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Saeed Khoshnood,1,2 Mohammad Savari,1,2 Effat Abbasi Montazeri,1,2 Ahmad Farajzadeh Sheikh1,2 1Infectious and Tropical Diseases Research Center, Health Research Institute, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran; 2Department of Microbiology, Faculty of Medicine, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, IranCorrespondence: Ahmad Farajzadeh SheikhInfectious and Tropical Diseases Research Center, Health Research Institute, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Khuzestan 61357-15794, IranTel +98 9161133491Fax +98 61 3333 2036Email farajzadehah@gmail.comIntroduction: Acinetobacter baumannii is an opportunistic pathogen responsible for nosocomial infections. The emergence of colistin-resistant A. baumannii is a significant threat to public health. The aim of this study was to investigate the molecular characterization and genotyping of clinical A. baumannii isolates in Southwestern Iran.Methods: A total of 70 A. baumannii isolates were collected from patients admitted to Imam Khomeini Hospital in Ahvaz, Southwestern Iran. Minimum inhibitory concentration test was conducted by using Vitek 2 system. The presence of biofilm-forming genes and colistin resistance-related genes were evaluated by PCR. The isolates were also examined for their biofilm formation ability and the expression of pmrA and pmrB genes. Finally, multilocus sequence typing (MLST) and PCR-based sequence group were used to determine the genetic relationships of the isolates.Results: Overall, 61 (87.1%) and 9 (12.8%) isolates were multidrug-resistant (MDR) and extensively drug-resistant (XDR), respectively. Colistin and tigecycline with 2 (2.8%) and 32 (45.7%) resistance rates had the highest effect. Among all the isolates, 55 (78.5%), 7 (10%), and 3 (4.3%) were strong, moderate, and weak biofilm producers, respectively. The frequency rates of biofilm-related genes were 64 (91.4%), 70 (100%), 56 (80%), and 22 (31.42%) for bap, ompA, csuE, and blaPER1, respectively. Overexpression of pmrA and pmrB genes was observed in two colistin-resistance isolates, but the expression of these genes did not change in colistin-sensitive isolates. Additionally, 37 (52.8%) and 8 (11.4%) isolates belonged to groups 1 (ICII) and 2 (IC I), respectively. MLST analysis revealed a total of nine different sequence types that six isolates belonged to clonal complex 92 (corresponding to ST801, ST118, ST138, ST 421, and ST735). Other isolates were belonging to ST133 and ST216, and two colistin-resistant (Ab4 and Ab41) isolates were belonging to ST387 and ST1812.Conclusion: The present study revealed the presence of MDR and XDR A. baumannii isolates harboring biofilm genes and emergence of colistin-resistant isolates in Southwestern Iran. These isolates had high diversity, which was affirmed by typing techniques. The control measures and regular surveillance are urgently needed to preclude the spread of these isolates.Keywords: Acinetobacter baumannii, drug resistance, colistin, MLST, clonal complex

Aghil Bahramian,1,2 Saeed Khoshnood,3,4 Aref Shariati,5 Farahnoosh Doustdar,2 Alireza Salimi Chirani2 Mohsen Heidary5,6 1Infectious Diseases and Tropical Medicine Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran; 2Department of Microbiology, School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran; 3Department of Microbiology, Faculty of Medicine, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran; 4Student Research Committee, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran; 5Department of Microbiology, School of Medicine, Iran University of Medical Sciences, Tehran, Iran; 6Student Research Committee, School of Allied Medical Sciences, Iran University of Medical Sciences, Tehran, Iran Introduction: Pseudomonas aeruginosa is the most common opportunistic pathogen associated with a broad range of infections, including cystic fibrosis, ocular, otitis media, and burn infections. The aim of this study was to show the frequency of the pilS2 gene, and its association with P. aeruginosa plasmid pKLC102 and PAPI-1 pathogenicity island among P. aeruginosa strains.Methods: The samples were collected from patients with cystic fibrosis, ocular, otitis media, and burn infections between January 2016 and November 2017. DNA was extracted using the DNA extraction kit and was used for PCR assay. PCR with 4 primer-pairs including 976 F/PAPI-1R, 4542 F/intF, SojR/4541 F, and intF/sojR was performed to identify PAPI-1. pKLC102 was detected using three other primer-pairs including cp10F/ cp10R, cp44F/cp44R, and cp97F/cp97R.Results: A total of 112 P. aeruginosa isolates were collected from patients with cystic fibrosis (36), burn (20), otitis media (26), and ocular (30) infections. The results of PCR showed that pilS2 gene was identified in 96 (85%) strains. PAPI-1–attB integration was detected among 38 (33.9%) isolates and the circular form of PAPI-1 detected among 17 (14%) isolates. In addition, 79 (70.5%) strains were found to be positive for pKLC102.Conclusion: We found that the majority of the isolates may be susceptible to transfer this significant island and the related element pKLC102 into recipient isolates lacking the island owing to high association of the PilS2 pilus with the islands in the studied strains. It is anticipated that strains isolated from burn and eye with the highest rate of PilS2, PAPI-1, and pKLC102 association have a high level of antibiotic resistance. Keywords: Pseudomonas aeruginosa, pilS2, cystic fibrosis, pKLC102, PAPI-1

