Tehran University Medical Journal

Background: Candida species are opportunistic yeasts that are capable of causing different infections and diseases among immunocompromised patients. Since Candida infections are major causes and frequent of septicemia in Neonatal Intensive Care Units (NICU), and they are associated with high morbidity and mortality rates, so obtaining adequate treatment seems necessary. Low birth weight preterm infants are especially vulnerable to these devastating infections. The aim of this study was to evaluate the drug susceptibility of Candida species colonized on the skin and mucous membrane of neonates to fluconazole, amphotericin B and caspofungin.
Methods: This study was carried out in the laboratory of medical mycology and serology, School of Public Health, Tehran University of Medical Sciences for the period of 7 months from June 2016 to December 2016. In this descriptive cross-sectional study, 23 isolates of Candida species including Candida parapsilosis, Candida albicans, Candida tropicalis, Candida guilliermondii and Candida krusei were studied. These under study isolates were previously isolated from skin and mucous membranes of neonates in NICU of Imam Khomeini Hospital and Children's Medical Center were identified by PCR-RFLP (Polymerase chain reaction-restriction fragment length polymorphism). Evaluation of antifungal drug susceptibility including fluconazole, amphotericin B and caspofungin was carried out. Antifungal susceptibility test was done according to the standard protocol Clinical and Laboratory Standards Institute (CLSI M27-A3) that is specific to the yeast fungi. Statistical analysis was done by using T-test in SPSS version 22 (IBM, Armonk, NY, USA) and P<0.05 was considered statistically significant.

Conclusion: According to the results, all isolated Candida species were more sensitive to amphotericin B and caspofungin than other antifungal drugs. In final conclusion, Finally, it is emphasized that antifungal susceptibility testing is necessary to prevent treatment failure or recurrence of disease.

Cutaneous leishmaniasis (CL) is an endemic parasitic disease of major health impact in many parts of the world and is caused by several species of the protozoan parasite Leishmania. Antimonial compounds (i.e glucantime and pentostam) are the first-line treatment for cutaneous leishmaniasis with emerging drug resistance as a problem. The control of Leishmania is further complicated by the emergence of drug-resistant parasites. In the clinical settings, resistance to SbV containing drugs is now well established and it was found to occur in South America, Europe, the Middle East and most notably in India. Clinical resistance to organic pentavalent antimonials, in the form of sodium stibogluconate (pentostam) or N-methylglucamine antimoniate (glucantime), has long been recognized. However, it is unknown whether the clinical failure of chemotherapy is attributable to the development of drug resistance mechanisms in the parasite or to a variety of host factors that might also contribute to low drug response. Reported rate of drug-resistance to antimonial compounds in Iran varies from 9.4% to 94.2% and there is not any comprehensive study on this issue. Indeed, in the endemic region treatment with SbV fails in more cases; thus, in general patients infected with resistant parasites are unresponsive although exceptions have been reported. This article aims to review the mechanisms of drug resistance to these compounds. The main resistance factors include genetical, enzymatic, intracellular (such as apoptosis and cytoskeleton changes) and resistance proteins. Also, mechanisms related to drug transport and intracellular activation are discussed. Various methods of drug resistance detection such as culture and molecular methods (i.e polymerase chain reaction) are reviewed. Although the exact mechanism of action glucantime is not clear, it seems that protein and gene factors involved in cellular drug entry are the main causes of drug resistance. Cross-sectional studies on meglumine antimoniate resistance in endemic areas of cutaneous leishmaniasis in Iran are highly recommended. Also, studies for evaluation of alternatives therapies for antimonial resistant cases are required.   

