scholarly journals Assessment of the microbiome during bacteriophage therapy in combination with systemic antibiotics to treat a case of staphylococcal device infection

Microbiome ◽  
2021 ◽  
Vol 9 (1) ◽  
Author(s):  
Andre Mu ◽  
Daniel McDonald ◽  
Alan K. Jarmusch ◽  
Cameron Martino ◽  
Caitriona Brennan ◽  
...  
Keyword(s):  
Bacterial Infections ◽  
Phage Therapy ◽  
Ecological Impacts ◽  
Skin Microbiome ◽  
Bacteriophage Therapy ◽  
Bacterial Diseases ◽  
Device Infection ◽  
Global Health Issue ◽  
Serious Bacterial Infections ◽  
Systemic Antibiotics

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.

scholarly journals Bacteriophage therapy: experience from the Eliava Institute, Georgia

2008 ◽  
Vol 29 (2) ◽  
pp. 96 ◽  
Author(s):  
Nina Chanishvili ◽  
Richard Sharp
Keyword(s):  
Soviet Union ◽  
Former Soviet Union ◽  
Bacterial Infections ◽  
Phage Therapy ◽  
Effective Means ◽  
Resistant Bacteria ◽  
Bacteriophage Therapy ◽  
Antibiotic Resistant ◽  
Bacterial Diseases ◽  
Wide Range

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.

scholarly journals Phage Therapy for a Multidrug-Resistant Acinetobacter baumannii Craniectomy Site Infection

2018 ◽  
Vol 5 (4) ◽  
Author(s):  
Stephanie LaVergne ◽  
Theron Hamilton ◽  
Biswajit Biswas ◽  
M Kumaraswamy ◽  
R T Schooley ◽  
...  
Keyword(s):  
Clinical Trials ◽  
Antibiotic Resistance ◽  
Acinetobacter Baumannii ◽  
Alternative Treatment ◽  
Bacterial Infections ◽  
Phage Therapy ◽  
Treatment Options ◽  
Multidrug Resistant ◽  
Site Infection ◽  
Bacteriophage Therapy

Abstract In the era of antibiotic resistance, alternative treatment options for multidrug-resistant bacterial infections are being explored. We present a case of multidrug-resistant Acinetobacter baumannii infection treated with bacteriophages. Clinical trials are needed to further investigate bacteriophage therapy as an option to treat multidrug-resistant bacterial infections.

scholarly journals Bacteriophage Rescue Therapy of a Vancomycin-Resistant Enterococcus faecium Infection in a One-Year-Old Child following a Third Liver Transplantation

Viruses ◽  
2021 ◽  
Vol 13 (9) ◽  
pp. 1785
Author(s):  
Kevin Paul ◽  
Maya Merabishvili ◽  
Ronen Hazan ◽  
Martin Christner ◽  
Uta Herden ◽  
...  
Keyword(s):  
Enterococcus Faecium ◽  
Bacterial Infections ◽  
Phage Therapy ◽  
Rescue Therapy ◽  
Close Relation ◽  
Neutralization Assay ◽  
Vancomycin Resistant Enterococcus ◽  
Bacteriophage Therapy ◽  
Vancomycin Resistant ◽  
One Year

Phage therapy is an experimental therapeutic approach used to target multidrug-resistant bacterial infections. A lack of reliable data with regard to its efficacy and regulatory hurdles hinders a broad application. Here we report, for the first time, a case of vancomycin-resistant Enterococcus faecium abdominal infection in a one-year-old, critically ill, and three times liver transplanted girl, which was successfully treated with intravenous injections (twice per day for 20 days) of a magistral preparation containing two Enterococcus phages. This correlated with a reduction in baseline C-reactive protein (CRP), successful weaning from mechanical ventilation and without associated clinical adverse events. Prior to clinical use, phage genome was sequenced to confirm the absence of genetic determinants conferring lysogeny, virulence or antibiotic resistance, and thus their safety. Using a phage neutralization assay, no neutralizing anti-phage antibodies in the patient’s serum could be detected. Vancomycin-susceptible E. faecium isolates were identified in close relation to phage therapy and, by using whole-genome sequencing, it was demonstrated that vancomycin-susceptible E. faecium emerged from vancomycin-resistant progenitors. Covering a one year follow up, we provide further evidence for the feasibility of bacteriophage therapy that can serve as a basis for urgently needed controlled clinical trials.

scholarly journals Bacteriophages as Alternatives to Antibiotics in Clinical Care

Antibiotics ◽  
2019 ◽  
Vol 8 (3) ◽  
pp. 138 ◽  
Author(s):  
Danitza Romero-Calle ◽  
Raquel Guimarães Benevides ◽  
Aristóteles Góes-Neto ◽  
Craig Billington
Keyword(s):  
Clinical Trials ◽  
Bacterial Infections ◽  
Ad Hoc ◽  
Phage Therapy ◽  
Clinical Care ◽  
Bacterial Diseases ◽  
Immunological Responses ◽  
Regulatory Guidance ◽  
Review Reports ◽  
New Treatments

