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Abstract Background Aminoglycosides have been a cornerstone of the treatment of nosocomial infections caused by Pseudomonas aeruginosa for over 80 years. However, escalating emergence of resistance poses a significant challenge. Therefore, this study aimed to investigate the prevailing patterns of aminoglycoside resistance among clinical isolates of P. aeruginosa in Iran; as well as the underlying resistance mechanisms observed in patients referred to Ardabil hospitals. Methods A total of 200 isolates from five hospitals were evaluated. The resistance profiles of P. aeruginosa isolates to tobramycin, amikacin, and netilmicin were determined using the disk diffusion method. The capacity of aminoglycoside-resistant isolates to form biofilms was assessed through a phenotypic assay, and the results were confirmed using the gene amplification technique. The presence of genes associated with aminoglycoside resistance was detected using polymerase chain reaction (PCR). Quantitative reverse transcription PCR (qRT-PCR) was performed to measure the expression levels of genes encoding the MexXY-OprM efflux pump and PhoPQ two-component system (TCS). Results The prevalence of aminoglycoside-resistant P. aeruginosa isolates was 48%, with 94.7% demonstrating multidrug resistance (MDR). All aminoglycoside-resistant P. aeruginosa strains exhibited biofilm-forming capabilities and harbored all the genes associated with biofilm production. Among the nine genes encoding 16S rRNA methylase and aminoglycoside-modifying enzymes, three genes were detected in these isolates: aac(6’)-Ib (85.4%), ant(2’’)-Ia (18.7%), and aph(3’)-VI (3.1%). Additionally, all aminoglycoside-resistant P. aeruginosa isolates carried mexY and phoP genes, although the expression levels of mexY and phoP were 75% and 87.5%, respectively. Conclusion Given the considerably high prevalence of aminoglycoside-resistant P. aeruginosa strains, urgent measures are warranted to transition towards the use of novel aminoglycosides and to uphold vigilant surveillance of resistance patterns.

Abstract Background Pseudomonas aeruginosa is a common cause of nosocomial infections. However, the emergence of multidrug-resistant strains has complicated the treatment of P. aeruginosa infections. While polymyxins have been the mainstay for treatment, there is a global increase in resistance to these antibiotics. Therefore, our study aimed to determine the prevalence and molecular details of colistin resistance in P. aeruginosa clinical isolates collected between June 2019 and May 2023, as well as the genetic linkage of colistin-resistant P. aeruginosa isolates. Results The resistance rate to colistin was 9% (n = 18) among P. aeruginosa isolates. All 18 colistin-resistant isolates were biofilm producers and carried genes associated with biofilm formation. Furthermore, the presence of genes encoding efflux pumps, TCSs, and outer membrane porin was observed in all colistin-resistant P. aeruginosa strains, while the mcr-1 gene was not detected. Amino acid substitutions were identified only in the PmrB protein of multidrug- and colistin-resistant strains. The expression levels of mexA, mexC, mexE, mexY, phoP, and pmrA genes in the 18 colistin-resistant P. aeruginosa strains were as follows: 88.8%, 94.4%, 11.1%, 83.3%, 83.3%, and 38.8%, respectively. Additionally, down-regulation of the oprD gene was observed in 44.4% of colistin-resistant P. aeruginosa strains. Conclusion This study reports the emergence of colistin resistance with various mechanisms among P. aeruginosa strains in Ardabil hospitals. We recommend avoiding unnecessary use of colistin to prevent potential future increases in colistin resistance.

Background: Antibiotic resistance represents a critical global concern within the medical community, posing significant challenges in the treatment of infections caused by drug-resistant pathogens. Over the years, broad-spectrum fluoroquinolones have been extensively used to treat infections caused by both Gram-positive and Gram-negative bacteria, including Pseudomonas aeruginosa. In this study, we decided to assess the prevalence of plasmid-mediated quinolone resistance mechanisms among clinical isolates of P. aeruginosa in Ardabil hospitals. Methods: We analyzed a total of 200 clinical isolates of P. aeruginosa, collected between June 2019 and May 2023. The antibiotic resistance profiles of these strains against various fluoroquinolone antibiotics were determined using the disk diffusion method. Additionally, we investigated the presence of qnrA, qnrB, qnrC, qnrD, and qnrS genes through polymerase chain reaction (PCR) analysis. Furthermore, we assessed the expression levels of efflux pump genes and outer membrane porin genes using the quantitative reverse transcription PCR (qRT-PCR) in fluoroquinolone-resistant P. aeruginosa strains. Results: Our findings revealed that 69% of P. aeruginosa strains were resistant to fluoroquinolones. The resistance rates for different fluoroquinolones were as follows: ciprofloxacin 55.5%, ofloxacin 62%, norfloxacin 53.5%, lomefloxacin 55.3%, and levofloxacin 55.5%. Notably, 78.9% of these strains exhibited multidrug resistance (MDR). Among the qnr genes, qnrB was the most prevalent (2.9%). No other qnr genes were identified. Interestingly, 75% of P. aeruginosa strains carrying the qnrB gene showed overexpression of efflux pump genes, while 100% exhibited down-regulation of the oprD gene. Conclusion: Given the high prevalence of fluoroquinolone-resistant P. aeruginosa clinical isolates in Ardabil hospitals and the multifactorial nature of resistance, continuous monitoring of antibiotic resistance trends and understanding the underlying resistance mechanisms are crucial for selecting appropriate treatment strategies.

Abstract Background and Aims The emergence of Pseudomonas aeruginosa (P. aeruginosa) antibiotic resistance is an important public health problem worldwide that can negatively affect infection control. Therefore, obtaining knowledge about antibiotic resistance mechanisms is necessary for infection control policies. This study aimed to determine the frequency of class C and D β‐lactamases in P. aeruginosa strains isolated from patients referred to Ardabil hospitals using phenotypic and genotypic tests. Methods Phenotypic detection of β‐lactamases including AmpC cephalosporinase, oxacillinase (OXA)‐type extended‐spectrum β‐lactamases (ESBLs), and OXA‐type carbapenemases were performed using the disk diffusion‐based methods. Amplification of genes encoding classes C (ampC and FOX genes) and D (OXA‐1, OXA‐2, OXA‐10, OXA‐23, and OXA‐48 genes) β‐lactamases was performed using the polymerase chain reaction (PCR) method. A quantitative reverse transcription PCR (qRT‐PCR) method was used to determine the expression level of the ampC gene among multiple drug‐resistant and imipenem‐resistant P. aeruginosa strains. Results In phenotypic tests, the prevalence of AmpC cephalosporinase, OXA‐type ESBLs, and OXA‐type carbapenemases were 52.5%, 7.2%, and 95.8%, respectively. In genotypic tests, the prevalence of ampC, FOX, OXA‐1, OXA‐2, OXA‐10, OXA‐23, and OXA‐48 genes were 100%, 0%, 4.3%, 60.8%, 42%, 29.7%, and 2.9%, respectively. In addition, the ampC gene overexpression was seen in 16 (33.3%) drug‐resistant P. aeruginosa clinical isolates. Conclusion Given the presence of class C and D β‐lactamases in clinical isolates of P. aeruginosa in Ardabil hospitals, early detection of these strains can help prevent the spread of resistant strains in hospital environments and subsequent treatment failure.

