Investigating the Effectiveness of mqsR-Peptide Nucleic Acid as a Novel Solution for the Eradication of Persister Cells in Clinical Isolates of Escherichia coli.

BACKGROUND: Bacterial persisters are non- or slow-growing phenotypic variants that may be responsible for recalcitrance and relapse of persistent infections and antibiotic failure. In Escherichia coli, mqsRA is a well-known type II toxin-antitoxin system associated with persister cell formation. This study aimed to investigate the efficiency of an antisense peptide nucleic acid (PNA) targeting mqsRA in eliminating E. coli persisters. METHODS: The study included 600 non-duplicated urine samples from adult patients with suspected urinary tract infections. The isolates were subjected to antimicrobial susceptibility testing and bacterial persister cells assay. The presence of mqsRA in the isolates was evaluated by polymerase chain reaction. Finally, expression of the mqsR and mqsA genes was assessed after exposure to normal conditions, stress, and different concentrations of mqsR-PNA (1 - 35 µM). RESULTS: The mqsR gene was significantly overexpressed under stress conditions, which was compensated by the PNA treatment. Complete inhibition of E. coli persister cells was achieved after overnight treatment with the anti-mqsR-PNA at concentrations ≥ 15 µM. CONCLUSIONS: The growth of E. coli persister cells can be inhibited by the anti-mqsR-PNA. Further studies are required to evaluate the effectiveness of this antisense PNA in both preclinical and clinical settings.

Effect of ZnO nanoparticles on biofilm formation and gene expression of the toxin-antitoxin system in clinical isolates of Pseudomonas aeruginosa.

BACKGROUND: Biofilm formation by Pseudomonas aeruginosa (P. aeruginosa) is known to be characteristic of this organism. This bacterium is considered one of the most life-threatening bacteria and has been identified as a priority pathogen for research by WHO. Biofilm-producing P. aeruginosa is a concern in many parts of the world due to antibiotic resistance. Alginate also plays an important role in the biofilm formation of P. aeruginosa as well as the emergence of antibiotic resistance in biofilms. In addition, the systems of toxin-antitoxin( TA) play an important role in biofilm formation. Metal nanoparticle(NP) such as zinc oxide (ZnO) also have extensive biological properties, especially anti-biofilm properties. Therefore, this study was conducted in relation to the importance of zinc oxide nanoparticles (ZnO NPs) in biofilm formation and also the correlation of gene expression of TA systems in clinical isolates of P. aeruginosa. METHODS: A total of 52 P. aeruginosa isolates were collected from burns (n = 15), UTI (n = 31), and trachea (n = 6) in hospitals in Ilam between May 2020 and October 2020. Biofilm formation was assessed using a microtiter plate assay. MIC and sub-MIC concentrations of ZnO NPs (10-30 nm with purity greater than 99.8%) in P. aeruginosa were determined. Subsequently, biofilm formation was investigated using sub-MIC concentrations of ZnO NPs. Finally, total RNA was extracted and RT- qPCR was used to determine the expression levels of genes of mazEF, mqsRA, and higBA of TA systems. RESULTS: Six isolates of P. aeruginosa were found to form strong biofilms. The results showed that ZnO NPs were able to inhibit biofilm formation. In our experiments, we found that the sub-MIC concentration of ZnO NPs increased the gene expression of antitoxins mazE and mqsA and toxin higB of TA systems treated with ZnO NPs. CONCLUSIONS: In the present study, ZnO NPs were shown to effectively inhibit biofilm formation in P. aeruginosa. Our results support the relationship between TA systems and ZnO NPs in biofilm formation in P. aeruginosa. Importantly, the expression of antitoxins mazE and mqsA was high after treatment with ZnO NPs, but not that of antitoxin higA.

Global Estimate of Clarithromycin Resistance in Clinical Isolates of Helicobacter pylori: a Systematic Review and Meta-Analysis.