Ahmad Farajzadeh Sheikh,1,2 Mojtaba Moosavian,1,2 Mahtab Abdi,2 Mohsen Heidary,3,4 Fatemeh Shahi,2 Nabi Jomehzadeh,5 Sakineh Seyed-Mohammadi,1,2,6 Morteza Saki,1,2,6 Saeed Khoshnood1,2,6 1Infectious and Tropical Diseases Research Center, Health Research Institute, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran; 2Department of Microbiology, Faculty of Medicine, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran; 3Department of Microbiology, Faculty of Medicine, Iran University of Medical Sciences,Tehran, Iran; 4Student Research Committee, School of Allied Medical Sciences, Iran University of Medical Sciences, Tehran, Iran; 5Abadan School of Medical Sciences, Abadan, Iran; 6Student Research Committee, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran Introduction: Shigellosis is a significant global human health problem, and Shigella is in charge of almost 165 million cases of this disease annually, of whom 163 million cases are in developing countries and 1.5 million cases are in developed countries. The main aims of the current survey were to identify Shigella spp. isolated from diarrheal patients by conventional biochemical tests, determine the antimicrobial susceptibility profiles by disk diffusion method, and detect the ipaH gene using the PCR assay.Methods: The bacterial isolates were identified as Shigella spp. by microbiological tests and were serogrouped by the slide agglutination test. Antimicrobial susceptibility testing was performed using the disk diffusion method. PCR was performed to detect the ipaH gene.Results: The Shigella strains were isolated from 522 patients with various diarrhea, including bloody diarrhea (3%), mucoid plus bloody diarrhea (1.9%), mucoid diarrhea (3.2%), and watery diarrhea (3.2%). Overall, 69 (13.2%) isolates were positive for Shigella spp., of which 34 (49.3%) serotypes were identified as Shigella flexneri, 22 (31.9%) serotypes were identified as Shigella sonnei, 9 (13%) serotypes were identified as Shigella boydii, and 4 (5.8%) serotypes were identified as Shigella dysenteriae. Antibiotic susceptibility tests revealed that the highest resistance percentage was related to ampicillin (82%) and trimethoprim-sulfamethoxazole (77%), and ciprofloxacin and ceftriaxone were the best antibiotics against Shigella isolates.Conclusion: We concluded that Shigella spp. can be considered as an etiological agent of diarrhea in southwest Iran. Since the drug resistance pattern of Shigella differs geographically and over time within a country, continuous and regular surveillance program is necessary. Keywords: Shigella, diarrhea, resistance, Iran

In recent years, the resistance rate to quinolone antibiotics has been increasing in Klebsiella pneumoniae. Plasmid-mediated quinolone resistance (PMQR) genes are one of the factors causing resistance to quinolones. Hence, this study aimed to determine the incidence of PMQR genes in clinical K. pneumoniae isolates from southwest Iran. In total, 96 K. pneumoniae isolates were identified during the study period. Sixty-seven (69.8%) isolates were resistant to at least one quinolone antibiotic. Resistance rates to levofloxacin, norfloxacin, nalidixic acid, ofloxacin, and ciprofloxacin were 50% (48/96), 56.3% (54/96), 60.4% (58/96), 62.5% (60/96), and 68.8% (66/96), respectively. The highest frequencies of PMQR genes were related to qnrS, aac (6')-Ib-cr, and qnrB genes with 85.1% (57/67), 83.6% (56/67) and 65.7% (44/67), respectively. The qnrD, qnrC, qepA, and qnrA were detected in 23.9% (16/67), 19.4% (13/67), 13.4% (9/67), and 6.0% (4/67) of isolates, respectively. This study was the first to report a high-frequency rate of PMQR genes in K. pneumoniae isolates from the clinical setting of Ahvaz, southwest Iran. As a result, antibiotic prescribing policies should be amended to hinder the further spread of PMQR genes in the studied region., Competing Interests: Declarations. Ethics approval and consent to participate: The proposal for this study and the experiments including any relevant details, was approved by the Ethics Committee of the Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran (No. IR.AJUMS.REC.1399.468). All experiments were performed in accordance with the Declaration of Helsinki guidelines and regulations. Informed consent was obtained from participants and confidentiality was maintained in accordance with the Helsinki Declaration. Consent for publication: Not applicable. Competing interests: The authors declare no competing interests., (© 2025. The Author(s).)

Background: Antibiotic heteroresistance is a common phenotype observed in a variety of pathogenic bacteria such as K. pneumonia: A subpopulation of cells with a higher MIC than the dominant population is defined as heteroresistance. Several studies have demonstrated colistin heteroresistance in K. pneumonia leading to treatment failures. Therefore, we performed a systematic meta-analysis to summarize the current evidence on the prevalence of colistin heteroresistance in K. pneumonia isolates., Methods: Multiple databases were searched to find relevant literature from 2008 to 2024, including PubMed, Scopus, Embase, and Web of Science., Results: The meta-analysis included eighteen articles. According to the random effects model, the pooled proportion of heteroresistant K. pneumoniae was 0.315 (95% CI: 0.179-0.492). The heterogeneity was substantial, with Q [17] = 335.020, I² = 94.93%, and p < 0.001, suggesting that heteroresistance rates varied widely across the 18 included studies., Conclusion: In conclusion, our findings revealed that a prevalence of colistin heteroresistant detected in approximately 31.5%, of K. pneumonia. These findings are obtained and highlighted in this meta-analysis as a new guidance document for diagnosing and treating K. pneumonia infections is needed to raise the awareness of infectious disease specialists, gastroenterologists, and microbiologists to the heteroresistance to colistin in patients with a K. pneumonia infection., Competing Interests: Declarations. Ethical approval: This project was approved by the Ilam University of Medical Sciences Ethics Committee(IR.MEDILAM.REC.1400.185). Clinical trial number: Not applicable. Consent for publication: Not applicable. Competing interests: The authors declare no competing interests., (© 2025. The Author(s).)

