarly journals Avoiding ventilator-associated pneumonia: Curcumin-functionalized endotracheal tube and photodynamic action

2020 ◽  
Vol 117 (37) ◽  
pp. 22967-22973
Author(s):  
Amanda C. Zangirolami ◽  
Lucas D. Dias ◽  
Kate C. Blanco ◽  
Carolina S. Vinagreiro ◽  
Natalia M. Inada ◽  
...  
Keyword(s):  
Endotracheal Tube ◽  
Bacterial Infections ◽  
Bacterial Resistance ◽  
Multidrug Resistant ◽  
Resistant Bacteria ◽  
Ventilator Associated Pneumonia ◽  
Hospital Acquired Infection ◽  
Hospital Acquired Infections ◽  
Hospitalization Costs ◽  
Hospital Acquired

Hospital-acquired infections are a global health problem that threatens patients’ treatment in intensive care units, causing thousands of deaths and a considerable increase in hospitalization costs. The endotracheal tube (ETT) is a medical device placed in the patient’s trachea to assist breathing and delivering oxygen into the lungs. However, bacterial biofilms forming at the surface of the ETT and the development of multidrug-resistant bacteria are considered the primary causes of ventilator-associated pneumonia (VAP), a severe hospital-acquired infection for significant mortality. Under these circumstances, there has been a need to administrate antibiotics together. Although necessary, it has led to a rapid increase in bacterial resistance to antibiotics. Therefore, it becomes necessary to develop alternatives to prevent and combat these bacterial infections. One possibility is to turn the ETT itself into a bactericide. Some examples reported in the literature present drawbacks. To overcome those issues, we have designed a photosensitizer-containing ETT to be used in photodynamic inactivation (PDI) to avoid bacteria biofilm formation and prevent VAP occurrence during tracheal intubation. This work describes ETT’s functionalization with curcumin photosensitizer, as well as its evaluation in PDI against Staphylococcus aureus, Pseudomonas aeruginosa, and Escherichia coli. A significant photoinactivation (up to 95%) against Gram-negative and Gram-positive bacteria was observed when curcumin-functionalized endotracheal (ETT-curc) was used. These remarkable results demonstrate this strategy’s potential to combat hospital-acquired infections and contribute to fighting antimicrobial resistance.

scholarly journals Review on Multiple Facets of Drug Resistance: A Rising Challenge in the 21st Century

2021 ◽  
Vol 11 (4) ◽  
pp. 197-214
Author(s):  
Mousumi Saha ◽  
Agniswar Sarkar
Keyword(s):  
Drug Resistance ◽  
Antibiotic Resistance ◽  
Bacterial Infections ◽  
Molecular Mechanisms ◽  
In Silico Analysis ◽  
Relevant Information ◽  
High Rate ◽  
Resistant Bacteria ◽  
Bacterial Strains ◽  
Potential Threat

With the advancements of science, antibiotics have emerged as an amazing gift to the human and animal healthcare sectors for the treatment of bacterial infections and other diseases. However, the evolution of new bacterial strains, along with excessive use and reckless consumption of antibiotics have led to the unfolding of antibiotic resistances to an excessive level. Multidrug resistance is a potential threat worldwide, and is escalating at an extremely high rate. Information related to drug resistance, and its regulation and control are still very little. To interpret the onset of antibiotic resistances, investigation on molecular analysis of resistance genes, their distribution and mechanisms are urgently required. Fine-tuned research and resistance profile regarding ESKAPE pathogen is also necessary along with other multidrug resistant bacteria. In the present scenario, the interaction of bacterial infections with SARS-CoV-2 is also crucial. Tracking and in-silico analysis of various resistance mechanisms or gene/s are crucial for overcoming the problem, and thus, the maintenance of relevant databases and wise use of antibiotics should be promoted. Creating awareness of this critical situation among individuals at every level is important to strengthen the fight against this fast-growing calamity. The review aimed to provide detailed information on antibiotic resistance, its regulatory molecular mechanisms responsible for the resistance, and other relevant information. In this article, we tried to focus on the correlation between antimicrobial resistance and the COVID-19 pandemic. This study will help in developing new interventions, potential approaches, and strategies to handle the complexity of antibiotic resistance and prevent the incidences of life-threatening infections.

scholarly journals Drug Resistance of Pathogens Causing Nosocomial Infection in Orthopedics from 2012 to 2017: A 6-Year Retrospective Study

