Antibody-Antibiotic Conjugates: A Comprehensive Review on Their Therapeutic Potentials Against BacterialInfections.

INTRODUCTION: Antibodies are significant agents in the immune system and have proven to be effective in treating bacterial infections. With the advancement of antibody engineering in recent decades, antibody therapy has evolved widely. AIM: This review aimed to investigate a new method as a therapeutic platform for the treatment of bacterial infections and explore the novel features of this method in conferring pathogen specificity to broad-spectrum antibiotics. MATERIAL AND METHODS: A literature review was conducted addressing the following topics about antibody-antibiotic conjugates (AACs): (1) structure and mechanism of action; (2) clinical effectiveness; (3) advantages and disadvantages. RESULT: Antibody conjugates are designed to build upon the progress made in the development of monoclonal antibodies for the treatment of diseases. Despite the growing emergence of antibiotic resistance among pathogenic bacteria worldwide, novel antimicrobials have not been sufficiently expanded to combat the global crisis of antibiotic resistance. A recently developed strategy for the treatment of infectious diseases is the use of AACs, which are specifically activated only in host cells. CONCLUSION: A novel therapeutic AAC employs an antibody to deliver the antibiotic to the bacteria. The AACs can release potent antibacterial components that unconjugated forms may not exhibit with an appropriate therapeutic index. This review highlights how this science has guided the design principles of an impressive AAC and discusses how the AAC model promises to enhance the antibiotic effect against bacterial infections.

Rapid eradication of vancomycin and methicillin-resistant Staphylococcus aureus by MDP1 antimicrobial peptide coated on photocrosslinkable chitosan hydrogel: in vitro antibacterial and in silico molecular docking studies.

Introduction: Antibiotic resistance and weak bioavailability of antibiotics in the skin due to systemic administration leads to failure in eradication of vancomycin- and methicillin-resistant Staphylococcus aureus (VRSA and MRSA)-associated wound infections and subsequent septicemia and even death. Accordingly, this study aimed at designing a photocrosslinkable methacrylated chitosan (MECs) hydrogel coated by melittin-derived peptide 1 (MDP1) that integrated the antibacterial activity with the promising skin regenerative capacity of the hydrogel to eradicate bacteria by burst release strategy. Methods: The MECs was coated with MDP1 (MECs-MDP1), characterized, and the hydrogel-peptide interaction was evaluated by molecular docking. Antibacterial activities of MECs-MDP1 were evaluated against VRSA and MRSA bacteria and compared to MECs-vancomycin (MECs-vanco). Antibiofilm activity of MECs-MDP1 was studied by our novel 'in situ biofilm inhibition zone (IBIZ)' assay, and SEM. Biocompatibility with human dermal fibroblast cells (HDFs) was also evaluated. Results and Discussion: Molecular docking showed hydrogen bonds as the most interactions between MDP1 and MECs at a reasonable affinity. MECs-MDP1 eradicated the bacteria rapidly by burst release strategy whereas MECs-vanco failed to eradicate them at the same time intervals. Antibiofilm activity of MECs-MDP1 were also proved successfully. As a novel report, molecular docking analysis has demonstrated that MDP1 covers the structure of MECs and also binds to lysozyme with a reasonable affinity, which may explain the inhibition of lysozyme. MECs-MDP1 was also biocompatible with human dermal fibroblast skin cells, which indicates its safe future application. The antibacterial properties of a photocrosslinkable methacrylated chitosan-based hydrogel coated with MDP1 antimicrobial peptide were successfully proved against the most challenging antibiotic-resistant bacteria causing nosocomial wound infections; VRSA and MRSA. Molecular docking analysis revealed that MDP1 interacts with MECs mainly through hydrogen bonds with reasonable binding affinity. MECs-MDP1 hydrogels eradicated the planktonic state of bacteria by burst release of MDP1 in just a few hours whereas MECs-vanco failed to eradicate them. inhibition zone assay showed the anti-biofilm activity of the MECs-MDP1 hydrogel too. These findings emphasize that MECs-MDP1 hydrogel would be suggested as a biocompatible wound-dressing candidate with considerable and rapid antibacterial activities to prevent/eradicate VRSA/MRSA bacterial wound infections.