Foot-and-mouth disease (FMD) is a significant transboundary animal disease that has a considerable economic impact on livestock systems worldwide. In order to determine the presence and type of FMD virus in Iran, a total of 90 samples of vesicular fluid and epithelial tissue were collected from the tongues, tooth pads, and hooves of clinically suspect cattle on 40 vaccinated farms in 9 provinces of Iran. These samples were collected during four years, from January 2019 to December 2022, and the vaccine was a locally produced polyvalent inactivated vaccine. The collected samples were analyzed using ELISA and isolation methods to identify and characterize the FMD virus. The results of the ELISA tests revealed that 66.66% of the samples were positive for FMD, and the serotypes of the virus were determined. Considering ELISA reslut, 62% of the samples were assigned to serotype O, 33% to serotype A, and 5% to serotype Asia-1. Furthermore, 90% of the positive samples were inoculated onto monolayer cultures of pig kidneys (IB-RS2) for isolation and antigen detection by serotype-specific ELISA kit. The great majority of detected serotype O viruses were from Esfahan province, while the most detected serotype A and serotype Asia-1 viruses were from Qom and Tehran provinces, respectively. These findings indicate that the ELISA and isolation methods are suitable for identifying and typing FMD viruses. The vaccination program in Iran, which includes three serotypes (O, A, and Asia-1), appears to be effective in controlling the spread of the disease. However, the continued circulation of these serotypes in most provinces suggests that ongoing surveillance and vaccination efforts are necessary., Competing Interests: Declarations. Competing interest: The authors declare no competing interest., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Helicobacter pylori ( H. pylori ) infection is a typical microbial agent that interferes with the complex mechanisms of gastric homeostasis by disrupting the balance between the host gastric microbiota and mucosa-related factors, ultimately leading to inflammatory changes, dysbiosis, and gastric cancer (GC). We searched this field on the basis of PubMed, Google Scholar, Web of Science, and Scopus databases. Most studies show that H. pylori inhibits the colonization of other bacteria, resulting in a less variety of bacteria in the gastrointestinal (GI) tract. When comparing the patients with H. pylori- positive and H. pylori -negative GC, the composition of the gastric microbiome changes with increasing abundance of H. pylori (where present) in the gastritis stage, whereas, as the gastric carcinogenesis cascade progresses to GC, oral and intestinal-type pathogenic microbial strains predominate. H. pylori infection induces a premalignant milieu of atrophy and intestinal metaplasia, and the resulting change in gastric microbiota appears to play an important role in gastric carcinogenesis. The effect of H. pylori -induced GC on GI microbiota is discussed in this review., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2025 Heidary, Akrami, Madanipour, Shakib, Mahdizade Ari, Beig, Khoshnood, Ghanavati and Bazdar.)

Background: Meningitis is highly prevalent in infant because their immune system is immature and they have less resistance to diseases. Among bacterial agents, Escherichia coli is recognized as one of the most important causes of meningitis in infants., Case Presentation: Herein, we report a case of late-onset meningitis, caused by E. coli (Patient:17-day-old female infant). The patient's body temperature was 39°C, and the initial diagnosis was sepsis. At the doctor's request, the patient underwent the basic tests and was hospitalized in the Neonatal Intensive Care Unit (NICU). In this case, blood culture and CSF culture were negative and positive, respectively. Echogenic particles were observed inside the bladder, indicating possible cystitis. The results of the antibiotic susceptibility tests showed that the meningitis-causing strain of E. coli was susceptible only to amikacin., Conclusion: Conducting LP and CSF culture seems to be the most important strategy for diagnosing meningitis. It is also recommended to perform LP before taking antibiotics. For identifying the infection, some factors such as fever, CRP test results, CSF parameters (leukocyte count, glucose level, and CSF culture results) should be considered to prevent misdiagnosis., Competing Interests: The authors declare that they have no competing interests., (Copyright © 2024 Asghari et al.)

Background: Vitamin D is a steroid hormone that protects against viral infections by influencing innate and adaptive immune responses. The effectiveness of vitamin D3 supplementation in COVID-19 is unknown. The study's goal was to elucidate the relationship between blood vitamin D levels and COVID-19 clinical outcomes by examining the effect of a single high dose of vitamin D3 on the length of hospital stay in COVID-19 patients., Methods: The descriptive, retrospective study was performed from March to May 2021 at a referral center for patients with COVID-19, in Bam, Iran. A checklist consisting of demographic variables was used to gather data, and laboratory assessments of serum 25(OH) D were evaluated and documented. The connection between serum vitamin D and patient clinical outcomes was investigated after patients were given a single oral dose of 200,000 IU of vitamin D3., Results: 71 COVID-19 patients were treated. Radiological results did not change substantially amongst individuals with various levels of 25(OH)D. After a single dosage of vitamin D3, mean blood levels of 25-hydroxyvitamin D increased considerably and the need for intubation and SpO 2 decreased, and as did the respiratory rate in patients requiring hospitalization due to COVID-19., Conclusion: A single administration of 200,000 IU of vitamin D3 significantly reduced the severity of COVID-19., Competing Interests: All of the authors declare that there are no commercial, personal, political, or any other potential conflicting interests related to the submitted manuscript., (Copyright © 2024 Mortazavi et al.)

Objectives: The study investigates how antibiotics affect biofilm formation and toxin gene expression in Clostridium difficile, which is essential for its survival and persistence., Methods: The study confirmed 25 strains of C. difficile and assessed biofilm formation. The MIC of metronidazole and vancomycin was determined through agar dilution, and the impact of sub-MIC levels on biofilm formation and eradication was investigated. Additionally, Real-time PCR was used to analyze the expression levels of target genes related to antibiotic treatment., Results: We found that certain genes, such as the ImmA/IrrE system, were associated with increased biofilm formation in isolates. Sub-MIC antibiotic levels influenced gene expression related to biofilm activities, particularly emphasizing the importance of toxin-antitoxin systems. The results suggest that antibiotics at sub-MIC levels may play a signaling role in promoting biofilm formation and gene expression in C. difficile., Conclusion: Our study suggests that toxin and antitoxin genes may impact C. difficile biofilm formation, while antibiotics could signal biofilm strengthening and gene expression increase., (© 2024. The Author(s), under exclusive licence to Springer Nature B.V.)

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., (© 2023 Wiley Periodicals LLC.)

Right atrial tuberculoma (RAT) are an exceedingly rare heart mass often caused by primary pulmonary tuberculosis (TB) in patients infected with human immunodeficiency virus (HIV). In HIV patients, the right atrium is not only a suitable location for tuberculoma formation, but also has a tendency for thrombus formation due to the thrombophilic state of HIV and the destructive effect of the HIV virus on the endothelial surface of the right atrium and subsequent thrombus formation. These masses can simply be detected by transthoracic echocardiography (TEE), but their differentiation from other cardiac pathologies requires histological examination. Herein, using a positive polymerase chain reaction test, we report a case of a previously diagnosed HIV-positive 24-year-old man who presented with a right atrial thrombus, dyspnea, and pleural effusion. Final histological examination identified the right atrial thrombus as a tuberculoma. The patient underwent open heart surgery to remove the mass and received prolonged postoperative TB therapy together with HIV drugs. Three-month follow-up showed some remaining dyspnea and lower extremity edema; however, TEE showed no recurrence of the RAT or thrombus., Competing Interests: The authors have no conflicts of interest to declare., (Copyright ©2024 The Author(s).)

