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Rivaroxaban is an anticoagulant drug that prevents forming of blood clots. In addition, it can be administered to prevent and treat thrombotic diseases such as atrial fibrillation, cardiac arrhythmia, heart valve disease, orthopedic surgery, and thrombophilia to reduce the risk of thrombosis. Various factors such as age, gender, diet, medications, and genetic factors effectively determine the dose of rivaroxaban. Genetic variability in drug-metabolizing enzymes, including the cytochrome P450 (CYP450) enzymes and especially CYP3A4, has been associated with rivaroxaban response. The current study aimed to identify the frequency of CYP3A4 common polymorphisms, as well as their association with rivaroxaban response in 100 patients of Arab descent (48.6% female). CYP3A4 gene polymorphisms were examined by the PCR-RFLP method, and the findings were analyzed by SPSS 16 software and t-test. The frequency of CYP3A4*1B/*1B, CYP3A4*1B/*1A, CYP3A4*1B/*1C, and CYP3A4*1A/*1C was 67.35%, 10.64%, 19.12% and 2.89%, respectively. According to our results, CYP3A4 *1B/*1B genotype was the most common, and patients with CYP3A4*1B/*1B alleles needed a higher daily dose of rivaroxaban than *1B/*1A, *1B/*1C, and *1A/*1C carriers (9.57 ± 1.54 mg/day, P=0.015). Therefore, according to the results, CYP3A4 gene polymorphism has an important effect on the dose of rivaroxaban required to maintain the International Normalized Ratio (INR) in the range of 2-3. Article info

The rising occurrence of infections generated by Escherichia coli and Klebsiella pneumoniae that produce extended-spectrum β-lactamase (ESBL) is reason for concern. Due to the recent emergence of multidrug-resistant microorganisms that develop ESBL. The purpose of this work was to detect the ESBLs in clinical isolates of E. coli and K. pneumoniae. 118 samples of E. coli and 63 isolates of K. pneumoniae were collected from clinical samples. Polymerase chain reaction was used to detect β-lactamase genes (i.e., blaTEM, blaSHV, and blaCTX-M). Phenotypic detection revealed that 48.31% and 85.19% of E. coli and K. pneumoniae produced ESBLs, respectively. Whereas screening of ESBL genes in both bacteria employing a multiplex PCR test revealed that 24.58% of the ESBL-producing E. coli strains contained blaTEM, 50.85% contained blaSHV, and 32.2% contained blaCTX-M. Nevertheless, in K. pneumoniae, 40.74% blaTEM, 35.19% blaSHV, and 64.81% blaCTX-M genes were present. Antimicrobial resistance profiles of E. coli and K. pneumoniae isolates to twenty antibiotics were observed to vary significantly. Additionally, it was determined that the majority of E. coli and K. pneumoniae isolates were multidrug resistant (MDR). Additionally, 80.51% of E. coli isolates were resistant to the AMC antibiotic, while 0.00% were resistant to IPM and MEM. From the other hand, the resistant proportion of K. pneumoniae isolates was heterogeneous, ranging from 69.84% against CAZ to 0.00% against CIP and G antibiotics. The blaSHV gene was the most widespread among different forms of ESBLs in E. coli, but the most common gene in K. pneumoniae isolates was blaCTX-M (64.81%).

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