scholarly journals Bacteriophage Therapy for Critical Infections Related to Cardiothoracic Surgery

Antibiotics ◽  
2020 ◽  
Vol 9 (5) ◽  
pp. 232 ◽  
Author(s):  
Evgenii Rubalskii ◽  
Stefan Ruemke ◽  
Christina Salmoukas ◽  
Erin C. Boyle ◽  
Gregor Warnecke ◽  
...  

(1) Objective: Bacterial resistance to conventional antibiotic therapy is an increasingly significant worldwide challenge to human health. The objective is to evaluate whether bacteriophage therapy could complement or be a viable alternative to conventional antibiotic therapy in critical cases of bacterial infection related to cardiothoracic surgery. (2) Methods: Since September 2015, eight patients with multi-drug resistant or especially recalcitrant Staphylococcus aureus, Enterococcus faecium, Pseudomonas aeruginosa, Klebsiella pneumoniae, and Escherichia coli infections were treated with bacteriophage preparations as a therapy of last resort according to Article 37 of the Declaration of Helsinki. Patients had infections associated with immunosuppression after organ transplantation or had infections of vascular grafts, implanted medical devices, and surgical wounds. Individualized phage preparations were administered locally, orally, or via inhalation for different durations depending on the case. All patients remained on conventional antibiotics during bacteriophage treatment. (3) Results: Patients ranged in age from 13 to 66 years old (average 48.5 ± 16.7) with seven males and one female. Eradication of target bacteria was reached in seven of eight patients. No severe adverse side effects were observed. (4) Conclusions: Phage therapy can effectively treat bacterial infections related to cardiothoracic surgery when conventional antibiotic therapy fails.

Author(s):  
Alain Dublanchet ◽  
Olivier Patey ◽  
Hubert Mazure ◽  
Max Liddle ◽  
Anthony M. Smithyman

Bacteriophages, viruses that are widespread throughout the world, are highly specific for bacteria, usually of a single species and often of a particular strain. After being discovered and isolated 100 years ago, their use, called phage therapy, was instituted in medicine two years later and quickly used around the world to treat various bacterial infections. In the West, phage therapy was overshadowed in the second half of the 20th century by antibiotic therapy, which was then thought to be the definitive solution. But because of the increase in bacterial resistance to antibiotics, the idea of using bacteriophages in medicine has been reawakened. The innumerable observations reported over the years in the literature constitute an invaluable experience. We and some of our colleagues have, in the last decade treated some patients compassionately. With the available documentation and our own experience we discuss the potential indications and limitations of phage therapy. The observation of the increasing number of therapeutic failures in the announced perspective of a post-antibiotic era, we believe, that the introduction of bacteriophages into the therapeutic arsenal seems conceivable today to two preconditions: that their production as biologic drug meets current regulatory standards and that the benefit-risk assessment was conducted in a modern setting. Phage therapy could be applied as a substitution or supplement to antibiotic therapy under multiple circumstances in different modes, precise indications and limits.


Author(s):  
Behnam Sisakhtpour ◽  
Arezoo Mirzaei ◽  
Vajihe Karbasizadeh ◽  
Nafiseh Hosseini ◽  
Mehdi Shabani ◽  
...  

