scholarly journals Prospects of Inhaled Phage Therapy for Combatting Pulmonary Infections

2021 ◽  
Vol 11 ◽  
Author(s):  
Xiang Wang ◽  
Zuozhou Xie ◽  
Jinhong Zhao ◽  
Zhenghua Zhu ◽  
Chen Yang ◽  
...  
Keyword(s):  
Targeted Delivery ◽  
Bacterial Infections ◽  
Phage Therapy ◽  
Respiratory Infections ◽  
Pulmonary Delivery ◽  
Drug Resistant ◽  
Pulmonary Infections ◽  
Bacterial Strains ◽  
Adjunct Treatment ◽  
New Antibiotics

With respiratory infections accounting for significant morbidity and mortality, the issue of antibiotic resistance has added to the gravity of the situation. Treatment of pulmonary infections (bacterial pneumonia, cystic fibrosis-associated bacterial infections, tuberculosis) is more challenging with the involvement of multi-drug resistant bacterial strains, which act as etiological agents. Furthermore, with the dearth of new antibiotics available and old antibiotics losing efficacy, it is prudent to switch to non-antibiotic approaches to fight this battle. Phage therapy represents one such approach that has proven effective against a range of bacterial pathogens including drug resistant strains. Inhaled phage therapy encompasses the use of stable phage preparations given via aerosol delivery. This therapy can be used as an adjunct treatment option in both prophylactic and therapeutic modes. In the present review, we first highlight the role and action of phages against pulmonary pathogens, followed by delineating the different methods of delivery of inhaled phage therapy with evidence of success. The review aims to focus on recent advances and developments in improving the final success and outcome of pulmonary phage therapy. It details the use of electrospray for targeted delivery, advances in nebulization techniques, individualized controlled inhalation with software control, and liposome-encapsulated nebulized phages to take pulmonary phage delivery to the next level. The review expands knowledge on the pulmonary delivery of phages and the advances that have been made for improved outcomes in the treatment of respiratory infections.

scholarly journals Phage Therapy for Multi-Drug Resistant Respiratory Tract Infections

Viruses ◽  
2021 ◽  
Vol 13 (9) ◽  
pp. 1809
Author(s):  
Joshua J. Iszatt ◽  
Alexander N. Larcombe ◽  
Hak-Kim Chan ◽  
Stephen M. Stick ◽  
Luke W. Garratt ◽  
...  
Keyword(s):  
Respiratory Tract Infections ◽  
Phage Therapy ◽  
Respiratory Infections ◽  
Current Evidence ◽  
Drug Resistant ◽  
Data Generation ◽  
Bacteriophage Therapy ◽  
Efficacy Data ◽  
New Antibiotics ◽  
Tract Infections

The emergence of multi-drug resistant (MDR) bacteria is recognised today as one of the greatest challenges to public health. As traditional antimicrobials are becoming ineffective and research into new antibiotics is diminishing, a number of alternative treatments for MDR bacteria have been receiving greater attention. Bacteriophage therapies are being revisited and present a promising opportunity to reduce the burden of bacterial infection in this post-antibiotic era. This review focuses on the current evidence supporting bacteriophage therapy against prevalent or emerging multi-drug resistant bacterial pathogens in respiratory medicine and the challenges ahead in preclinical data generation. Starting with efforts to improve delivery of bacteriophages to the lung surface, the current developments in animal models for relevant efficacy data on respiratory infections are discussed before finishing with a summary of findings from the select human trials performed to date.

scholarly journals Bacteriophages: what role may they play in life after spinal cord injury?

Spinal Cord ◽  
2021 ◽  
Author(s):  
Lorenz Leitner ◽  
Shawna McCallin ◽  
Thomas M. Kessler
Keyword(s):  
Spinal Cord ◽  
Spinal Cord Injury ◽  
Clinical Practice ◽  
High Risk ◽  
General Population ◽  
Bacterial Infections ◽  
Phage Therapy ◽  
Drug Resistant ◽  
Cord Injury ◽  
High Risk Populations

AbstractBacterial infections are the leading cause of death in people with a spinal cord injury (SCI). Bacteriophages (phages) are viruses that solely infect and kill bacteria. The idea of using phages to treat bacterial infections, i.e., phage therapy, is very promising and potentially allows a more specific and personalized treatment of bacterial infections than antibiotics. While multi-drug resistant infections affect individuals from the general population, alternative therapeutic options are especially warranted in high-risk populations, such as individuals with SCI. However, more clinical data must be collected before phage therapy can be implemented in clinical practice, with numerous possible, subsequent applications.

scholarly journals Imaging Sensitive and Drug-Resistant Bacterial Infection with [11C]-TMP: In Vitro and First-in-Human Evaluation