BACKGROUND: A high resistance rate to clarithromycin usually leads to failure to eradicate Helicobacter pylori. The aim of the present study was to review recent data on H. pylori resistance towards clarithromycin in clinical studies worldwide. METHODS: PubMed/Medline, Web of Science, and Embase were used for a systematic review from 1 January 2011 to 13 April 2021 to retrieve the clinical trial studies. Data were analyzed according to publication year, age, geographic area, and minimum inhibitory concentration (MIC). Statistical analysis was done by STATA version 14.0 (College Station, Texas). RESULTS: From a total of 4,304 articles, 89 articles related to clinical studies were selected for analysis. The overall H. pylori clarithromycin resistance rate was 34.95%. Based on continents, the highest and lowest pooled estimate of the bacterial resistance rates were observed in Asia (35.97%) and North America (7.02%), respectively. The highest and the lowest pooled estimate of H. pylori resistance rate to clarithromycin based on country were obtained in Australia (93.4%) and USA (7%), respectively. CONCLUSIONS: H. pylori resistance to clarithromycin in most parts of the world is more than 15%, so it is recommended that each country, after estimating the rate of resistance to clarithromycin, determine the treatment/eradication pattern for H. pylori infection.

Mixed oral biofilms are controlled by the interspecies interactions of Fusobacterium nucleatum.

BACKGROUND: Fusobacterium nucleatum (F. nucleatum) is an integral component of supra- and subgingival biofilms, especially more prevalent in subgingival areas during both periodontal health and disease. AIMS: In this review, we explore the physical, metabolic, and genetic interactions that influence the role of F. nucleatum in the formation of mixed oral biofilms. The role of F. nucleatum in antibiotic resistance in oral biofilms was discussed and some therapeutic strategies were proposed. METHODS: PubMed, Scopus, Google Scholar, and the Web of Science were extensively searched for English-language reports. RESULTS: F. nucleatum-derived proteins such as RadD, Fap2, FomA, and CmpA are involved in direct interactions contributing to biofilm formation, while autoinducer-2 and putrescine are involved in metabolic interactions. Both groups are essential for the formation and persistence of oral biofilms. This study highlights the clinical relevance of targeted interactions of F. nucleatum in supra- and subgingival oral biofilms. CONCLUSIONS: By focusing on these interactions, researchers and clinicians can develop more effective strategies to prevent biofilm-related disease and reduce the spread of antibiotic resistance. Further research in this area is warranted to explore the potential therapeutic interventions that can be derived from understanding the interactions of F. nucleatum in oral biofilm dynamics.

Molecular characterizations of antibiotic resistance, biofilm formation, and virulence determinants of Pseudomonas aeruginosa isolated from burn wound infection.

BACKGROUND: Burn injuries result in disruption of the skin barrier against opportunistic infections. Pseudomonas aeruginosa is one of the main infectious agents colonizing burn wounds and making severe infections. Biofilm production and other virulence factors along with antibiotic resistance limit appropriate treatment options and time. MATERIALS AND METHODS: Wound samples were collected from hospitalized burn patients. P. aeruginosa isolates and related virulence factors identified by the standard biochemical and molecular methods. Antibiotic resistance patterns were determined by the disc diffusion method and ß-lactamase genes were detected by polymerase chain reaction (PCR) assay. To determine the genetic relatedness amongst the isolates, enterobacterial repetitive intergenic consensus (ERIC)-PCR was also performed. RESULTS: Forty P. aeruginosa isolates were identified. All of these isolates were biofilm producers. Carbapenem resistance was detected in 40% of the isolates, and blaTEM (37/5%), blaVIM (30%), and blaCTX-M (20%) were the most common ß-lactamase genes. The highest resistance was detected to cefotaxime, ceftazidime, meropenem, imipenem and piperacillin, and 16 (40%) isolates were resistant to these antibiotics. The minimum inhibitory concentrations (MIC) of colistin was lower than 2 µg/mL and no resistance was observed. Isolates were categorized to 17 MDR, 13 mono-drug resistance, and 10 susceptible isolates. High genetic diversity was also observed among the isolates (28 ERIC types) and most carbapenem-resistant isolates were classified into four main types. CONCLUSION: Antibiotic resistance, particularly carbapenem resistance was considerable among the P. aeruginosa isolates colonizing burn wounds. Combining carbapenem resistance with biofilm production and virulence factors would result in severe and difficult-to-treat infections.

