Nanotechnology in the Diagnosis and Treatment of Antibiotic-Resistant Infections

The development of antimicrobial resistance (AMR), along with the relative reduction in the production of new antimicrobials, significantly limits the therapeutic options in infectious diseases. Thus, novel treatments, especially in the current era, where AMR is increasing, are urgently needed. There are several ongoing studies on non-classical therapies for infectious diseases, such as bacteriophages, antimicrobial peptides, and nanotechnology, among others. Nanomaterials involve materials on the nanoscale that could be used in the diagnosis, treatment, and prevention of infectious diseases. This review provides an overview of the applications of nanotechnology in the diagnosis and treatment of infectious diseases from a clinician’s perspective, with a focus on pathogens with AMR. Applications of nanomaterials in diagnosis, by taking advantage of their electrochemical, optic, magnetic, and fluorescent properties, are described. Moreover, the potential of metallic or organic nanoparticles (NPs) in the treatment of infections is also addressed. Finally, the potential use of NPs in the development of safe and efficient vaccines is also reviewed. Further studies are needed to prove the safety and efficacy of NPs that would facilitate their approval by regulatory authorities for clinical use

Bacteriophages in Infectious Diseases and Beyond—A Narrative Review

The discovery of antibiotics has revolutionized medicine and has changed medical practice, enabling successful fighting of infection. However, quickly after the start of the antibiotic era, therapeutics for infectious diseases started having limitations due to the development of antimicrobial resistance. Since the antibiotic pipeline has largely slowed down, with few new compounds being produced in the last decades and with most of them belonging to already-existing classes, the discovery of new ways to treat pathogens that are resistant to antibiotics is becoming an urgent need. To that end, bacteriophages (phages), which are already used in some countries in agriculture, aquaculture, food safety, and wastewater plant treatments, could be also used in clinical practice against bacterial pathogens. Their discovery one century ago was followed by some clinical studies that showed optimistic results that were limited, however, by some notable obstacles. However, the rise of antibiotics during the next decades left phage research in an inactive status. In the last decades, new studies on phages have shown encouraging results in animals. Hence, further studies in humans are needed to confirm their potential for effective and safe treatment in cases where there are few or no other viable therapeutic options. This study reviews the biology and applications of phages for medical and non-medical uses in a narrative manner

CRISPR therapeutic tools for complex genetic disorders and cancer (Review)

One of the fundamental discoveries in the field of biology is the ability to modulate the genome and to monitor the functional outputs derived from genomic alterations. In order to unravel new therapeutic options, scientists had initially focused on inducing genetic alterations in primary cells, in established cancer cell lines and mouse models using either RNA interference or cDNA overexpression or various programmable nucleases [zinc finger nucleases (ZNF), transcription activator-like effector nucleases (TALEN)]. Even though a huge volume of data was produced, its use was neither cheap nor accurate. Therefore, the clustered regularly interspaced short palindromic repeats (CRISPR) system was evidenced to be the next step in genome engineering tools. CRISPR-associated protein 9 (Cas9)-mediated genetic perturbation is simple, precise and highly efficient, empowering researchers to apply this method to immortalized cancerous cell lines, primary cells derived from mouse and human origins, xenografts, induced pluripotent stem cells, organoid cultures, as well as the generation of genetically engineered animal models. In this review, we assess the development of the CRISPR system and its therapeutic applications to a wide range of complex diseases (particularly distinct tumors), aiming at personalized therapy. Special emphasis is given to organoids and CRISPR screens in the design of innovative therapeutic approaches. Overall, the CRISPR system is regarded as an eminent genome engineering tool in therapeutics. We envision a new era in cancer biology during which the CRISPR-based genome engineering toolbox will serve as the fundamental conduit between the bench and the bedside; nonetheless, certain obstacles need to be addressed, such as the eradication of side-effects, maximization of efficiency, the assurance of delivery and the elimination of immunogenicity

Role of the CRISPR system in controlling gene transcription and monitoring cell fate (Review)

Even though the accrual of transcripts is implicated in distinct disease states, our knowledge regarding their functional role remains obscure. The CRISPR system has surged at the forefront of genome engineering tools in the field of RNA modulation. In the present review, we discuss some exciting applications of the CRISPR system, including the manipulation of RNA sequences, the visualization of chromosomal loci in living cells and the modulation of transcription. The CRISPR system has been documented to be very reliable and specific in altering gene expression, via leveraging inactive catalytically dead CRISPR-associated protein 9 (Cas9). In the present review, the CRISPR system is presented as an eminent tool for the meticulous analysis of gene regulation, loci mapping and complex pathways

