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The recent prevalence of novel "coronavirus disease 2019" has expanded quickly globally, causing a universal pandemic. Herein, an effort was constructed to design a potent drug to inhibit the main protease of SARS-Cov-2 (3CLp) by means of structure-based drug design. A large library of the compounds was used for virtual screening. After molecular docking and ADME studies, we selected a compound with a better binding affinity to the 3CLp active site and acceptable ADME properties compared to the selected positive control drug. Molecular dynamic (MD) simulation (200 ns) and Molecular Mechanics-Poisson Boltzmann Surface Area (MM-PBSA) were used for further analysis. MD simulation outcomes have proved that the 3CLp-ZINC31157475 complex possesses a considerable value of dynamic properties such as flexibility, stability, compactness, and binding energy. Our MM-PBSA computation illustrates that ZINC31157475 is more potent (-88.03 kcal mol-1) than nelfinavir (-19.54 kcal mol-1) against COVID-19 3CLp. Further, we have determined that the main residues of the 3CLp interact with ligands from per-residue binding energy. In conclusion, we suggest that ZINC31157475 can potentially treat COVID-19 by inhibition of the 3CLp. However, in-vitro and in-vivo study is essential for approval of this suggestion.
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INTRODUCTION: Human Cytomegalovirus (HCMV) is the most important viral pathogen in people undergoing bone marrow transplantation (BMT). HCMV detection in the early stages makes is possible to save the patients' lives through immediate and timely treatment. The aim of this study was to investigate the status of HCMV using the real-time PCR method in BMT patients in Kermanshah, west of Iran. METHODS: HCMV monitoring was done in 120 patients who underwent BMT, 38 allogeneic cases and 82 autologous cases, using the ELISA serology test before transplantation. The participants were followed up 100 days after transplantation for HCMV detection in blood samples using real-time PCR. Preemptive therapy started with Ganciclovir and Foscarnet when the viral load was > 200 HCMV DNA copies/ml. RESULTS: Despite preemptive therapy, infection recurred in less than 1 month. HCMV recurred more frequently in patients undergoing allogenic transplation versus those receiving autologous transplantation. Recurrence was seen in 5 patients receiving allogenic transplantation. HCMV recurrence occurred in five patients with allogeneic transplantation. Twelve patients undergoing allogeneic or autologous transplantation (83%) and a virus load of > 1000 copies/ml showed HCMV-related symptoms. Three patients died, two due to HCMV-related pneumonia and the other one due to a fungal infection. CONCLUSION: Real-time PCR may be a useful method for quantification and monitoring of HCMV recurrence and may be helpful in choosing more efficient HCMV preemptive treatment in BMT recipients.
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BACKGROUND: Human brucellosis is a multisystem disease with a wide range of clinical signs which often leads to misdiagnosis and treatment delay. Early diagnosis of this disease can prevent the serious complications and mismanagements. This study aimed to evaluate the hematological parameters with predictive value for the diagnosis of brucellosis. METHODS: In this prospective case-control study which was done during 2015-2017 in Imam Reza Hospital, Kermanshah Province, west Iran, 100 patients with a confirmed diagnosis of brucellosis (brucellosis group) and 100 healthy individuals (control group) were studied. The hematological parameters, including hemoglobin (Hb), red blood cell (RBC), white blood cell (WBC) count, lymphocyte count, neutrophil count, platelet count (PLTs), mean platelet volume (MPV), platelet distribution width (PDW), erythrocyte sedimentation rate (ESR), and C-reactive protein (CRP) of both groups were recorded. The data were statistically compared between the brucellosis and the control groups. RESULTS: The mean age of patients and healthy groups was 44.04 ± 23.11 and 37.92 ± 24.80, respectively (P = 0.062). The WBC, CRP and neutrophil counts were significantly higher in the brucellosis group (P < 0.05). Based on the receiver operating characteristic (ROC) analysis, the sensitivity and specificity were 54% and 66% for the WBC, 45% and 71% for the neutrophil and 65% and 72% for the CRP, respectively. There was no statistically significant difference between the two groups in terms of Hb, RBC, WBC, lymphocyte and platelet count, MPV, PDW and ESR (P > 0.05). CONCLUSION: The results of this study indicate that WBC, CRP and neutrophil count can be used as valuable markers in the preliminary diagnosis of brucellosis. However, further researches are required to standardize these parameters for various forms of brucellosis.