Objective(s): Tuberculosis (TB), a contagious disease caused by Mycobacterium tuberculosis (M. tuberculosis), remains a health problem worldwide and this infection has the highest mortality rate among bacterial infections. Current studies suggest that intranasal administration of new TB vaccines could enhance the immunogenicity of M. tuberculosis antigens. Hence, we aim to evaluate the protective efficacy and immunogenicity of HspX/EsxS fusion protein of M. tuberculosis along with ISCOMATRIX and PLUSCOM nano-adjuvants and MPLA through intranasal administration in a mice model.Materials and Methods: In the present study, the recombinant fusion protein was expressed in Escherichia coli and purified and used to prepare different nanoparticle formulations in combination with ISCOMATRIX and PLUSCOM nano-adjuvants and MPLA. Mice were intranasally vaccinated with each formulation three times at an interval of 2 weeks. Three weeks after the final vaccination, IFN-γ, IL-4. IL-17, and TGF-β concentrations in the supernatant of cultured splenocytes of vaccinated mice as well as serum titers of IgG1 and IgG2a and sIgA titers in nasal lavage were determined.Results: According to obtained results, intranasally vaccinated mice with formulations containing ISCOMATRIX and PLUSCOM nano-adjuvants and MPLA could effectively induce IFN-γ and sIgA responses. Moreover, both HspX/EsxS/ISCOMATRIX/MPLA and HspX/EsxS/PLUSCOM/MPLA and their BCG booster formulation could strongly stimulate the immune system and enhance the immunogenicity of M. tuberculosis antigens.Conclusion: The results demonstrate the potential of HspX/EsxS-fused protein in combination with ISCOMATRIX, PLUSCOM, and MPLA after nasal administration in enhancing the immune response against M. tuberculosis antigens. Both nanoparticles were good adjuvants in order to promote the immunogenicity of TB-fused antigens. So, nasal immunization with these formulations, could induce immune responses and be considered a new TB vaccine or a BCG booster.

Background: Urinary tract infection (UTI) is one of the most prevalent bacterial diseases worldwide. Escherichia coli is a well-known etiological agent of UTI. The emergence and spread of metallo-beta-lactamase (MBL)-producing E. coli is a serious threat to public health. This study aimed to investigate the antibiotic resistance pattern and prevalence of MBL-producing E. coli isolated from UTI. Methods: From January 2020 to June 2021, 1200 urine specimens were collected from patients suspected of having UTI. Antibiotic susceptibility testing was carried out by the disk diffusion method. The prevalence of MBL (blaVIM, blaIMP, blaSPM, and blaNDM) genes was determined by the polymerase chain reaction (PCR) method. Results: The highest susceptibility was observed against amikacin (96%) and gentamicin (95%). The isolates were mostly resistant against ampicillin (72%) and cephalothin (60%). All carbapenem-resistant isolates were MBL-positive. Based on the results of PCR, 75% of the isolates were blaNDM-positive. Conclusion: Resistance to some antibiotics, such as ampicillin and cephalothin, was high, and their prescription must be restricted. The prevalence of MBL-producing isolates was not high; however, due to the high level of resistance against other antibiotics, continuous monitoring of MBL-producing isolates is highly essential.

Hospital wastewater can contaminate the environment with antibiotic-resistant and virulent bacteria. We analyzed wastewater samples from four hospitals in Ardabil province, Iran for Enterococcus faecium and Enterococcus faecalis using culture and molecular methods. We also performed antimicrobial susceptibility testing and polymerase chain reaction testing for resistance and virulence genes. Out of 141 enterococci isolates, 68.8% were E. faecium and 23.4% were E. faecalis. Ciprofloxacin and rifampicin showed the highest level of resistance against E. faecalis and E. faecium isolates at 65%. High-level gentamicin resistance (HLGR), high-level streptomycin resistance (HLSR), ampicillin, and vancomycin resistance were observed in 25, 5, 10, and 5.15% of E. faecium, and 15, 6, 15, and 3.03% of E. faecalis isolates, respectively. The ant(6′)-Ia and ant(3′)-Ia genes that were responsible for streptomycin resistance were observed in HLSR isolates and aph(3′)-IIIa and aac(6′) Ie-aph(2″)-Ia genes accounting for gentamicin resistance were detected in HLGR isolates. vanA was the predominant gene detected in vancomycin-resistant isolates. The majority of isolates were positive for gelE, asa1, esp, cylA, and hyl virulence genes. We found that drug-resistant and virulent E. faecalis and E. faecium isolates were prevalent in hospital wastewater. Proper treatment strategies are required to prevent their dissemination into the environment. HIGHLIGHTS The prevalence of E. faecium isolates in hospital wastewater was three times higher than that of E. faecalis isolates.; Five percent of E. faecium and 3% of E. faecalis isolates were vancomycin-resistant.; The rate of HLSR was almost four times the rate of HLGR among Enterococcus spp.; Almost all of the isolates were multidrug-resistant.; The majority of E. faecalis and E. faecium isolates contained multiple virulence genes simultaneously.;

Abstract Background This study was aimed to evaluate the prevalence and molecular characteristics of ciprofloxacin resistance among 346 Escherichia coli isolates collected from clinical specimens (n = 82), healthy children (n = 176), municipal wastewater (n = 34), hospital wastewater (n = 33), poultry slaughterhouse wastewater (n = 12) and livestock (n = 9) slaughterhouse wastewater in Iran. Methods Ciprofloxacin minimum inhibitory concentration (MIC) was determined by agar dilution assay. Phylogroups and plasmid-mediated quinolone resistance (PMQR) genes were identified using PCR. Mutations in gyrA, gyrB, parC, and parE genes and amino acid alterations were screened through sequencing assay. The effect of efflux pump inhibitor (PAβN) on ciprofloxacin MICs in ciprofloxacin-resistant isolates was investigated using the microdilution method. Results In total, 28.03% of E. coli isolates were phenotypically resistant to ciprofloxacin. Based on sources of isolation, 64.63%, 51.51%, 33.33%, 14.70%, 10.22% and 8.33% of isolates from clinical specimens, hospital wastewater, livestock wastewater, municipal wastewater, healthy children and poultry wastewater were ciprofloxacin-resistant, respectively. Eighty-one point eighty-one percent (Ser-83 → Leu + Asp-87 → Asn; 78.78% and Ser-83 → Leu only; 3.03% (of ciprofloxacin-resistant E. coli isolates showed missense mutation in GyrA subunit of DNA gyrase, while no amino-acid substitution was noted in the GyrB subunit. DNA sequence analyses of the ParC and ParE subunits of topoisomerase IV exhibited amino-acid changes in 30.30% (Ser-80 → Ile + Glu-84 → Val; 18.18%, Ser-80 → Ile only; 9.10% and Glu-84 → Val only; 3.03%0 (and 15.38% (Ser-458 → Ala) of ciprofloxacin-resistant E. coli isolates, respectively. The PMQR genes, aac(6')-Ib-cr, qnrS, qnrB, oqxA, oqxB, and qepA were detected in 43.29%, 74.22%, 9.27%, 14.43%, 30.92% and 1.03% of ciprofloxacin-resistant isolates, respectively. No isolate was found to be positive for qnrA and qnrD genes. In isolates harboring the OqxA/B efflux pump, the MIC of ciprofloxacin was reduced twofold in the presence of PAβN, as an efflux pump inhibitor. The phylogroups B2 (48.45%) and A (20.65%) were the most predominant groups identified in ciprofloxacin-resistant isolates. Conclusions This study proved the high incidence of ciprofloxacin-resistant E. coli isolates in both clinical and non-clinical settings in Iran. Chromosomal gene mutations and PMQR genes were identified in ciprofloxacin resistance among E. coli population.

