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International Journal of Molecular... Apr 2022Bacteriophages offer an alternative for the treatment of multidrug-resistant bacterial diseases as their mechanism of action differs from that of antibiotics. However,... (Review)
Review
Bacteriophages offer an alternative for the treatment of multidrug-resistant bacterial diseases as their mechanism of action differs from that of antibiotics. However, their application in the clinical field is limited to specific cases of patients with few or no other alternative therapies. This systematic review assesses the effectiveness and safety of phage therapy against multidrug-resistant bacteria through the evaluation of studies published over the past decade. To that end, a bibliographic search was carried out in the PubMed, Science Direct, and Google Scholar databases. Of the 1500 studies found, 27 met the inclusion criteria, with a total of 165 treated patients. Treatment effectiveness, defined as the reduction in or elimination of the bacterial load, was 85%. Except for two patients who died from causes unrelated to phage therapy, no serious adverse events were reported. This shows that phage therapy could be an alternative treatment for patients with infections associated with multidrug-resistant bacteria. However, owing to the phage specificity required for the treatment of various bacterial strains, this therapy must be personalized in terms of bacteriophage type, route of administration, and dosage.
Topics: Anti-Bacterial Agents; Bacteria; Bacterial Infections; Bacteriophages; Drug Resistance, Multiple, Bacterial; Humans; Phage Therapy
PubMed: 35562968
DOI: 10.3390/ijms23094577 -
GMS Hygiene and Infection Control 2022: In recent years, resistance to antibiotics has become a global threat, and alternatives to antibiotics have become an area of research. The main alternative methods... (Review)
Review
: In recent years, resistance to antibiotics has become a global threat, and alternatives to antibiotics have become an area of research. The main alternative methods are briefly described in this review. However, the main focus is bacteriophage-related therapy. Bacteriophages are viruses which, due to the production of the enzyme endolysin, are able to kill bacterial host cells. Bacteriophage therapies have a long tradition. Their potential to function as antibiotics lies in their bactericidal activity and specificity in killing bacteria without infecting or affecting eukaryotic cells. : To systematically review the outcomes of bacteriophage therapy in patients with bacterial infections. : The MEDLINE, EMBASE, Web of Science and CENTRAL databases were searched electronically using search terms referring to bacteriophages, endolysins and antimicrobial resistance. After the literature was screened for their titles and abstracts, full-text reviews considering inclusion/exclusion criteria were performed. Data concerning patients with bacterial infections, treatment with either bacteriophages or its enzyme endolysin and their outcomes were extracted and analysed. : Thirteen publications were identified that met all inclusion criteria. Data extraction shows that bacteriophages or endolysins have the potential to combat bacterial infections and significantly reduce inflammatory mediators. However, 3 out of 4 randomized controlled trials revealed that there was no significant difference between phage/endolysin treated patients and control group. Significant clinical improvements were seen in cohort and case studies. A few minor side effects were reported. : Although there are countries in which bacteriophages are prescribed as an alternative to established antibiotics, this valuable experience has yet to be examined sufficiently in clinical trials conducted to modern standards. Despite improvements in symptoms shown in the reviewed clinical trials, the infection and the bacteria themselves were rarely completely eradicated. Therefore, no definite answer can be given as to effectiveness, and further clinical trials are necessary.