Objective: This research study was undertaken to investigate antimicrobial resistance patterns and the prevalence of hospital-acquired infections (HAIs). The study focuses on common microorganisms responsible for HAIs and explores emerging challenges posed by antimicrobial drug-resistant isolates., Methods: A comprehensive analysis of 123 patients with HAIs, hospitalized in surgical department and intensive care unit (ICU) at Imam Khomeini Hospital, Ilam, Iran, was conducted over a six-month period. Pathogenic bacterial isolates, including methicillin-resistant Staphylococcus aureus (MRSA) and vancomycin-resistant Staphylococcus aureus (VRSA), were isolated and subjected to antibiotic susceptibility testing., Results: The study findings revealed a significant prevalence of multidrug-resistant (MDR) isolates, of which 73.3% were MRSA. Notably, 6.7% of S. aureus isolates exhibited resistance to vancomycin, indicating the emergence of VRSA. Respiratory infections were identified as the most prevalent HAI, constituting 34.67% of cases, often arising from extended ICU stays and invasive surgical procedures. Furthermore, patients aged 60 and above, particularly those associated with MDR, exhibited higher vulnerability to HAI., Conclusions: This research sheds light on the intricate interplay between drug resistance and HAI, highlighting the imperative role of rational antibiotic use and infection control in addressing this critical healthcare challenge., (© 2024. The Author(s), under exclusive licence to Springer Nature B.V.)

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., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2024 The Author(s).)

Background and Aims: Emergence of multidrug resistance in non-fermenting Gram-negative bacilli is a threat to public health. Combination therapy is a strategy for the treatment of antibiotic-resistant infections., Methods: In this cross-sectional study, a total of 63 nonduplicate clinical isolates of Acinetobacter baumannii and Pseudomonas aeruginosa  were collected from various specimens. Identification of bacterial isolates was performed by phenotypic and molecular tests. Antibiotic susceptibility patterns and detection of β-lactamase genes were determined using the broth microdilution and polymerase chain reaction (PCR) techniques, respectively. Then, the combined effects analysis was determined by the checkerboard method. Based on the status of resistance to carbapenems (imipenem and meropenem), 25 isolates of each genus were selected for further investigation., Results: For A. baumannii, bla OXA-23 , bla OXA-58 , and bla OXA-48 genes were positive in 21 (84%), 17 (68%), and 11 (44%) of isolates, respectively. In P. aeruginosa isolates, bla VIM was the most common gene (44%) and other genes including bla IMP , bla NDM , and bla OXA-23 were found in nine (36%), six (24%), and three (12%) isolates, respectively. Meropenem (MER)-tigecycline (TIG) had a significant synergistic effect against 20 (80%) A. baumannii ( p  value < 0.001). This combination was also efficient against 5 (20%) P. aeruginosa isolates. Moreover, the other combination, tigecycline-amikacin (TIG-AMK) was effective against 10 (40%) A. baumannii isolates. The combination of colistin (COL) and MER showed a significant synergistic effect against 21 (84%) A. baumannii ( p  value < 0.001) and 17 (68%) P. aeruginosa isolates ( p  value < 0.001)., Conclusion: The MER-TIG and COL-MER combinations are promising options against resistant bacteria. Our study could be helpful for the development of a new treatment recommendation., Competing Interests: The authors declare no conflict of interest., (© 2024 The Authors. Health Science Reports published by Wiley Periodicals LLC.)

Non-specific chronic constrictive pericarditis is a rare and debilitating chronic infection in developed countries and its rapid diagnosis and treatment has not affected its outcome and complication. A 15-year-old male, well nourished, negative HIV test, and without a history of previous pulmonary tuberculosis, was admitted to our hospital for exertional dyspnea (New York Heart Association, NYHA, functional class II). Our patient had had no pulmonary tuberculosis during childhood, had received anti-tuberculosis treatment, and was referred to our center for further surgical pericardiectomy., Competing Interests: The authors declare that they have no competing interests., (Copyright © 2024 Sabzi et al.)

The rising issue of antibiotic resistance has made treating Pseudomonas aeruginosa infections increasingly challenging. Therefore, vaccines have emerged as a viable alternative to antibiotics for preventing P. aeruginosa infections in susceptible individuals. With its superior accuracy, high efficiency in stimulating cellular and humoral immune responses, and low cost, mRNA vaccine technology is quickly replacing traditional methods. This study aimed to design a novel mRNA vaccine by using in silico approaches against P. aeruginosa. The research team identified five surface and antigenic proteins and selected their appropriate epitopes with immunoinformatic tools. These epitopes were then examined for toxicity, allergenicity and homology. The researchers also checked their presentation and identification by major histocompatibility complex cells and other immune cells through valuable tools like molecular docking. They subsequently modeled a multi-epitope protein and optimized it. The mRNA was analyzed in terms of structure and stability, after which the immune system's response against the new vaccine was simulated. The results indicated that the designed mRNA construct could be an effective and promising vaccine that requires laboratory and clinical trials., (© The Author(s) 2024. Published by Oxford University Press.)