Background: Methotrexate (MTX) is commonly used in the hematology-oncology units and is frequently associated with adverse effects. High-dose methotrexate (HDMTX) is indicated in the treatment of acute lymphoblastic leukemia (ALL), osteosarcoma, systemic non-Hodgkin lymphoma and primary central nervous system (CNS) lymphoma. The side effect profile of MTX varies markedly according to dose. The aim of this study was to evaluate the uses and adverse effects of HDMTX in a cancer center in north of Iran.
Methods: This cross-sectional descriptive study carried out in Emam Sajjad Hospital, Ramsar, Iran from June 2016 to July 2017. Doses more than 500 mg/m2 of MTX was considered as a high-dose. Hydration status, evaluation of the renal and hepatic function, blood tests, urine pH, doses and frequencies of leucovorin administration, measurement of serum levels of MTX and side effects were evaluated. Recommendations of UpToDate 2017 were considered as standards of administration of HDMTX.
Results: Forty-four courses of HDMTX were evaluated in this study. HDMTX were prescribed for lymphoma (30 cases), ALL (8 cases) and osteosarcoma (6 cases). In all patients, hydration was done with 1340.9±894 normal saline plus 25 ml sodium bicarbonate 8.4%, one to two hours before HDMTX. The solution used for dilution of MTX was 5% dextrose (1022.7±105.5 ml). Urine pH was not measured in any patient. The frequency of leucovorin administration was 5.64±3.03 times with doses of 17.6±1.7 mg/m2 every 6 hours. Serum levels of MTX were not measured in any patient. Blood urea nitrogen and creatinine measurement was carried out before administration of HDMTX in all patients. The most common adverse effects were nausea (64.4%), anxiety (44%) and headache (43.2%).
Conclusion: The appropriate aspects of HDMTX usage were good hydration, urine alkalinization with bicarbonate and administration of leucovorin in patients receiving HDMTX, whereas monitoring of serum levels of MTX and administration of bicarbonate based on urinary pH were not done in any of the patients.
 

Background: 2-phenylethanol is a colorless and aromatic compound with antimicrobial effects which is used extensively in perfumes and cosmetics, as well as in the food industry. Chronic vulvovaginal candidiasis is a vulvovaginal inflammation which is caused by Candida spp. Resistance to clotrimazole which is one of the most common drugs in the treatment of this disease was reported in many patients. In order to improve the treatment, the effect of 2-phenyl ethanol was investigated in combination with clotrimazole on Candida species isolated from chronic vulvovaginal candidiasis.
Methods: This interventional study was performed in Iran University of Medical Sciences from February, 2016 until December, 2016 on Candida species isolated from women with chronic candidial vulvovaginitis who had been referred to Lolagar Hospital of Tehran. All specimens were examined by direct microscopy, culturing on Candida CHROMagar medium (to primary identification), sabouraud dextrose agar medium) to preservation the isolates) and determining the internal transcribed spacer (ITS) sequence (in order to final determination of Candida species). Then clotrimazole and 2-phenyl ethanol alone and in combination, was examined on isolated species, according to Clinical and Laboratory Standards Institute (CLSI) M27-A3 protocol (micro-broth dilution method). Finally, findings were analyzed.
Results: From 40 detected strains of Candida species in this study, 95% were Candida albicans and 5% were Candida africana. The mean minimum inhibitory concentration (MIC) and minimum fungicidal concentration (MFC) of clotrimazole were 24.73±28.87 µg/ml and 30.18±33.004 µg/ml, respectively and the mean MIC and MFC of 2-phenylethanol were 2580±932.38 µg/ml and 3200±1403.29 µg/ml, respectively. The MIC50 and MIC90 of clotrimazole were 16 and 64 µg/ml, respectively. The MIC50 and MIC90 of 2-phenylethanol were both 3200 µg/ml. Most of the isolates were resistant to clotrimazole (82.5%). In combination test, the mean MIC of 2-phenylethanol and clotrimazole alone were 3200±0 µg/ml and 56±40.16 µg/ml, respectively. The fractional inhibitory concentration index (FICI) range was 0.14-0.37. Also, there was a significant difference between clotrimazole MIC values alone and in combination (P= 0.021).
Conclusion: The synergistic effect was observed in combination of clotrimazole and 2-phenylethanol.