Introduction: Urinary tract infections (UTIs) are the most prevalent infections in patients worldwide. Escherichia coli is considered as the most prevalent etiological agent of UTIs. The prevalence of extended-spectrum beta-lactamase (ESBL)-producing isolates is a health care concern worldwide. The aims of this study was to determine antibiotic resistance profiles and the prevalence of the blaCTXM, blaSHV, and blaTEM genes in E. coli isolated from clinical samples obtained from patients with UTIs. Methods: From September 2019 to March 2021, a total of 1200 urine samples were collected and analyzed from patients suspected of having UTI referred to Amir-Al-Momenin hospital of Zabol, Sistan and Baluchistan province, south-east of Iran. Antibiotic resistance patterns and the prevalence of the blaCTXM, blaSHV and blaTEM genes were determined using the disk diffusion method and PCR, respectively. Results: The isolates were mostly resistance against ampicillin and trimethoprim-sulfamethoxazole, with 66% and 54% of all isolates being resistant. Also, the isolates investigated were highly susceptible against meropenem and gentamycin (95%). The prevalence of the blaCTX, blaSHV, and blaTEM genes was 22%, 30%, and 24%, respectively. Conclusion: Resistance against ampicillin and trimethoprim-sulfamethoxazole was high, therefore their prescription must be restricted. In addition, the expressions of the blaCTXM, blaSHV, and blaTEM genes were alarmingly high. In order to control the spread of infections by these isolates, constant monitoring of antibiotic resistance patterns is necessary.

Background & objectives: Carbapenems are the main antibiotics for the treatment of infections caused by multidrug-resistant (MDR) Pseudomonas aeruginosa (P. aeruginosa). The aims of this study were to determine the prevalence of gene encoding outer membrane porin protein (OprD) in carbapenem-resistant P. aeruginosa strains as well as to assess the role of insertion sequence (IS) elements in the inactivation of OprD porin and the emergence of carbapenem resistance. Methods: In this study, 103 clinical isolates of P. aeruginosa including 58, 42 and 23 strains resistant to imipenem, meropenem, and doripenem were used, respectively. The isolates were collected from patients referred to Ardabil hospitals. The presence of oprD gene and IS elements were investigated using polymerase chain reaction (PCR) and sequencing methods. P. aeruginosa PAO1 standard isolate was used as the positive control strain for oprD gene. Results: The frequency of oprD gene among carbapenem-resistant P. aeruginosa strains isolated from Ardabil hospitals was 96.5%. Furthermore, IS elements were not observed in the investigated isolates. Conclusion: Based on the results of this study, the presence of IS elements did not involve in the inactivation of outer membrane porin OprD and resistance to carbapenems among P. aeruginosa clinical strains in Ardabil. Therefore, an investigation of the role of other mutations in reducing the expression of oprD gene and increasing P. aeruginosa resistance to carbapenems is recommended.

This updated systematic review and meta-analysis follows two aims: 1) to assess Mycobacterium tuberculosis (M. tuberculosis) antibiotic resistance in Iran from 2013 to 2020 and, 2) to assess the trend of resistance from 1999 to 2020. Several national and international databases were systematically searched through MeSH extracted keywords to identify 41 published studies addressing drug-resistant M. tuberculosis in Iran. Meta-analysis was done based on the PRISMA protocols using Comprehensive Meta-Analysis software. The average prevalence of resistance to first- and second-line anti-TB drugs, multidrug-resistant TB (MDR-TB) and extensively drug-resistant TB (XDR-TB) in new and previously treated tuberculosis (TB) cases in Iran during 2013–2020 were as follows: isoniazid 6.9%, rifampin 7.9%, ethambutol 5.7%, pyrazinamide 20.4%, para-aminosalicylic acid 4.6%, capreomycin 1.7%, cycloserine 1.8%, ethionamide 11.3%, ofloxacin 1.5%, kanamycin 3.8%, amikacin 2.2%, MDR-TB 6.3% and XDR-TB 0.9%. Based on the presented data, M. tuberculosis resistance to first- and second-line anti-TB drugs, as well as MDR-TB, was low during 2013–2020 in Iran. Furthermore, there was a declining trend in TB drug resistance from 1999 to 2020. Hence, to maintain the current decreasing trend and to control and eliminate TB infection in Iran, continuous monitoring of resistance patterns is recommended.

Background and objectives: Urinary tract infection (UTI) is the most prevalent infection and Escherichia coli (E. coli) is one of the main causes of UTI worldwide. Integrons are mobile genetic elements considered to be responsible for dissemination of multi-drug resistance infections. Therefore, the aims of this study were to investigate the antibiotic resistance patterns and distribution of class I, II and III integrons among E. coli isolated from patients. Methods: In this descriptive cross-sectional study, from Jun 2020 to March 2021, in total, 70 non-duplicate strains of E. coli were isolated from patients with UTI referred to Amiralmomenin hospital, Zabol, Iran. Antibiotic resistance patterns were determined using Kirby-Bauer’s disk diffusion method and Clinical and Laboratory Standards Institute (CLSI) guidelines. Class I, II and III integrons were detected using polymerase chain reaction (PCR). Results: The isolates showed high resistance toward ampicillin (77.1%), trimethoprim- sulfamethoxazole (58.5%) and ceftriaxone (35%), whereas were mostly susceptible to meropenem (97%). Based on results of PCR, 34 (48.6%) and 3 (4.3%) isolates were classified as class I and class II integron-positive strains, respectively. Conclusion: Resistance rate to ampicillin, ceftriaxone and trimethoprim-sulfamethoxazole was at a high level and their prescription should be restricted. Class I integron is widely distributed among E. coli isolates and play a crucial role in the emergence of antibiotic resistance

Polymorphisms of vitamin D receptors (VDRs), ApaI, BsmI, FokI, and TaqI might affect susceptibility to tuberculosis (TB). In this systematic review and meta-analysis, all published articles which investigated the effects of these polymorphisms on the risk of TB in the Iranian population were retrieved.PubMed and Scopus were searched with no date or language restrictions. In this meta-analysis, the Comprehensive Meta-Analysis (CMA) version 2.0 and random effects model were applied. The association of polymorphisms with TB risk was assessed by measuring the odds ratio (ORs) at 95% CI. Heterogeneity was investigated based on Cochran Q-test and I2-index statistics. The significance level was set at 0.05. Also, Egger's regression intercept was determined to measure publication bias.A total of six articles on Iranian populations were included. TaqI (5/6 included studies) showed a significant association with the increased risk of TB based on ORs (allele comparison: 1.57 (1.0, 2.3), p-value: 0.02; additive model of tt/TT: 1.57 (0.9, 2.5), p-value: 0.05; recessive model (tt/Tt + TT): 1.99 (1.2, 3.2), p-value: 0.00; dominant model (tt + Tt/TT): 1.98 (1.1, 3.5), p-value: 0.01). BsmI showed a significant positive effect on TB risk only in its dominant genotype (bb + bB/BB) (1.44 (1.0, 1.9); p-value: 0.02). FokI and ApaI did not show any significant effects on TB development in Iranian populations. Findings showed the significant effect of TaqI polymorphism in all genetic models and the dominant model of BsmI on the increased risk of TB. However, the effects of TaqI and BsmI should be further investigated in a larger sample size.