2021 ◽  
Author(s):  
Iris K Lee ◽  
Daniel A Jacome ◽  
Joshua K Cho ◽  
Vincent Tu ◽  
Anthony Young ◽  
...  
Keyword(s):  
Bacterial Infection ◽  
Mammalian Cells ◽  
Bacterial Infections ◽  
The Body ◽  
Response Monitoring ◽  
Drug Resistant ◽  
Bacterial Strains ◽  
Critical Question ◽  
In Vitro Uptake

Recently, several molecular imaging strategies have developed to image bacterial infections in humans. Nuclear approaches, specifically positron emission tomography (PET), affords sensitive detection and the ability to non-invasively locate infections deep within the body. Two key radiotracer classes have arisen: metabolic approaches targeting bacterial specific biochemical transformations, and antibiotic-based approaches that have inherent selectivity for bacteria over mammalian cells. A critical question for clinical application of antibiotic radiotracers is whether resistance to the template antibiotic abrogates specific uptake, thus diminishing the predictive value of the diagnostic test. We recently developed small-molecule PET radiotracers based on the antibiotic trimethoprim (TMP), including [11C]-TMP, and have shown their selectivity for imaging bacteria in preclinical models. Here, we measure the in vitro uptake of [11C]-TMP in pathogenic susceptible and drug-resistant bacterial strains. Both resistant and susceptible bacteria showed similar in vitro uptake, which led us to perform whole genome sequencing of these isolates to identify the mechanisms of TMP resistance that permit retained radiotracer binding. By interrogating these isolate genomes and a broad panel of previously sequenced strains, we reveal mechanisms where uptake or binding of TMP radiotracers can potentially be maintained despite the annotation of genes conferring antimicrobial resistance. Finally, we present several examples of patients with both TMP-sensitive and drug-resistant infections in our first-in-human experience with [11C]-TMP. This work underscores the ability of an antibiotic radiotracer to image bacterial infection in patients, which may allow insights into human bacterial pathogenesis, infection diagnosis, and antimicrobial response monitoring.

scholarly journals Antibiotics in Development for the Treatment of Resistant Bacterial Disease

2017 ◽  
Vol 53 (1) ◽  
pp. 38-40 ◽  
Author(s):  
Ryan Kidd ◽  
Scot Walker
Keyword(s):  
Bacterial Infections ◽  
Morbidity And Mortality ◽  
Bacterial Disease ◽  
Drug Resistant ◽  
New Antibiotics

Many bacterial infections can be treated with the use of antibiotics. These medications continue to reduce morbidity and mortality; unfortunately, their use has brought about drug-resistant pathogens that produce difficult-to-treat infections, which require more extreme treatments. New antibiotics are needed to combat this ever-evolving resistance pathogenesis.

scholarly journals Metabolic profiling and antibacterial activity of Eryngium pristis Cham. & Schltdl. - prospecting for its use in the treatment of bacterial infections

2021 ◽  
Vol 5 (1) ◽  
pp. 020-028
Author(s):  
Fernandes Laura Silva ◽  
da Costa Ygor Ferreira Garcia ◽  
de Bessa Martha Eunice ◽  
Ferreira Adriana Lucia Pires ◽  
do Amaral Corrêa José Otávio ◽  
...  
Keyword(s):  
Antibacterial Activity ◽  
Bioactive Compounds ◽  
Metabolic Profile ◽  
Bacterial Infections ◽  
Ethanolic Extract ◽  
Multidrug Resistant ◽  
Gas Chromatography Mass Spectrometry ◽  
Resistant Bacteria ◽  
Bacterial Strains ◽  
New Antibiotics

Morbidity and mortality of the infected patients by multidrug-resistant bacteria have increased, emphasizing the urgency of fight for the discovery of new innovative antibiotics. In this sense, natural products emerge as valuable sources of bioactive compounds. Among the biodiversity, Eryngium pristis Cham. & Schltdl. (Apiaceae Lindl.) is traditionally used to treat thrush and ulcers of throat and mouth, as diuretic and emmenagogue, but scarcely known as an antimicrobial agent. With this context in mind, the goals of this study were to investigate the metabolic profile and the antibacterial activity of ethanolic extract (EE-Ep) and hexane (HF-Ep), dichloromethane (DF-Ep), ethyl acetate (EAF-Ep) and butanol (BF-Ep) fractions from E. pristis leaves. Gas Chromatography-Mass Spectrometry (GC-MS) was performed to stablish the metabolic profile and revealed the presence of 12 and 14 compounds in EAF-Ep and HF-Ep, respectively. β-selinene, spathulenol, globulol, 2-methoxy-4-vinylphenol, α-amyrin, β-amyrin, and lupeol derivative were some of phytochemicals identified. The antibacterial activity was determined by Minimal Inhibitory Concentration (MIC) using the broth micro-dilution against eight ATCC® and five methicillin-resistant Staphylococcus aureus (MRSA) clinical strains. HF-Ep was the most effective (MIC ≤ 5,000 µg/µL), being active against the largest part of tested Gram-positive and Gram-negative bacterial strains, including MRSA, with exception of Escherichia coli (ATCC 25922) and Pseudomonas aeruginosa (ATCC 9027) and (ATCC 27853). These results suggest that E. pristis is a natural source of bioactive compounds for the search of new antibiotics which can be an interesting therapeutic approach to recover patients mainly infected by MRSA strains.