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BACKGROUND AND OBJECTIVES: Integrons play a major role in the transmission and accumulation of resistance factors in multidrug resistant bacteria. This study was aimed to evaluate the gene cassettes of class I integron and antimicrobial resistance in isolates of Citrobacter with multidrug resistance (MDR). MATERIALS AND METHODS: Ninety isolates of Citrobacter spp. were collected from the largest hospital in Kermanshah, Iran. Antimicrobial resistance patterns were determined using disc diffusion method. The class I integron were detected by PCR. The integrase positive isolates were further analyzed for the presence of gene cassettes using 5' and 3' conserved sequences (CSs) primers and PCR products were sequenced. The data were analyzed using the chi-square test. RESULTS: Of 90 Citrobacter isolates, 46 (51.1%) were multidrug resistant. Class I integron and gene cassettes were determined in 30 isolates (65.2%). Gene cassettes were found which contained genes encoded resistance to aminoglycosides and trimethoprim and a putative gene. Gene cassettes of dfrA12-orfF-aadA2, dfrA1-aadA1, aadA1 and dfrA15-aadA2 were also found in Citrobacter isolates. CONCLUSION: Our results indicate there is a high frequency of class I integron among multi-drug resistant strains of Citrobacter isolated from clinical settings. A high frequency of class I integron associated gene cassettes, in particular dfr and aadA, present in MDR strains of Citrobacter. This data indicates an important role of integrons in the creation and transmission of MDR strains in health care centers.
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INTRODUCTION: Klebsiella pneumoniae (K. pneumoniae) is an important opportunistic pathogen causes serious community and hospital-acquired infections, which is highly resistant to antibiotics. We aimed to determine the frequency of multidrug resistant (MDR) and molecular typing of clinical isolates of K. pneumoniae. METHODOLOGY: One hundred isolates of K. pneumoniae were collected from clinical samples in three general hospitals in Kermanshah. The antimicrobial susceptibility and extended-spectrum beta-lactamases (ESBL) production of isolates were determined using disk diffusion and combined disk methods, respectively. The blaCTX-M gene, class I and II integrons were detected using polymerase chain reaction. The blaCTX-M positive isolates were selected for genotyping using pulsed-field gel electrophoresis (PFGE). RESULTS: MDR phenotype was observed in 56% of isolates. The 40% of isolates were ESBL positive and 35 isolates contained blaCTX-M. Class I and II of integrons were detected in 50 (89.2%) and 39 (69.6%) of MDR isolates, respectively. PFGE patterns of K. pneumoniaeblaCTX-M positive isolates indicated 19 clusters (X1-19) with different genotype patterns. CONCLUSIONS: The study findings highlight the concern of circulating MDR strains of K. pneumoniae with blaCTX-M and class I and II integrons in Kermanshah hospitals. The presence of integrons among isolates may facilitate the spread of new resistance genes in this bacterium. Therefore, surveillance for the spread of MDR strains of this bacterium is recommended in hospitals.
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BACKGROUND AND OBJECTIVES: Citrobacter freundii is an opportunistic pathogen causing nosocomial infections and resistant to various antibiotics. We aimed to determine the clonal relationship of C. freundii isolates using Pulsed-Field Gel Electrophoresis (PFGE). MATERIALS AND METHODS: Fifty clinical isolates of C. freundii were collected from the main hospital in Kermanshah. After antibiotic susceptibility testing and screening for extended-spectrum beta lactamase (ESBL), all isolates were genotyped by PFGE. The DNA fragment patterns were analysed using Gelcompar II version 6.6 software. The Dice coefficient was used to calculate similarities for cluster analysis. RESULTS: The PFGE results of 12 (24%) and 38 (76%) ESBL positive and negative isolates, respectively, produced 39 clusters (X1-39) with different genotype patterns. The X1 and X2 clusters were the major clusters, each contained 3 isolates from different hospital wards. However, the majority of isolates showed a high genotypic diversity. CONCLUSION: Results revealed the genotypic diversity of C. freundii isolates indicating the various sources for the bacterial isolates. However, the presence of isolates with similar genotypes indicates the common origin for these strains and may reflect the strain dissemination within the hospital wards, in particular in infectious ward and intensive care unit.
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BACKGROUND: Aseptic meningitis is the most common type of meningitis and is characterized by meningeal inflammation that is not linked to identifiable bacterial pathogens in cerebrospinal fluid (CSF). OBJECTIVES: This study aimed to evaluate the frequency of aseptic meningitis caused by herpesviruses, namely herpes simplex types I and II (HSV-1, HSV-2), Epstein-Barr virus (EBV), cytomegalovirus (CMV) and varicella-zoster virus (VZV). PATIENTS AND METHODS: A total of 196 CSF samples were collected from patients with suspected meningitis. All samples were smear- and culture-negative for bacterial pathogens. The biochemical and cytological findings of CSF samples were also recorded. DNA was extracted from samples and PCR with specific primers was carried out to detect viruses. RESULTS: The 196 samples derived from 100 (52%) men and 96 (48%) women ranging in age from one day to 86 years with an average age of 32.3 ± 25.3 years. Of them, 8 (4.08%) samples yielded positive results, including 5 (2.55%) cases of VZV infection and 3 (1.53%) cases of HSV-1 infection. No cases of HSV-2, CMV or EBV infection were detected. CSF protein and glucose levels among positive cases were all in the normal range. CONCLUSIONS: The results indicate a considerable rate of herpesvirus infection in patients with aseptic meningitis, and that VZV is the most common herpesvirus to cause infection followed by HSV-1. Our results also showed that a moderate increase in the WBC count and predominance of lymphocytes can be valuable clues in diagnosing viral meningitis. Given the different approaches of drug therapy in bacterial and viral meningitis, use of molecular methods is necessary in hospitals to rapidly discriminate between them.