PubMed: 35111563
DOI: 10.3205/dgkh000404 -
Systematic Reviews Oct 2023Food-borne diseases are a global public health issue with 1 in 10 people falling ill after eating contaminated food every year. In response, the food industry has... (Meta-Analysis)
Meta-Analysis Review
Food-borne diseases are a global public health issue with 1 in 10 people falling ill after eating contaminated food every year. In response, the food industry has implemented several new pathogen control strategies, such as biotechnological tools using the direct application of bacteriophages for biological control. We have undertaken a systematic review and meta-analysis that evaluated the efficiency of patented phages as a biological control for food-borne pathogens and determined the physical-chemical characteristics of the antimicrobial effect. Included and excluded criteria was developed. Included criteria: Phage patent files with an application in biological control on food and scientific articles and book chapters that used phages patented for food biological control. Excluded criteria: Patent documents, scientific articles, and book chapters that included phage therapy in humans, animals, and biological control on plants but did not have an application on food were not considered in our study. The systematic analysis identified 77 documents, 46 scientific articles, and 31 documents of patents and 23 articles was included in the meta-analysis. Listeria monocytogenes and Salmonella sp. comprised most of the targets identified in the screening, so that we focused on these strains to do the meta-analysis. There are a total of 383 and 192 experiments for Listeria and Salmonella phages for quantitative data analysis.Indexing databases for the bibliographic search (Scopus, Web of Science (WoS) and PubMed (Medline) were addressed by an automated script written in Python 3 Python Core Team (2015) and deposited on GitHub ( https://github.com/glenjasper ).A random-effects meta-analysis revealed (i) significant antimicrobial effect of Listeria phages in apple, apple juice, pear, and pear juice, (ii) significant antimicrobial effect of Salmonella phages in eggs, apple, and ready-to-eat chicken, (iii) no heterogeneity was identified in either meta-analysis, (iv) publication bias was detected for Listeria phages but not for Salmonella phages. (v) ListShield and Felix01 phages showed the best result for Listeria and Salmonella biological control, respectively, (vi) concentration of phage and bacteria, time and food had significant effect in the biological control of Listeria, (vii) temperature and time had a significant effect on the antimicrobial activity of Salmonella phages. The systematic review and meta-analyses to determine the efficiency of bacteriophages previously patented against pathogenic bacteria on dairy products, meat, fruits and vegetables. Besides, the discovering of key factors for efficacy, so that future applications of phage biotechnology in foods can be optimally deployed.
Topics: Anti-Infective Agents; Bacteriophages; Foodborne Diseases; Listeria monocytogenes; Meat
PubMed: 37898821
DOI: 10.1186/s13643-023-02352-9 -
Molecular Biotechnology Apr 2022The CRISPR-Cas genome editing system is an intrinsic property of a bacteria-based immune system. This employs a guide RNA to detect and cleave the PAM-associated target... (Review)
Review
The CRISPR-Cas genome editing system is an intrinsic property of a bacteria-based immune system. This employs a guide RNA to detect and cleave the PAM-associated target DNA or RNA in subsequent infections, by the invasion of a similar bacteriophage. The discovery of Cas systems has paved the way to overcome the limitations of existing genome editing tools. In this review, we focus on Cas proteins that are available for gene modifications among which Cas9, Cas12a, and Cas13 have been widely used in the areas of medicine, research, and diagnostics. Since CRISPR has been already proven for its potential research applications, the next milestone for CRISPR will be proving its efficacy and safety. In this connection, we systematically review recent advances in exploring multiple variants of Cas proteins and their modifications for therapeutic applications.
Topics: CRISPR-Cas Systems; DNA; Gene Editing; RNA; RNA, Guide, CRISPR-Cas Systems
PubMed: 34741732
DOI: 10.1007/s12033-021-00422-8 -
Der Orthopade Feb 2022The treatment of bone and prosthesis infections remains difficult despite modern treatment concepts. Further tools for the improvement of treatment outcome are...
BACKGROUND
The treatment of bone and prosthesis infections remains difficult despite modern treatment concepts. Further tools for the improvement of treatment outcome are desirable. Preclinical studies provide promising evidence of the efficacy of bacteriophages for the treatment of bone and joint infections.
OBJECTIVES
The present work provides a systematic review of the clinical application of bacteriophages for the treatment of bone and joint infections.
MATERIALS AND METHODS
A systematic search was performed in PubMed to identify primary clinical data on the use of phage therapy in patients with bone and joint infection.
RESULTS
Eight case reports and three case series were included in the study. Indications for phage therapy were periprosthetic joint infection (n = 12, 52.2%), fracture-related infection (n = 9, 39.1%), osteomyelitis (n = 1, 4.4%) and sacroiliac joint infection after cement augmentation of a metastasis (n = 1, 4.4%). Interventions were heterogeneous; phages were administered intravenously, injected intraoperatively into the joint, applied locally intraoperatively, or administered via drains. In combination with antibiotic therapy, complete infection eradication was achieved in 18 patients (78.3%). No side effects were reported in 91.3% of patients.
CONCLUSION
Bacteriophages represent a promising treatment option for bone and prosthesis infections in combination with antibiotic therapy. Future clinical trials with a higher level of evidence are required for the successful translation of bacteriophage therapy into clinical practice.
