Klebsiella pneumoniae vaccine studies in animal models.

The treatment of Klebsiella pneumoniae is faced with challenges demanding the development of a vaccination strategy. However, no approved and globally available vaccine exists yet. This study aimed to systematically review all published data on K. pneumoniae vaccines in animal models. Without time restrictions, electronic databases were searched using appropriate keywords. The retrieved studies were screened and the data of those that matched our inclusion criteria were collected and analyzed. In total, 2027 records were retrieved; of which 35 studies were included for systematic review. The most frequently used animal model was BALB/c mice. Proteins, polysaccharides, and their combinations (conjugates) were the most common vaccine candidates used. The amount of antigen, the route used for immunization, and the challenge strategy was varying in the studies and were chosen based on several factors such as the animal model, the type of antigen, and the schedule of immunization. Almost all studies claimed that their vaccine was effective/protective, indicated by increasing survival rate, reducing organ bacterial load, and eliciting protective antibody and/or cytokine responses. Altogether, the information presented here will assist researchers to have a better look at the K. pneumoniae vaccine candidates and to take more effective steps in the future.

Phenotypic, genotypic, and metabolic resistance mechanisms of ESKAPE bacteria to chemical disinfectants: a systematic review and meta-analysis.

BACKGROUND: The presence of resistant ESKAPE pathogens to antimicrobials including chemical disinfectants (ChDs) is a serious threat to public health worldwide. In the present study, we systematically reviewed published reports on mechanisms beyond ChD resistance of ESKAPE bacteria. RESEARCH DESIGN AND METHODS: Several databases without date limitations were searched. Studies focused on the ChD resistance/tolerance mechanisms of ESKAPE bacteria were included. Meta-analysis was done to assess the frequency of tolerance and genes in ESKAPE clinical isolates. By screening of initial 6733 records, finally, 41 studies were included. RESULTS: The overall tolerance to at least one ChD was 48.6%. Pseudomonas aeruginosa and Acinetobacter baumannii were highly ChD-resistant. In several studies, phenotypic changes including changes in general morphology, pump function, cell surface, and membrane, as well as metabolic changes were observed after ChD addition. The resistance gene frequency was 70.2% for norfloxacin efflux pump genes, 40.6% for qac major facilitator superfamily genes, and 22.2% for qac small multidrug resistance genes. CONCLUSION: We systematically reviewed the effect of various mechanisms in the resistance process of ESKAPE bacteria to ChDs. However, except for the impact of genes, the numbers of studies investigating other mechanisms were very limited, demanding carrying out more studies in this field.

Comparison of Therapeutic Effect and Safety of Oral and Rectal Use of Acetaminophen on Patent Ductus Arteriosus in Preterm Infants: Clinical Randomized Trial.

The prevalence of patent ductus arteriosus (PDA) in preterm infants is high. There is little information about the therapeutic effect and safety of rectal acetaminophen in the treatment of PDA. We aimed to compare the therapeutic effect and safety of oral and rectal acetaminophen on PDA in preterm infants. This study was a single-blind randomized clinical trial using 40 preterm infants. The cases were hospitalized in the neonatal intensive care unit of Mohammad Kermanshahi and Imam Reza hospitals of Kermanshah. Subjects were randomly divided into 2 groups, the first group was treated with oral acetaminophen and the second group was treated with rectal acetaminophen. The presence of PDA and response to treatment was assessed based on pre- and post-treatment echocardiographic criteria. The likelihood of complications or prohibition of acetaminophen use was assessed with paraclinical tests before and after treatment. The neonates were in the age range of 30 to 35 weeks. Twenty-one cases (52.5%) were boys and 19 cases (47.5%) were girls. Two cases in the oral-acetaminophen group and 1 case in the rectal-acetaminophen group needed the second round of treatment. There was no difference between the success of treatment and the type of treatment. The study showed that there was no difference between PDA treatment of preterm infants with oral and rectal acetaminophen. Also, no side effects were observed in treatment with any of the treatments. Therefore, it could be suggested that in infants who are intolerant to oral acetaminophen, the rectal form can be used.

Clinical and laboratory characteristics of children with severe and nonsevere COVID-19 in Kermanshah, west of Iran: A retrospective study.