Prevalence of linezolid resistance in Streptococcus pneumoniae isolates: a systematic review and meta-analysis.

Aim: This study aimed to understand the current level of linezolid (LNZ) resistance in Streptococcus pneumoniae isolates reported over the past 10 years. Material & methods: An electronic search was conducted for the following keywords: ((Streptococcus pneumoniae [title/abstract]) OR (Pneumococcus [title/abstract]) OR (Pneumococci [title/abstract]) AND (linezolid [title/abstract]) OR (Zyvox [title/abstract])) OR (Zyvoxid [title/abstract])). Result: Out of all the studies, 80 had a cross-sectional design, while 11 followed a cohort approach. The prevalence of LNZ resistance among S. pneumoniae isolates ranged from 0% to 4.86%. Discussion: Urgent, high-powered, randomized, controlled trials with participants from endemic regions are needed to gain a comprehensive understanding of the impact on and significance of LNZ treatment to patients.

Designing a novel multi-epitopes pan-vaccine against SARS-CoV-2 and seasonal influenza: in silico and immunoinformatics approach.

The merger of COVID-19 and seasonal influenza infections is considered a potentially serious threat to public health. These two viral agents can cause extensive and severe lower and upper respiratory tract infections with lung damage with host factors. Today, the development of vaccination has been shown to reduce the risk of hospitalization and mortality from the COVID-19 virus and influenza epidemics. Therefore, this study contributes to an immunoinformatics approach to producing a vaccine that can elicit strong and specific immune responses against COVID-19 and influenza A and B viruses. The NCBI, GISAID, and Uniprot databases were used to retrieve sequences. Linear B cell, Cytotoxic T lymphocyte, and Helper T lymphocyte epitopes were predicted using the online servers. Population coverage of MHC I epitopes worldwide for SARS-CoV-2, Influenza virus H3N2, H3N2, and Yamagata/Victoria were 99.93%, 68.67%, 68.38%, and 85.45%, respectively. Candidate epitopes were linked by GGGGS, GPGPG, and KK linkers. Different epitopes were permutated several times to form different peptides and then screened for antigenicity, allergenicity, and toxicity. The vaccine construct was analyzed for physicochemical properties, conformational B-cell epitopes, interaction with Toll-like receptors, and IFN-gamma-induced. Immune stimulation response of final construct was evaluated using C-IMMSIM. Eventually, the final construct sequence was codon-optimized for Escherichia coli K12 and Homo sapiens to design a multi-epitope vaccine and mRNA vaccine. In conclusion, due to the variable nature of SARS-CoV-2 and influenza proteins, the design of a multi-epitope vaccine can protect against all their standard variants, but laboratory validation is required.Communicated by Ramaswamy H. Sarma.

Nitrofurantoin: properties and potential in treatment of urinary tract infection: a narrative review.

Nitrofurantoin (NF), a wide-spectrum antibiotic accessible since 1953, is utilized widely to treat urinary tract infections as it usually stays active against drug-resistant uropathogen. The use of Nitrofurantoin has increased exponentially since new guidelines have repositioned it as first-line therapy for uncomplicated lower urinary tract infection (UTI). To, although fluoroquinolones are usually used to re-evaluate the first- and second-line therapies for treating uncomplicated UTI, their level of utilization is thought to be inappropriately excessive and will eventually have a detrimental impact; thus, we hypothesize that NF might be the best choice for this condition, because of its low frequency of utilization and its high susceptibility in common UTI pathogens. It can be concluded from this review that NF can be considered as the most effective drug in the treatment of acute urinary infection, but due to the long-term side effects of this drug, especially in elderly patients, it is essential to introduce some criteria for prescribing NF in cases of chronic UTI.