Introduction: Helicobacter pylori ( H. pylori ) induces gastritis by stimulating Th17 cells and related cytokines. The aim of our study was to investigate the synergistic effect of metformin with amoxicillin as an antibiotic in inhibiting H. pylori and modulating the immune response in a rat model., Methods: Forty-five male Sprague-Dawley rats were divided into seven groups and infected with H. pylori . Over the course of 14 days, all animals were treated with metformin and amoxicillin alone and in combination. The antibacterial activity of metformin was evaluated by growth curves and colony counts. The immunoregulatory effect on Treg/Th17 balance was assessed by flow cytometry, and the cytokine profile of IL-17A, IL-1 β , IL-6, IL-8, TGF- β , and IL-10 was determined by ELISA. The effect of metformin on gene expression of cagA and IL-8 was investigated by RT-PCR. Pathological changes were assessed by hematoxylin and eosin (H&E) staining and immunohistochemical (IHC) staining., Results: Metformin showed weak antibacterial activity against clinically isolated H. pylori . However, the combination of metformin and amoxicillin (AMX) showed strong synergistic antibacterial activity ( Σ FIC = 0.24). Compared with AMX, metformin reduced inflammation and tissue damage but resulted in increased bacterial growth. During metformin administration, both TGF- β levels and Treg cells increased dramatically ( P = 0.002). In synergy with AMX, metformin decreased the effective dose of antibiotic to eradicate H. pylori ., Conclusions: The combination of metformin with potential antibiotics such as AMX had a positive effect on the relief of H. pylori -related inflammation by inducing Treg cells while successfully eliminating H. pylori ., Competing Interests: No conflict of interest was reported by the authors., (Copyright © 2023 Hassan Valadbeigi et al.)

Aim: Both immunocompetent and healthy individuals can become life-threateningly ill when exposed to the hypervirulent (hvKp) strains of Klebsiella pneumoniae (Kp). The main objectives of this study were to evaluate the presence of ampC-lactamase genes, biofilm formation, and antibiotic resistance in clinical strains of hvKp and cKp (classical K. pneumoniae)., Materials and Methods: Kp strains were collected from patients referred to Shahidzadeh Hospital in Behbahan City, Khuzestan Province, Iran. Several techniques were used to identify hvKp. The hypermucoviscosity phenotype was determined using the string test. Isolates that developed dark colonies on tellurite agar were assumed to be hvKp strains. If any of the iucA, iutA, or peg-344 genes were detected, the isolates were classified as hvKp. Phenotypic and genotypic detection of AmpC β-lactamases of hvKp strains was performed by the combined disk method and polymerase chain reaction, respectively. In addition, crystal violet staining was used to determine the biofilm formation of these isolates., Results: For this study, 76 non-duplicative isolates of Kp were collected. Overall, 22 (28.94%) strains had positive string test results, and 31 (40.78%) isolates were grown in tellurite-containing medium. The genes iucA and iutA or peg-344 were found in 23.68% of all Kp strains and in 50% of tellurite-resistant isolates, respectively. The most effective antibiotics against hvKp isolates were tetracycline (85.52%) and chloramphenicol (63.15%). Using the cefoxitin disc diffusion method, we observed that 56.57% (43/76) of the strains were AmpC producer. A total of 30.26% (n = 23/76) of the isolates tested positive for at least one ampC gene, including blaDHA (52.63%, n = 40), blaCIT (40.78%, n = 31), blaACC (19.76%, n = 15), blaMOX (25%, n = 19), and blaFOX (43.42%, n = 33). Biofilm formation analysis revealed that most hvKp isolates were weak (n = 6, 40%) and moderate (n = 5, 33.33%) biofilm producers., Conclusion: Healthcare practitioners should consider the possibility of the existence and acquisition of hvKp everywhere. The exact mechanisms of bacterial acquisition are also unknown, and it is unclear whether the occurrence of infections is related to healthcare or not. Thus, there are still many questions about hvKp that need to be investigated., (© The Author(s) 2023. Published by Oxford University Press on behalf of Applied Microbiology International.)

Background: The syndrome of periodic fever, aphthous stomatitis, pharyngitis, and cervical adenitis (PFAPA syndrome) is the most common type of recurrent fever in childhood. The aim of this study was evaluation of the levels of blood cells, vitamin D, and inflammatory factors in children with PFAPA syndrome., Methods: This retrospective descriptive study was conducted on the recorded information of children with PFAPA syndrome referred to the children's specialty clinic of Imam Khomeini Hospital in Ilam city from March 2021 to February 2022. Complete demographic information, presence of underlying disease, changes in blood cells, vitamin D level and inflammatory factors were obtained from the patients' records. Diagnosis of PFAPA syndrome was performed according to Thomas' criteria., Results: This study was conducted on 40 children with PFAPA syndrome. The majority of patients were male and in the age range of 3 - 4 years. The results show that the average percentage of neutrophil and lymphocyte cells in the blood of patients was 54.45% and 40.62%, respectively. Also, 6 (15%), 3 (7.5%), and 31 (77.5%) patients had normal neutrophil levels, neutropenia, and neutrophilia, respectively. Regarding lymphocyte cells, 26 (65%), 8 (20%), and 6 (15%) people had normal lymphocyte level, lymphocytosis and lymphopenia, respectively. ESR levels increased in all patients (average percentage: 16.72). CRP level was negative in 9 (22.5%) and +1 in 19 (47.5%) patients, respectively. The results showed that 33 (82.5%) patients were deficient in vitamin D level., Conclusions: The etiology and pathogenesis of PFAPA is still unknown; however, the rapid response to corticosteroid therapy is the indication of an immune deregulation. Treatment guidelines for PFAPA syndrome based on controlled studies are needed, as well as a better understanding of the disease itself.

Background: Disinfectants and antiseptics inhibit the dissemination of pathogenic organisms in hospitals but often cause disinfectant-resistant microorganisms, an important factor for nosocomial infection. This study aimed to evaluate the correlation between qacΔE efflux pump gene and its resistance to disinfectants among Escherichia coli clinical isolates., Methods: A total of 97 E. coli isolates were isolated from patients with urinary tract infections. The minimum inhibition concentration (MIC) value of chlorhexidine and benzalkonium chloride was determined using broth microdilution method. Effect of efflux pumps was assessed by MIC test in the presence of phenylalanine-arginine β-naphthylamide (PAβN), and then the qacΔE efflux pump gene was detected using polymerase chain reaction (PCR)., Result: Of the isolates, 85.6% and 61.9% were resistant to chlorhexidine and benzalkonium chloride, respectively. Following the treatment of isolates with the efflux pump's inhibitor, PAβN, the MIC value of chlorhexidine and benzalkonium chloride decreased in 75.2% and 57.7% of the isolates, respectively. A significant correlation was found between PAβN treatment and the change in the resistant strains to susceptible strains (p = 0.021). The qacΔE gene was detected in 84.5% (n = 82) of the isolates, and the presence of the gene amongst disinfectant-resistant strains was also significant (p < 0.001)., Conclusions: It is suggested to conduct other studies on other efflux pumps, as well as to periodically monitor the resistance to disinfectants. Substances inhibiting efflux pumps and neutral compounds are effective in the reduction of resistance to disinfectants. New disinfectants and drugs should be designed.