Antimicrobial resistance and biofilm formation capacity among Acinetobacter baumannii strains isolated from patients with burns and ventilator-associated pneumonia.

BACKGROUND: Acinetobacter baumannii is a pathogen responsible for nosocomial infections, especially in patients with burns and ventilator-associated pneumonia (VAP). The aims of this study was to compare the biofilm formation capacity, antimicrobial resistance patterns and molecular typing based on PFGE (Pulsed-Field Gel Electrophoresis) in A. baumannii isolated from burn and VAP patients. MATERIALS AND METHODS: A total of 50 A. baumannii isolates were obtained from burn and VAP patients. In this study, we assessed antimicrobial susceptibility, biofilm formation capacity, PFGE fingerprinting, and the distribution of biofilm-related genes (csuD, csuE, ptk, ataA, and ompA). RESULTS: Overall, 74% of the strains were multidrug resistant (MDR), and 26% were extensively drug-resistant (XDR). Regarding biofilm formation capacity, 52%, 36%, and 12% of the isolates were strong, moderate, and weak biofilm producers. Strong biofilm formation capacity significantly correlated with XDR phenotype (12/13, 92.3%). All the isolates harbored at least one biofilm-related gene. The most prevalent gene was csuD (98%), followed by ptk (90%), ataA (88%), ompA (86%), and csuE (86%). Harboring all the biofilm-related genes was significantly associated with XDR phenotype. Finally, PFGE clustering revealed 6 clusters, among which cluster No. 2 showed a significant correlation with strong biofilm formation and XDR phenotype. CONCLUSION: Our findings revealed the variable distribution of biofilm-related genes among MDR and XDR A. baumannii isolates from burn and VAP patients. A significant correlation was found between strong biofilm formation capacity and XDR phenotype. Finally, our results suggested that XDR phenotype was predominant among strong-biofilm producer A. baumannii in our region.

Survey on phenotypic resistance in Enterococcus faecalis: comparison between the expression of biofilm-associated genes in Enterococcus faecalis persister and non-persister cells.

BACKGROUND: Phenotypic resistance is considered as a serious therapeutic challenge for which a definitive remedy has not been discovered yet. Biofilm and persister cell formation are two well-studied phenotypic resistance phenomena, leading to the recalcitrance and relapse of different types of chronic infections. The presence of persister cells in biofilm structures seems to be one of the main factors contributing to the relapse of infections and treatment failure. Given the dormant and inert nature of persister cells, they can be easy targets for the immune system factors. Biofilm formation can be a survival strategy for the defenseless persister cells. Thus, this study was aimed to evaluate the expression of biofilm-associated genes in Enterococcus faecalis persister and non-persister cells. METHODS: Vancomycin susceptibility and biofilm formation ability were investigated among 95 E. faecalis clinical isolates using microtiter broth dilution and microtiter plate assays, respectively. PCR was used to determine the presence of biofilm-related genes (gelE, esp, and agg) among the vancomycin-susceptible, biofilm producer E. faecalis isolates (91 isolates). Minimum bactericidal concentration for biofilms (MBCB) were determined for vancomycin using the MTP assay. Bacterial persister assay was performed using an enzymatic lysis assay. Finally, the expression of biofilm-related genes was compared between the persister and non-persister isolates of E. faecalis using real-time qPCR. RESULTS: E. faecalis isolates showed a high level of susceptibility (95.8%) to vancomycin (MIC < 1 µg/mL). The gelE, esp, and agg genes were found in 91 (100%), 72 (79.12), and 74 (81.32) of the isolates, respectively. All the E. faecalis isolates were tolerant to vancomycin in the biofilm condition, showing a MBCB of > 2500 µg/mL. Based on the enzymatic lysis assay, only 3 isolates, out of the 91, had the ability to form persister cells. The expression of biofilm-associated genes was higher among the persister compared to non-persister E. faecalis isolates. CONCLUSIONS: Biofilm-associated persister cells indicated a high vancomycin tolerance compared to non-persister cells. Moreover, persister isolates showed a higher tendency for biofilm formation and a higher expression level of the biofilm-associated genes, compared to non-persister isolates.