Antimicrobial resistance is increasing despite new treatments being employed. With a decrease in the discovery rate of novel antibiotics, this threatens to take humankind back to a “pre-antibiotic era” of clinical care. Bacteriophages (phages) are one of the most promising alternatives to antibiotics for clinical use. Although more than a century of mostly ad-hoc phage therapy has involved substantial clinical experimentation, a lack of both regulatory guidance standards and effective execution of clinical trials has meant that therapy for infectious bacterial diseases has yet to be widely adopted. However, several recent case studies and clinical trials show promise in addressing these concerns. With the antibiotic resistance crisis and urgent search for alternative clinical treatments for bacterial infections, phage therapy may soon fulfill its long-held promise. This review reports on the applications of phage therapy for various infectious diseases, phage pharmacology, immunological responses to phages, legal concerns, and the potential benefits and disadvantages of this novel treatment.

scholarly journals Phage Therapy in the Treatment of Infectious Diseases: An Overview

2021 ◽  
Vol 11 (1) ◽  
pp. 126-131
Author(s):  
Mahsa Jalili ◽  
Nastaran Ansari ◽  
Somaye Bakhtiari ◽  
Farid Azizi Jalilian
Keyword(s):  
Antibiotic Resistance ◽  
Infectious Diseases ◽  
Bacterial Infections ◽  
Phage Therapy ◽  
New Drugs ◽  
Bacterial Diseases ◽  
New Methods ◽  
Bacterial Contaminant ◽  
New Perspective ◽  
Therapy Studies

Today, we are facing the spread of antibiotic resistance in various microbial communities. Also, researchers are using new methods to replace conventional treatments to prevent chronic bacterial infections. Hence, the used of phages or bacterial contaminant particles are now used as an effective method in the treatment of many infectious diseases. Several studies have suggested that the use of bacteriophages is effective in treating some bacterial diseases. Therefore, the present study was performed to evaluate phage therapy studies against infections caused by bacterial infections. The use of bacteriophages as new targets in the treatment of bacterial diseases restricts the development of infectious diseases. Bacteriophages can provide a new perspective in the development of new drugs to reduce the rate of bacterial infections. Also, it seems more research should be done in this field and more developed techniques should be used to evaluation of new phages.

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 ◽  
...  
Keyword(s):  
Antibiotic Therapy ◽  
Bacterial Infections ◽  
Bacterial Resistance ◽  
Phage Therapy ◽  
Cardiothoracic Surgery ◽  
Drug Resistant ◽  
Bacteriophage Therapy ◽  
Surgical Wounds ◽  
Implanted Medical Devices ◽  
Conventional Antibiotics

(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.

scholarly journals Quantitative Models of Phage-Antibiotics Combination Therapy

2019 ◽  
Author(s):  
Rogelio A. Rodriguez-Gonzalez ◽  
Chung-Yin Leung ◽  
Benjamin K. Chan ◽  
Paul E. Turner ◽  
Joshua S. Weitz
Keyword(s):  
Combination Therapy ◽  
Bacterial Infections ◽  
Phage Therapy ◽  
System Level ◽  
Global Public Health ◽  
Bacteriophage Therapy ◽  
Therapeutic Success ◽  
Health Crisis ◽  
Bacterial Mutants

AbstractThe spread of multi-drug resistant (MDR) bacteria is a global public health crisis. Bacteriophage therapy (or “phage therapy”) constitutes a potential alternative approach to treat MDR infections. However, the effective use of phage therapy may be limited when phage-resistant bacterial mutants evolve and proliferate during treatment. Here, we develop a nonlinear population dynamics model of combination therapy that accounts for the system-level interactions between bacteria, phage and antibiotics for in-vivo application given an immune response against bacteria. We simulate the combination therapy model for two strains of Pseudomonas aeruginosa, one which is phage-sensitive (and antibiotic resistant) and one which is antibiotic-sensitive (and phage-resistant). We find that combination therapy outperforms either phage or antibiotic alone, and that therapeutic effectiveness is enhanced given interaction with innate immune responses. Notably, therapeutic success can be achieved even at sub-inhibitory concentrations of antibiotics, e.g., ciprofloxacin. These in-silico findings provide further support to the nascent application of combination therapy to treat MDR bacterial infections, while highlighting the role of innate immunity in shaping therapeutic outcomes.

scholarly journals Therapy of Experimental Pseudomonas Infections with a Nonreplicating Genetically Modified Phage

2004 ◽  
Vol 48 (10) ◽  
pp. 3817-3822 ◽  
Author(s):  
Steven Hagens ◽  
André Habel ◽  
Uwe von Ahsen ◽  
Alexander von Gabain ◽  
Udo Bläsi
Keyword(s):  
Survival Rate ◽  
Bacterial Infections ◽  
Phage Therapy ◽  
Lethal Dose ◽  
Survival Rates ◽  
Genetically Engineered ◽  
Lytic Phage ◽  
Bacteriophage Therapy ◽  
Genes Encoding