High burden of MDR, XDR, PDR, and MBL producing Gram negative bacteria causing infections in Kermanshah health centers during 2019-2020.

Background and Objectives: Microorganisms producing Metallo-Beta-Lactamase (MBL) are a threat and cause of concern as they have become one of the most feared resistance mechanisms. This study was designed to explore the prevalence of MBL production in clinical isolates of Gram negative bacteria using phenotypic MBL detection. Materials and Methods: A total of 248 isolates were collected from various clinical samples and were evaluated for carbapenem resistance and MBL production. All strains were screened for MBL production using Double Disk Confirmatory Test (DDCT). Results: The results of screening for MBL production using phenotypic disk diffusion method showed that in the 85 isolates were carbapenemase positive; including, 10 (16.1%) Klebsiella pneumoniae, 9 (14.5%) Escherichia coli, 58 (93.6%) Acinetobacter baumannii, and 8 (12.9%) Pseudomonas aeruginosa isolates. Also, 83 (97.6) Carbapenemase-producing isolates were resistant to at least four classes of antimicrobials (MDR). Conclusion: A. baumannii was the most common carbapenem resistant bacterium in medical centers in Kermanshah. Significant multiple drug resistance (MDR) incidence was observed compared to different classes of antibiotics.

Global prevalence of Clostridioides difficile in 17,148 food samples from 2009 to 2019: a systematic review and meta-analysis.

BACKGROUND: Clostridioides (Clostridium) difficile is an important infectious pathogen, which causes mild-to-severe gastrointestinal infections by creating resistant spores and producing toxins. Spores contaminated foods might be one of the most significant transmission ways of C. difficile-associated infections. This systematic review and meta-analysis study were conducted to investigate the prevalence of C. difficile in food. METHODS: Articles that published the prevalence of C. difficile in food in PubMed, Web of Science, and Scopus databases were retrieved using selected keywords between January 2009 and December 2019. Finally, 17,148 food samples from 60 studies from 20 countries were evaluated. RESULTS: The overall prevalence of C. difficile in various foods was 6.3%. The highest and lowest levels of C. difficile contamination were detected to seafood (10.3%) and side dishes (0.8%), respectively. The prevalence of C. difficile was 4% in cooked food, 6.2% in cooked chicken and 10% in cooked seafood. CONCLUSIONS: There is still little known concerning the food-borne impact of C. difficile, but the reported contamination might pose a public health risk. Therefore, to improve the food safety and prevent contamination with C. difficile spores, it is necessary to observe hygienic issues during foods preparation, cooking and transfer.

Ebanga™: The most recent FDA-approved drug for treating Ebola.

Ebolavirus (EBOV) is a virulent pathogen that causes Ebola virus disease (EVD), which is a life-threatening human condition with a fatality rate of up to 90%. Since the first outbreak in Africa in 1976, several outbreaks and epidemics of EBOV have occurred across the globe. While EVD is recognized as a serious threat to human health and outbreaks occur almost every year, the treatment options for the disease are limited. In designing therapeutic strategies against EBOV infection, viral structural proteins, such as glycoprotein (GP), could be an excellent target for neutralizing the virus. According to the latest research, GP-specific antibodies are the most efficient post-exposure treatments for EVD. Ansuvimab-zykl, i.e., mAb114 (Ebanga™), is a recent FDA-approved human immunoglobulin monoclonal antibody targeting EBOV GP. This review provides a brief overview of the pharmacological effects and safety profile of ansuvimab in clinical trials and provides insights into the precise mechanism of this new drug for treating EVD.

Evaluation of Brucellosis Vaccines: A Comprehensive Review.