Abstract Background Widespread misuse of antibiotics caused bacterial resistance increasingly become a serious threat. Bacteriophage therapy promises alternative treatment strategies for combatting drug-resistant bacterial infections. In this study, we isolated and characterized a novel, potent lytic bacteriophage against multi-drug resistant (MDR) Acinetobacter baumannii and described the lytic capability and endolysin activity of the phage to evaluate the potential in phage therapy. Methods A novel phage, pIsf-AB02, was isolated from hospital sewage. The morphological analysis, its host range, growth characteristics, stability under various conditions, genomic restriction pattern were systematically investigated. The protein pattern of the phage was analyzed, and the endolysin activity of the phage was determined under the non-denaturing condition on SDS-PAGE. The optimal lytic titer of phage was assessed by co-culture of the phage with clinical MDR A. baumannii isolates. Finally, HeLa cells were used to examine the safety of the phage. Results The morphological analysis revealed that the pIsf-AB02 phage displays morphology resembling the Myoviridae family. It can quickly destroy 56.3% (27/48) of clinical MDR A. baumannii isolates. This virulent phage could decrease the bacterial host cells (from 108 CFU/ml to 103 CFU/ml) in 30 min. The optimum stability of the phage was observed at 37 °C. pH 7 is the most suitable condition to maintain phage stability. The 15 kDa protein encoded by pIsf-AB02 was detected to have endolysin activity. pIsf-AB02 did not show cytotoxicity to HeLa cells, and it can save HeLa cells from A. baumannii infection. Conclusion In this study, we isolated a novel lytic MDR A. baumannii bacteriophage, pIsf-AB02. This phage showed suitable stability at different temperatures and pHs, and demonstrated potent in vitro endolysin activity. pIsf-AB02 may be a good candidate as a therapeutic agent to control nosocomial infections caused by MDR A. baumannii.


2021 ◽  
Author(s):  
Ramasamy Palaniappan ◽  
Govindan Dayanithi

Bacteriophages are bacterial cell-borne viruses that act as natural bacteria killers and they have been identified as therapeutic antibacterial agents. Bacteriophage therapy is a bacterial disease medication that is given to humans after a diagnosis of the disease to prevent and manage a number of bacterial infections. The ability of phage to invade and destroy their target bacterial host cells determines the efficacy of bacteriophage therapy. Bacteriophage therapy, which can be specific or nonspecific and can include a single phage or a cocktail of phages, is a safe treatment choice for antibiotic-resistant and recurrent bacterial infections after antibiotics have failed. A therapy is a cure for health problems, which is administered after the diagnosis of the diseases in the patient. Such non-antibiotic treatment approaches for drug-resistant bacteria are thought to be a promising new alternative to antibiotic therapy and vaccination. The occurrence, biology, morphology, infectivity, lysogenic and lytic behaviours, efficacy, and mechanisms of bacteriophages’ therapeutic potentials for control and treatment of multidrug-resistant/sensitive bacterial infections are discussed. Isolation, long-term storage and recovery of lytic bacteriophages, bioassays, in vivo and in vitro experiments, and bacteriophage therapy validation are all identified. Holins, endolysins, ectolysins, and bacteriocins are bacteriophage antibacterial enzymes that are specific. Endolysins cause the target bacterium to lyse instantly, and hence their therapeutic potential has been explored in “Endolysin therapy.” Endolysins have a high degree of biochemical variability, with certain lysins having a wider bactericidal function than antibiotics, while their bactericidal activities are far narrower. Bacteriophage recombinant lysins (chimeric streptococcal–staphylococcal constructs) have high specificity for a single bacterial species, killing only that species (lysin (CF-301) is focused to kill methicillin resistant Staphylococcus aureus (MRSA)), while other lysins have a broader lytic activity, killing several different bacterial species and hence the range of bactericidal activity. New advances in medicine, food safety, agriculture, and biotechnology demonstrate molecular engineering, such as the optimization of endolysins for particular applications. Small molecule antibiotics are replaced by lysins. The chapter discusses the occurrences of lytic phage in pathogenic bacteria in animals and humans, as well as the possible therapeutic effects of endolysins-bacteriophage therapy in vivo and in vitro, demonstrating the utility and efficacy of the therapy. Further developments in the bacteriophage assay, unique molecular-phage therapy, or a cocktail of phage for the control of a broad range of drug-resistant bacteria-host systems can promote non-antibiotic treatment methods as a viable alternative to conventional antibiotic therapy.


Spinal Cord ◽  
2021 ◽  
Author(s):  
Lorenz Leitner ◽  
Shawna McCallin ◽  
Thomas M. Kessler

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.