relBE toxin-antitoxin system as a reliable anti-biofilm target in Pseudomonas aeruginosa.

AIMS: The ability of the pathogenic bacterium Pseudomonas aeruginosa to produce biofilms has made it more difficult to treat its infections with current antibiotics. Several genes are involved in biofilm production, and toxin-antitoxin (TA) loci have been reported to be responsible for the regulation of biofilm-associated genes. This study was aimed at evaluating various TA loci in P. aeruginosa to find a reliable target in order to disrupt biofilm formation. METHODS AND RESULTS: Thirty clinical isolates of P. aeruginosa were assessed for biofilm production as well as the presence of various TA loci in their genomes. The relBETA locus was present in all 30 P. aeruginosa isolates but its expression was not detectable in isolates that did not show biofilm production. Quantitative real-time -PCR (q-PCR) also demonstrated that the expression of relBE was higher in isolates with stronger biofilm-producing capability. Knocking out the relBE locus in one biofilm-producing P. aeruginosa isolate led to the cessation of biofilm-producing capacity in that isolate and eliminated the expression of ndvB, which is among the genes involved in biofilm production. CONCLUSIONS: These results inferred the involvement of relBE TA locus in the regulation of biofilm production in P. aeruginosa and indicated the possibility of relBE as an anti-biofilm target for this pathogen.

Novel Antimicrobial Target in Acinetobacter Baumannii.

BACKGROUND: Resistance to multiple drugs is one of the biggest challenges in managing infectious diseases. Acinetobacter baumannii is considered a nosocomial infection. According to the multiple roles of the toxin-antitoxin system, this system can be considered an antimicrobial target in the presence of bacteria. With the impact on bacterial toxin, it can be used as a new antibacterial target. The purpose of this study was to determine the mazEF genes as a potent antimicrobial target in A. baumannii clinical isolates. METHODS: The functionality of mazEF genes was evaluated by qPCR in fifteen A. baumannii clinical isolates. Then, the mazE locus was targeted by peptide nucleic acid (PNA). RESULTS: The results showed a significant difference in the mean number of copies of mazF gene in normal and stress conditions. Also, we found that at a concentration of 15 µM of PNA the bacteria were killed and confirmed by culture on LB agar. CONCLUSIONS: This research is the first step in introducing mazEF TA loci as a sensitive target in A. baumannii. However, more studies are needed to test the effectiveness in vivo. In addition, the occurrence and potential for activation of the TA system, mazEF in other pathogenic bacteria should be further investigated.

In Vitro and In Silico Investigation of some Type II TA Genes in H. Pylori.

