scholarly journals Phage Therapy in the 21st Century: Is There Modern, Clinical Evidence of Phage-Mediated Efficacy?

2021 ◽  
Vol 14 (11) ◽  
pp. 1157
Author(s):  
Stephen T. Abedon ◽  
Katarzyna M. Danis-Wlodarczyk ◽  
Diana R. Alves
Keyword(s):  
Bacterial Infection ◽  
Bacterial Infections ◽  
Clinical Evidence ◽  
Phage Therapy ◽  
Clinical Success ◽  
Clinical Results ◽  
Clinical Settings ◽  
Infection Treatment ◽  
Double Blinded ◽  
Phage Treatment

Many bacteriophages are obligate killers of bacteria. That this property could be medically useful was first recognized over one hundred years ago, with 2021 being the 100-year anniversary of the first clinical phage therapy publication. Here we consider modern use of phages in clinical settings. Our aim is to answer one question: do phages serve as effective anti-bacterial infection agents when used clinically? An important emphasis of our analyses is on whether phage therapy-associated anti-bacterial infection efficacy can be reasonably distinguished from that associated with often coadministered antibiotics. We find that about half of 70 human phage treatment reports—published in English thus far in the 2000s—are suggestive of phage-mediated anti-bacterial infection efficacy. Two of these are randomized, double-blinded, infection-treatment studies while 14 of those studies, in our opinion, provide superior evidence of a phage role in observed treatment successes. Roughly three-quarters of these potentially phage-mediated outcomes are based on microbiological as well as clinical results, with the rest based on clinical success. Since many of these phage treatments are of infections for which antibiotic therapy had not been successful, their collective effectiveness is suggestive of a valid utility in employing phages to treat otherwise difficult-to-cure bacterial infections.

scholarly journals The Ecology of Phage Resistance: The Key to Successful Phage Therapy?

2020 ◽  
Author(s):  
Marissa Gittrich ◽  
Yunxiao Liu ◽  
Funing Tian ◽  
Audra Crouch ◽  
Ho Bin Jang ◽  
...  
Keyword(s):  
Antibiotic Resistance ◽  
Bacterial Infections ◽  
Natural Variation ◽  
Phage Therapy ◽  
Phage Resistance ◽  
Clinical Settings ◽  
Viral Sequence ◽  
Bacterial Gene ◽  
Microbial Host ◽  
Host Genes

: As antibiotic resistance undermines efforts to treat bacterial infections, phage therapy is being increasingly considered as an alternative in clinical settings and agriculture. However, a major concern in using phages is that pathogens will develop resistance to the phage. Due to the constant evolutionary pressure by phages, bacteria have evolved numerous mechanisms to block infection. If we determine the most common among them, we could use this knowledge to guide phage therapeutics. Here we compile data from 88 peer-reviewed studies where phage resistance was experimentally observed and linked to a bacterial gene, then assessed these data for patterns. In total, 141 host genes were identified to block infection against one or more of 80 phages (representing five families of the Caudovirales) across 16 microbial host genera. These data suggest that bacterial phage resistance is diverse, but even well-studied systems are understudied, and there are gaping holes in our knowledge of phage resistance across lesser-studied regions of microbial and viral sequence space. Fortunately, scalable approaches are newly available that, if broadly adopted, can provide data to power ecosystem-aware models that will guide harvesting natural variation towards designing effective, broadly applicable phage therapy cocktails as an alternative to antibiotics.

scholarly journals Targeted Stimuli-Responsive Mesoporous Silica Nanoparticles for Bacterial Infection Treatment

2020 ◽  
Vol 21 (22) ◽  
pp. 8605 ◽  
Author(s):  
Montserrat Colilla ◽  
María Vallet-Regí
Keyword(s):  
Mesoporous Silica ◽  
Bacterial Infection ◽  
Silica Nanoparticles ◽  
Bacterial Infections ◽  
Mesoporous Silica Nanoparticles ◽  
Antimicrobial Treatment ◽  
Stimuli Responsive ◽  
Comprehensive Description ◽  
Infection Treatment ◽  
External Stimuli

The rise of antibiotic resistance and the growing number of biofilm-related infections make bacterial infections a serious threat for global human health. Nanomedicine has entered into this scenario by bringing new alternatives to design and develop effective antimicrobial nanoweapons to fight against bacterial infection. Among them, mesoporous silica nanoparticles (MSNs) exhibit unique characteristics that make them ideal nanocarriers to load, protect and transport antimicrobial cargoes to the target bacteria and/or biofilm, and release them in response to certain stimuli. The combination of infection-targeting and stimuli-responsive drug delivery capabilities aims to increase the specificity and efficacy of antimicrobial treatment and prevent undesirable side effects, becoming a ground-breaking alternative to conventional antibiotic treatments. This review focuses on the scientific advances developed to date in MSNs for infection-targeted stimuli-responsive antimicrobials delivery. The targeting strategies for specific recognition of bacteria are detailed. Moreover, the possibility of incorporating anti-biofilm agents with MSNs aimed at promoting biofilm penetrability is overviewed. Finally, a comprehensive description of the different scientific approaches for the design and development of smart MSNs able to release the antimicrobial payloads at the infection site in response to internal or external stimuli is provided.