Background: Helicobacter pylori is a gastrointestinal pathogen that infects around half of the world's population. H. pylori infection is the most severe known risk factor for gastric cancer (GC), which is the second highest cause of cancer-related deaths globally. We conducted a systematic review and meta-analysis to assess the global prevalence of GC in H. pylori-infected individuals., Methods: We performed a systematic search of the PubMed, Web of Science, and Embase databases for studies of the prevalence of GC in H. pylori-infected individuals published from 1 January 2011 to 20 April 2021. Metaprop package were used to calculate the pooled prevalence with 95% confidence interval. Random-effects model was applied to estimate the pooled prevalence. We also quantified it with the I 2 index. Based on the Higgins classification approach, I 2 values above 0.7 were determined as high heterogeneity., Results: Among 17,438 reports screened, we assessed 1053 full-text articles for eligibility; 149 were included in the final analysis, comprising data from 32 countries. The highest and lowest prevalence was observed in America (pooled prevalence: 18.06%; 95% CI: 16.48 - 19.63; I 2 : 98.84%) and Africa (pooled prevalence: 9.52%; 95% CI: 5.92 - 13.12; I 2 : 88.39%). Among individual countries, Japan had the highest pooled prevalence of GC in H. pylori positive patients (Prevalence: 90.90%:95% CI: 83.61-95.14), whereas Sweden had the lowest prevalence (Prevalence: 0.07%; 95% CI: 0.06-0.09). The highest and lowest prevalence was observed in prospective case series (pooled prevalence: 23.13%; 95% CI: 20.41 - 25.85; I2: 97.70%) and retrospective cohort (pooled prevalence: 1.17%; 95% CI: 0.55 - 1.78; I 2: 0.10%)., Conclusions: H. pylori infection in GC patients varied between regions in this systematic review and meta-analysis. We observed that large amounts of GCs in developed countries are associated with H. pylori. Using these data, regional initiatives can be taken to prevent and eradicate H. pylori worldwide, thus reducing its complications., (© 2023. BioMed Central Ltd., part of Springer Nature.)

Introduction: Nosocomial infections (NIs) are a major challenge worldwide. Identification of antibiotic resistance pattern extended spectrum beta-lactamases (ESBLs) and carbapenem-resistant Enterobacteriaceae (CRE) were the objectives of this study., Methods: In this cross-sectional study, the antimicrobial susceptibility pattern of bacterial isolates collected from patients with NIs in ICU was determined. Overall, 42 Escherichia coli and Klebsiella pneumoniae isolates from different infection sites were used to determine phenotypic tests of ESBLs, Metallo-β-lactamases (MBLs) and CRE. Detection of ESBLs, MBLs and CRE genes were performed by the polymerase chain reaction (PCR) method., Results: From 71 patients with NIs, 103 different bacterial strains were isolated. The most frequently isolated bacteria were E. coli (n = 29; 28.16%), Acinetobacter baumannii (n = 15; 14.56%), and K. pneumoniae (n = 13; 12.26%). Also, the rate of multidrug-resistant (MDR) isolates was 58.25% (60/103). Based on phenotypic confirmation tests, 32 (76.19%) isolates of E. coli and K. pneumoniae produced ESBLs, and 6 (14.28%) isolates were identified as CRE producers. PCR showed the high prevalence of the bla CTX-M (n = 29; 90.62%) in ESBL genes. In addition, bla NDM was detected in 4 (66.66%), bla OXA-23 in 3 (50%), and bla OXA-48 gene in 1 (16.66%) isolates. The bla VIM , bla KPC , and bla IMP genes were not detected in any of the isolates., Conclusion: The Gram-negative bacteria E. coli, A. baumannii, and K. pneumoniae with high resistance levels were the most common bacteria causing NIs in the ICU. This study for the first time identified bla OXA-11 , bla OXA-23 , and bla NDM-1 genes in E. coli and K. pneumoniae in Ilam city of Iran., (© 2023. The Author(s), under exclusive licence to Springer Nature B.V.)

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.

Background and Aims: Resistance to antibiotics and the capability to develop biofilm as two main virulent determinants of Klebsiella pneumoniae have important role in infection persistence. The aim of the study was to evaluate the association between the prevalence of aminoglycoside resistance and virulence genes and biofilm formation capacity in K. pneumoniae strains isolated from hospitalized patients in South-West of Iran., Methods: A total of 114 non-duplicate clinical isolates of K. pneumoniae collected from Ahvaz teaching hospitals. Identification of species was performed by biochemical tests and then confirmed by polymerase chain reaction (PCR) of rpoB gene. The susceptibility to antibiotics was determined by Kirby-Bauer disk diffusion method. Biofilm formation was assessed by microtiter plate method. Finally, PCR was conducted to detect virulence gene determinants including fimbrial genes, aminoglycoside modifying enzymes- and 16S rRNA methylase (RMTase) genes., Results: Totally, all collected strains were carbapenem resistant and showed multidrug- and extensively drug-resistance phenotype (75% and 25%, respectively). Seventy-one percent ( n  = 81) of isolates were non-susceptible to aminoglycosides. Among aminoglycoside antibiotics, K. pneumoniae isolates showed the highest and lowest resistance rates to tobramycin (71%) and the amikacin (25%), respectively. All biofilm producer strains were positive for the presence virulence determinants including ecpA, fimA, mrkD , and mrkA . Of 81 aminoglycosides non-susceptible isolates 33% were positive for the presence ant (2″)-Ia as the most prevalent gene followed by aac (3')-IIa and armA (27%), aac (6')-Ib (18%), and aph (3')-Ia (15%)., Conclusion: K. pneumoniae isolates showed the highest and the lowest aminoglycoside resistance rates to tobramycin and amikacin, respectively. Majority of isolates were biofilm producers and there was significant association between antibiotic resistance pattern and the strength of biofilm production. The ant(2″)-Ia, aac (3')-IIa , and armA genes in aminoglycoside-resistant isolates., Competing Interests: The authors declare no conflict of interest., (© 2023 The Authors. Health Science Reports published by Wiley Periodicals LLC.)