Streptococcus (S.) agalactiae colonizes in the female genitourinary and lower gastrointestinal tracts and is responsible for a wide range of infections in newborns, pregnant women and non-pregnant adults. Therefore, antibiotic prophylaxis and infection treatment against S. agalactiae is important. The aim of this study was to determine the prevalence of S. agalactiae antibiotic resistance in Iranian patients, especially among pregnant women. A systematic literature search was conducted in PubMed, Scopus, Google Scholar and the Scientific Information Database (SID) databases by using related keywords and without any time limitation. A total of 26 studies reporting the prevalence of S. agalactiae antibiotic resistance in Iran met our predefined inclusion and exclusion criteria and were included in the meta-analysis. High rates of S. agalactiae antibiotic resistance in pregnant women were found against tetracycline (96.2%), trimethoprim-sulfamethoxazole (84.7%), cefotaxime (41.3%), clindamycin (26.8%) and erythromycin (21%). Additionally, resistance to penicillin (4.2%), ampicillin (2.7%), cefazolin (7.6%), vancomycin (2.4%), ceftriaxone (12.5%), ciprofloxacin (13.6%) and nitrofurantoin (0%) was low. Our results revealed that penicillin and ampicillin among penicillin-tolerant Iranian pregnant women, and vancomycin and cefazolin among penicillin-allergic women are still drugs of choice in intrapartum prophylaxis for preventing S. agalactiae vertical transmission and early-onset neonatal disease.

Background. Carbapenems are the last-line therapy for multidrug-resistant (MDR) infections caused by Enterobacterales, including those caused by Enterobacter species. However, the recent emergence of carbapenem-resistant (CR) and extended-spectrum β-lactamase (ESBL)-producing Enterobacteriaceae pathogens, which are resistant to nearly all antibiotics, has raised concerns among international healthcare organizations. Hence, because there is no comprehensive data in Iran, the current study aimed to evaluate the prevalence of antibiotic resistance among Enterobacter species, especially CR and ESBL-producing strains, in Iran. Methods. The literature search was performed up to June 21, 2021, in national and international databases using MeSH-extracted keywords, i.e., Enterobacter, antibiotic resistance, carbapenem, ESBL, and Iran. Study selection was done based on the predefined inclusion and exclusion criteria, and data analysis was carried out using the Comprehensive Meta-Analysis (CMA) software. Results. The pooled prevalence of Enterobacter species resistant to various antibiotics is as follows: imipenem 16.6%, meropenem 16.2%, aztreonam 40.9%, ciprofloxacin 35.3%, norfloxacin 31%, levofloxacin 48%, gentamicin 42.1%, amikacin 30.3%, tobramycin 37.2%, tetracycline 50.1%, chloramphenicol 25.7%, trimethoprim/sulfamethoxazole 52%, nalidixic acid 49.1%, nitrofurantoin 43%, ceftriaxone 49.3%, cefixime 52.4%, cefotaxime 52.7%, ceftazidime 47.9%, cefepime 43.6%, and ceftizoxime 45.5%. The prevalence rates of MDR and ESBL-producing Enterobacter species in Iran were 63.1% and 32.8%, respectively. Conclusion. In accordance with the warning of international organizations, our results revealed a high prevalence of ESBL-producing Enterobacter species in Iran, which is probably associated with the high prevalence of Enterobacter species resistant to most of the assessed antibiotics, especially MDR strains. However, the resistance rate to carbapenems was relatively low, and these drugs can still be considered as drugs of choice for the treatment of Enterobacter infections in Iran. Nevertheless, continuous monitoring of drug resistance along with antibiotic therapy based on the local data and evaluation of the therapeutic efficacy of new antibiotics or combination therapeutic strategies, such as ceftazidime/avibactam, meropenem/vaborbactam, plazomicin, and eravacycline, is recommended.

Introduction: Based on the World Health Organization reports, infections caused by ampicillin-resistant Haemophilus influenzae strains are a major threat to public health and need urgent therapy with new antibiotics. Given the lack of a previous comprehensive study on the prevalence of the antibiotic resistance of H. influenzae in Iran, this systematic review and meta-analysis was performed to increase the knowledge about antibiotic resistance status of this pathogenic agent. Materials and Methods: For the purpose of the study, the articles related to the subject of interest and published up to August 2018 were searched in several English and Persian databases, including PubMed, Scopus, Web of Science, Scientific Information Database, and Magiran. The search process was accomplished using the following keywords: “Antibiotic resistance”, “H. influenzae”, and “Iran”. The data were pooled from 13 eligible studies reporting the prevalence of antibiotic resistance of H. influenzae in Iran. Results: The prevalence of H. influenzae resistance to various antibiotics in Iran, including ampicillin, amoxicillin, cephalexin, cefixime, ceftazidime, cefotaxime, and ceftizoxime, were obtained as 54.8%, 66.6%, 28.6%, 62%, 21.3%, 22.3%, 23.2%, respectively.These rates were reported as 27.7%, 46.7%, 53%, 82.6%, 40.3%, 30.8% for chloramphenicol, tetracycline, trimethoprim/sulfamethoxazole, penicillin, erythromycin, and ciprofloxacin, respectively. Additionally, ceftriaxone, gentamicin, amikacin, kanamycin, rifampin, azithromycin, and clindamycin had the H. influenzae resistance rates of 33.1%, 40.2%, 45.8%, 44.4%, 18.5%, 17.4%, and 71.3%, respectively. Conclusion: The majority of the antibiotics tested in Iran showed a high rate of resistance to H. influenzae. This may cause serious problems in the treatment of infections in the future. Therefore, precautionary measures, such as monitoring antibiotic prescription and resistance and using the new classes of antibiotics, are necessary.

Objective(s): A new strategy in recent studies is using effective tuberculosis (TB) subunit vaccines combined with appropriate carriers and adjuvants which have shown promising results in preclinical and clinical studies. The aim of the present study was to evaluate the PLGA:DDA hybrid nanoparticles (NPs) for subcutaneous delivery of a novel multistage subunit vaccine along with MPLA adjuvant against Mycobacterium tuberculosis (M. tuberculosis). Materials and Methods: PLGA and PLGA:DDA NPs containing HspX/EsxS fusion protein and MPLA were prepared by double emulsion method (w/o/w). After characterization, these NPs were subcutaneously administered to BALB/c mice aged 6-8 weeks old. Immunogenicity of formulations were assessed by measuring the level of IFN-γ, IL-4, IL-17 and TGF-β cytokines as well as IgG1, IgG2a and IgA antibodies using ELISA. Results: Both particles had spherical shape and smooth surface with 316.7 ± 12.7 nm in size, surface charge of -33 ± 1.7 mV, and encapsulation efficiency of 92.2 ± 2% for PLGA NPs and 249.7 ± 16.7 nm in size, surface charge of 39 ± 1.8 mV, and encapsulation efficiency of 35.7 ± 1.4% for PLGA:DDA NPs. The highest IFN-γ response and also IgG2a and IgG1 antibodies titers were observed in groups immunized with PLGA:DDA/HspX/EsxS/MPLA and PLGA:DDA/HspX/EsxS/MPLA as booster as well as PLGA:DDA/HspX/EsxS and PLGA:DDA/HspX/EsxS as booster. Conclusion: With regard to effective induction of IFN-γ and IgG2a immune responses, PLGA:DDA hybrid NP along with MPLA adjuvant have good potentials for improving the immunogenicity of HspX/EsxS multistage subunit vaccine as well as promoting BCG efficacy as a BCG prime-boost.