Today, nanoscience has grown and developed in various medical and therapeutic areas, including cancer treatment. On the other hand, cancer and its types have been rumored and inclusive and many people suffer from this fatal and deadly disease. Currently, existing therapeutic method, including chemotherapy, radiotherapy, and etc., along with the therapeutic effect, cause complications that are unpleasant for patients. Hence, scientists and researchers are looking to develop and improve treatment options and methods to deal with this serious disease. Today, nanoscience and nanotechnology have become widespread, and its various fields, including nanoparticles, are widely used for a variety of applications, especially for delivery of drugs and diagnostic items and imaging cases. Nanotechnology-based release systems have a significant impact on the release of cancer drugs. Advances in bio-materials and bio-engineering are contributing to new approaches to nanoparticles that may create a new way for the improvement of cancer patients. Nano-technology in the drug release system has had a great impact on the selection of cancer cells, the release of a targeted drug, and overcoming the limitations of conventional chemotherapy. At the present many drug delivery systems are now made of nanoparticles, and various substances have been used as drug-stimulating agents or as a reinforcing agent to improve the efficacy of the treatment and durability and stability and also the safety of anticancer drugs. The materials used to release cancer drugs are divided into various categories such as polymer, magnetic, biomolecules. In the meantime, polymer nanoparticles have been organized in the carriers of anti-cancer nanoparticles due to the process of easy production, biocompatibility, and biodegradability. Although the loading of hydrophilic compounds is still confronted with limitations, due to the diversity of nanoparticle structures, it is possible to encapsulate various molecules. Also, surface changes and modification such as binding to antibodies and target ligands can also be applied to these materials, to act as target drug delivery to increase the effectiveness of treatment process. In this article, we will have an overview of cancer disease and cancer drugs and also nanoparticles and their contribution to cancer treatment.

Cancer is one of the most dangerous health problems of today modern societies which has an increasing rate especially in developing countries. There are many diverse ongoing treatment attempts trying to defeat cancer. Despite that, scientists have been unable to find a permanent cure for this disease. In many cases although there is a successful first response in patients, cancer cells are finally able to withstand therapeutic procedures and even use chemo-resistance to take advantage of treatments to facilitate tumor growth, resulting in cancer remission. Therefore, and mostly in recent two decades, scientists have been trying to choose their treatments just as smart to be able to conquer cancer. One of the best methods of this smart defense is to target weak points of neoplastic cells and use them for designing drugs. In this case it would be most probable for cancer cells not to have a chance to confront and cause chemo-resistance. Total endeavors to fulfill this goal are named “targeted cancer therapy”. This therapeutic approach is mostly consisted of two different procedures: 1- designing and using specific drugs to target cancer cells’ mutated genes; which will be defined by checking the genetic background of tumor cells for each specific cancer type. EGFR, RAS, VEGF and HIF-1α are among the pathways that have already been used as targets. 2- The other procedure could be methods that would carry drugs directly to unhealthy cells to prevent further side effects for normal cells of patients. It would be possible by designing specific antibodies to target antigens of neoplastic cells. Ribonucleic sequences (miRNAs and siRNAs) are also very promising as new drugs and nanoparticles have enabled us to increase drug concentration in tumors. The ultimate goal of these new experiments is to suggest specific drugs for each patient based on the nature of one's disease and genetic background, which will bring about "personalized medicine" era. Using valid new references, this review article first presents targets that are currently being used for this targeted therapy, their logic of choice and the drugs that have already been produced for clinical trials. Smart methods of drug delivery are also presented and discussed afterwards.

Background: Escherichia coli (E. coli) is one of the most important infectious agents in patients undergoing prostate biopsy. It belongs to a large family of gram-negative rods, Enterobacteriaceae. This family includes members of the normal flora of the intestine that are only occasionally pathogenic. Recent considerations of rectal colonization with fluoroquinolone-resistant E. coli shows the need to change strategy of treatment of infection in patients undergoing prostate biopsy. Therefore, the purpose of this study was to determine molecular typing of fluoroquinolone resistant (FQR) E. coli rectal isolates and associated infections in patients undergoing prostate biopsy.
Methods: In this prospective cohort study, rectal swabs were collected from 158 male patients before prostate biopsy at the Urology Research Center of Sina Hospital, Tehran, Iran, from March 2015 to February 2016. The FQR organisms were isolated using selective media, and antibiotic susceptibility pattern was determined for following antibiotics, ampicillin, levofloxacin, cotrimoxazole, amoxicillin-clavulanate, cefazolin, ceftazidime, cefepime, gentamicin, piperacillin-tazobactam, nitrofurantoin, amikacin, fosfomycin, imipenem. In general, phylogenetic background, prevalence of E. coli sequence type 131 (ST131) and its subclones (H30 and H30-Rx ST131) were compared in two groups of FQR E. coli rectal colonization and clinical isolates.
Results: In total, 73 patients had a positive rectal culture for FQR gram-negative bacteria, the most prevalent isolate of which was E. coli. Phylogenetic group B2 was most predominant, followed by A, E, C and D, B1 and F. The antibiotic susceptibility patterns for the FQR organisms showed high levels of resistance to ampicillin and trimethoprim-sulfamethoxazole, while the resistance to amikacin, fosfomycin and imipenem remained very low. In general, antibiotic resistance to several antibiotic was mainly detected in group B2 and with ST131 genotype. Despite the increase in infections among patients colonized with strains of E. coli ST131, its frequency was almost statistically significant between colonized and infected groups.
Conclusion: The ST131 pathogen has a high prevalence in rectal colonization and post prostate biopsy infections, which showed widespread resistance to common antibiotics.

