Acute Kidney Injury Caused Due to Colistin Therapy: A Case Report Study Analysis

An abrupt bout of kidney damage or failure that lasts a few hours to a few days is referred to as acute renal failure (ARF) or acute kidney injury (AKI). Nephrotoxicity is classified into the following categories: R-risk, I-injury, F-failure, L-loss of function, and E-end stage renal failure. It is inherited, brought on by medications, and associated with diabetes, liver diseases, and heart issues. Typically, a drug's dose-dependent nephrotoxicity affects its severity. Multi-medication resistant (MDR) infections have led to an unprecedented increase in the use of Colistin medicine. Pseudomonas aeruginosa, Klebsiella pneumoniae, and other gram-negative bacteria are to blame. One type of bacteria is Acinetobacter baumannii. This paper will provide the case of a 62-year-old male patient who was admitted to the hospital after receiving a diagnosis of venous thromboembolism and anemia. Human-acquired pneumonia results from Acinetobacter baumannii's multidrug resistance, which makes the bacteria only responsive to the antibiotics colistin and azithromycin meropenem. Two days after commencing the (Oliguria-500) medicine, there was a decrease in urine production. The renal parenchyma showed changes, and the levels of creatinine were elevated to 3.18 mg/dL. USG has been seen. Laboratory results indicate that he suffered from AKI Colistin and demonstrates strong (Naranjo score: 8) usually connected to AKI. Drug dosages were not changed. It was routine practice to monitor BUN and creatinine levels. The amount of urine produced increased to 2450 mL 15 days following treatment. Respiratory failure is one of the neurological side effects of collistin was ignored. On discharge day, the patient was stable and doing well. It seems from this that if the medication is beneficial and the risk is manageable, there is no reason to stop taking it; however, careful observation is needed. Diminish the quantity of adverse reactions

Streptococcus pneumoniae - stress hormone interactions

Streptococcus pneumoniae is one of the most important bacterial pathogens of humans causing a wide range of mild to life-threating diseases. It is also a commensal microorganism in the nasopharynx of up to 60% of people. Fundamental aspects of its ability for transition from colonisation to an infectious state as well as how bacterial-host interactions influence this process are largely unknown. In the field of microbial endocrinology, it has been well established in mainly Gram-negative bacteria that stress hormones such as norepinephrine epinephrine and dopamine play an essential role in determining the outcome of bacterial infections. This study successfully established the conditions to investigate S. pneumoniae-stress hormone interactions using modified serum-SAPI media. 13 mutants lacking two-component regulatory system and 4 two-component system fusion reporter strains were created, and examined for their role in S. pneumoniae-stress hormone interactions. This study demonstrated that S. pneumoniae is stress hormone responsive and has mechanisms to recognise and process host stress hormones by a transferrin-iron delivery mechanism, which evidence suggests might be mediated via the TCS09 system since hormone-induced growth and radiolabelled norepinephrine and Fe uptake were reduced in a ΔTCS09 mutant. In addition, the pneumococcal response to stress hormone exposure resulted in a change in cell-cell association from chains into diplococci and cell morphology by reducing cell size and the capsule. Furthermore, the pneumococcal exposure to norepinephrine also increased biofilm formation and significantly altered metabolism. The analysis of in vivo experiments indicated that a stress hormone encounter might trigger translocation from the nasopharynx into the lungs, which may enhance S. pneumoniae in its transition from commensal to pathogen. Therefore, the pneumococcal ability to respond to host stress signals may be key to its capacity to cause life-threatening pneumonia, septicaemia and meningitis

Functional assessment of microbial superoxide dismutase isozymes suggests a differential role for each isozyme.

Microbes can have multiple enzymes that are able to catalyse the same enzymatic reactions but may differ in structure. These are known as isozymes. It is assumed that isozymes have the same functional role for cells. Contrary to this assumption, we hypothesised that isozymes can confer different functions for microbial cells despite catalysing the same reactions. To test this hypothesis, we studied the role of superoxide dismutases (SOD) in Klebsiella pneumoniae, the causative agent of several nosocomial and community-acquired infections, in infection relevant assays. SODs are responsible for detoxification of toxic superoxide radicals. K. pneumoniae genome contains three superoxide dismutase genes, sodA, sodB, and sodC coding for Mn-, Fe- and CuZn- co-factored SODs, respectively. By creating and testing single, double, and triple SOD mutants, we investigated the regulatory interactions among SOD and determined the role of each isozyme in oxidative stress resistance, biofilm formation, cell morphology, metabolism, and in vivo colonization and persistence. Our results demonstrate that SOD isozymes in K. pneumoniae have unique roles beyond oxidative stress resistance, and there is a regulatory interplay among SODs

Host stress hormone norepinephrine stimulates pneumococcal growth, biofilm formation and virulence gene expression.

