Infectious disorders drug targets最新文献

Background: Sulbactam-durlobactam (SUL-DUR) has been tested in vitro for its ability to generate resistance in clinical isolates of Acinetobacter species. According to prior studies, combining durlobactam with sulbactam causes sulbactam-resistant isolates to become more active and revert to susceptibility. We aimed to conduct a systematic review of the in vitro activity of SUL-DUR on A. baumannii (Ab) isolates, including carbapenem-resistant A. baumannii (CRAb), to provide an overview for physicians dealing with Ab infections.

Methods: The following keywords were searched in the PubMed, Google Scholar, and EMBASE databases to look for eligible original works that have been published without restrictions till June 30, 2023: A. baumannii and sulbactam-durlobactam, SUL-DUR, durlobactam, and sulbactam-ETX2514. We also searched clinicaltrials.gov and the Clinical Trials Registry of India (CTRI) for clinical trials involving sulbactamdurlobactam and Acinetobacter.

Results: There were a total of 852 abstracts found. Among them, 633 articles with titles, abstracts, and keywords were reviewed, and 574 articles were removed after the initial screening. A total of 59 full-text eligible articles were evaluated, and 51 of them were eliminated because they did not satisfy the criteria set for inclusion. The full texts of the final 8 in vitro studies on A. baumanii and sulbactam/durlobactam were further evaluated. There were 5 trials on A. baumanii and sulbactam/durlobactam found on clinicaltrials.gov and the Clinical Trial Registry of India (CTRI).

Conclusion: The findings from the studies show that SUL-DUR might be a successful therapeutic option for multidrug-resistant-Ab infections. Future clinical trials will be required to validate the possibility of using this combination to treat multidrug-resistant A. baumannii infections.

Introduction: The onset of prosthetic joint infections (PJIs) is characterized by early onset defined as within 90 days of the procedure, delayed onset defined as within 3 to 12 months, and late onset defined as over 12 months. In only a scant number of case reports, Mycobacterium flavescens associated infections are typically found in sputum cultures and associated with various forms of penetrating joint traumas, particularly post-surgical interventions. Due to its rarity in presentation among cases of PJIs, we have presented a case of PJI caused by Mycobacterium flavescens.

Case presentation: We have, herein, reported a case of a 70-year-old male presenting with stabbing left knee pain over the past several months along with accompanying erythema and swelling with the presence of purulent discharge. Outpatient cultures have shown the growth of Mycobacterium flavescent; subsequently, the patient underwent a 2-stage revision arthroplasty and was treated with a three-drug regimen and implant 5 months later. Although being an atypical cause of PJIs, we emphasize the importance of considering NTM as a differential for immunocompromised patients, especially those with prior surgical intervention.

Discussion: Mycobacterium spp. related PJIs manifest clinical features similar to other bacteriacausing PJIs, such as warm, indurated edema at the surgical site resulting in wound dehiscence and joint effusion. Diagnosis of Mycobacterium spp. related PJIs includes history and physical examination findings, serum inflammatory markers, synovial fluid analysis, and culture. Concurrently with surgical interventions, utilization of antimicrobial agents provides additional control in Mycobacterium- related PJI. Mycobacterium flavescens should be included among other NTMs as a possible cause of PJIs.

Background: There is no comprehensive information about the circulating serotypes of Streptococcus pneumoniae in Iran in recent years. This study aimed to summarize information about the changes over a decade in the serotype prevalence of S. pneumoniae in Iran.

Methods: We performed a comprehensive search in PubMed/Medline, Web of Science, Science Direct, and the Iranian Database, such as Magiran and SID, from January 2011 to February 2023. The systematic process, in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA), was carried out by two researchers who were both independent and calibrated. Statistical analyses were carried out using Comprehensive Meta-Analysis software. Identifying and measuring heterogeneity were done using I² and the chi-square test. Finally, Begg's rank correlation test was used in combination with a funnel plot to evaluate any possible publication bias.

Results: The search returned 16 relevant results, with a total of 1575 isolates. Of those studies, eight studies reported the distribution of S. pneumoniae serotypes among patients, three studies among healthy individuals, and five studies among both groups. As the meta-analysis revealed, the most common serotypes were 23F (n = 299, 14.1% [95% CI: 9.7-19.9]; I² = 84.3%; P<0.001 for heterogeneity), 19F (n = 221, 13.4% [95% CI: 9.9-17.9; I² = 76.7%; P<0.001 for heterogeneity]), and 19A (n = 102, 8.7% [95% CI: 6.5-11.7; I² = 54.3%; P<0.001 for heterogeneity]). Moreover, Begg's test (P = 0.160, 0.173, and 0.176 for 23F, 19F, and 19A, respectively) showed no evidence of publication bias.

Conclusion: Based on our pooled results, the majority of the serotypes of pneumococci in the Iranian population were 23F, 19F, and 19A, respectively, over the last decade. The findings can be valuable in selecting effective pneumococcal vaccine candidates and targeted antibiotics in Iranian patients.