Background: Metronidazole resistant clostridium difficile is one of significant pathogens in Iran. It is one of the WHO-declared microbial resistance emergencies. Prevalence of metronidazole resistant clostridium difficile is rising. The aim of this study was to detect prevalence of metronidazole-resistant clostridium difficile using meta-analysis in Iran.
Methods: This study was conducted as a meta-analysis. Articles and derivatives were reviewed by two researchers. Initially, each of the researchers searched the databases separately and used all available Persian and English articles in Kurdistan University of Medical Sciences, Iran, from October 2017 to February 2018. Persian databases (including Magiran, Irandoc, Barakat and SID) and international databases (including PubMed, Sciencedirect, and Scopus) were searched during this period (2007-2016) with a combination of phrases and keywords. The list of references to these studies has also been evaluated and relevant articles have been included in the study. First, all the articles were extracted and then duplicated articles were deleted using the EndNote software, version X6 (Thomson Reuters™, New York, NY, USA) through the search for electronic banks. Such that the high heterogeneity (50% Results: From the search of medical databases at first, 68 articles were selected. In total, 19 remaining studies entered the meta-analysis phase. In this study, the overall prevalence of clostridium difficile is 32.57% (CI95%: 21.86-44.30); in 2016 it was 55.25% (CI95%: 50.22-60.19) and in 2009 was14.26% (CI95%: 12.32-16.37). The heterogeneity was estimated to be 98.7% (CI95%: 98.5-98.8).
Conclusion: Based on the results of this study, the prevalence of metronidazole resistant clostridium difficile in Iran is high and increasing.

Currently, there are about 37 million people worldwide living with human immunodeficiency virus (HIV) /AIDS, with an estimated two million new cases per year globally. According to estimates from the World Health Organization (WHO), only 75% of the population with HIV know their status. Initially, HIV infection was associated with significantly increased rates of mortality and morbidity. However, the rapid advances in treatment and the advent of different classes of antiretroviral drugs over time have led to change the face of HIV/AIDS from a deadly infection to chronic and manageable disease. There is strong evidence that HIV-infected patients undergoing antiretroviral therapy have longer lives and are less likely to transmit infection to their sexual partners. Since the introduction of zidovudine in 1987 as the first antiretroviral drug, significant strides have been made in antiretroviral therapy. The introduction of potent antiretroviral drugs for the treatment of HIV infection has been one of the significant events in the evolution of modern medicine. Antiretroviral therapy refers to the use of drugs in the treatment of HIV. Generally, these drugs are categorized based on the steps of the HIV life cycle suppressed by them. There are six main classes of antiretroviral agents including nucleoside/ nucleotide reverse transcriptase inhibitors, non-nucleoside reverse transcriptase inhibitors, protease inhibitors, fusion inhibitors, co-receptor inhibitors, and integrase inhibitors. Combination antiretroviral therapy should be considered for HIV patients to achieve the highest viral suppression rate, and to reduce the risk of resistance development and morbidity and mortality associated with AIDS. Achieving and maintaining HIV viral load suppression among treated patients has remarkably increased over the last years due to the development of potent and well-tolerated agents which can be co-formulated as a once-daily single-tablet or fixed-dose combination for simplification. However, there are some limitations preventing patients to benefit from this treatment. The main goals of HIV therapy in the future are to overcome the limitations of current treatment, including side effects. This review will provide an overview of advances in the current antiretroviral drugs by focusing on their pharmacokinetics, mechanism of action, dosing recommendations, and adverse events for each drug class.