Background & objectives: In recent years, Acinetobacter baumannii has been shown to be associated with several nosocomial infections, including pneumonia, bacteraemia, urinary tract infections, wound infection and meningitis. This organism can survive in the hospital environment and rapidly develops resistance to many antibiotics. The molecular genotyping can increase our knowledge about the spread of A. baumannii strains from one hospital to another and their drug resistance. Therefore, this study aimed to determine the prevalence of antibiotic resistance profile as well as phylogenetic relationships of A. baumannii strains in Shahrekord teaching hospitals. Methods: In this study, antibacterial susceptibility patterns of A. baumannii strains isolated from different clinical specimens (urine, blood, sputum) to amikacin, ampicillin/sulbactam, aztreonam, cefepime, ceftazidime, ciprofloxacin, gentamycin, imipenem, meropenem, norfloxacin, ofloxacin, piperacillin/tazobactam, tobramycin were tested using disk diffusion )Kirby-Bauer( method. Finally, genotyping of A. baumannii strains was performed using REP-PCR method. Results: During this study, 50 samples of patients were identified as A. baumannii) 71%(, and their drug resistance rates were assessed. All A. baumannii strains were resistant to ceftazidime and cefepime and also a high rate of resistance to aztreonam, norfloxacin, ciprofloxacin, amikacin, imipenem, gentamycin, and ampicillin-sulbactam were observed. On the other hand, our results demonstrated nine genotype groups among A. baumannii strains based on REP-PCR method. Conclusion: Due to the high prevalence of antibiotic resistance among isolated A. baumannii strains, similarities between different genotypes and the dispersion of these genotypes in different parts of Shahrekord hospitals, the implementation of infection control programs in different parts of the hospital is necessary.

Objective: To estimate the prevalence of antibiotic resistance of Neisseria species in Iran. Methods: A systematic and electronic search using relevant keywords in major national and international databases was performed until 6th July, 2018 in order to find studies reporting the prevalence of antibiotic resistance of Neisseria species in Iran. Results: A total of nine studies were found to be eligible based on predefined inclusion and exclusion criteria. Our analysis indicated that the prevalence of Neisseria gonorrhoeae resistance to different antibiotics was as follows: 66.9% to penicillin, 59.1% to ciprofloxacin, 11.1% to ceftriaxone, 21.6% to spectinomycin, 13.8% to cefixime, 82.4% to co-trimoxazole, 52.7% to tetracycline, 29.9% to gentamicin, 87.5% to ampicillin, 11.1% to azithromycin, 2.2% to chloramphenicol, 50.1% to cefepime and 50.0% to vancomycin. Antimicrobial resistance rates of Neisseria meningitidis was as follows: 30.0% to penicillin, 33.3% to amoxicillin, 33.3% to cephalexin, 55.6% to ampicillin and 0.0% to ciprofloxacin, ceftriaxone, cefotaxime, amikacin, co-trimoxazole, gentamicin, kanamycin, chloramphenicol and ceftizoxime. Conclusion: Neisseria gonorrhoeae and Neisseria meningitidis isolates of Iran show resistance to different types of antibiotics. Therefore, care should be exercised for the use of penicillin, ciprofloxacin, co-trimoxazole, tetracycline, gentamicin, ampicillin, cefepime and vancomycin for gonococcal infections, and also with respect to the use of penicillin, amoxicillin, ampicillin and cephalexin for meningococcal infections in Iran.

Objectives:Streptococcus pyogenes is associated with mild to severe infections, particularly in children and young adults. Proper antimicrobial treatment of S. pyogenes infections is important to prevent post-streptococcal complications. Therefore, the purpose of this meta-analysis was to evaluate the prevalence of S. pyogenes antibiotic resistance among Iranian children. Methods: We identified all published studies up to 20 March 2019 related to S. pyogenes antibiotic resistance by searching Persian and English electronic databases. Search terms included S. pyogenes, children, and Iran. Out of 1022 publications, 12 articles were eligible and included based on the inclusion and exclusion criteria. Results: Our analysis indicated the following prevalence pattern for S. pyogenes antimicrobial resistance in Iran: 4.2% to penicillin, 38.3% to amoxicillin, 5.4% to erythromycin, 12.0% to azithromycin, 12.6% to clarithromycin, 12.4% to clindamycin, 15.3% to rifampicin, 8.1% to ceftriaxone, 17.6% to cefixime, 36.9% to ampicillin, 14.1% to vancomycin, 8.4% to chloramphenicol, 30.4% to tetracycline, 8.8% to cefotaxime, 82.8% to trimethoprim/sulfamethoxazole, 39.6% to gentamicin, 11.9% to ofloxacin, 28.3% to carbenicillin, 3.1% to ciprofloxacin, 6.1% to imipenem, 18.2% to cephalothin, 57.6% to tobramycin, 49.3% to kanamycin, 79.0% to cloxacillin, 12.9% to cephalexin, 10.7% to cefazolin, and 89.5% to amoxicillin-clavulanic acid. Conclusions: Our findings suggest penicillin (in non-allergic children) and macrolides, lincosamides, and narrow-spectrum cephalosporins (in penicillin-allergic children) as the treatments of choice in Iran.

Background. In recent years, antibiotic-resistant pathogens including penicillin-nonsusceptible Streptococcus pneumoniae (PNSP) have posed serious threats against human health. The aim of this meta-analysis was to investigate the prevalence of Streptococcus pneumoniae drug resistance particularly the incidence of PNSP strains in Iran. Methods. A systematic search was done in national and international electronic databases using Persian and English keywords. Up until May 20, 2020, a total of 58 publications were detected as eligible articles based on the inclusion and exclusion criteria, and then the selected studies were enrolled for data extraction and meta-analysis according to the PRISMA guidelines. Results. A high rate of PNSP (46.9%) and multidrug-resistant (MDR) S. pneumoniae (45.3%) in our isolates were evident. Furthermore, total frequency resistance to other drugs in S. pneumoniae was as follows: erythromycin 41.1%, azithromycin 53.2%, tetracycline 39.9%, levofloxacin 1.7%, rifampin 1.2%, clindamycin 31.7%, vancomycin 1.7%, trimethoprim/sulfamethoxazole 63.9%, chloramphenicol 20%, ceftriaxone 10.9%, amoxicillin 30.5%, ciprofloxacin 8.3%, imipenem 6.1%, linezolid 0%, and cefotaxime 8.3%. Conclusion. Although the overall prevalence of cephalosporin- and carbapenem-resistant Streptococcus pneumoniae was low, penicillin-resistant strains, especially PNSP, could become a significant challenge to the healthcare system in Iran. Hence, the prescription of penicillin as the first-choice antibiotic in the treatment of S. pneumoniae infections should be avoided.