Background: A probiotic is a living microorganism that promotes host health when grown under appropriate conditions. Kidney stones are one of the universal agonizing diseases that have increased dramatically in recent years. One of the causes of this disease is hyperoxaluria (HOU), which is known to be an important factor in the formation of oxalate stones and is manifested by high levels of oxalate in the urine. In addition, about 80% of kidney stones contain oxalate, and decomposition of this material by microbes is one way to dispose of it., Methods: Therefore, we examined a bacterial mixture containing Lactobacillus plantarum, Lactobacillus casei, Lactobacillus acidophilus, and Bifidobacterium longum to prevent of oxalate production in Wistar rats with kidney stones. We divided the rats into 6 groups defined in the method., Results: The results of this study clearly show a decrease in urinary oxalate levels by exogenous means by L. plantarum, L. casei, L. acidophilus, and B. longum at the beginning of the experiment. Therefore, these bacteria can be used to control and prevent the formation of kidney stones., Conclusions: However, further studies should be conducted on the effects of these bacteria, and it is recommended to identify the gene responsible for the degradation of oxalate in order to develop a new probiotic.

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 β-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 bla TEM (37/5%), bla VIM (30%), and bla CTX-M (20%) were the most common β-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., (© 2023 The Authors. Journal of Clinical Laboratory Analysis published by Wiley Periodicals LLC.)

Background: Knowledge of global clarithromycin (CLA)-resistant rates of Helicobacter pylori ( H. pylori ) is crucial for decision of the most appropriate eradication therapies with good clinical outcomes. Therefore, this review and meta-analysis aimed to evaluate the global prevalence of the CLA resistance in H. pylori to provide some guidance for selecting the first-line antibiotics., Method: A comprehensive search was performed for relevant literature until April 2021 in PubMed, Embase, and Web of Science databases. Freeman-Tukey double arcsine transformation was performed to estimate the weighted pooled prevalence of resistance., Results: The meta-analysis included 248 articles. The prevalence of CLA-resistant H. pylori was 27.53% (95% CI [25.41-29.69]). The heterogeneity between reports was significant (I 2 = 97.80%, P < 0.01). The resistance rate increased from 24.28% in 2010-2017 to 32.14% in 2018-2021 ( P < 0.01). Iran, with 38 articles, has the most report. Nevertheless, Switzerland, Portugal, and Israel had the highest resistance rates (67.16%, 48.11%, and 46.12%, respectively). The heterogeneity between the continents and the antimicrobial susceptibility methods also interpreted standard guidelines and breakpoints was insignificant ( P > 0.05)., Conclusion: Overall CLA resistance rate was 27.53%, worldwide. The difference in CLA resistance rate among the included studies can be due to several reasons such as differences in antibiotic prescription rates in various geographic areas, use of different breakpoints or inaccurate criteria in performed studies, and the emergence of multidrug-resistant (MDR) strains., Competing Interests: Morteza Saki is a PeerJ Academic Editor. The authors declare that they have no competing interests., (© 2023 Sholeh et al.)

Scenarios for monitoring land cover on a large scale, involving large volumes of data, are becoming more prevalent in remote sensing applications. The accuracy of algorithms is important for environmental monitoring and assessments. Because they performed equally well throughout the various research regions and required little human involvement during the categorization process, they appear to be resilient and accurate for automated, big area change monitoring. Malekshahi City is one of the important and at the same time critical areas in terms of land use change and forest area reduction in Ilam Province. Therefore, this study aimed to compare the accuracy of nine different methods for identifying land use types in Malekshahi City located in Western Iran. Results revealed that the artificial neural network (ANN) algorithm with back-propagation algorithms could reach the highest accuracy and efficiency among the other methods with kappa coefficient and overall accuracy of approximately 0.94 and 96.5, respectively. Then, with an overall accuracy of about 91.35 and 90.0, respectively, the methods of Mahalanobis distance (MD) and minimum distance to mean (MDM) were introduced as the next priority to categorize land use. Further investigation of the classified land use showed that good results can be provided about the area of the land use classes of the region by applying the ANN algorithm due to high accuracy. According to those results, it can be concluded that this method is the best algorithm to extract land use maps in Malekshahi City because of high accuracy., (© 2023. The Author(s), under exclusive licence to Springer Nature Switzerland AG.)

Encapsulation of amoxicillin (AMX) for drug delivery against Helicobacter pylori infection and aspirin-induced ulcers in rat's stomachs was performed using docosahexaenoic acid (DHA)-loaded chitosan/alginate (CA) nanoparticles (NPs) developed by ionotropic gelation method. The physicochemical analyses of the composite NPs were performed by scanning electron microscopy, Fourier transform infrared spectroscopy, zeta potential, X-ray diffraction, and atomic force microscopy. The encapsulation efficiency of AMX was increased to 76% by incorporating DHA, which resulted in a reduction in the particle size. The formed CA-DHA-AMX NPs effectively adhered to the bacteria and rat gastric mucosa. Their antibacterial properties were more potent than those of the single AMX and CA-DHA NPs as demonstrated by the in vivo assay. The composite NPs attained higher mucoadhesive potential during food intake than during fasting ( p = 0.029). At 10 and 20 mg/kg AMX, the CA-AMX-DHA showed more potent activities against H. pylori than the CA-AMX, CA-DHA, and single AMX. The in vivo study showed that the effective dose of AMX was lower when DHA was included, indicating better drug delivery and stability of the encapsulated AMX. Both mucosal thickening and ulcer index were significantly higher in the groups receiving CA-DHA-AMX than in the groups receiving CA-AMX and single AMX. The presence of DHA declines the pro-inflammatory cytokines including IL-1β, IL-6, and IL-17A. The synergistic effects of AMX and the CA-DHA formulation increased the biocidal activities against H. pylori infection and improved ulcer healing properties., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Khoshnood, Negahdari, Kaviar, Sadeghifard, Abdullah, El-Shazly and Haddadi.)