Topics: Anti-Bacterial Agents; Arthritis, Infectious; Bacteriophages; Humans; Osteomyelitis; Phage Therapy; Prosthesis-Related Infections
PubMed: 34499212
DOI: 10.1007/s00132-021-04148-y -
A systematic review and modeling of the effect of bacteriophages on O157:H7 reduction in vegetables.Heliyon Dec 2023Prevention and control of food pathogens are important for public health and O157:H7 infections are known as one of the most important food-borne bacterial diseases... (Review)
Review
Prevention and control of food pathogens are important for public health and O157:H7 infections are known as one of the most important food-borne bacterial diseases transmitted to humans. Vegetables can be a major source of O157:H7 bacteria. Bacteriophages have been considered in recent years as a natural method for controlling pathogens with minimal damage to the quality of vegetables. The performance of these natural antimicrobial agents is affected by various factors including time, temperature, phage and bacterial dose, method of phage application and origin of phages. The aim of the present study was to conduct a systematic review of the works that have examined the effect of different factors to reduce O157:H7 bacteria by its specific phages and model their effect. In our study, 10 articles were chosen after applying the inclusion and exclusion criteria mentioned in the methodology. The multivariate regression results showed that time, temperature, and method of phage application revealed a positive influence on the phage function, and with each unit of increase, the O157:H7 reduction increases by 0.4 %, 3 % and 0.94 % respectively, and 6 % for phage dose, but not statistically significant (P = 0.44). In addition, commercial-type phages were more effective than wild-type phages and this result was statistically significant (Beta = 0.99; P = 0.001). The results of this study indicate that the various factors, such as temperature, time, method of phage application and type of vegetables can play an important role to reduce O157:H7 in vegetables.
PubMed: 38058426
DOI: 10.1016/j.heliyon.2023.e22961 -
European Journal of Clinical... Aug 2023Bacteriophages (phages) are very promising biological agents for the prevention and control of bacterial biofilms. However, little is known about the parameters that can... (Review)
Review
Bacteriophages (phages) are very promising biological agents for the prevention and control of bacterial biofilms. However, little is known about the parameters that can influence the efficacy of phages on biofilms. This systematic review provides a summary and analysis of the published data about the use of phages to control pre-formed biofilms in vitro, suggesting recommendations for future experiments in this area. A total of 68 articles, containing data on 605 experiments addressing the efficacy of phages to control biofilms in vitro were included, after a search conducted in Web of Science, Embase, and Medline (PubMed). The data collected from each experiment included information about biofilm growth conditions, phage characteristics, treatment conditions and biofilm reduction. In most cases, biofilms were formed in the surface of microtiter plates (82.5%); the median time for biofilm formation was 24 h, as is the median treatment duration. Quantification of biofilm biomass (52.6%), viable cells (25.5%) and metabolic activity (17.9%) were the most common biofilm assessment methods. Correlation analysis revealed that some phage parameters can influence the treatment outcome: higher phage concentrations were strongly associated with improved biofilm control, leading to higher levels of biofilm reduction, and phages with higher burst sizes and shorter latent periods seem to be the best candidates to control biofilms in vitro. However, the great variability of the methodologies used prompts the need for the development of standardized in vitro methodologies to characterize phage/biofilm interactions and to assess the efficacy of phages to control biofilms.
Topics: Humans; Bacteriophages; Biofilms
PubMed: 37407800
DOI: 10.1007/s10096-023-04638-1 -
Antibiotics (Basel, Switzerland) Nov 2020Bacterial resistance to antibiotics has catalysed interest in alternative antimicrobial strategies. Bacteriophages (phages) are viruses of bacteria with a long history... (Review)
Review
Bacterial resistance to antibiotics has catalysed interest in alternative antimicrobial strategies. Bacteriophages (phages) are viruses of bacteria with a long history of successful therapeutic use. Phage therapy is a promising antibacterial strategy for infections with a biofilm component, including recalcitrant bone and joint infections, which have significant social, financial and human impacts. Here, we report a systematic review of the safety and efficacy of phage therapy for the treatment of bone and joint infections. Three electronic databases were systematically searched for articles that reported primary data about human phage therapy for bone and joint infections. Two authors independently assessed study eligibility and performed data extraction. Seventeen reports were eligible for inclusion in this review, representing the treatment of 277 patients. A cautionary, crude, efficacy estimate revealed that 93.1% ( = 258/277) achieved clinical resolution, 3.3% ( = 9/277) had improvement and 3.6% ( = 10/277) showed no improvement. Seven of the nine reports that directly commented on the safety of phage therapy did not express safety concerns. The adverse effects reported in the remaining two were not severe and were linked to the presence of contaminating endotoxins and pre-existing liver pathology in a patient treated with high-titre intravenous phage therapy. Three other reports, from 1940-1987, offered general comments on the safety of phage therapy and documented adverse effects consistent with endotoxin co-administration concomitant with the use of raw phage lysates. Together, the reports identified by this review suggest that appropriately purified phages represent a safe and highly efficacious treatment option for complex and intractable bone and joint infections.