Background: The ineffectiveness of hemodialysis fistulas causes high costs and increases mortality and morbidity rates. The efficacy of drug-coated balloon and nondrug-coated balloon in dysfunctional arteriovenous Fistula was evaluated over six month period.
Methods: In this randomized clinical trial, a total of a total of 50 hemodialysis patients who referred to Imam Reza Hospital in Kermanshah for failing of arteriovenous fistula in 2018 year, were randomly divided into two separate groups of drug-coated balloon angioplasty and non-drug coated balloon angioplasty. All of these procedures were done with the same surgeon. Patients were followed-up for 6 months. Variables and data of patients like age, gender, diabetes mellitus, hypertension, and location of arteriovenous fistula were documented and analyzed by SPSS software, version 21 (SPSS Inc., Chicago, IL, USA) using statistical tests. T-test and chi-square test were used for data analysis and the significance level was considered less than 0.05.

The highly contagious new coronavirus virus, SARS-CoV-2, was first appeared in Wuhan, China in late 2019. The virus has spread to 216 countries, including Iran, until 7 September 2020. So far, the number of people infected by the new corona virus and died from the disease is 27032617 and 881464 worldwide, respectively. Therefore, it is necessary to introduce the available treatments for this virus, as a global dilemma. Articles for this review study were selected from Embase, Medline and Google Scholar. Published full articles in English, English full articles published from 1st December 2019 to 23rd July 2020, were included. The search terms included combinations of COVID-19, SARS-COV-2, chloroquine, convalescent plasma, antiviral, antibacterial, Remidesivir, hydroxychloroquine, chloroquine phosphate, vaccines and monoclonal antibodies. There were no restrictions on the types of study eligible for inclusion. Different available therapies generally can be divided into small molecules and biological products. Among the small molecule drugs used for COVID-19 patients Remdesivir, Favilavir, and hydroxychloroquine have been associated with considerable success in disease control. Separation and transfusion of plasma from blood of improved COVID-19 patients to new patients and the use of recombinant Angiotensin converting enzyme 2 (ACE2) have been two very successful biological therapies in the treatment of COVID-19 disease. However, many efforts are being made by researchers around the world to make other effective and promising biological products. The development of a safe and effective vaccine can lead to great success in eradicating the disease. Also, the production of anti-SARS-CoV-2 monoclonal antibodies and using of stem cell-based therapeutics can be a great success in treating the disease. In addition, according to the miRNA properties, many efforts have been made to inhibit the production of viral proteins using natural miRNAs or artificial siRNAs. It has been proposed that aptamers derived from SELEX can be used for the diagnosis and treatment of COVID-19. Subsequently, since the size of miRNAs is at the nanometer level, they can easily incorporate to the targeted exosomes and be delivered via circulation in human blood to the infected cells such as lung cells. Interestingly, miRNAs can be delivered into the lung by inhalation.

Background: Nicolau syndrome is a rare condition that happens after intramuscular injection. All the intramuscular injections may have mild to moderate complications such as pain, focal abscess, nerve complication and anaphylactic reactions. Among these complications, wide necrosis of the skin like Nicolau syndrome happens very rarely. In this condition, Patients typically report acute, intense pain, immediately after drug injection and it is followed by an erythematous macular evolving after 24 hours into a livedoid violaceous patch with dendritic extensions. The study has been reported a case report of a 6-month-old infant who suffered from Nicolau syndrome after the injection of pentavalent vaccine.
Methods: A 6-month-old girl infant without a history of any disease was referred to the emergency department with the signs of erythema, edema and purple like discoloration in the vaccine injection site at the left tight, after vaccination. One hour after admission, in the lower limb severe edema along with an extension of a dark red to purple discoloration happened on different parts of foot and after 5 days they turned necrotic. The infant suffered from Nicolau syndrome after the injection of the pentavalent vaccine.