Background and Objectives: Nowadays, high-level aminoglycosides and ampicillin resistant Enterococcus species are among the most common causes of nosocomial infections. The present study was conducted to determine the prevalence of high-level resistance to aminoglycosides and ampicillin among clinical isolates of Enterococcus species in Ardabil, Iran. Materials and Methods: In this cross–sectional study, a total of 111 Enterococcus species were collected from different clinical specimens between 2013 and 2015. Enterococcus species were identified using standard phenotypic and genotypic methods. BHI agar screen and agar dilution methods were used for detection of high-level gentamicin and streptomycin resistance (HLGR and HLSR) and minimal inhibitory concentration (MIC) of ampicillin, respectively. Results: Of 111 clinical isolates, 59 (53.2%) and 25 (22.5%) isolates were E. faecalis and E. faecium, respectively, based on the PCR results. Totally, 60.3% and 56.7% of isolates were HLGR and HLSR, respectively, as well as 51.35% were HLGR plus HLSR. Among HLGR isolates, 36 (61.01%), 18 (72%) and 13 (48.14%) were E. faecium, E. faecalis and non-faecalis non-faecium species, respectively. Among HLSR isolates, 33 (55.93%), 16 (64%) and 14 (51.85%) were E. faecalis, E. faecium and non-faecalis non-faecium species, respectively. All HLGR isolates contained aac(6´)Ie-aph(2″)Ia gene. Overall, the prevalence of high-level ampicillin resistance among Enterococcus species was 17.1%. For E. faecalis, E. faecium and non-faecalis non-faecium species, ampicillin resistance rates were as follows: 11 (40.74%), 7 (28%) and 1 (1.69%), respectively. For aminoglycoside antibiotics, the resistance rate was significantly higher in E. faecium isolates and for ampicillin it was higher in E. faecalis isolates. Conclusion: The frequency of high-level aminoglycoside resistant enterococcal isolates in our hospital was high and significant ampicillin resistance was noticed. This would require routine testing of enterococcal isolates for HLAR and ampicillin susceptibility.

Background. Campylobacter species are one of the main causes of bacterial food poisoning worldwide. Recently, WHO reported that the emergence of fluoroquinolone-resistant Campylobacter species is becoming a public health issue around the world. The aim of the present systematic review and meta-analysis was to evaluate the prevalence of the antimicrobial susceptibility patterns of Campylobacter species, especially fluoroquinolone-resistant strains isolated from human and animal origins in Iran. Methods. Using related keywords and without date and language limitations, a comprehensive literature search was conducted in PubMed, Scopus, ISI Web of Knowledge, Google Scholar, and SID to identify relevant studies on the prevalence of the antimicrobial susceptibility patterns of Campylobacter species in Iran. Results. A total of 34 reports (9 in Persian and 25 in English) were selected based on inclusion and exclusion criteria. Disk diffusion, E-test, and agar dilution were common methods used for antimicrobial susceptibility testing. The antibiotic resistance profiles of Campylobacter species against fluoroquinolones were as follows: 53.6%, 41.8%, and 0% to ciprofloxacin for C. jejuni, C. coli, and C. lari, respectively, 24.3% and 25.1% to enrofloxacin for C. jejuni and C. coli, respectively, 59.6% and 49.2% to nalidixic acid for C. jejuni and C. coli, respectively, and 87.3% and 64.7% to ofloxacin for C. jejuni and C. coli, respectively. Conclusion. Our findings revealed a high prevalence of fluoroquinolone-resistant Campylobacter species in Iran. This calls for the use of more effective antibiotics with low resistance rates including aminoglycosides, chloramphenicol, and imipenem.

Objective(s): Production of effective tuberculosis (TB) vaccine is necessity. However, the development of new subunit vaccines is faced with concerns about their weak immunogenicity. To overcome such problems, polymers-based vaccine delivery systems have been proposed to be used via various routes. The purpose of this study was to determine the potential of polymeric particles as future vaccine delivery systems/adjuvants for parenteral and non-parenteral immunization against TB. Materials and Methods: PubMed, Scopus, Science-Direct, and the ISI web of knowledge databases were searched for related keywords. A total of 420 articles, written up to June 25, 2016, were collected on the potential of polymeric particles as TB vaccine delivery systems after parenteral and non-parenteral immunization. Thirty-one relevant articles were selected by applying inclusion and exclusion criteria. Results: It was shown that the immunogenicity of TB vaccines had been improved by using biodegradable and non-biodegradable synthetic polymers as well as natural polymers and they are better able to enhance the humoral and cellular immune responses, compared to TB vaccines alone. The present study revealed that various polymeric particles, after M. tuberculosis challenge in animal models, provide long-lasting protection against TB. PLGA (poly (lactide-co-glycolide)) and chitosan polymers were widely used as TB vaccine delivery systems/adjuvants. Conclusion: It seems that PLGA and chitosan polymers are well-suited particles for the parenteral and non-parenteral administration of TB vaccines, respectively. Non-biodegradable synthetic polymers in comparison with biodegradable synthetic and natural polymers have been used less frequently. Therefore, further study on this category of polymers is required.

Introduction: More than two billion people are latently infected with Mycobacterium tuberculosis. Most tuberculosis (TB)-subunit vaccines currently in various stages of clinical trials are designed for prevention of active TB, but not to prevent reactivation of latent TB-infection. Thus, there is an urgent need for an effective multi-stage vaccine based on early-expressed and latently-expressed antigens that prevents both acute and latent infections. Areas covered: Here, we reviewed the published pre-clinical and clinical studies of multi-stage subunit vaccines against TB, and the protective capacities of the vaccines were compared with BCG, either alone or in combination with different vaccine delivery systems/adjuvants. The results revealed that multi-stage subunit vaccines induced a wide variety of immune-responses to all forms of TB, including CD8 + T-cell-mediated cytolytic and IFN-γ responses comparable to those induced by the BCG. They could potentially be used as a booster vaccine to improve the efficacy of the BCG. Expert commentary: Multi-stage TB-vaccines could boost BCG-primed immunity, decrease bacterial loads and provide efficient protection against progressive TB-infection, especially in the latent phase. These types of vaccines administered before and after TB-infection can act as pre-exposure, post-exposure and even therapeutic vaccines. In the near future, these vaccines could provide a new generation of prime-vaccines or BCG prime-boosters.

Background: Development of drug resistance to Staphylococcus aureus (S. aureus) has led to the use of older antibiotics such as macrolide-lincosamide-streptogramin B (MLSB) for the treatment of infections. MLSB resistance can be caused by several mechanisms, however, one of the predominant reasons is target modification mediated by erm genes. The objective of this study is to determine the prevalence of erm genes and the frequency of constitutive MLSB (cMLSB), inducible MLSB (iMLSB), and MS phenotypes using D-test and polymerase chain reaction (PCR) methods. Methods:D-test was performed on 110 clinical specimens of S. aureus collected from Kashani and Hajar Hospitals in Shahrkord from October 2014 to May 2015. After sampling, DNA extraction was performed by simple boiling method and, in order to detect erm genes, multiplex PCR was carried out on erythromycin resistant isolates using specific primers. Results:The result of this study revealed that among 110 S. aureus isolates examined, 35 (31.8%) were MRSA and frequency of cMLSB, iMLSB, and MS resistant phenotypes were 22 (20%), 9 (8.2%), and 2 (1.8%), respectively. The genes ermA, ermB, and ermC were detected in 27 (24.5%), 28 (25.4%), and 26 (23.6%) isolates. Conclusion:This study demonstrated that cMLSB was the most common phenotype among isolated S. aureus. Moreover, another interesting point to notice in our study was the high frequency of the ermB gene in iMLSB resistant phenotypes.