The Hematology of Bacterial Infections in Premature Infants

PEDIATRICS ◽  
1976 ◽  
Vol 57 (6) ◽  
pp. 839-853 ◽  
Author(s):  
A. Zipursky ◽  
J. Palko ◽  
R. Milner ◽  
G. I. Akenzua
Keyword(s):  
Bacterial Infection ◽  
Direct Effect ◽  
Premature Infants ◽  
Bacterial Infections ◽  
Clinical Evidence ◽  
Intravascular Coagulation ◽  
Qualitative Changes

A series of premature infants was studied for the presence of bacterial infection. On the basis of clinical evidence and bacteriological studies, they were divided into three groups in which sepsis was considered to be proven, possible, or unlikely. Band neutrophil counts were elevated most frequently in the "sepsis-proven" group and the elevation occurred usually within 24 hours of onset of signs of disease. Qualitative changes in neutrophils (Döhle bodies, toxic granulation, and vacuolization) were more frequent in the sepsis-proven group and, together with the band count, provided valuable techniques for the diagnosis of bacterial infections. Thrombocytopenia occurred frequently in the sepsis-proven group and seemed to result from increased utilization or destruction of platelets rather than failure of production. In such cases, evidence of intravascular coagulation was minimal and it was concluded that thrombocytopenia had resulted from a direct effect of the bacteria or its products on platelets and/or endothelium.

scholarly journals Adjunct phage treatment enhances the effectiveness of low antibiotic concentration against Staphylococcus aureus biofilms in vitro

2018 ◽  
Author(s):  
James Dickey ◽  
Véronique Perrot
Keyword(s):  
Staphylococcus Aureus ◽  
Bacterial Infections ◽  
Phage Therapy ◽  
Bacterial Biofilms ◽  
High Concentration ◽  
Antibiotic Concentration ◽  
Treatment Regimens ◽  
Resistant Strains ◽  
Phage Treatment

AbstractPhage therapy is drawing more interest as antibiotic resistance becomes an ever more serious threat to public health. Bacterial biofilms represent a major obstacle in the fight against bacterial infections as they are inherently refractory to many types of antibiotics. Treating biofilms with phage has shown promise in a handful of experimental and case studies. However, quantification of the effect of phage combined with antibiotics is needed to pave the way for larger clinical trials. Here we explore the effect of using phage in combination with a total of nine antibiotics, applied simultaneously or as a pretreatment before antibiotics are applied to in vitro biofilms of Staphylococcus aureus. Most antibiotics alone were ineffective at low concentration (2×MIC), but the addition of phage to treatment regimens led to substantial improvements in efficacy. At high concentration (10×MIC), antibiotics alone were effective, and in most cases the addition of phage to treatment regimens did not improve efficacy. Using phage with rifampin was also very effective at reducing the outgrowth of resistant strains during the course of treatment.

scholarly journals Radioimmunotherapy for solid tumors: spotlight on Glypican-1 as a radioimmunotherapy target

2021 ◽  
Vol 13 ◽  
pp. 175883592110229
Author(s):  
Dhanusha Sabanathan ◽  
Maria E. Lund ◽  
Douglas H. Campbell ◽  
Bradley J. Walsh ◽  
Howard Gurney
Keyword(s):  
Solid Tumors ◽  
Clinical Utility ◽  
Clinical Evidence ◽  
Clinical Success ◽  
Clinical Results ◽  
Current Treatment ◽  
Dose Fractionation ◽  
Treatment Paradigm ◽  
Potential Clinical Utility ◽  
Diagnosis Therapy

Radioimmunotherapy (i.e., the use of radiolabeled tumor targeting antibodies) is an emerging approach for the diagnosis, therapy, and monitoring of solid tumors. Often using paired agents, each targeting the same tumor molecule, but labelled with an imaging or therapeutic isotope, radioimmunotherapy has achieved promising clinical results in relatively radio-resistant solid tumors such as prostate. Several approaches to optimize therapeutic efficacy, such as dose fractionation and personalized dosimetry, have seen clinical success. The clinical use and optimization of a radioimmunotherapy approach is, in part, influenced by the targeted tumor antigen, several of which have been proposed for different solid tumors. Glypican-1 (GPC-1) is a heparan sulfate proteoglycan that is expressed in a variety of solid tumors, but whose expression is restricted in normal adult tissue. Here, we discuss the preclinical and clinical evidence for the potential of GPC-1 as a radioimmunotherapy target. We describe the current treatment paradigm for several solid tumors expressing GPC-1 and suggest the potential clinical utility of a GPC-1 directed radioimmunotherapy for these tumors.

