Colistin resistance mechanisms in Gram-negative bacteria: a Focus on Escherichia coli.

Multidrug-resistant (MDR) Escherichia coli strains have rapidly increased worldwide, and effective antibiotic therapeutic options are becoming more restricted. As a polymyxin antibiotic, colistin has a long history of usage, and it is used as a final line of treatment for severe infections by Gram-negative bacteria (GNB) with high-level resistance. However, its application has been challenged by the emergence of E. coli colistin resistance. Hence, determining the mechanism that confers colistin resistance is crucial for monitoring and controlling the dissemination of colistin-resistant E. coli strains. This comprehensive review summarizes colistin resistance mechanisms in E. coli strains and concentrates on the history, mode of action, and therapeutic implications of colistin. We have mainly focused on the fundamental mechanisms of colistin resistance that are mediated by chromosomal or plasmid elements and discussed major mutations in the two-component systems (TCSs) genes and plasmids that transmit the mobilized colistin resistance resistant genes in E. coli strains.

Viral vector and nucleic acid vaccines against COVID-19: A narrative review.

After about 2 years since the first detection of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections in Wuhan, China, in December 2019 that resulted in a worldwide pandemic, 6.2 million deaths have been recorded. As a result, there is an urgent need for the development of a safe and effective vaccine for coronavirus disease 2019 (COVID-19). Endeavors for the production of effective vaccines inexhaustibly are continuing. At present according to the World Health Organization (WHO) COVID-19 vaccine tracker and landscape, 153 vaccine candidates are developing in the clinical phase all over the world. Some new and exciting platforms are nucleic acid-based vaccines such as Pfizer Biontech and Moderna vaccines consisting of a messenger RNA (mRNA) encoding a viral spike protein in host cells. Another novel vaccine platform is viral vector vaccine candidates that could be replicating or nonreplicating. These types of vaccines that have a harmless viral vector like adenovirus contain a genome encoding the spike protein of SARS-CoV-2, which induces significant immune responses. This technology of vaccine manufacturing has previously been used in many human clinical trials conducted for adenoviral vector-based vaccines against different infectious agents, including Ebola virus, Zika virus, HIV, and malaria. In this paper, we have a review of nucleic acid-based vaccines that are passing their phase 3 and 4 clinical trials and discuss their efficiency and adverse effects.

A Comprehensive Review of the Protein Subunit Vaccines Against COVID-19.

Two years after severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), in December 2019, the first infections were identified in Wuhan city of China. SARS-CoV-2 infection caused a global pandemic and accordingly, 5.41 million deaths worldwide. Hence, developing a safe and efficient vaccine for coronavirus disease 2019 (COVID-19) seems to be an urgent need. Attempts to produce efficient vaccines inexhaustibly are ongoing. At present time, according to the COVID-19 vaccine tracker and landscape provided by World Health Organization (WHO), there are 161 vaccine candidates in different clinical phases all over the world. In between, protein subunit vaccines are types of vaccines that contain a viral protein like spike protein or its segment as the antigen assumed to elicit humoral and cellular immunity and good protective effects. Previously, this technology of vaccine manufacturing was used in a recombinant influenza vaccine (RIV4). In the present work, we review protein subunit vaccines passing their phase 3 and 4 clinical trials, population participated in these trials, vaccines manufactures, vaccines efficiency and their side effects, and other features of these vaccines.

Cabotegravir/Rilpivirine: the last FDA-approved drug to treat HIV.

INTRODUCTION: The development of long-acting (LA) drugs has changed the management of common medical conditions for human replication immunodeficiency virus (HIV). Cabenuva (cabotegravir/Rilpivirine) is the first LA antiretroviral injectable drug composed of nano-formulation of cabotegravir (CAB) and rilpivirine (RPV). AREAS COVERED: In this review article, we aim to have a brief overview of results of major clinical trials that administrated Cabotegravir/Rilpivirine for patients considering the efficacy and safety profiles. Moreover, we discuss about CAB and RPV chemical structure, mechanism of action, activity against drug-sensitive and -resistant HIV, and pharmacodynamics/pharmacokinetics properties. EXPERT OPINION: Based on the results of the ATLAS and FLAIR trials, Cabotegravir/Rilpivirine regimen once-monthly has shown equal effectivity to oral combination antiretroviral therapy (cART) in maintaining HIV-1 suppression in patients. Furthermore, ATLAS-2 M study revealed the non-inferiority of Cabotegravir/Rilpivirine regimen every 8 weeks compared to every 4 weeks. The injectable LA ART reduces the number of treatment intake as well as increases adherence, especially in patients with HIV-related stigma. Administration of extended-release agents probably minimize the risk of treatment-related toxicity and resistance related to sub-optimal adherence to oral ART, so Cabotegravir/Rilpivirine can be suggested as a suitable alternative for HIV infection control in current era.

An overview on inactivated and live-attenuated SARS-CoV-2 vaccines.

After about 2 years since severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), first infections were detected in Wuhan city of China in December 2019, which was followed by a worldwide pandemic with a record of 5.41 million deaths. Due to urgent need for the development of a safe and effective vaccine for coronavirus disease 2019 (COVID-19), attempts for producing efficient vaccines are inexhaustibly continuing. According to a report by the World Health Organization (WHO) on COVID-19 vaccine tracker and landscape, there are 149 vaccine candidates all over the world. Inactivated SARS-CoV-2 vaccines as a conventional vaccine platform consist of whole virus particles grown in cell culture and inactivated by chemicals. Because of benefits such as antigenic similarity to real virion inducing humoral and cellular immune responses and ease for transport and storage, these vaccines, including the vaccines produced by Bharat Biotech, Sinopharm, and Sinovac, are in use at large scales. In this study, we have a review on inactivated SARS-CoV-2 vaccines that are passing their phase 3 and 4 clinical trials, population which was included in the trials, vaccine producers, the efficiency, adverse effects, and components of vaccines, and other vaccine features.