Infectious disorders drug targets最新文献

Introduction: Persistent bacteremia, despite the susceptibility of the causative organism to appropriate antimicrobial therapy, presents a major clinical challenge. In such cases, early identification and control of the infectious source are essential to prevent complications and reduce mortality.

Case presentation: We report the case of a 59-year-old woman with persistent Methicillin-resistant Staphylococcus Aureus (MRSA) bacteremia following spinal surgery. Despite multiple days of intravenous antibiotic therapy, her blood cultures remained positive for MRSA. A tagged white blood cell (Technetium-99) scan revealed an abscess in the right sacroiliac joint. Surgical drainage of the abscess led to clinical improvement and resolution of bacteremia. Interestingly, cultures of the abscess fluid grew Enterococcus faecalis rather than MRSA.

Discussion: This case underscores the importance of early source control in the management of persistent bacteremia. Even when the pathogen isolated from the presumed source differs from that in the bloodstream, drainage can play a critical role in resolving systemic infection.

Conclusion: Early source control should be pursued in persistent bacteremia, regardless of initial culture results. Imaging studies may assist in locating occult sources, and successful drainage may contribute to clinical improvement even when the primary bloodstream pathogen is not isolated from the source.

It is a known fact that HIV infection remains a serious public health problem throughout the world, and the need to constantly develop new antiretroviral drugs to combat HIV emerges from the fact that repetitive mutations occurring in viral enzymes make this virus resistant to antiretroviral drugs. This resistance causes failure of treatment, and hence, for many years, extensive research has been to discover newer possibilities for fighting this disease at a molecular level, along with many long-standing and expensive clinical trials. Many scientific research programs have either been discarded or unsuccessful. However, the research has not stopped, and in the process, many heterocyclic scaffolds have been used to build up novel drug molecules to combat this disease. A literature survey reveals that many heterocycles have been explored and were found to be very useful in treating different types of viral infections. This concise and rigorous literature explains the journey and highlights the various strategies to develop new anti-HIV drug candidates.

Background: Tuberculosis is an infectious disease caused by Mycobacterium tuberculosis. The current treatment protocols for pulmonary tuberculosis are quite effective, even though the treatment requires 3-6 months. The current treatment protocols for extrapulmonary tuberculosis are based on the same drugs that are used for pulmonary tuberculosis. However, the success rates are much lower for certain types of extrapulmonary tuberculosis, such as tuberculous meningitis. Tuberculous meningitis is one of the very few diseases attributable to bacteria that have a very high short-term mortality rate among diagnosed patients, even after treatment with antibiotics that are effective for pulmonary tuberculosis. For example, rifampicin is highly effective for the treatment of pulmonary tuberculosis, but its effectiveness for the treatment of tuberculous meningitis is much lower. The reason for the lower effectiveness of rifampicin against tuberculous meningitis is that it has low Blood-Brain Barrier (BBB) permeability, which results in lower concentrations of the drug at the required sites in the central nervous system.

Methods: In this work, ligands having improved BBB permeability and pharmacokinetic and pharmacodynamic properties, either similar to or better than that of rifampicin, have been designed. The BBB permeability of the designed molecules was assessed by using pkCSM, a machine- learning model. Pharmacokinetic properties, drug-likeness, and synthesizability were assessed by using SWISS-MODEL. The binding affinity of the designed drugs was assessed by using AutoDock Vina. A customized scoring function, StWN score, was used for a quantitative weighted assessment of all the properties of interest to rank the designed molecules.

Results: In this study, drug-like ligands have been designed that have been predicted to have high BBB permeability as well as high affinity for RNA polymerase β of Mycobacterium tuberculosis.

Conclusion: The best ligands generated by the tools employed were selected as potential drugs to address the current need for better options for the treatment of tuberculous meningitis.

Introduction: Cervical cancer is among the most common types of cancer in women and is associated with human papillomavirus (HPV) infection. The association between cervical cancer and high-risk HPV infection has been well documented. However, the effect of simultaneous infection with high- and low-risk HPV or low-risk HPV alone on the risk of developing cervical malignancy remains unanswered in guidelines.

Method: We investigated the association of high and low-risk HPVs (HR or LR) genotypes with cervical carcinoma risk and pathological and cytological information in cases recruited from a population- based cohort study of 790 patients. Correlation matrix and t-test were used for analysis.

Results: The percentage of HR+LR and HR-HPV16/18 were 9.30% and 11.20% in class II, 7.15% and 7.10% in class IV, and 7.15% and 5.80% in As-CUS smears. Interestingly, concurrent infection with HR-HPV and LR-HPV types led to a significant reduction in the risk of developing malignancy compared to the high-risk group (OR=0.3 (0.098-0.925), pvalue= 0.04). The percentage of individuals with cervical malignancy was 10.2% and 28.2% within the co-infected and the HR-HPV participants.

Conclusion: Our findings suggest that simultaneous infection with high- and low-risk HPV may reduce the risk of cervical malignancy.