Brucellosis is a bacterial zoonosis caused by Brucella spp. which can lead to heavy economic losses and severe human diseases. Thus, controlling brucellosis is very important. Due to humans easily gaining brucellosis from animals, animal brucellosis control programs can help the eradication of human brucellosis. There are two popular vaccines against animal brucellosis. Live attenuated Brucella abortus strain 19 (S19 vaccine) is the first effective and most extensively used vaccine for the prevention of brucellosis in cattle. Live attenuated Brucella melitensis strain Rev.1 (Rev.1 vaccine) is the most effective vaccine against caprine and ovine brucellosis. Although these two vaccines provide good immunity for animals against brucellosis, the expense of persistent serological responses is one of the main problems of both vaccines. The advantages and limitations of Brucella vaccines, especially new vaccine candidates, have been less studied. In addition, there is an urgent need for new strategies to control and eradicate this disease. Therefore, this narrative review aims to present an updated overview of the available different types of brucellosis vaccines.

Comparison of clinical, radiological and laboratory findings in discharged and dead patients with COVID-19.

Background: Coronavirus disease 19 (COVID-19) is a recently described infectious disease caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Iran was the first country where the SARS-Cov-2 was detected in the Middle East. In the current study, we aimed to evaluate the clinical, radiological and laboratory findings in hospitalized COVID-19 confirmed cases in Iran. Methods: The clinical manifestations, radiological data, laboratory findings, and the underlying diseases of the patients with COVID-19 were obtained from electronic medical records. Next, this information was compared in discharged and dead patients. Results: Overall, 4028 patients with COVID-19 including 3088 discharged, 778 dead, and 162 still hospitalized patients were enrolled in this study. The highest percentage of people who recovered (55%) was between 30 and 60 years old and the highest percentage of deaths (74.4%) was more than 60 years old. Based on demographic data, 50.05% were female and 49.95% were male. Clinical evaluations revealed that dyspnea (56.9%), cough (31.4%) and fever (17.8%) were the most manifestations. Comorbidities were significantly higher in the dead group. Laboratory analysis revealed abnormalities in lymphocyte count (LYM), erythrocyte sedimentation rate (ESR), and inflammatory biomarkers such as C-reactive protein (CRP). The most prevalent computed tomography (CT) scan data were ground-glass opacity (GGO) (30.5%) and consolidation (9.4%). Conclusions: Laboratory parameters and clinical and radiological findings help to evaluate the follow-up of the disease in patients. Age and comorbidities are factors that predispose people to COVID-19. Further research is needed to evaluate the effects of various factors on the progression of COVID-19 infection.

Antecedentes: La enfermedad por coronavirus de 19 (COVID-19) es una enfermedad infecciosa recientemente descrita causada por el síndrome respiratorio agudo severo por coronavirus 2 (SARS-CoV-2). Irán fue el primer país de Oriente Medio donde se detectó SARS-Cov-2. En el estudio actual, nuestro objetivo fue evaluar los hallazgos clínicos, radiológicos y de laboratorio en pacientes hospitalizados con confirmación de COVID-19 en Irán. Métodos: Se obtuvieron las manifestaciones clínicas, los datos radiológicos, los hallazgos de laboratorio y las enfermedades subyacentes de los registros clínicos electrónicos. Seguidamente, se comparó esta información con los pacientes dados de alta y fallecidos. Resultados: A nivel global, se incluyó en este estudio a 4.028 pacientes con COVID-19, de los cuales 3.088 habían recibido el alta, 778 habían fallecido, y 162 seguían hospitalizados. El mayor porcentaje de recuperaciones (55%) se produjo entre las personas de 30 a 60 años, y el mayor porcentaje de muertes (74,4%) se dio en los mayores de 60 años. Sobre la base de los datos demográficos, el 50,05% fueron mujeres y el 49,95% varones. Las evaluaciones clínicas revelaron que la disnea (56,9%), la tos (31,4%) y la fiebre (17,8%) fueron las manifestaciones más prevalentes. Las comorbilidades fueron significativamente más elevadas en el grupo de fallecidos. Las analíticas revelaron anomalías en cuanto a recuento linfocitario, tasa de sedimentación eritrocitaria (ESR), y biomarcadores inflamatorios tales como proteína C reactiva (PCR). Los datos procedentes de la tomografía computarizada (TC) fueron opacidad en vidrio esmerilado (GGO) (30,5%) y consolidación (9,4%). Conclusiones: Los parámetros de laboratorio y los hallazgos clínicos y radiológicos ayudan a evaluar el seguimiento de la enfermedad en los pacientes. La edad y las comorbilidades son factores que predisponen a las personas a la COVID-19. Es necesaria más investigación para evaluar los efectos de los diversos factores en la progresión de la infección por COVID-19.