Background: Multidrug-resistant Pseudomonas aeruginosa (MDR P. aeruginosa) is known as a serious threat to human health worldwide. Limited information is available concerning the prevalence of MDR P. aeruginosa in Iran. The aim of the present study was to investigate the relative frequency of MDR P. aeruginosa in different parts of Iran. Materials and Methods: Using appropriate keywords and well-known English and Persian database, available data about MDR P. aeruginosa in Iran were retrieved. After applying predefined criteria, relevant studies were selected. Results: By using random-effect models, the pooled incidence of MDR P. aeruginosa was estimated 58% (95% confidence interval [CI]; 0.54–0.61). The highest and lowest prevalence of MDR P. aeruginosa were observed in Tehran (100%) (95% CI; 0.94–1.00) and Zahedan (16%) (95% CI; 0.10–0.24), respectively. The highest resistance rate was against ceftazidime (50%) (95% CI; 0.46–0.54) and amikacin (50%) (95% CI; 0.46–0.54). Conclusion: Our findings are of concern since they demonstrate the high prevalence rate of MDR P. aeruginosa in the majority of Iranian hospitals.

ABSTRACT Background and Objectives: Pseudomonas aeruginosa is an important non-fermenting gram-negative hospital-acquired pathogen. Treatment of P. aeruginosa infections has become more challenging due to overexpression of efflux pumps. The aim of the present study was to apply in silico analysis to evaluate the structure of the efflux pump regulatory protein, MexR, and impact of mutation on its stability and function. Methods: Different bioinformatics tools including EXPASY, PROTEER, TECCOFFE, iStable, I-Mutant 2, STRING, ESPript, GOR IV, and PDB were used in the study. Results: Aliphatic and instability indices were 104.15, and 46.52, respectively, indicating that the protein has a relatively short half-life. Most mutations decreased protein stability. Twenty-four mutations were identified as deleterious, with negative impact on the protein’s function. Conclusion: Determination of structure, variability, and function of MexR could be useful for modeling of treatment and control of multidrug resistant P. aeruginosa, with overexpressed efflux pump. We found that MexR is a relatively unstable and conserved protein and the majority of mutations decrease its stability. Keywords: Pseudomonas aeruginosa, MexR protein, Drug resistance, drug resistance multiple.

Introduction: Susceptibility to tuberculosis (TB) infection varies in individuals and is linked to genetic variations in the toll-like receptors (TLRs) genes. The current study employed a systematic literature review and meta-analysis to describe the most prevalent single nucleotide polymorphisms (SNPs) from various TLRs and to assess the association between these polymorphisms and tuberculosis susceptibility. Methods: The PubMed, Google Scholar, Scopus, and ISI Web of Knowledge databases were searched for all articles published before May 25, 2015, that contained the target keywords. Following the application of the inclusion and exclusion criteria, a total of 37 relevant articles were identified that examined the association between the TLRs gene polymorphism and susceptibility to tuberculosis.Result: A meta-analyses approach to the research determined that there is a statistically significant association between TLR1 rs4833095, TLR6 rs5743810, and TLR8 rs3788935 in the allelic model and also TLR1 rs4833095, TLR1 rs5743018, TLR2 rs5743708, TLR6 rs5743810, and TLR8 rs3761624 in the co-dominant model with increased or decreased susceptibility to tuberculosis. No associations were observed between the other TLRs polymorphisms and tuberculosis risk.Discussion: Several studies have found that host genetic factors, such as SNPs in TLRs gene, may increase an individual’s susceptibility to tuberculosis. Therefore, the identification of these SNPs is important to investigate immune responses to TB.Conclusion: The present study concluded that there is an association between some polymorphisms of TLRs and tuberculosis risk. Thus, for a better understanding about the role of SNPs to TB susceptibility, additional studies on alternative TLRs SNPs are needed.

Objective(s): An efficient vaccine against TB is an urgent need. TB peptides are safe candidate but they are weak immunogens and needs to be potentiated by adjuvant/delivery systems. The main purpose of the present study was to determine the potential of CHT based NPs containing ESAT-6 antigen of M. tuberculosis for inducing mucosal and systemic immune responses after intranasal and subcutaneous injection in mice model. Materials and Methods: CHT and TMC based NPs were prepared by coating of cationic polymer on the anionic peptide by ionic gelation method and their characteristics were evaluated by scanning electron microscopy (SEM) and dynamic light scattering (DLS). Physical stability of NPs was studied within 30 days. Finally, the ability of formulated NPs to elicit immune responses in BALB/c mice were evaluated following nasal and subcutaneous immunization. Results: The best weight ratio of antigen to polymer (CHT or TMC) was 1:2. CHT and TMC NPs had a mean size of 356.3 ± 42.20, and 470.3 ± 48.21 nm, respectively. NPs were stable up to 15 days. CHT:ESAT-6 NPs gave higher serum IgG1 and IgG total responses and TMC:ESAT-6 NPs induced high titers of IgG2a and IFN-g. Conclusion: Regards to the importance of cellular immune responses in effective protection against TB, and also the solubility in physiological pH, TMC NPs are more efficient adjuvant/antigen delivery system for immunization against TB.

Summary: The spa gene occurs in all strains of Staphylococcus aureus (S. aureus), can function as a genetic marker and might be used distinguish strains at the species level. Hence, due to these advantages, we used spa typing and the Based Upon Repeat Pattern (BURP) to assign the clonal and phylogenetic relationships of S. aureus strains. The sensitivity of S. aureus strains to methicillin was determined using agar disk diffusion. The extracted DNA from 56 isolates of S. aureus was subjected to PCR to detect the spa gene with specific primers. The spa typing method was performed for each of the isolates, and then, BURP was used to cluster spa types (spa-CCs). Finally, using relevant software, the phylogenic tree was drawn. The results of this study showed that 25 out of 56 (44.6%) isolates were resistant to methicillin. The typing of S. aureus isolates revealed 24 different spa types among 56 isolates, and BURP analysis clustered the 24 spa types into 5 spa clonal complexes (CCs) and 12 singletons. The process of spa typing, in combination with BURP analysis, provides an efficient method for investigating phylogenetic and clonal relationships among clinical isolates and can be useful for monitoring bacterial spread between hospitals and communities as well as between and within hospitals. Keywords: Staphylococcus aureus, spa gene, BURP, Phylogenetic relationships

Objective(s):Helicobacter pylori (H. pylori) is a pathogenic bacterium that colonizes the stomachs of approximately 50% of the world’s population. Resistance of H. pylori to antibiotics is considered as the main reason for the failure to eradicate this bacterium. The aim of this study was to determine the rate of resistant H. pylori strains to various antimicrobial agents in different areas of Iran. Materials and Methods: A systematic review of literatures on H. pylori antibiotic resistance in Iran was performed within the time span of 1997 to 2013. Data obtained from various studies were tabulated as following, 1) year of research and number strains tested, 2) number of H. pylori positive patients, 3) study place, 4) resistance of H. pylori to various antibiotics as percentage, and 5) methods used for evaluation of antibiotic resistance. Results: Over the period, a total of 21 studies on H. pylori antibiotic resistance have been conducted in different parts of Iran. In these studies, H. pylori resistance to various antibiotics, including metronidazole, clarithromycin, amoxicillin, tetracycline, ciprofloxacin, levofloxacin and furazolidone were 61.6%, 22.4% ,16.0%, 12.2%, 21.0%, 5.3% and 21.6%, respectively. We found no study on H. pylori resistance to rifabutin in Iran. Conclusion: Compared to the global average, we noted that the prevalence of H. pylori resistance to metronidazole, clarithromycin, amoxicillin, and tetracycline has been rapidly growing in Iran. This study showed that in order to determine an appropriate drug regimen against H. pylori, information on antibiotic susceptibility of the bacterium within different geographical areas of Iran is required.