A mystery pathogen that has not yet infected the entire world's population is predicted to be the cause of Disease X, which will be contagious. According to WHO scientists, 50 million people are expected to die from Disease X, which would be 20 times deadlier than coronavirus disease 2019 (COVID-19). Many international initiatives are currently in motion to get ready for future pandemics. These include updating the International Health Regulation and the European Legislation, establishing the Health Emergency Preparedness and Response Authority (HERA), establishing international hubs, taking on the international challenge of developing a vaccine for Disease X within 100 days of recognition of emerging Pathogen X, and updating the preparedness plan of National Institute of Allergy and Infectious Diseases. Our current review's main objective is to determine whether black seeds (Nigella Sativa) can manage Disease X. It has been established by several studies that black seeds (N. sativa) have antiviral, antibacterial, antimicrobial, immunomodulatory, anti-inflammatory, and antioxidant properties, which would be useful in the management of Disease X. Black seeds (N. sativa) may be utilized in conjunction with supportive care and symptomatic therapy to manage Disease X in early phases. Future randomized controlled clinical trials would further evaluate the safety and effectiveness of black seeds (N. sativa) in patients with Disease X.

Background: The alarming increase in antibiotic resistance urges alternative and efficacious antimicrobial solutions. Historically, medicinal plants have been used for therapeutic purposes, such as relieving pain and healing wounds. The evaluation of the natural therapeutic effects of medicinal plants in a manner that resembles how humans typically consume them is lacking. In this study, many medicinal plants known to have some antimicrobial effects, including Frankincense, Garlic, Myrrh, and Ginger, were evaluated for their direct antibacterial activity in raw form.

Materials and methods: The direct antimicrobial activity of medicinal plants was evaluated against a variety of Gram-positive and Gram-negative bacterial strains, such as Staphylococcus aureus (S. aureus.), Acinetobacter baumannii and Klebsiella pneumoniae using agar well diffusion method and turbidity measurements in suspension culture.

Results: Out of all the tested medicinal plants, only raw garlic (Allium sativum) powder, when dissolved in water or vinegar, offered a straightforward antibacterial activity. A combination of garlic extract and vinegar increased antibacterial activity. Aqueous garlic extracts displayed robust antimicrobial activity against many resistant bacteria. Other medicinal plants used in this study had absent or minimal antibacterial effects.

Conclusion: Only garlic in its raw form was effective against antibiotic-resistant bacteria. The increase in the antibacterial activity of garlic when combined with vinegar suggests synergistic activity of garlic. The straightforward antibacterial action of raw garlic may be strategically harnessed to combat the continuous challenge of increasing antibiotic resistance. This work promotes additional testing of more natural products (in raw form) and assesses their therapeutic effects clinically.

Tuberculosis (TB) spreads through droplets that contain Mycobacterium tuberculosis (Mtb) and can infect susceptible people. Due to different risk factors, people have different susceptibility ranges towards TB. The risk factors are classified into three main groups, including bacterial, environmental, and host factors. Literature review reveals that the most important host risk factors are aging, male gender, genetics, epigenetics, having an impaired immune system, diabetes, malignancy, malnutrition, anemia, and pregnancy. The risk factors contribute to the increase in TB cases through inflammation, increased contact with TB patients, disruption of immune genes, changes in gene expression, increased activity of Mtb, damage to cellular immunity, reactivation of Latent TB Infection (LTBI), increased susceptibility to TB, compromised immunity, and changes in the proportion of T cell subgroups, respectively. Therefore, identification of the infection source and high-risk people and timely treatment of the patients can reduce TB mortality and help control the disease.

Background: Iran has a relatively high prevalence of H. pylori, which correlates with high-risk areas for gastric cancer worldwide.

Methods: Our study aimed to investigate the underlying genetic mechanisms associated with resistance to metronidazole (frxA, rdxA), clarithromycin (23S rRNA), tetracycline (16S rRNA), and fluoroquinolone (gyrA) in H. pylori-positive dyspeptic patients using PCR and sequencing. We further examined the potential correlation between resistance profiles and various virulence genotypes.

Results: The rates of genetic mutations associated with resistance to metronidazole, fluoroquinolone, clarithromycin, and tetracycline were found to be 68%, 32.1%, 28.4%, and 11.1%, respectively. Well-documented multiple antibiotic resistance mutations were detected, such as rdxA and frxA (with missense and frameshift alterations), gyrA (Asp91, Asn87), 23S rRNA (A2142G, A2143G), and 16S rRNA (triple-base-pair substitutions AGA926-928→TTC). The cagA+ and vacA s1/m1 types were the predominant genotypes in our study. With the exception of metronidazole and tetracycline, no significant correlation was observed between the cagA+ and cagL+ genotypes and resistance-associated mutations.

Conclusion: The prevalence of antibiotic resistance-associated mutations in H. pylori was remarkably high in this region, particularly to metronidazole, ciprofloxacin, and clarithromycin. By conducting a simultaneous screening of virulence and resistance genotypes, clinicians can make informed decisions regarding the appropriate therapeutic regimen to prevent the escalation of antibiotic resistance against H. pylori infection in this specific geographical location.