Background and Aims: The study aimed to collect and compare clinical and laboratory findings of children with severe and nonsevere COVID-19 in Kermanshah City, located in the west of Iran. Methods: The study was conducted on 500 children with COVID-19 hospitalized in Mohammad-Kermanshahi Hospital in Kermanshah City. Pediatric COVID-19 was confirmed by reverse transcription-polymerase chain reaction (RT-PCR) test using respiratory secretion samples. Medical records were reviewed and information related to demographic characteristics, underlying diseases, clinical manifestations, laboratory findings, and chest computed tomography (CT) scans were all extracted from electronic and paper records. Patients were divided into three groups according to the severity of the disease: mild, moderate, and severe. Clinical and laboratory findings were compared between the groups and the collected data were analyzed by statistical methods. Results: Out of 500 patients, 286 were boys and 214 were girls. Of the patients, 321 cases were only COVID-19, while 179 patients were diagnosed as Multisystem Inflammatory Syndrome in Children (MIS-C) positive. The average age of COVID-19 patients was 3.85 ± 4.48 and of MIS-C patients was 3.1 ± 3.5. In order, fever, cough, and heart disorders were the most common symptoms in patients with COVID-19 and MIS-C, respectively. In terms of disease severity, 246 patients had mild disease, 19 patients had moderate disease, and 56 patients had severe disease. In severe patients, the average number of white blood cells (WBC) was higher, while the average number of lymphocytes was lower. Also, in these patients, the average age was lower, and most of them had respiratory distress. In mild patients, often cough, diarrhea, and vomiting were observed. Conclusion: The results of our study showed that laboratory factors such as WBC count, lymphocyte count, CT findings, Respiratory distress, cough, diarrhea, and vomiting can be used to evaluate the severity of COVID-19 in children.

A systematic review and meta-analysis on the antibiotic resistance of Neisseria meningitidis in the last 20 years in the world.

BACKGROUND: Neisseria meningitidis is one of the most important causes of meningitis and pathogens-associated deaths in developing and developed countries. Effective anti-microbial agents are pivotal to treat and control N. meningitidis infections. The aim of the present study was to systematically review published studies on the antibiotic resistance of N. meningitidis in the last 20 years (2000-2020) in the world. METHODS: Published researches were identified through a literature search using reputable databases including PubMed, Scopus, and Web of Science. Finally, 24 studies were included for a random-effects model meta-analysis. RESULTS: The overall resistance to most commonly used antibiotics such as ceftriaxone, cefotaxime, ciprofloxacin and rifampin was low, ranging from 1 to 3.4%. However, non-sensitivity to penicillin, as the first-line antibiotic against N. meningitidis, was higher (27.2%). Altogether, the resistance to the first-line antibiotics (except penicillin) is still low indicating these drugs are effective against meningococcal meningitis. We also found a significant gap between MIC and disk diffusion for evaluating resistance to antibiotics in which disk diffusion overestimate the resistance rate. CONCLUSIONS: To properly management and prevent the spread of N. miningitidis isolates resistant antibiotics, it is necessary to monitor the pattern of antibiotic susceptibility regionally and globally using the MIC methods.

Immunoinformatics and molecular dynamics studies to predict T-cell-specific epitopes of four Klebsiella pneumoniae fimbriae antigens.

Klebsiella pneumoniae (K. pneumoniae) is a causative agent of severe infections in humans. There is no publically available vaccine for K. pneumoniae infections yet. Here, using comprehensive immunoinformatics methods, T-cell-specific epitopes of four type 1 fimbriae antigens of K. pneumoniae were predicted and evaluated as potential vaccine candidates. Both CD8+ (class I) and CD4+ (class II) T-cell-specific epitopes were predicted and the epitopes similar to human proteome were excluded. Subsequently, the windows of class-II epitopes containing class-I epitopes were determined. The immunogenicity, IFN-γ production and population coverage were also estimated. Using the 3D structure of HLA and epitopes, molecular docking was carried out. Two best epitopes were selected for molecular dynamics studies. Our prediction and analyses resulted in the several dominant epitopes for each antigen. The docking results showed that all selected epitopes can bind to their restricted HLA molecules with high affinity. The molecular dynamics results indicated the stability of system with minimum possible deviation, suggesting the selected epitopes can be promising candidates for stably binding to HLA molecules. Altogether, our results suggest that the selected T-cell-specific epitopes of K. pneumoniae fimbriae antigens, particularly the two epitopes confirmed by molecular dynamics, can be applied for vaccine development. However, the in vitro and in vivo studies are required to authenticate the results of the present study.Communicated by Ramaswamy H. Sarma.

Effect of Vigna radiata, Tamarix ramosissima and Carthamus lanatus extracts on Leishmania major and Leishmania tropica: An in vitro study.

Objective: Current therapy strategies of leishmaniasis have some problems such as high cost, toxicity and side effects. Plant extracts can be a source of drugs to control leishmaniasis. In this study, the effect of hydroalcoholic and chloroformic extracts of Vigna radiata, Tamarix ramosissima, and Carthamus lanatus on Leishmania major and L. tropica was studied. Methods: The plant samples were collected from west of Iran and their extracts were prepared. Anti-promastigote activity assay of all extracts was done using tetrazolium-dye assay. Results: Only high concentrations of V. radiata and C. lanatus were able to inhibit Leishmania, while both high and low concentrations of T. ramosissima had antileishmanial effect. No difference was observed between hydroalcoholic with chloroformic extract of each plant. Conclusion: Altogether, the results revealed the antileishmanial activity of T. ramosissima extracts against L. major and L. tropica, indicating its potential as an antileishmanial agent.