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Showing 3 results for Drug Resistance
Study of STAT3 Expression in Different Phases of Patients with Chronic Myeloid Leukemia
Peyman Yousefi, Shahrbano Rostami, Nasrin Alizadeh Ghandfurosh, Saeed Mohammadi, Mohsen Nikbakht, Laya Ghadyaninejhad, Bahram Chahardouli,
Volume 13, Issue 2 (7-2019)
Abstract
Background and Aim: Chronic myeloid leukemia(CML) is a clonal myeloproliferative disease, characterized by BCR/ABL translocation. Using tyrosine kinase inhibitors such as Imatinib, treatment for this disease has progressed remarkably. However, resistance to tyrosine kinase inhibitor is a major obstacle. Signal transducer and activator of transcription 3(STAT3) is an important transcription factor in proliferation and survival of several cancers. The aim of this study was to determine the expression of STAT3 and its role in drug resistant CML patients treated with Imatinib.
Materials and Methods: Peripheral blood was collected from 71 CML patients in different phases of the disease and 10 healthy individuals. After extracting RNA and synthesizing cDNA, expression of STAT3 gene was measured using Real-Time PCR technique. The expression of STAT3 was normalized to ABL control gene. Then expression levels were compared with the control group.
Results: The results showed that expression of STAT3 in the diagnostic stage was significantly higher than healthy individuals(p=0.0001). STAT3 expression was not significantly different from MMR and the control group. STAT3 expression was significantly higher in non-mutated and mutated ABL kinase domain Imatinib resistant patients as compared to patitents in MMR stage (p=0.0014 & p=0.003). This difference was not significant between the two resistant groups. Blastic phase patients had no significant difference in the expression of STAT3 with the control group.
Conclusion: Considering the results of this study and the role of STAT3 in cell proliferation and survival, the targeting of STAT3 seems to be an effective option in the treatment of resistant patients.

Synergism of Linezolid and Rifampin to Combat Multidrug-Resistant Environmental Enterococci Isolates
Mobina Noori, Leila Fozouni, Ania Ahani Azari,
Volume 16, Issue 3 (8-2022)
Abstract
Background and Aim: Wastewater is one of the most dangerous and important sources of pathogens and their treatment does not always guarantee the elimination of pathogenic bacteria. Enterococci, as opportunistic pathogenic bacteria, fastidious and cause of nosocomial infections, have a wide environmental distribution and one of the routes of their transmission to humans is water and wastewater. The increasing rate of drug- resistance among bacteria indicates the need for investigation of novel antibacterial agents or their combination effects. The aim of this study was to investigate the effect of linezolid in combination with rifampin on the elimination of multidrug- resistant enterococci in two treatment plants in Golestan province. 
Materials and Methods: Enterococcus species from eighty samples were isolated from treatment plants in two cities of the Golestan Province (North of Iran) including Gorgan and Bandar-e Torkaman during January-June 2021. The isolates were identified based on the most probable number (MPN), filtration, microbiological tests and finally by using specific gene detection by ddlE primer with polymerase chain reaction. Kirby Bauer performed an antibiotic resistance pattern according to CLSI- 2020 guidelines for six classes of antibiotics. The minimum inhibitory concentration of linezolid was determined individually and by synergist effect with rifampin by broth microdilution method. 
Results: After phenotypic and molecular diagnosis (PCR) of raw and treated wastewater samples, in 32 (40%) wastewater samples, enterococci species were identified and confirmed. Tetracycline was the least effective so, about 100% of Enterococcus faecalis and Enterococcus faecium isolates were resistant to it. The prevalence of linezolid-resistant E. faecalis was 11%. A total of 20 enterococcal isolates (62.5%) had multiple resistance. The concentration of linezolid in combination with rifampin, which inhibited 90% growth of the isolates (MIC90) was 1μg /ml, four-fold lower than linezolid alone (MIC90=4 μg/ml). In addition, none of the enterococci isolates showed resistance to the linezolid/rifampin combination (P=0.001).
Conclusion: The results of this research confirmed the presence of enterococci resistant to vancomycin and other antibiotics in the wastewater treatment plant samples in Golestan province. The favorable combination effect of linezolid and rifampin on the inhibition of multi-drug resistant isolates implies their synergy.
 

Comparison of the Antibacterial Efficacy of Fosfomycin and Cefiderocol Against Multidrug-Resistant and Extensively Drug-Resistant Uropathogenic Klebsiella Pneumoniae Isolates
Leila Fozouni, Fatemeh Omidi, Sara Malekpour Kolbadinezhad,
Volume 20, Issue 1 (4-2026)
Abstract
Background and Aim: Klebsiella pneumoniae is among the most important pathogens responsible for nosocomial infections worldwide. In recent years, multidrug-resistant (MDR) and extensively drug-resistant (XDR) K.pneumoniae, the causative agent of urinary tract infections (UTI), have emerged as a major global health problem. This study aimed to investigate the prevalence of MDR and XDR K.pneumoniae originating from urinary infections and to compare their antimicrobial susceptibility to fosfomycin and cefiderocol.
Materials and Methods: This descriptive cross-sectional study was conducted using 208 urine samples from hospitalized individuals during 2023-24. After identifying carbapenemase-producing K.pneumoniae strains by phenotypic and genotypic (PCR) tests, MDR and XDR isolates were identified using the Kirby-Bauer method and broth microdilution test according to the CLSI-2021 guideline. The minimum inhibitory concentrations of cefiderocol and fosfomycin were determined using broth microdilution and agar dilution, respectively.
Results: Of the 57 carbapenemase-producing K.pneumoniae isolates, about 84% were collected from urine samples of patients hospitalized for more than 1 week and hospitalized in the intensive care unit (P<0.05), of which the highest level of resistance was observed to aztreonam (84.21%), followed by tetracycline (57.90%). Among the carbapenemase-positive K.pneumoniae isolates, 87.72% exhibited multidrug resistance, and 57.90% demonstrated extensive drug resistance. No significant differences were observed between age groups and gender in antimicrobial resistance (P=0.06). The effects of different fosfomycin concentrations showed that the highest growth changes were observed at concentrations of 16 μg/mL and 32 μg/mL, and 90% of the MDR and XDR strains were inhibited at concentrations of 64 and 512 μg/mL, respectively, with susceptibility rates equal to or greater than 92%. In determining the minimum inhibitory concentration of cefiderocol, the susceptibility rates of K.pneumoniae isolates that were multi- and extensively resistant to it were confirmed to be 88% and 79%, respectively.
Conclusion: Considering the antibacterial effect and potential of fosfomycin in laboratory conditions, which is estimated to be 1.3 times that of cefiderocol, the results of this study suggest that fosfomycin may be effective in treating urinary tract infections with high drug resistance.

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