BACKGROUND: In addition to antibiotic resistance, the entry of Helicobacter pylori into the persistence phase leads to recurrent and chronic infections, as well as the development of antibiotic resistance in persister cells. METHODS: In this study, after genetic confirmation of H. pylori in 20 biopsy specimens, the prevalence of the type II TA systems mazEF, relEB, yafQ/dinJ was investigated. Also, the most common system observed in the study in terms of structure, evolution, and molecular interaction was evaluated by bioinformatics tools. RESULTS: The results of the PCR test on 20 biopsy samples were positive for ureA and glmM genes. Moreover, yafQ/ dinJ was the only module positive in half of the samples (10 samples) in the PCR technique. The toxin residues and their interactions with the cognate antitoxin residues are revealed by docking analysis results. Furthermore, the multiple sequence alignment (MSA) of the YafQ toxin showed that this toxin has a low polymorphism among H. pylori species. The evolutionary study showed that the yafQ toxin had the highest sequence similarity among the bacteria Helicobacter cetorm (60% similarity) and Muricauda olearia (57.35 % similarity). CONCLUSIONS: Collectively, the data of the present study indicate that the YafQ/DinJ is the dominant type II TA system and has the highest frequency among the studied systems in H. pylori, and further studies are required to elucidate its exact role in this bacterium.

The characterization of bacterial communities of oropharynx microbiota in healthy children by combining culture techniques and sequencing of the 16S rRNA gene.

The high incidence of bacterial respiratory infections has led to a focus on evaluating the human respiratory microbiome. Studies based on culture-based and molecular methods have shown an increase in the bacterial community that includes the bacterial phyla Firmicutes, Bacteroidetes, Actinobacteria, and Proteobacteria in the oropharynx of healthy individuals. Therefore, recognizing this microbial compound and subsequently identifying those carriers of specific pathogens can be of great help in predicting future infections and their control. In this prospective study, we sought to characterize the bacterial communities of the respiratory microbiome in healthy children aged between 3 and 6 years old by combining both cultural techniques and sequencing of the 16S rRNA gene. Seventy-seven oropharynx samples using Dacron swabs were collected from 77 healthy children in the kindergartens of Ilam, Iran. Bacterial identification was performed by phenotypic methods and in house developed PCR-based sequencing (the V1-V9 hypervariable region of the bacterial 16S ribosomal RNA gene). In total, 346 bacterial isolates were characterized based on phenotypic and sequencing-based molecular methods. The 3 most predominant phyla were Firmicutes (74%), Proteobacteria (22%), and Actinobacteria (4%). At the level of the genus, Staphylococci (coagulase-positive and coagulase-negative) and Streptococci were dominant. Also, the most commonly identified potentially pathogenic colonisers were S. aureus (75%), Enterobacteriaceae spp. (40.1%), and A. baumannii (15.6%). The present study identified 3 phyla and 9 family of bacteria in the oropharyngeal microbiome. Remarkably, the presence of potential pathogenic bacteria in the nasopharynx of healthy children can predispose them to infectious diseases, and also frequent exposure to human respiratory bacterial pathogens are further risk factors.

The role of gibberellic acid and zinc sulfate on biochemical performance relate to drought tolerance of white bean under water stress.

In this study the effects of zinc sulfate and gibberellin on agro physiological of white bean under water deficiency were studied. Therefore, an experiment was conducted in a split-split plot design based on a randomized complete block with three replications in two places. The experimental factors included three irrigation levels, spraying of zinc sulfate in four levels and two levels of non-spraying and spraying of gibberellin. Analysis of measured data indicated that the water stress had a significant effect on all traits, except proline amount and 100 seeds weight. Spraying of zinc sulfate showed a significant effect on all traits except carotenoid value. Application of gibberellin had a significant effect on all traits except ion leakage, carotenoids, number of seeds per pod and grain yield. The interaction effect of stress×zincsulfate×gibberellin was significant on all traits except number of seeds per pod. In addition, comparison of means at 5% level, showed that application of 1.5 ml L-1of zinc sulfate plus gibberellin improved bean biochemical properties. Under optimum water level, using of 4.5 ml L-1of zinc sulfate and under severe water stress conditions, using of 4.5 ml L-1 of zinc sulfate plus gibberellin are recommended for obtaining the maximum crop performance.

Effect of native growth promoting bacteria and commercial biofertilizers on growth and yield of wheat (Triticum aestivum) and barley (Hordeum vulgare) under salinity stress conditions.