Background: Considering the frequency of MRSA strains in hospitals and medical centers as well as in different communities, it seems necessary and important to observe the use of appropriate drugs in order to reduce antibiotic resistance and reduce the economic costs of treatment. This study aimed to investigate the antibiotic resistance pattern of MRSA isolated from blood and wound samples of patients. The study patients were hospitalized in different departments in a number of Tehran University of Medical Sciences hospitals.
Methods: In this descriptive cross-sectional study from September 2021 to February 2022, the blood and wound samples of the patients were collected and referred to laboratory. Staphylococcus aureus had identified by phenotypic and biotypic tests. MRSA isolates were screened by showing resistance to Cefoxitin by disc diffusion method and finally confirmed by examining the mecA gene by PCR. The microbial resistance pattern of MRSA was also measured by disk diffusion method and resistance to Vancomycin was confirmed by E.test.

Results: 41 isolates from 87 Staphylococcus aureus samples were confirmed as MRSA by present the mecA gene. The mecA gene was detected in all MRSA by PCR method. The antibiotic resistance pattern showed the highest sensitivity to Vancomycin and Linezolid with 100% sensitivity and the highest resistance to three antibiotics Erythromycin, Ceftriaxone and Cloxacillin with 97.57%by disk diffusion method. The most MRSA strains were isolated from the ICU department with 13 cases and the least MRSA strains were isolated from the two NICU and pediatric departments with one case.The majority of the population infected with MRSA belonged to the age group of 40-65 years. Conclusion: The prevalence of microbial resistance with high dispersion was obtained among MRSA strains isolated from clinical samples; which indicates a significant increase in resistant strains and requires a quick and timely diagnosis to prescribe the appropriate antibiotic.

Results: The findings of the present study showed that the average age in the group with perforation was 48.7 and in the group without perforation was 42.04. In the non-perforated group, 58.5% of the patients were male, and in the group with perforation, 82.2% of the patients were male. In terms of smoking, 29.6% were smokers in the group without perforation and 50.4% were smokers in the group with perforation. Opium consumption was about 15.6% in people without perforation and about 33.3% in people with perforation. In terms of NSAID use, the prevalence was 35.6% in the group without perforation and 27.4% in the group with perforation. PPI consumption was 46.7% in the group without perforation and 21.5% in the group with perforation. In terms of the prevalence of H.pylori infection, the prevalence in the non-perforated group was 45.2% and in the perforated group it was 30.4%. The previous history of PUD was 56.3% in the non-perforated group and 37.8% in the group with perforation. Conclusion: There was a significant difference between cigarette and opium consumption in the perforated and non-perforated groups, and PPI consumption in these two groups. In general, the prevalence of PUD was higher in males in both perforated and non-perforated types. Fuzzy results also confirmed the effect of risk factors concordance with perforation.

Background: Neutropenia refers to a decrease in the absolute number of neutrophils in the blood circulation, certain drugs are used in connection with the treatment of neutropenia. Therefore, the aim of this study is to investigate and compare the efficacy of filgrastim and lenograstim drug treatment in patients with neutropenia in a systematic review.
Methods: This study is a systematic review study conducted in connection with the comparison of the effectiveness of filgrastim and lenograstim in neutropenic patients based on the search in Google scholar, PubMed, ScienceDirect, Irandoc, SID, Magiran databases in the time range of January 2000 to August 2023. This systematic review was based on the criteria of the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement, including systematic search of databases, organization of documents for review, selection of studies, information extraction and finally presentation of the final report. The keywords used for searching in this study were selected based on published primary studies and MESH, and after a detailed examination of the study questions, they were selected according to the PECO criteria.

Results: 1099 articles were identified in the review of the investigated databases, and after removing duplicate articles, unrelated articles, as well as articles that did not have access to their full text or did not have the required information, eight studies were the final phase, and were checked. Out of the eight selected articles, three articles declared the effectiveness of lenograstim more than filgrastim. Two articles mentioned the greater effect of filgrastim and three articles published in recent years declared the effect of two drugs to be the same. Among these articles, the studies that considered the drug dosage to be the same in the investigated groups and the studies that had a larger statistical population in order to generalize to the society are more important.