PubMed: 33182795
DOI: 10.3390/antibiotics9110795 -
Clinical Microbiology and Infection :... Dec 2022The intestinal microbiome provides a reservoir for antibiotic resistance genes (ARGs). The neonatal microbiome is more susceptible to disturbance from external factors... (Review)
Review
BACKGROUND
The intestinal microbiome provides a reservoir for antibiotic resistance genes (ARGs). The neonatal microbiome is more susceptible to disturbance from external factors than the established microbiome in later life.
OBJECTIVES
In this review, we systematically summarize studies which investigated the intestinal resistome in neonates.
DATA SOURCES
MEDLINE and Embase databases were searched.
STUDY ELIGIBILITY CRITERIA
We included original studies which investigated ARGs in stool or rectal swabs in neonates using molecular diagnostics.
METHODS OF DATA SYNTHESIS
Two authors independently extracted data, which were summarized in tables.
RESULTS
Our search identified 2701 studies, of which 23 (22 cohorts) were included. The studies show that the neonatal intestine harbours a high abundance and variety of ARGs, even in the absence of direct antibiotic exposure. The most commonly found ARGs confer resistance to aminoglycosides, β-lactams, macrolides, tetracyclines, or multidrug resistance. There is evidence that ARGs can be transferred from mothers to neonates. Interestingly, however, compared to mothers, neonates are reported to have a higher abundance of ARGs. One likely reason for this is the bacterial phylogenetic composition with a high abundance of Gammaproteobacteria in neonatal stool. Factors that have been associated with a higher abundance of ARGs are intrapartum and neonatal antibiotic use. Breastfeeding and neonatal probiotic use have been associated with a lower abundance of ARGs. Antibiotics during pregnancy, delivery mode, or sex are reported to have little effect. However, this might be because studies were underpowered and because it is difficult to account for effect modifiers.
CONCLUSIONS
The neonatal intestine seems to have a lower colonization resistance, which could make it easier for antibiotic-resistant populations to establish themselves. Future studies will help in the development of evidence-based interventions to modulate the abundance of ARGs in neonates, for example, by the use of pre- and probiotics and bacteriophages.
Topics: Infant, Newborn; Pregnancy; Female; Humans; Phylogeny; Drug Resistance, Microbial; Anti-Bacterial Agents; Bacteria; Intestines
PubMed: 35868586
DOI: 10.1016/j.cmi.2022.07.014 -
Antibiotics (Basel, Switzerland) Sep 2022Trials of phage therapy have not consistently reported efficacy. This contrasts with promising efficacy rates from a sizeable and compelling body of observational... (Review)
Review
Trials of phage therapy have not consistently reported efficacy. This contrasts with promising efficacy rates from a sizeable and compelling body of observational literature. This systematic review explores the reasons why many phage trials have not demonstrated efficacy. Four electronic databases were systematically searched for safety and/or efficacy trials of phage therapy. Sixteen trials of phage therapy were included, in which 378 patients received phage. These were divided into historical (pre-2000; N = 3; = 76) and modern (post-2000; N = 13; = 302) trials. All 13 modern trials concluded that phage therapy was safe. Six of the 13 modern trials were exclusively safety trials. Seven modern trials investigated both safety and efficacy; efficacy was observed in two. Two of three historical trials did not comment on safety, while adverse effects in the third likely reflected the use of phage preparations contaminated with bacterial debris. None of the historical trials contained evidence of efficacy. The evidence from trials is that phage therapy is safe. For efficacy to be observed a therapeutic amount of the right phage(s) must be delivered to the right place to treat infections containing enough susceptible bacterial cells. Trials that have not demonstrated efficacy have not fulfilled one or more elements of this principle.
PubMed: 36289998
DOI: 10.3390/antibiotics11101340