Infective Endocarditis by Moraxella Species: A Systematic Review

Moraxella catarrhalis is the most clinically relevant species among Moraxella spp. For decades, it was considered to be part of the normal human flora in the upper respiratory tract. However, since the late 1970s, considerable evidence has proposed that M. catarrhalis is an important pathogen in the human respiratory tract. Even though Infective Endocarditis (IE) is rarely caused by Moraxella spp., these infections can be problematic due to the lack of experience in their management. The aim of this study was to systematically review all published cases of IE by Moraxella spp. A systematic review of PubMed, Scopus and Cochrane library (through 8 December 2021) for studies providing epidemiological, clinical, microbiological data as well as treatment data and outcomes of IE by Moraxella spp. was performed. A total of 27 studies, containing data for 31 patients, were included. A prosthetic valve was present in 25.8%. Mitral valve was the most commonly infected site. Fever, sepsis and embolic phenomena were the most common clinical presentations. Cephalosporins, aminoglycosides, aminopenicillins and penicillin were the most commonly used antimicrobials. Overall mortality was 12.9%

Infective Endocarditis by <em>Moraxella</em> Species: A Systematic Review

Moraxella catarrhalis is the most clinically relevant species among Moraxella spp. For decades, it was considered to be part of the normal human flora in the upper respiratory tract. However, since the late 1970s, considerable evidence has proposed that M. catarrhalis is an important pathogen in the human respiratory tract. Even though Infective Endocarditis (IE) is rarely caused by Moraxella spp., these infections can be problematic due to the lack of experience in their management. The aim of this study was to systematically review all published cases of IE by Moraxella spp. A systematic review of PubMed, Scopus and Cochrane library (through 8 December 2021) for studies providing epidemiological, clinical, microbiological data as well as treatment data and outcomes of IE by Moraxella spp. was performed. A total of 27 studies, containing data for 31 patients, were included. A prosthetic valve was present in 25.8%. Mitral valve was the most commonly infected site. Fever, sepsis and embolic phenomena were the most common clinical presentations. Cephalosporins, aminoglycosides, aminopenicillins and penicillin were the most commonly used antimicrobials. Overall mortality was 12.9%

<i>Kocuria</i> Species Infections in Humans—A Narrative Review

Kocuria species are catalase-positive and coagulase-negative Gram-positive coccoid bacteria that belong to the family Micrococcaceae, order Actinomycetales, and class Actinobacteria. Even though they may be relatively rare, they have been increasingly reported as the causes of human infections lately. The present study aims to review all published cases of Kocuria spp. infections in humans reporting data on epidemiology, microbiology, antimicrobial susceptibility, antimicrobial treatment, and mortality. A narrative review was performed based on a search of Pubmed and Scopus databases in the literature. In total, 73 studies provided data on 102 patients with Kocuria spp. infections. The mean age of patients was 47 years, and 68.3% were male. The most common types of infection were bacteremia (36.3%), skin and soft tissue infection (18.6%), endophthalmitis (15.7%), infective endocarditis (13.7%), and peritonitis (11.8%), most commonly peritoneal–dialysis-associated. The most frequently isolated species was K. kristinae (46.1%), and antimicrobial resistance was lower for vancomycin (7%) and tetracyclines (6.7%). Vancomycin (47%), cephalosporins (39.6%), and quinolones (36.6%) were the most commonly used antimicrobials. The empirical antimicrobial treatment of Kocuria spp. infections should include vancomycin as long as antimicrobial susceptibility results are pending. The infection outcome mainly depends on the type of infection and is higher for infective endocarditis. Endophthalmitis is associated with increased rates of low visual acuity after treatment

Infective Endocarditis by <i>Yersinia</i> Species: A Systematic Review

Yersinia spp. are non-spore-forming Gram-negative bacilli. They comprise only three species known to cause disease in humans, namely Y. pestis, Y. enterocolitica and Y. pseudotuberculosis. Since infective endocarditis (IE) is rarely caused by Yersinia, the management of these infections can be problematic due to the lack of experience. The purpose of this study was to systematically review all published cases of IE by Yersinia species in the literature. A systematic review of PubMed, Scopus and Cochrane Library (through 1 November 2020) for studies providing epidemiological, clinical and microbiological information as well as data on treatment and outcomes of IE caused by Yersinia species was performed. A total of 12 studies, containing data of 12 patients, were included. A prosthetic valve was present in 17% of patients. The mitral valve was the most commonly infected site, followed by the aortic valve. Fever, sepsis and embolic phenomena were common clinical signs, followed by heart failure. Aminoglycosides, cephalosporins and quinolones were the most commonly used antimicrobials. Clinical cure was noted in 83%, while overall mortality was 17%. This systematic review describes IE by Yersinia and provides information on patients’ epidemiology, clinical signs and the related therapeutic strategies and outcomes