ABSTRACT Bacteriophage therapy of bacterial infections has received renewed attention owing to the increasing prevalence of antibiotic-resistant pathogens. A side effect of many antibiotics as well as of phage therapy with lytic phage is the release of cell wall components, e.g., endotoxins of gram-negative bacteria, which mediate the general pathological aspects of septicemia. Here we explored an alternative strategy by using genetically engineered nonreplicating, nonlytic phage to combat an experimental Pseudomonas aeruginosa infection. An export protein gene of the P. aeruginosa filamentous phage Pf3 was replaced with a restriction endonuclease gene. This rendered the Pf3 variant (Pf3R) nonreplicative and concomitantly prevented the release of the therapeutic agent from the target cell. The Pf3R phage efficiently killed a wild-type host in vitro, while endotoxin release was kept to a minimum. Treatment of P. aeruginosa infections of mice with Pf3R or with a replicating lytic phage resulted in comparable survival rates upon challenge with a minimal lethal dose of 3. However, the survival rate after phage therapy with Pf3R was significantly higher than that with the lytic phage upon challenge with a minimal lethal dose of 5. This higher survival rate correlated with a reduced inflammatory response elicited by Pf3R treatment relative to that with the lytic phage. Therefore, this study suggests that the increased survival rate of Pf3R-treated mice could result from reduced endotoxin release. Thus, the use of a nonreplicating modified phage for the delivery of genes encoding proteins toxic to bacterial pathogens may open up a new avenue in antimicrobial therapy.

An Overview on the Application of Bacteriophage Therapy in Combating Antibiotics Resistance: A Review

2021 ◽  
Vol 6 (1) ◽  
pp. 113-119
Author(s):  
A. F. Aishat ◽  
◽  
S. B. Manga ◽  
I. O. Obaroh ◽  
R. J. Bioku ◽  
...  
Keyword(s):  
Bacterial Infections ◽  
Phage Therapy ◽  
Multidrug Resistant ◽  
Antibiotics Resistance ◽  
Therapeutic Approaches ◽  
Bacteriophage Therapy ◽  
Advantages And Disadvantages ◽  
Naturally Occurring ◽  
Bacterial Viruses ◽  
Novel Therapeutic

The practice of phage therapy, which uses bacterial viruses (phages) to treat bacterial infections, has been around for almost a century. The universal decline in the effectiveness of antibiotics has generated renewed interest in revisiting this practice. Conventionally, phage therapy relies on the use of naturally-occurring phages to infect and lyse bacteria at the site of infection. Biotechnological advances have further expanded the repertoire of potential phage therapeutics to include novel strategies using bioengineered phages and purified phage lytic proteins. Current research on the use of phages and their lytic proteins, specifically against multidrug resistant bacterial infections, suggests phage therapy has the potential to be used as either an alternative or a supplement to antibiotic treatments. Antibacterial therapies, whether phage- or antibioticbased, have relative advantages and disadvantages accordingly. Many considerations must be taken into account when designing novel therapeutic approaches for preventing and treating bacterial infections. Although much is still unknown about the interactions between phage, bacteria, and human host, the time to take phage therapy seriously seems to be rapidly approaching Keywords: Antibiotic resistance; Antimicrobial; Bacteriophage; Biofilms; Multidrug resistance; Phage; Phage safety; Therapy.

scholarly journals Growing Trend of Fighting Infections in Aquaculture Environment—Opportunities and Challenges of Phage Therapy

Antibiotics ◽  
2020 ◽  
Vol 9 (6) ◽  
pp. 301
Author(s):  
Justyna D. Kowalska ◽  
Joanna Kazimierczak ◽  
Patrycja M. Sowińska ◽  
Ewelina A. Wójcik ◽  
Andrzej K. Siwicki ◽  
...  
Keyword(s):  
Bacterial Resistance ◽  
Phage Therapy ◽  
Antimicrobial Treatment ◽  
Bacteriophage Therapy ◽  
Promising Alternative ◽  
Bacterial Diseases ◽  
Treatment And Prevention ◽  
The Status ◽  
Antibiotics Use ◽  
The Right

Phage therapy, a promising alternative to antimicrobial treatment of bacterial diseases, is getting more and more popular, especially due to the rising awareness of antibiotic resistance and restrictions in antibiotics’ use. During recent years, we observed a growing trend of bacteriophages’ application in aquaculture, which in each year reports high losses due to bacterial diseases. This review provides an update of the status of bacteriophage therapy for the treatment and prevention of infections in the aquatic environment. As it is still mostly in the scientific stage, there are a few constraints that may prevent effective therapy. Therefore, specific characteristics of bacteriophages, that can act in favor or against their successful use in treatment, were described. We underlined aspects that need to be considered: specificity of phages, bacterial resistance, safety, immune response of the host organism, formulation, administration and stability of phage preparations as well as bacteriophages’ influence on the environment. The biggest challenge to overcome is finding the right balance between the desired and problematic characteristics of bacteriophages. Finally, regulatory approval challenges may be encountered by bacteriophage manufacturers. Even though there are still some technical constraints connected with the global use of bacteriophage therapy, it was concluded that it can be successfully applied in aquaculture.

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