Microbiome ◽  
2021 ◽  
Vol 9 (1) ◽  
Author(s):  
Andre Mu ◽  
Daniel McDonald ◽  
Alan K. Jarmusch ◽  
Cameron Martino ◽  
Caitriona Brennan ◽  
...  

Abstract Background Infectious bacterial diseases exhibiting increasing resistance to antibiotics are a serious global health issue. Bacteriophage therapy is an anti-microbial alternative to treat patients with serious bacterial infections. However, the impacts to the host microbiome in response to clinical use of phage therapy are not well understood. Results Our paper demonstrates a largely unchanged microbiota profile during 4 weeks of phage therapy when added to systemic antibiotics in a single patient with Staphylococcus aureus device infection. Metabolomic analyses suggest potential indirect cascading ecological impacts to the host (skin) microbiome. We did not detect genomes of the three phages used to treat the patient in metagenomic samples taken from saliva, stool, and skin; however, phages were detected using endpoint-PCR in patient serum. Conclusion Results from our proof-of-principal study supports the use of bacteriophages as a microbiome-sparing approach to treat bacterial infections.


2020 ◽  
Vol 2 (3) ◽  
pp. 78-79
Author(s):  
Roberto Badaro

Bacteriophages are viruses that infect and parasitize bacteria. The current increase in the incidence of antibiotic resistance in human bacteria has favoredthe study of phages as a therapeutic alternative (phage therapy). Phage therapy is defined as the administration of virulent phages directly to a patient to lyse the bacterial pathogen that is causing a clinically severe infection. The ideal route of administration and modification of bacteriopaghes genetically to deactivate bacterial resistance genes is the next future to antibiotic recovery sensitivity of MDR organisms.


Viruses ◽  
2021 ◽  
Vol 13 (9) ◽  
pp. 1809
Author(s):  
Joshua J. Iszatt ◽  
Alexander N. Larcombe ◽  
Hak-Kim Chan ◽  
Stephen M. Stick ◽  
Luke W. Garratt ◽  
...  

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.


2008 ◽  
Vol 29 (2) ◽  
pp. 96 ◽  
Author(s):  
Nina Chanishvili ◽  
Richard Sharp

The lysis of bacteria by bacteriophage was independently discovered by Frederick Twort and Felix d?Herelle but it was d?Herelle who proposed that bacteriophage might be applied to the control of bacterial diseases. Within the former Soviet Union (FSU), bacteriophage therapy was researched and applied extensively for the treatment of a wide range of bacterial infections. In the West, however, it was not explored with the same enthusiasm and was eventually discarded with the arrival of antibiotics. However, the increase in the incidence of multi-antibiotic-resistant bacteria and the absence of effective means for their control has led to increasing international interest in phage therapy and in the long experience of the Eliava Institute. The Eliava Institute of Bacteriophage, Microbiology and Virology (IBMV), which celebrates its 85th anniversary in 2008, was founded in Tbilisi in 1923 through the joint efforts of d?Herelle and the Georgian microbiologist, George Eliava.


2019 ◽  
Vol 7 (4) ◽  
pp. 1437-1447 ◽  
Author(s):  
Mengxue Ma ◽  
Xiangmei Liu ◽  
Lei Tan ◽  
Zhenduo Cui ◽  
Xianjin Yang ◽  
...  

Implant materials are prone to bacterial infections and cause serious consequences, while traditional antibiotic therapy has a long treatment cycle and even causes bacterial resistance.


2019 ◽  
Vol 98 (4) ◽  
pp. 137-144

The paper describes the basic sources and principles of antibiotic therapy in contemporary medicine in which the ability to treat bacterial infections may be lost. The main reason for that is the increasing resistance of bacterial pathogens to antibiotics. A possible solution is to implement a comprehensive program of antibiotic stewardship incorporating adequate consideration of indication and selection of antimicrobial agents including appropriate duration and way of administration. Another important component of the comprehensive approach to bacterial resistance and antibiotic therapy is adequately applied antibiotic prophylaxis in surgery.


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