Every year witnesses an outbreak of some or the other zoonotic disease that causes the unparalled loss of human life. The year 2022 presented the outbreak of Crimean Congo haemorrhagic fever (CCHF), which brought unprecedented challenges to individuals as well as to the healthcare system all around the world, making it a serious health concern. Rising health concerns have highlighted the importance of managing and decreasing the further transmission of the CCHF virus. CCHF is one of tick-borne viral diseases, which spreads due to various reasons like changes in global warming, environmental influences, and other ecological factors. All these factors somehow impact the disease prevalence. This disease has a negative impact on both humans and livestock. The diverse climate and significant livestock population of India make it susceptible to the prevalence of CCHF. Therefore, it is the need of the hour to develop some strategies in order to tackle the challenges posed by CCHF. This article includes all the cases of CCHF that have occurred in India from the year 2011, along with the fatality rates associated with this disease. Also this study discusses the need to explore some specific drugs for the management and prevention of such diseases. In addition, the pathogenesis of the disease progression, along with some protective measures suggested by the government has been described for prevention of CCHF. Subsequently, this article attempted to draw attention towards the risk that may be posed by CCHF in the coming scenario, emphasizing the importance of taking proactive measures in anticipation of such risks.

Background: Alzheimer's disease (AD) is the most common neurological disorder, affecting more than 50 million individuals worldwide and causing gradual but progressive cognitive decline. The rising cost of medical treatment is mostly attributable to AD. There are now mainly a few slightly symptomatic therapeutic options accessible. Although this is not the primary reason, the failure to develop effective treatments for AD is often attributed to the disease's complicated pathophysiology and the wide range of underlying ideas.

Objective: Studies undertaken over the past decade have aimed to find novel methods of overcoming these barriers and effectively delivering drugs to the central nervous system. As a result, nanotechnology provides a promising alternative to the standard means of administering anti-amyloidosis drugs, enhancing expectations for a successful treatment of Alzheimer's disease. These therapeutic implications of using nanoparticle-based approaches for the treatment of Alzheimer's disease are discussed in this paper.

Methodology: Published articles from PubMed, SciFinder, Google Scholar, ClinicalTrials.org, and the Alzheimer Association reports were carefully examined to compile information on the various strategies for combating AD. That has been studied to summarize the recent advancements and clinical studies for the treatment of Alzheimer's disease (AD). Statistics is the study and manipulation of data, including ways to gather, review, analyze, and draw conclusions from data.

Conclusion: The biology of the BBB and its processes of penetration must be carefully taken into account while creating DDSs. If we have a better grasp of the disease's mechanism, we might be able to overcome the shortcomings of current treatments for AD. Different DDSs show interesting properties for delivering medication tailored to the brain. This review paper examines the recent applications of DDSs in diverse domains. By selecting the best targeting vectors and optimizing the combination of carriers, multifunctionalized DDS may be produced, and these DDS have a significant impact on AD therapy potential. To develop DDSs with the best therapeutic efficacy and manageable side effects, experts from a variety of fields may need to contribute their efforts. Currently, the therapeutic use of nanotechnology-based DDSs appears to be a promising prospect for AD therapy, and as the pathophysiology of AD is better understood, this strategy will develop over time.

Background: The concern about the global spread of resistant malaria has made the researchers not focus only on the treatment of established infections but relatively more on the prevention of the disease.

Objective: This study evaluates the chemopreventive activity of ketoconazole in a murine malarial model.

Method: Five out of seven groups of mice were pretreated for five days with proguanil (PRG), sulfadoxine/ pyrimethamine (SP), 10, 20, and 40 mg/kg body weight (b.w) of ketoconazole (KET10, KET20, and KET40), before being infected (on the sixth day) with Plasmodium berghei. Two other groups were infected-not-treated (INT) and not-infected-nor-treated (NINT). At 72 hours postinfection, five out of ten mice in each group were sacrificed to assess parasitemia, chemoprevention, hematologic, hepatic, and renal parameters. The remaining mice were observed for 28 days to determine their mean survival day post-infection (SDPI).

Results: All ketoconazole groups, except KET10, demonstrated 100% chemoprevention and significantly higher mean SDPI (p<0.001) in relation to INT (negative control). There was no significant difference in the mean SDPI observed in KET20 in relation to PRG or NINT (healthy control). A dose-related increase (p<0.01) in the mean plasma urea was observed when ketoconazole groups were compared to one another: KET10 versus KET20 (p<0.01) and KET20 versus KET40 (p<0.01). Sulfadoxine/pyrimethamine demonstrated significantly reduced mean plasma urea (p<0.001) and creatinine (p<0.05) in relation to INT and NINT, respectively. While PRG demonstrated significantly higher mean red blood cell (RBC), hemoglobin (HGB), and hematocrit (HCT) in relation to INT.

Conclusion: Ketoconazole possesses prophylactic antimalarial activity with associated dose-related renal impairment. Sulfadoxine/pyrimethamine demonstrated renoprotective potentials, while PRG prevented malaria-associated anemia.