Background: Host signals are being shown to have a major impact on the bacterial phenotype. One of them is the endogenously produced catecholamine stress hormones, which are also used therapeutically as inotropes. Recent work form our laboratories have found that stress hormones can markedly increase bacterial growth and virulence. This report reveals that Streptococcus pneumoniae, a commensal that can also be a major cause of community acquired and nosocomial pneumonia, is highly inotrope responsive. Therapeutic levels of the stress hormone norepinephrine increased pneumococcal growth via a mechanism involving provision of iron from serum-transferrin and inotrope uptake, as well as enhancing expression of key genes in central metabolism and virulence. Collectively, our data suggests that Streptococcus pneumoniae recognises host stress as an environmental cue to initiate growth and pathogenic processes. Results: Effects of a clinically attainable concentration of norepinephrine on S. pneumoniae pathogenicity were explored using in vitro growth and virulence assays, and RT-PCR gene expression profiling of genes involved in metabolism and virulence. We found that norepinephrine was a potent stimulator of growth, via a mechanism involving norepinephrine-delivery of transferrin-iron and internalisation of the inotrope. Stress hormone exposure also markedly increased biofilm formation. Importantly, gene profiling showed that norepinephrine significantly enhanced expression of genes involved in central metabolism and host colonisation. Analysis of the response of the pneumococcal pspA and pspC mutants to the stress hormone showed them to have a central involvement in the catecholamine response mechanism. Conclusions: Collectively, our evidence suggests that the pneumococcus has mechanisms to recognise and process host stress hormones to augment its virulence properties. The ability to respond to host stress signals may be important for the pneumococcal transition from colonization to invasion mode, which is key to its capacity to cause life-threatening pneumonia, septicaemia and meningitis

Plasma levels of BAFF and APRIL are elevated in patients with asthma in Saudi Arabia

B-cell activation factor (BAFF) and a proliferation-inducing ligand (APRIL) are members of the tumor necrosis factor superfamily of cytokines and can induce B cell activation, differentiation, and antibody production via interaction with their receptors, including transmembrane activator, calcium modulator, and cyclophilin ligand interactor (TACI), B-cell maturation antigen (BCMA), and B-cell activating factor receptor (BAFF-R). Herein, we assessed the plasma protein levels of BAFF and APRIL in patients with asthma to determine whether their expression is correlated with total IgE production and examined the surface expression of BAFF/APRIL receptors on B cells. Blood samples were collected from 47 patients with controlled asthma symptoms and 20 healthy normal controls, and plasma levels of APRIL, BAFF, and total IgE protein were quantified by corresponding ELISA assays. Furthermore, lymphocytes were isolated and B cells were analyzed for the presence of BAFF-R, BCMA, and TACI receptors using flow cytometry. Our results showed that IgE, BAFF, and APRIL plasma levels were markedly increased in patients with asthma compared with healthy controls. Moreover, expression of BAFF-R and BCMA, but not that of TACI, was significantly increased in patients with asthma compared with healthy controls. Overall, the findings suggest BAFF and APRIL as key mediators of asthma, and determination of their plasma levels may be useful in monitoring asthma symptoms and treatment response

Analyzing the Difference in the Length of Stay (LOS) in Moderate to Severe COVID-19 Patients Receiving Hydroxychloroquine or Favipiravir