Procalcitonin Testingreduce Unnecessary Antibiotic Use in Bacterial Infection

2019 ◽  
Vol 2 (1) ◽  
pp. 1-3
Author(s):  
Attabak Toofani Milani ◽  
Mahshid Mohammadian ◽  
Sadegh Rostaminasab ◽  
Roghayeh Paribananaem ◽  
Zohre Ahmadi ◽  
...  
Keyword(s):  
Antibiotic Therapy ◽  
Bacterial Infection ◽  
Diagnostic Test ◽  
Bacterial Infections ◽  
Intervention Studies ◽  
Antibiotic Use ◽  
Clinical Suspicion ◽  
Diagnostic Biomarker ◽  
Clinical Routine ◽  
Initial Rise

Conventional diagnostic test have limitations to deferential diagnosis in clinical suspicion ofbacterial infection cases, that in some cases lead to inappropriate antibiotic therapy and increases antibiotic resistance. A new diagnostic insight is procalcitonin (PCT) test to improve diagnosis of bacterial infections and to guide antibiotic therapy. Serum PCT levels are of useful test as a biomarker in patients with bacterial infections for several reasons. Initial rise of PCT levels due to bacterial infection, subsequent sequential PCT levels can be used to assess the effectiveness and duration of antibiotic therapy. Based on clinical researches results, in bacterial infections, promising good results obtained when use of PCT used as differential diagnostic test. But further intervention studies are needed before use of PCT in clinical routine tests. The goal of this review is to study the PCT reliability as infections diagnostic biomarker.

Cancer Immunology and CAR-T Cells: A Turning Point Therapeutic Approach in Colorectal Carcinoma with clinical insight

2020 ◽  
Vol 20 ◽  
Author(s):  
Suman K Ray ◽  
Yamini Meshram ◽  
Sukhes Mukherjee
Keyword(s):  
T Cells ◽  
Colorectal Carcinoma ◽  
Cancer Immunotherapy ◽  
Clinical Evidence ◽  
Ex Vivo ◽  
Clinical Success ◽  
Recent Decade ◽  
Molecular Immunology ◽  
Car T ◽  
Engineered T Cells

: Cancer immunotherapy endeavours in harnessing delicate strength and specificity of immune system for therapy of different malignancies including colorectal carcinoma. The recent challenge for cancer immunotherapy is to practice and develop molecular immunology tools to create tactics that efficiently and securely boost antitumor reactions. After several attempts of deceptive outcomes, the wave has lastly altered and immunotherapy has become a clinically confirmed treatment for several cancers. Immunotherapeutic methods include administration of antibodies or modified proteins that either block cellular activity or co-stimulate cells through immune control pathways, cancer vaccines, oncolytic bacteria, ex vivo activated adoptive transfer of T cells and natural killer cells. Engineered T cells are used to produce a chimeric antigen receptor (CAR) to treat different malignancies including colorectal carcinoma in a recent decade. Despite considerable early clinical success, CAR-T therapies are associated with some side effects and sometimes display minimal efficacy. It gives special emphasis on the latest clinical evidence with CAR-T technology and also other related immunotherapeutic methods with promising performance, and highlighted how this therapy can affect therapeutic outcome and next upsurge as a key clinical aspect of colorectal carcinoma. In this review we recapitulate the current developments produced to improve the efficacy and specificity of CAR-T therapies in colon cancer.

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 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 Comparison of the clinical outcomes of skin bridge loop ileostomy and traditional loop ileostomy in patients with low rectal cancer

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Hui Ye ◽  
Shujuan Huang ◽  
Jie Yu ◽  
Qichang Zhou ◽  
Changlei Xi ◽  
...  
Keyword(s):  
Rectal Cancer ◽  
Low Anterior Resection ◽  
Clinical Evidence ◽  
Loop Ileostomy ◽  
Loop Group ◽  
Clinical Results ◽  
Low Rectal Cancer ◽  
Analog Scale ◽  
Traditional Group ◽  
Bridge Group

AbstractTo compare the clinical results of patients with low rectal cancer who underwent skin bridge loop ileostomy and traditional loop ileostomy, and provide clinical evidence for choosing a better ostomy method. We retrospectively collected data of 118 patients with rectal cancer who underwent low anterior resection and loop ileostomy. To investigate the patients characteristics, postoperative stoma-related complications and the frequency of exchanged ostomy bags. The differences of these indicators between the two groups of patients who underwent skin bridge loop ileostomy and traditional loop ileostomy were compared. The Visual Analog Scale (VAS) score of the skin bridge loop ileostomy group was lower than that of the traditional ileostomy loop group (P < 0.05). The skin bridge group had a lower Discoloration, Erosion, Tissue overgrowth (DET) score and incidence of mucocutaneous separation than the traditional group at the 1st and 2nd weeks after operation (P < 0.05). The average number of weekly exchanged ostomy bags was significantly less in the skin bridge group than in the traditional group within 4 weeks after surgery (P < 0.05). Our experience demonstrates that the skin bridge loop ileostomy may significantly reduce early postoperative stoma-related complications, the frequency of exchanged ostomy bags and patients’ medical costs after discharge.

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