2020 ◽  
Author(s):  
Xiaowei Yang ◽  
Runsheng Guo ◽  
Banglin Xie ◽  
Qi Lai ◽  
Jiaxiang Xu ◽  
...  
Keyword(s):  
Drug Resistance ◽  
Retrospective Study ◽  
Antimicrobial Resistance ◽  
Bacterial Infections ◽  
Multidrug Resistant ◽  
Dynamic Monitoring ◽  
Resistant Bacteria ◽  
Clinical Microbiology Laboratory ◽  
Valuable Insight ◽  
E Coli

Abstract Background: Hospital-acquired infections (HAIs) are an emerging global problem that increases in-hospital mortality, length of stay, and cost. We performed a 6-year retrospective study to provide valuable insight into appropriate antibiotic use in HAI cases. We also aimed to understand how hospitals could reduce pathogen drug resistance in a population that overuses antibiotics.Methods: All data (2012–2017) were obtained from the Hospital Information Warehouse and Clinical Microbiology Laboratory.Results: We isolated 1392 pathogen strains from patients admitted to the orthopedics department during 2012–2017. Escherichia coli (14.7%, 204/1392), Enterobacter cloacae (13.9%, 193/1392), and Staphylococcus aureus (11.3%, 157/1392) were the most common pathogens causing nosocomial infections. The dominant Gram-negative bacterium was E. coli, with high resistance to ampicillin, levofloxacin, cotrimoxazole, gentamicin, and ciprofloxacin, in that order. E. coli was least resistant to amikacin, cefoperazone-sulbactam. The most dominant Gram-positive bacterium was S. aureus, highly resistant to penicillin and ampicillin, but not resistant to fluoroquinolones and cotrimoxazole. Analysis of risk factors related to multidrug-resistant bacteria showed that patients with open fractures were significantly more susceptible to methicillin-resistant S. aureus infections (p < 0.05). Additionally, extended-spectrum β-lactamase-producing E. coli infections occurred significantly more often in patients with degenerative diseases (p < 0.05). Elderly patients tended to be more susceptible to multidrug-resistant bacterial infections, but this outcome was not statistically significant.Conclusions:Antimicrobial resistance is a serious problem in orthopedics. To effectively control antimicrobial resistance among pathogens, we advocate extensive and dynamic monitoring of MDR bacteria, coupled with careful use of antibiotics.

scholarly journals Detection of Quorum-Sensing Molecules for Pathogenic Molecules Using Cell-Based and Cell-Free Biosensors

Antibiotics ◽  
2020 ◽  
Vol 9 (5) ◽  
pp. 259 ◽  
Author(s):  
Craig Miller ◽  
Jordon Gilmore
Keyword(s):  
Quorum Sensing ◽  
Bacterial Infections ◽  
Bacterial Resistance ◽  
Genetic Material ◽  
Treatment Strategies ◽  
Signaling Molecules ◽  
Resistant Bacteria ◽  
Acute Infections

Since the discovery and subsequent use of penicillin, antibiotics have been used to treat most bacterial infections in the U.S. Over time, the repeated prescription of many antibiotics has given rise to many antibiotic-resistant microbes. A bacterial strain becomes resistant by horizontal gene transfer, where surviving microbes acquire genetic material or DNA fragments from adjacent bacteria that encode for resistance. In order to avoid significant bacterial resistance, novel and target therapeutics are needed. Further advancement of diagnostic technologies could be used to develop novel treatment strategies. The use of biosensors to detect quorum-sensing signaling molecules has the potential to provide timely diagnostic information toward mitigating the multidrug-resistant bacteria epidemic. Resistance and pathogenesis are controlled by quorum-sensing (QS) circuits. QS systems secrete or passively release signaling molecules when the bacterial concentration reaches a certain threshold. Signaling molecules give an early indication of virulence. Detection of these compounds in vitro or in vivo can be used to identify the onset of infection. Whole-cell and cell-free biosensors have been developed to detect quorum-sensing signaling molecules. This review will give an overview of quorum networks in the most common pathogens found in chronic and acute infections. Additionally, the current state of research surrounding the detection of quorum-sensing molecules will be reviewed. Followed by a discussion of future works toward the advancement of technologies to quantify quorum signaling molecules in chronic and acute infections.

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