scholarly journals Evaluation of antibacterial activity of vitamin C against human bacterial pathogens

2023 ◽  
Vol 83 ◽  
Author(s):  
S. Mumtaz ◽  
S. Mumtaz ◽  
S. Ali ◽  
H. M. Tahir ◽  
S. A. R. Kazmi ◽  
...  
Keyword(s):  
Antibacterial Activity ◽  
Vitamin C ◽  
Bacterial Infections ◽  
Unmet Need ◽  
Diffusion Method ◽  
Gram Negative Bacteria ◽  
Bacterial Strains ◽  
Gram Positive ◽  
Gram Negative ◽  
Adjunct Treatment

Abstract Now a day’s multidrug resistance phenomenon has become the main cause for concern and there has been an inadequate achievement in the development of novel antibiotics to treat the bacterial infections. Therefore, there is an unmet need to search for novel adjuvant. Vitamin C is one such promising adjuvant. The present study was aimed to elucidate the antibacterial effect of vitamin C at various temperatures (4°C, 37°C and 50°C) and pH (3, 8, and 11), against Gram-positive and Gram-negative bacteria at various concentrations (5-20 mg/ml) through agar well diffusion method. Growth inhibition of all bacterial strains by vitamin C was concentration-dependent. Vitamin C significantly inhibited the growth of Gram-positive bacteria: Bacillus licheniformis (25.3 ± 0.9 mm), Staphylococcus aureus (22.0 ± 0.6 mm), Bacillus subtilis (19.3 ± 0.3 mm) and Gram-negative bacteria: Proteus mirabilis (27.67 ± 0.882 mm), Klebsiella pneumoniae (21.33±0.9 mm), Pseudomonas aeruginosa (18.0 ± 1.5 mm) and Escherichia coli (18.3 ± 0.3 mm). The stability of vitamin C was observed at various pH values and various temperatures. Vitamin C showed significant antibacterial activity at acidic pH against all bacterial strains. Vitamin C remained the stable at different temperatures. It was concluded that vitamin C is an effective and safe antibacterial agent that can be used in the future as an adjunct treatment option to combat infections in humans.

scholarly journals Comparative Analysis ofViperidaeVenoms Antibacterial Profile: a Short Communication for Proteomics

2011 ◽  
Vol 2011 ◽  
pp. 1-4 ◽  
Author(s):  
Bruno L. Ferreira ◽  
Dilvani O. Santos ◽  
André Luis dos Santos ◽  
Carlos R. Rodrigues ◽  
Cícero C. de Freitas ◽  
...  
Keyword(s):  
Staphylococcus Epidermidis ◽  
Bacterial Infections ◽  
Multidrug Resistant ◽  
Drug Resistant ◽  
Future Design ◽  
Important Health ◽  
New Antibiotics ◽  
Resistant Strains ◽  
Lachesis Muta ◽  
Pharmacological Potential

Bacterial infections involving multidrug-resistant strains are one of the ten leading causes of death and an important health problem in need for new antibacterial sources and agents. Herein, we tested and compared four snake venoms (Agkistrodon rhodostoma, Bothrops jararaca, B. atrox and Lachesis muta) against 10 Gram-positive and Gram-negative drug-resistant clinical bacteria strains to identify them as new sources of potential antibacterial molecules. Our data revealed that, as efficient as some antibiotics currently on the market (minimal inhibitory concentration (MIC) = 1–32 μg mL−1),A. rhodostomaandB. atroxvenoms were active againstStaphylococcus epidermidisandEnterococcus faecalis(MIC = 4.5 μg mL−1), whileB. jararacainhibitedS. aureusgrowth (MIC = 13 μg ml−1). As genomic and proteomic technologies are improving and developing rapidly, our results suggested thatA. rhodostoma, B. atroxandB. jararacavenoms and glands are feasible sources for searching antimicrobial prototypes for future design new antibiotics against drug-resistant clinical bacteria. They also point to an additional perspective to fully identify the pharmacological potential of these venoms by using different techniques.

scholarly journals Novel Lytic Phages Protect Cells and Mice against Pseudomonas aeruginosa Infection