Background: The coronavirus 2019 (COVID-19) disease, caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus led to a global pandemic. HCQ and FPV were used early in the pandemic as a treatment modality for COVID-19. Various studies evaluated the HCQ and FPV effectiveness, based on the mortality endpoint and showed conflicting results. We hypothesize that analyzing the difference in the LOS as a significant endpoint would be of a major interest, especially for healthcare providers, to prevent a lengthy hospitalization and disease progression. Methods: This is a retrospective observational study, conducted via a medical chart review of COVD-19 patients who were admitted between April 2020 and March 2021 with a moderate to severe illness. The LOS endpoint was tested using the paired Wilcoxon signed-rank (WSR) model. Prior to using the WSR model, the balance between the HCQ and FPV groups, the propensity score matching, the LOS distribution, and the normality assumptions were tested. Two sensitivity statistical analyses were conducted to confirm the results (stratified log-rank test and U Welch test after transforming the LOS by the squared root values). Results: A total of 200 patients were included for the analysis: 83 patients in the HCQ group and 117 patients in the FPV group. Thirty-seven patients were matched in each group. The LOS data was positively skewed and violated the normality (Shapiro–Wilk p < 0.001) and had an unequal variance (Levene’s test, p = 0.019). The WSR test showed no statistical significance in the LOS endpoint, with a median of −0.75 days (95% confidence interval: −4.0 to 2.5, p = 0.629), in favor of the HCQ group (four days), in comparison to seven days of the FPV group. The WSR findings were further confirmed with the stratified log rank test (p = 740) and the U Welch test (p = 391). Conclusions: The study concluded that the HCQ and FPV treatments have a comparable effectiveness in terms of the LOS in the moderate to severe COVID-19 patients. This study highlights the importance of analyzing the LOS as a relevant endpoint, in order to prevent the costs of a lengthy hospitalization and disease progression. The current study also emphasizes the importance of applying the appropriate statistical testing when dealing with two-sample paired data and analyzing non-parametric data such as the LOS

SARS-CoV-2: An Overview of Virus Genetics, Transmission, and Immunopathogenesis

The human population is currently facing the third and possibly the worst pandemic caused by human coronaviruses (CoVs). The virus was first reported in Wuhan, China, on 31 December 2019 and spread within a short time to almost all countries of the world. Genome analysis of the early virus isolates has revealed high similarity with SARS-CoV and hence the new virus was officially named SARS-CoV-2. Since CoVs have the largest genome among all RNA viruses, they can adapt to many point mutation and recombination events; particularly in the spike gene, which enable these viruses to rapidly change and evolve in nature. CoVs are known to cross the species boundaries by using different cellular receptors. Both animal reservoir and intermediate host for SARS-CoV-2 are still unresolved and necessitate further investigation. In the current review, different aspects of SARS-CoV-2 biology and pathogenicity are discussed, including virus genetics and evolution, spike protein and its role in evolution and adaptation to novel hosts, and virus transmission and persistence in nature. In addition, the immune response developed during SARS-CoV-2 infection is demonstrated with special reference to the interplay between immune cells and their role in disease progression. We believe that the SARS-CoV-2 outbreak will not be the last and spillover of CoVs from bats will continue. Therefore, establishing intervention approaches to reduce the likelihood of future CoVs spillover from natural reservoirs is a priority

Nanotheranostics to target antibiotic-resistant bacteria: Strategies and applications

Various health agencies, such as the European Medical Agency (EMA), Centers for Disease Control and Prevention (CDC), and World Health Organization (WHO), timely cited the upsurge of antibiotic resistance as a severe threat to the public health and global economy. Importantly, there is a rise in nosocomial infections among covid-19 patients and in-hospitalized patients with the delineating disorder. Most of nosocomial infections are related to the bacteria residing in biofilm, which are commonly formed on material surfaces. In biofilms, microcolonies of various bacteria live in syntropy; therefore, their infections require a higher antibiotic dosage or cocktail of broad-spectrum antibiotics, aggravating the severity of antibiotic resistance. Notably, the lack of intrinsic antibacterial properties in commercial-grade materials desires to develop newer functionalized materials to prevent biofilm formation on their surfaces. To devise newer strategies, materials prepared at the nanoscale demonstrated reasonable antibacterial properties or enhanced the activity of antimicrobial agents (that are encapsulated/chemically functionalized onto the material surface). In this manuscript, we compiled such nanosized materials, specifying their role in targeting specific strains of bacteria. We also enlisted the examples of nanomaterials, nanodevice, nanomachines, nano-camouflaging, and nano-antibiotics for bactericidal activity and their possible clinical implications