Salinity is one of the main obstacles to the production of crops in dry regions of the world. This study focuses on the effects of different strains of plant growth promoting rhizobacteria (PGPR) isolated from native soils on the physiological responses of wheat and barley plants under normal and salt stress conditions. Soil samples were collected from a field in Ilam province, in Iran and bacterial isolates were isolated and screened for salt tolerance, included siderophore and ACC-deaminase production and phosphate solubilizing. Thereafter a two-years greenhouse experiment was conducted as a completely randomized block design with four replications. The applied treatments included bacterial inoculation at five levels (B0: non-inoculation, B1: Siderophore producing + salt-tolerant bacteria, B2: phosphate solubilizing + salt-tolerant bacteria, B3: ACC-deaminase producing + salt-tolerant bacteria, B4: Barvar-2 biological fertilizer, B5: Biofarm-2 biological fertilizer) and salt stress at three levels (S1: 0 dS/m, S2: 4 dS/m, S3: 8 dS/m). Results showed that phosphate solubilizing+ salt-tolerant bacteria resulted in the highest barley grain yield at 4 dS/m salinity level and had no significant difference with ACC-deaminase producing + salt-tolerant bacteria and Barvar-2 biological fertilizer and Biofarm-2 biological fertilizer. The highest proline content in wheat and barley observed in Siderophore producing+ salt-tolerant bacteria at 8 dS/m by 17.48 and 23.42, respectively, followed by phosphate solubilizing+ salt-tolerant bacteria by 16.53 and 19.78. Therefore, the application of isolated growth promoting bacteria can be recommended as an effective biofertilizer in Ilam province.

Phenotypic and Genotypic Characterization of ESBL-, AmpC-, and Carbapenemase-Producing Klebsiella pneumoniae and Escherichia coli Isolates.

OBJECTIVES: Drug resistance among gram-negative bacteria is a worldwide challenge. Due to the importance of drug-resistant Klebsiella pneumoniae and Escherichia coli strains in hospital-acquired infections, we aimed to determine the phenotypic and genotypic characteristics of ESBL-, AmpC-, and carbapenemase-producing isolates obtained from hospitalized patients in Tehran and Ilam (Iran). MATERIALS AND METHODS: In total, 90 K. pneumoniae isolates and 65 E. coli isolates were collected from various infections. Phenotypic identification of bacterial isolates was performed using standard methods. Phenotypic screening of ESBL, AmpC, and carbapenemase enzymes was carried out. Detection of ESBL, AmpC, and carbapenemase genes was also performed by the PCR method. RESULTS: Phenotypic detection tests showed that 36 (40%) K. pneumoniae and 23 (35.4%) E. coli isolates were ESBL producers. Moreover, 18 (20%) and 6 (9.2%) K. pneumoniae and E. coli isolates were AmpC producers, respectively. Modified Hodge test results indicated that 39 (43.3%) K. pneumoniae and 18 (27.7%) E. coli isolates produced carbapenemase. Molecular tests showed that 40% of K. pneumoniae and 36.9% of E. coli isolates were ESBL positive. AmpC was detected in 24.4 and 13.8% of K. pneumoniae and E. coli isolates. Carbapenemase was detected in 34 (37.8%) K. pneumoniae and 13 (20%) E. coli isolates. -Conclusion: In this study, 3 K. pneumoniae isolates simultaneously carried ESBL, AmpC, and carbapenemase genes. Up-to-date strategies such as combination therapy or utilization of new antimicrobial agents might help to combat such drug-resistant organisms.

Association analysis of tolerance to dieback phenomena and trunk form using ISSR markers in Quercus brantii.