2021 ◽  
Author(s):  
Feng Chen ◽  
Xingjun Cheng ◽  
Jianbo Li ◽  
Xiefang Yuan ◽  
Xiuhua Huang ◽  
...  
Keyword(s):  
Pseudomonas Aeruginosa ◽  
Mouse Models ◽  
Bacterial Infections ◽  
Phage Therapy ◽  
Inflammatory Responses ◽  
Multi Drug Resistance ◽  
Bacterial Strains ◽  
Genetic Traits

With the fast emergence of serious antibiotic resistance and the lagged discovery of novel antibacterial drugs, phage therapy for pathogenic bacterial infections has acquired great attention in the clinics. However, development of therapeutic phages also faces tough challenges, such as laborious screening and time to generate effective phage drugs since each phage may only lyse a narrow scope of bacterial strains. Identifying highly effective phages with broad host ranges is crucial for improving phage therapy. Here, we isolated and characterized several lytic phages from various environments specific for Pseudomonas aeruginosa by testing their growth, invasion, host ranges, and potential for killing targeted bacteria. Importantly, we identified several therapeutic phages (HX1, PPY9, and TH15) with broad host ranges to lyse laboratory strains and clinical isolates of P. aeruginosa with multi-drug resistance (MDR) both in vitro and in mouse models. In addition, we analyzed critical genetic traits related to the high-level broad host coverages by genome sequencing and subsequent computational analysis against known phages. Collectively, our findings establish that these novel phages may have potential for further development as therapeutic options for patients who fail to respond to conventional treatments. IMPORTANCE Novel lytic phages isolated from various environmental settings were systematically characterized for their critical genetic traits, morphology structures, host ranges against laboratory strains and clinical multi-drug resistant (MDR) Pseudomonas aeruginosa, and antibacterial capacity both in vitro and in mouse models. First, we characterized the genetic traits and compared with other existing phages. Furthermore, we utilized acute pneumonia induced by laboratorial strain PAO1, and W19, an MDR clinical isolate and chronic pneumonia by agar beads laden with FDR1, a mucoid phenotype strain isolated from the sputum of a cystic fibrosis (CF) patient. Consequently, we found that these phages not only suppress bacteria in vitro but also significantly reduce the infection symptom and disease progression in vivo, including lowered bug burdens, inflammatory responses and lung injury in mice, suggesting that they may be further developed as therapeutic agents against MDR P. aeruginosa.

scholarly journals Antibacterial Activity of Ulva fasciata against Multidrug Resistant Bacterial Strains

2014 ◽  
Vol 19 ◽  
pp. 40-51 ◽  
Author(s):  
M. Chandrasekaran ◽  
Venugopalan Venkatesalu ◽  
G. Adaikala Raj ◽  
S. Krishnamoorthy
Keyword(s):  
Antibacterial Activity ◽  
Ethyl Acetate ◽  
Bacterial Infections ◽  
Ethyl Acetate Extract ◽  
Shigella Flexneri ◽  
Biosphere Reserve ◽  
Gulf Of Mannar ◽  
Drug Resistant ◽  
Bacterial Strains ◽  
Ulva Fasciata

The present study was conducted to evaluate the antibacterial activity of different organic solvent increasing polarity viz., hexane, chloroform, ethyl acetate, acetone and methanol extracts of Ulva fasciata (Chlorophyceae) were collected from Kanniyakummari, Gulf of Mannar biosphere Reserve, Tamilnadu, India. Marine green algae extracts of U. fasciata against multi-drug resistant standard and clinical bacterial strains viz., Bacillus subtilis, Streptococcus pyogenes, Escherichia coli, Klebsiella pneumoniae, Pseudomonas aeruginosa, Salmonella typhimurium, Vibrio cholerae, Shigella flexneri, Proteus mirabilis and P. vulgaris. The ethyl acetate extracts of U. fasciata showed highest antibacterial activity against all the bacterial strains tested. The mean zone of inhibition produced by the extracts in disc diffusion assays were ranged from 7.1 mm to 15.0 mm. The Minimum Inhibitory Concentrations (MIC) were between 125 μg/ml and 500 μg/ml, while the Minimum Bactericidal Concentrations (MBC) were between 250 μg/ml and 1000 μg/ml. The highest mean of zone inhibition (15.0 mm) and lowest MIC (125 μg/ml) and MBC (250 μg/ml) values were observed in ethyl acetate extract of U. fasciata against B. subtilis. The ethyl acetate extract of the U. fasciata showed the presence of phytochemicals, terpenoids, tannins and phenolic compounds in U. fasciata than the other solvents extracts. The present results of the ethyl acetate extract of U. fasciata can be used as an antibacterial substance for the treatment of multi drug resistant bacterial infections

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