Investigation of drug regimens and treatment outcome in patients with Mycobacterium Simiae: a systematic review.

INTRODUCTION: Mycobacterium simiae (M.simiae), a non-tuberculous mycobacterium (NTM), rare causes infection including localized pulmonary to disseminated disease in immunocompromised patients. An optimal pharmacological management practice has not yet been defined for this infection. This study investigates drug regimens and treatment outcomes in patients with M. simiae to describe different drug regimen with the therapeutic response. AREAS COVERED: The three databases PubMed, Scopus, and Web of science were systematically searched from June 1994 to June 2021 to retrieve relevant articles. The inclusion criterion included studies, which reported treatment outcomes in patients with M. simiae infections. Treatment success was defined as the achievement of culture conversion, and the improvement of the symptoms and radiologic signs among the patients. EXPERT OPINION: Data of 223 patients were retrieved from 40 studies. Duration of the treatment regimens used in different studies ranged from 2 to 12 months. The most common treatment regimens administered for M. simiae infection were as follows: clarithromycin, rifampin, ethambutol, moxifloxacin, or ciprofloxacin and amikacin plus cotrimoxazole or pyrazinamide in some regimens. Macrolides, such as clarithromycin, combined with quinolones (such as moxifloxacin) and TMP/SMX, which are used in combination, had the most significant effect on eliminating the pulmonary signs of M. simiae.

COVID-19 in HIV-positive patients: A systematic review of case reports and case series.

INTRODUCTION: Coronavirus disease 2019 (COVID-19) and acquired immune deficiency syndrome (AIDS) are two viral diseases for which there are currently no definitive treatments. Nowadays, because of the health system's focus on the COVID-19 epidemic, the control of human immunodeficiency virus (HIV) has received less attention. In this review, we will discuss the characteristics of COVID-19 in HIV-positive patients. MATERIAL AND METHODS: Using the PRISMA guideline, the databases of Scopus, PubMed, and Web of Science were searched systematically from January 1, 2019 to February 24, 2021. The following keywords were used: "Human Immunodeficiency Virus," "acquired immune deficiency syndrome," "HIV," "AIDS," "COVID-19," "severe acute respiratory syndrome coronavirus 2," "novel coronavirus," "SARS-CoV-2," "nCoV disease," "SARS2," and "2019-nCoV disease." RESULTS: Twenty-one percent of studies were conducted in the USA (n = 13), 16% in China (n = 10), and 13% in Italy (n = 8), respectively. The majority of the patients were men (74.3%). Tenofovir disoproxil fumarate was used in 47.4% of patients, emtricitabine in 58.4%, and lamivudine in 34.8% to treat HIV. Symptoms of HIV patients with COVID-19 included coughing (81.3%), fever (62.8%), and dyspnea (60%). Hydroxychloroquine (39.34%) and azithromycin (36.58%) were the common treatment options for COVID-19. The total death rate in HIV-positive patients with COVID-19 was about 9%. CONCLUSION: In the current systematic review, we demonstrated that HIV-positive patients co-infected with COVID-19 have high comorbidity of hypertension and diabetes mellitus. HIV/COVID-19 co-infection might have negatively influenced the HIV treatment and diagnosis, which indicates the need to regularly screen HIV patients in the COVID-19 pandemic.