Oak decline is a complex syndrome in which several damaging agents interact and bring about a serious dieback in tree condition. Genetic diversity is a key factor for better adoption of natural populations to environmental stresses. The objective of this research was to identify the association of polymorphism patterns of different reproducible genomic Inter simple sequence repeats (ISSR markers) to level of dieback phenomena and also growth type in 18 different stands of Persian oak in central Zagros region. Totally, 180 trees were sampled and evaluated for growth type, tree diameter at breast height (DBH) and level of tree dieback. Genomic DNAs extracted of fresh leaves amplified using 15 multi-locus ISSR primers. The population structure determined using the Bayesian model-based clustering method implemented in STRUCTURE software by Monte Carlo Markov Chain (MCMC) method. Five distinct sub-populations (K=5) determined by the log likelihood of the data.  Genome wide association study (GWAS) performed using the generalized linear model (GLM) and the mixed linear model (MLM) with Kinship matrix. Informative alleles recognized for level of tolerance to dieback and tree growth type traits. It was observed a significant co-segregation for phenotypic data and some of amplified fragments. Identification of these informative DNA markers can be utilized for pre-screening of high quality oak seedlings in early growth stages and better management in restoration of damaged stands.

Effects of non-tuberculous mycobacteria on BCG vaccine efficacy: A narrative review.

The Mycobacterium tuberculosis bacterial pathogen is responsible for the ongoing global tuberculosis (TB) epidemic. Bacille Calmette-Guérin (BCG), the only currently approved TB vaccine, is successful in preventing disseminated disease in newborns. However, it has a variable efficacy against pulmonary TB in adults. This protective effect of the vaccine varies greatly among different populations and geographical areas, which the increased exposure of particular populations to non-tuberculous mycobacteria (NTM) is considered as one of the reasons for this issue. Numerous studies have shown that exposure to NTM species causes the host immune system to be improperly primed. It has also been suggested that NTM species may be blamed for reduction in BCG vaccine effectiveness against M. tuberculosis. The increased exposure of certain populations to NTM has diverse effects on BCG efficacy. Moreover, the exposure to NTM can induce opposite effects on BCG efficacy depending on the NTM exposure route and survivability. A detailed understanding of the impact of NTM exposure on the efficacy of the BCG vaccine is essential for ongoing efforts to develop new TB vaccines as it may ultimately be a crucial success factor. The aim of this study was to review the findings of the studies focusing on the effects of NTM on BCG vaccine efficacy in animal models.

Epidemiology of first- and second-line drugs-resistant pulmonary tuberculosis in Iran: Systematic review and meta-analysis.

Drug resistance among Mycobacterium tuberculosis (MTB) strains is a growing concern in developing countries. We conducted a comprehensive search for relevant studies in Iran on PubMed, Scopus, and Embase until June 12, 2020. Our study focused on determining the prevalence of antibiotic resistance in MTB isolates, with subgroup analyses based on year, location, and drug susceptibility testing (DST) methods. Statistical analyses were performed using STATA software. Our meta-analysis included a total of 47 articles. Among new TB cases, we found the following prevalence rates: Any-resistance to first-line drugs: 31 % (95 % CI, 24-38), mono-drug resistance: 15 % (95 % CI, 10-22), and multidrug resistance to first-line drugs: 6 % (95 % CI, 4-8). There was a significant variation in the rate of MDR among new TB cases based on the year of publication, location, and DST methods (P < 0.0001). We observed substantial variability in multidrug-resistant TB rates among new cases across the studies. Stratified analyses revealed that publication years and DST methods significantly affected resistance rates. Studies from southern and central Iran reported higher any-drug resistance rates, suggesting regional differences. Among retreatment cases, the prevalence rates were as follows: Any resistance: 68 % (95 % CI 58-78), mono-resistance: 19 % (95 % CI 7-34), multidrug resistance: 28 % (95 % CI 15-43). Our study revealed that the prevalence of drug-resistant TB (DR-TB) among TB cases in Iran is higher than the global average. Particularly, MDR-TB among retreatment TB cases is a significant public health issue.

Survey in Iran of clarithromycin resistance in Helicobacter pylori isolates by PCR-RFLP.