The recent outbreaks of Nipah viral infection were associated with severe respiratory illness, lethal encephalitis, and an extremely high mortality rate. As there are no approved antiviral medications, patients with NiV infections are currently treated with repurposed or investigational antivirals and supportive care. This review examines the potential health benefits of N. sativa in the treatment of NiV infection. To identify relevant studies, the literature was searched in online databases like Medline/PubMed, Google Scholar, Science Direct, and reference lists. Through its antiviral, anti-inflammatory, antioxidant, anticonvulsant, immunomodulatory, bronchodilatory, and other properties, a number of studies have demonstrated that N. sativa is effective against a variety of viral infections, inflammatory conditions, neurological and respiratory illnesses, and other conditions. As a result, in the treatment of NiV-infected patients, N. sativa could be added as an adjuvant treatment alongside repurposed or investigational antivirals and supportive care. The efficacy of N. sativa in the treatment of NiV infection will be determined by the results of upcoming randomized controlled clinical trials.

Arsenic is an environmental toxicant and its toxicity is a global health problem affecting millions of people. Arsenic exposure occurs from natural geological sources leaching into aquifers, contaminating drinking water and may also occur from mining and other industrial processes. Both cancerous, noncancerous and immunological complications are possible after arsenic exposure. The many other target organs like lungs, thymus, spleen, liver, heart, kidney, and brain. Arsenic-mediated neuro, as well as immunotoxicity, is the main concern of this review. Long-term arsenic exposure can lead to various neurological dysfunctions, which may cause neurobehavioral defects and biochemical impairment in the brain, this might negatively affect one's quality of life in later stages. Arsenic also alters the levels of various neurotransmitters such as serotonin, dopamine and norepinephrine in the brain which produces neurotoxic effects and immunological deficiency. So, it is crucial to understand the neurotoxic mechanism of arsenic trioxide-mediated cerebro neurodegenerative and immunerelated alterations. One of the major mechanisms by which it exerts its toxic effect is through an impairment of cellular respiration by inhibition of various mitochondrial enzymes, and the uncoupling of oxidative phosphorylation. This review focuses on the various toxic mechanisms responsible for arsenic-mediated neurobehavioral and immune-related changes. Therefore, this review provides a critical analysis of mitochondrial dysfunctions, oxidative stress, glutamate excitatory, inflammatory and apoptosis-related mechanistic aspects in arsenic-mediated immunotoxicity, neurotoxicity, and neurodegenerative changes.

India has the largest problem of tuberculosis (TB) infection globally (estimated at about 35-40 crores cases), and around 18-36 lakh develop active tuberculosis annually. Latent TB is defined as a state of persistent immune response to stimulation by Mycobacterium tuberculosis antigens with no evidence of clinically manifested active TB. The progression of a latent infection to active tuberculosis increases several-fold in children < 5 years of age and in people with some or the other form of an immunocompromising condition. Therefore, to cater to this gigantic problem of tuberculosis, it is necessary to have awareness about latent tuberculosis infection (LTBI) amongst clinicians and to prioritise its diagnosis and treatment in high-risk groups. India plans to end TB well before the deadline set by the World Health organisation (WHO). However, this can only be achieved with effective strategies targeting LTBI. Multiple treatment regimens have been approved for LTBI treatment, and all have comparable efficacy. The selection of one regimen over the other depends on various factors, such as availability, risk of adverse events, age, and drug interactions. Recently, the WHO, as well as the Revised National TB Control Programme (RNTCP), have updated their guidelines on TB preventive treatment in 2020 and 2021, respectively. This review has been especially prepared to acknowledge the differences in approach to LTBI in developed and developing countries.

Background: Dog bites are a worldwide problem that disproportionately affects children. It might be difficult to keep in mind that even a man's closest buddy can be dangerous to people. In light of the significant morbidity and mortality associated with dog bites, we report, herein, an intriguing case in which a two-year-old boy appeared with eyelid facial lacerations as a result of a dog bite.

Case presentation: A two-year-old boy presented with bleeding around the right and left eyes. Local examination of the eyes revealed laceration and disfiguration of the left orbit and abrasion around the right eye. Preoperatively, parenteral antibiotics were started and continued postoperatively. Dressing was done for the right eye. Lid reconstruction surgery for the left eye was scheduled and it was carried out under general anaesthesia. The child was monitored for a month and showed satisfactory wound healing with no visible scars or complications.

Discussion: The standard treatment for bites is direct suture, grafting, or local flaps, depending on the type of wound and the surgeon's preference, regardless of the time since the attack. Crush wounds are difficult to treat because the damage to the tissues is often so profound that amputation is unavoidable.

Conclusion: The global injuries caused by dog bites are the consequence of uncommon illnesses and often manifest as peri-orbital and ocular lesions. Most rabies cases occur in underserved rural and urban areas, with a high frequency of stray dogs without immunisation.