Background: This study aimed to survey the presence of flagellin gene flaA in isolated Helicobacter pylori. Methods: One hundred gastric biopsies were collected by a gastroenterologist and inoculated in enrichment medium under microaerophilic conditions. DNA was extracted and polymerase chain reaction (PCR) was performed using the designed primer. Findings: PCR products showed that all extracted DNA were positive for flaA gene. Conclusion: We found flaA gene to be present in all clinical isolates. As it is highly similar to standard Helicobacter pylori strains, it can be used to detect the mentioned bacteria.

مقدمه: افزایش شیوع سویه‌های هلیکوباکتر پیلوری مقاوم در برابر آنتی‌بیوتیک مهم‌ترین عامل در تعیین نتیجه‌ی درمان با آنتی‌بیوتیک می‌باشد. بنابراین، استفاده از روش‌های قابل اعتماد، آسان، سریع و ارزان در تعیین حساسیت آنتی‌بیوتیکی ضروری است. در حال حاضر هیچ توصیه‌ی استانداردی برای سنجش این ارگانیسم سخت‌گیر وجود ندارد و معیارهای تفسیری برای تعیین حساسیت یا مقاومت باکتری هنوز استاندارد نشده است. از روش‌های مرسوم در تعیین حساسیت آنتی‌بیوتیکی باکتری‌ها استفاده از روش‌های دیسک دیفیوژن (Modified disk diffusion method یا MDDM) و E-test (Epsilometer test) است. هدف از این مطالعه، ارزیابی مقایسه‌ای نتایج روش‌های دیسک دیفیوژن و E-test برای تعیین حساسیت آنتی‌بیوتیکی ایزوله‌های هلیکوباکتر پیلوری نسبت به سه آنتی‌بیوتیک مترونیدازول، کلاریترومایسین و آموکسی‌سیلین بود. روش‌ها: در این مطالعه 30 ایزوله‌ی هلیکوباکتر پیلوری از نمونه‌های بیوپسی جدا شد و حساسیت هلیکوباکتر پیلوری نسبت به مترونیدازول، کلاریترومایسین و آموکسی‌سیلین بر اساس پروتکل CLSI (Clinical and laboratory standards institute)، توسط روش‌های دیسک دیفیوژن و E-test مقایسه گردید. علاوه بر این، حداقل غلظت مهاری (Minimum inhibitory concentration یا MIC) برای ایزوله‌های مقاوم به سه آنتی‌بیوتیک تعیین شد. یافته‌ها: 30 ایزوله‌ی هلیکوباکتر پیلوری که سنجش حساسیت آنتی‌بیوتیکی روی آن‌ها صورت گرفت، در هر دو روش دیسک دیفیوژن و E-test، 3/53 درصد به مترونیدازول، 6/16 درصد به کلاریترومایسین و 10 درصد نسبت به آموکسی‌سیلین مقاوم بودند. نتیجه‌گیری: این مطالعه نشان داد که هر دو روش تعیین حساسیت هلیكوباكتر پیلوری نسبت به آنتی‌بیوتیک‌های مترونیدازول، کلاریترومایسین و آموکسی‌سیلین نتایج یکسانی داشتند. بنابراین، در شرایط آزمایشگاه (In vitro) استفاده از روش دیسک دیفیوژن می‌تواند جایگزین روش E-test در تعیین مقاومت آنتی‌بیوتیکی برای هلیکوباکتر پیلوری باشد. واژگان کلیدی: هلیکوباکتر پیلوری، مقاومت آنتی‌بیوتیکی، روش دیسک دیفیوژن،

Background: Helicobacter pylori (H. pylori) resistance to antibiotics has become a global problem and is an important factor in determining the outcome of treatment of infected patients. The purpose of this study was to determine the H. pylori resistance to clarithromycin, metronidazole, and amoxicillin in gastrointestinal disorders patients. Materials and Methods: In this study, a total of 260 gastric antrum biopsy specimens were collected from patients with gastrointestinal disorders who referred to Endoscopy Section of the Isfahan Hospitals. The E-test and Modified Disk Diffusion Method (MDDM) were used to verify the prevalence of antibiotic resistance in 78 H. pylori isolates to the clarithromycin, metronidazole, and amoxicillin. Results: H. pylori resistance to clarithromycin, metronidazole, and amoxicillin were 15.3, 55.1, and 6.4%, respectively. In this studyΈ we had one multidrug resistance (MDR) isolates from patient with gastritis and peptic ulcer disease. Conclusion: Information on antibiotic susceptibility profile plays an important role in empiric antibiotic treatment and management of refractive cases. According to the results obtained in this study, H. pylori resistance to clarithromycin and metronidazole was relatively high. MDR strains are emerging and will have an effect on the combination therapy.

Background: The rising frequency of methicillin resistant Staphylococcus aureus (MRSA) has led to an increased use of antibiotics such as macrolide, lincosamide, streptogramin B (MLSB) for the treatment of S. aureus infections. Resistance to MLSBin S. aureus is commonly encoded by erm genes, which can be constitutive MLSB (cMLSB) or inducible MLSB (iMLSB). The purpose of this study was to determine the frequency of cMLSB, iMLSB, and MS phenotypes using D-test and polymerase chain reaction (PCR) methods. Materials and Methods: A total of 215 isolates of S. aureus were collected from January 2010 to May 2012 from Al-Zahra Hospital in Isfahan. PCR was performed for detection of mecA gene on all isolates using specific primers. The frequency of MLSB-resistant isolates was determined using D-test, and then a multiplex PCR was performed for detection of ermA, ermB, and ermC genes. Results: Among 215 S. aureus isolates examined, 82 (40.9%) were MRSA, and iMLSB, cMLSB, and MS resistance phenotypes had a frequency of 9 (4.18%), 58 (26.9%), and 11 (5.1%), respectively. Among nine isolates with iMLSBresistance phenotype, four isolates contained ermC gene, two isolates ermB gene, and one isolate ermA gene. Two isolates did not have any erm gene. Conclusion: In the current study, cMLSBwas the most frequent phenotype and ermC was the most common gene in iMLSBresistant phenotypes.

Background: Helicobacter pylori antimicrobial resistance is an important factor responsible for treatment failure. The purpose of this study was evaluating the prevalence of point mutations in clarithromycin-resistant clinical isolates of H. pylori in Isfahan city of Iran. Materials and Methods: Thirty isolates of H. pylori from 130 biopsy specimens were isolated by culture and confirmed by biochemical and PCR tests. The MIC of clarithromycin antibiotic for 30 clinical isolates of H. pylori was determined by E-test method. The point mutations in the 288 bp of 23S rRNA gene of H. Pylori were investigated in four clarithromycin-resistant clinical isolates by PCR followed by sequencing. Results: Among 30 isolates of H. pylori, 4 cases were resistant to clarithromycin. One point mutation was found at position T2243C in the 23S rRNA gene in all resistance isolates. Conclusions: In our study, H. pylori resistance to clarithromycin associated with point mutation at position 2243 (T2243C).