The aims of this study were to assess primary resistance of H. pylori strains isolated from adult patients of Ilam, Iran to antibacterial agents (amoxicillin, clarithromycin, metronidazole and tetracycline) and detection of clarithromycin, azithromycin, clarithromycin, metronidazole and tetracycline resistance by disc diffusion. Fifty biopsies were taken from gastric mucosa of the antrum and body regions of adult patients by gastroscopy, and were cultured on Helicobacter pylori selective medium. The susceptibility of H. pylori strains showed that 44, 6, 6, 4 and 16% were resistance to metronidazole, amoxicillin, tetracycline, azithromycin, and clarithromycin, respectively. Polymerase chain reaction- restriction fragment length polymorphism analysis showed that all clarithromycin resistance isolates had A2143G mutation and PCR amplicons from these strains upon digestion by BsaI restriction enzyme resulted in 319 and 106 base pair fragments. Because most of physicians in Ilam do not use amoxicillin in triple therapy of H. pylori infection, isolates showed low rate of resistance to amoxicillin.

Antimicrobial resistance among clinical Vibrio cholerae non-O1/non-O139 isolates: systematic review and meta-analysis.

Non-O1/non-O139 Vibrio cholerae (NOVC) are nonpathogenic or asymptomatic colonizers in humans, but they may be related to intestinal or extra-intestinal (severe wound infections or sepsis) infections in immunocompromised patients.The present study aimed to evaluate the weighted pooled resistance (WPR) rates in clinical NOVC isolates based on different years, areas, quality, antimicrobial susceptibility testing (AST), and resistance rates. We systematically searched the articles in PubMed, Scopus, and Embase (until January 2020). Data analyses were performed using the Stata software program (version 17). A total of 16 studies that had investigated 824 clinical NOVC isolates were included in the meta-analysis. The majority of the studies were conducted in Asia (n = 14) and followed by Africa (n = 2). The WPR rates were as follows: erythromycin 10%, ciprofloxacin 5%, cotrimoxazole 27%, and tetracycline 13%. There was an increase in resistance to ciprofloxacin, nalidixic acid, and gentamicin, norfloxacin during the period from 2000 to 2020. On the contrary, there was a decreased resistance to erythromycin, tetracycline, chloramphenicol, cotrimoxazole, ampicillin, streptomycin, kanamycin, and neomycin during the period from 2000 to 2020. The lowest resistance rate were related to gentamicin, kanamycin, ciprofloxacin, and chloramphenicol against NOVC strains. However, temporal changes in antimicrobial resistance rate were found in our study. We established continuous surveillance, careful appropriate AST, and limitations on improper antibiotic usage, which are essential, especially in low-income countries.

Trends in the Antibiotic Resistance of Non-Tuberculous Mycobacteria in Iran: A Systematic Review and Meta-Analysis.

Background: Non-tuberculous mycobacteria (NTM) infections have been continuously increasing as major concerns of public health in Iran. Because innate resistance of NTM species, the treatment of these infections is difficult task, but until now resistance pattern of NTM and suitable regimens are not determined. Methods: We systematically searched the relevant studies in PubMed, Scopus, and Embase (Until Dec 2022). All statistical analyses were carried out using the statistical package R. Results: Eleven studies included in the analysis were performed in 6 provinces and investigated 1223 NTM clinical species. The majority of the studies originated in Tehran. Among the first-line anti-TB drugs, almost all NTM species were highly resistant to first-line anti-TB drugs. No significant difference in the isoniazid resistance rate was found in the slow or rapid-growing species and Runyon's classification of NTM isolates. A decreased in the prevalence of ciprofloxacin, clarithromycin, and moxifloxacin resistance were showed in during 2013-2022 years. Conclusion: Most investigated antibiotics have a minor effect on NTM species and a steady increase of resistance has been seen in last few years then, need more-effective alternative regimens is clear.