Prevalence of Clostridioides difficile contamination in the healthcare environment and instruments: A systematic review and meta-analysis.

Introduction: Worldwide, Clostridioides difficile infection is becoming one of the most common healthcare-associated infections. Management and control of this infection in healthcare facilities are associated with screening for environmental and instrumental C. difficile contamination. This systematic review and meta-analysis aimed to assess the overall prevalence of C. difficile in hospital settings, medical devices, and instruments. Methods: Four main databases, PubMed, Web of Science, Google Scholar, and Scopus, were searched using the keywords Clostridioides difficile, Clostridium difficile, C. difficile, clostridia, Clostridium spp., hospital environments, antibiotic associate colitis, intensive care unit, and ward in combination as a search strategy. The PRISMA checklist was used for selecting eligible studies. Results: A total of 11 eligible articles published between 2012 and 2021 were included. The overall pooled prevalence of C. difficile in hospital environments was 14.9%. The highest and lowest prevalence were reported for India (51.1%) and the USA (1.6%), respectively. The highest prevalence was reported for beds (46.3%). A significant heterogeneity was seen between C. difficile prevalence in hospital environments in different samples. The highest and lowest prevalence was reported for floor corners (63.2%) and privacy curtains (1.4%), respectively. Conclusions: In conclusion, hospitals' medical devices and environmental surfaces are considered a crucial source of Clostridioides difficile infection. In this regard, we strongly recommend revising and improving the cleaning and disinfection methods in hospitals and quality control of cleaning adequacy.

An update review of globally reported SARS-CoV-2 vaccines in preclinical and clinical stages.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the causative agent of the rapidly spreading pandemic COVID-19 in the world. As an effective therapeutic strategy is not introduced yet and the rapid genetic variations in the virus, there is an emerging necessity to design, evaluate and apply effective new vaccines. An acceptable vaccine must elicit both humoral and cellular immune responses, must have the least side effects and the storage and transport systems should be available and affordable for all countries. These vaccines can be classified into different types: inactivated vaccines, live-attenuated virus vaccines, subunit vaccines, virus-like particles (VLPs), nucleic acid-based vaccines (DNA and RNA) and recombinant vector-based vaccines (replicating and non-replicating viral vector). According to the latest update of the WHO report on April 2nd, 2021, at least 85 vaccine candidates were being studied in clinical trial phases and 184 candidate vaccines were being evaluated in pre-clinical stages. In addition, studies have shown that other vaccines, including the Bacillus Calmette-Guérin (BCG) vaccine and the Plant-derived vaccine, may play a role in controlling pandemic COVID-19. Herein, we reviewed the different types of COVID-19 candidate vaccines that are currently being evaluated in preclinical and clinical trial phases along with advantages, disadvantages or adverse reactions, if any.

Bacterial co-infections with SARS-CoV-2.

The pandemic coronavirus disease 2019 (COVID-19), caused by Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), has affected millions of people worldwide. To date, there are no proven effective therapies for this virus. Efforts made to develop antiviral strategies for the treatment of COVID-19 are underway. Respiratory viral infections, such as influenza, predispose patients to co-infections and these lead to increased disease severity and mortality. Numerous types of antibiotics such as azithromycin have been employed for the prevention and treatment of bacterial co-infection and secondary bacterial infections in patients with a viral respiratory infection (e.g., SARS-CoV-2). Although antibiotics do not directly affect SARS-CoV-2, viral respiratory infections often result in bacterial pneumonia. It is possible that some patients die from bacterial co-infection rather than virus itself. To date, a considerable number of bacterial strains have been resistant to various antibiotics such as azithromycin, and the overuse could render those or other antibiotics even less effective. Therefore, bacterial co-infection and secondary bacterial infection are considered critical risk factors for the severity and mortality rates of COVID-19. Also, the antibiotic-resistant as a result of overusing must be considered. In this review, we will summarize the bacterial co-infection and secondary bacterial infection in some featured respiratory viral infections, especially COVID-19.