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., (© 2022 The Authors. Journal of Clinical Laboratory Analysis published by Wiley Periodicals LLC.)

Introduction: Toxin-antitoxin systems (TAs) are highly conserved in Mycobacterium tuberculosis (Mtb). The TAs role in maintaining and disseminating drug resistance in bacterial populations has been indicated. So, we aimed to analyze the expression level of mazEF-related genes in drugsusceptible and multidrug-resistant (MDR) Mtb isolates under isoniazid (INH) and rifampin (RIF) stress., Methods: We obtained 23 Mtb isolates, including 18 MDR and 5 susceptible isolates, from the Ahvaz Regional TB Laboratory collection. The expression levels of mazF3, mazF6, and mazF9 toxin genes, and mazE3, mazE6, and mazE9 antitoxin genes in MDR and susceptible isolates were evaluated by quantitative real-time PCR (qRT-PCR) after exposure to RIF and INH., Results: The mazF3, F6, and F9 toxin genes were overexpressed in at least two MDR isolates in the presence of RIF and INH, in contrast to mazE antitoxin genes. More MDR isolates were induced to overexpress mazF genes by RIF than INH (72.2% vs. 50%). Compared to the H37Rv strain and susceptible isolates, the expression levels of mazF3,6 by RIF and mazF3,6,9 by INH were significantly upregulated in MDR isolates (p<0.05), but no remarkable difference was detected in the expression level of mazF9 genes by INH between these groups. In susceptible isolates, the expression levels of mazE3,6 by RIF and mazE3,6,9 by INH were induced and enhanced significantly compared to MDR isolates, but there was no difference between MDR and H37Rv strain., Conclusion: Based on the results, we propose that mazF expression under RIF/INH stress may be associated with drug resistance in Mtb in addition to mutations, and the mazE antitoxins may be related to enhanced susceptibility of Mtb to INH and RIF. Further experiments are needed to investigate the exact mechanism underlying the TA system's role in drug resistance., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Objectives: Brucellosis is one of the most prevalent zoonotic diseases common between humans and animals. Despite eradication efforts, the burden of the disease is well-known in endemic countries and in countries where brucellosis has not been an important health issue until recently. The aim of this study was to evaluate the prevalence, diagnosis, and manifestations of brucellosis., Methods: In this study, PubMed, Web of Science, Scopus, Embase, and Google scholar databases were systematically searched to find studies published from 2011 to 2021. The search was conducted using text words and Medical Subject Headings (MeSH) Terms on the prevalence of brucellosis. Stata software 14.0 was used for all analyses., Results: Based on the results, the pooled prevalence of brucellosis was 15.27% (95% CI: 9.68-21.86; heterogeneity I 2 index: 97.43; p < 0.001) for man and 15.33% (95% CI: 7.19-25.75; heterogeneity I 2 index: 98.19; p < 0.001) for woman. Age (coefficient: 0.240; p = 0.861) showed no significant effect on heterogeneity among studies. Egger's test indicated a significant publication bias for the prevalence of brucellosis (coefficient 3.894; p = 0.800), and publication year (coefficient: 0.114; p = 0.861) showed no significant effect on heterogeneity among studies. Egger's test indicated a significant publication bias for the prevalence of brucellosis (coefficient 3.894; p < 0.001). Moreover, the trim-and-fill method exhibited that the adjusted prevalence of brucellosis (18.30%, 95% CI: 14.10-22.52) was not significantly different from the original prevalence of brucellosis., Conclusion: The pooled estimate for brucellosis prevalence was estimated as 15.53%. To better understand the epidemiology of brucellosis globally, more extensive studies are needed to be conducted throughout the world, especially in developing and low-income countries., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Khoshnood, Pakzad, Koupaei, Shirani, Araghi, Irani, Moradi, Pakzad, Sadeghifard and Heidary.)

For around three decades, the fluoroquinolone (FQ) antibiotic ciprofloxacin has been used to treat a range of diseases, including chronic otorrhea, endocarditis, lower respiratory tract, gastrointestinal, skin and soft tissue, and urinary tract infections. Ciprofloxacin's main mode of action is to stop DNA replication by blocking the A subunit of DNA gyrase and having an extra impact on the substances in cell walls. Available in intravenous and oral formulations, ciprofloxacin reaches therapeutic concentrations in the majority of tissues and bodily fluids with a low possibility for side effects. Despite the outstanding qualities of this antibiotic, Salmonella typhi, Staphylococcus aureus, Escherichia coli , and Pseudomonas aeruginosa have all shown an increase in ciprofloxacin resistance over time. The rise of infections that are resistant to ciprofloxacin shows that new pharmacological synergisms and derivatives are required. To this end, ciprofloxacin may be more effective against the biofilm community of microorganisms and multi-drug resistant isolates when combined with a variety of antibacterial agents, such as antibiotics from various classes, nanoparticles, natural products, bacteriophages, and photodynamic therapy. This review focuses on the resistance mechanisms of bacteria against ciprofloxacin and new approaches for enhancing its efficacy., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Shariati, Arshadi, Khosrojerdi, Abedinzadeh, Ganjalishahi, Maleki, Heidary and Khoshnood.)

Acinetobacter baumannii ( A. baumannii ) is now considered a highly resistant pathogen to various types of antibiotics. Therefore, tracking the source of its prevalence and continuous control is crucial. This study aimed to determine antibiotic resistance and perform various molecular typing methods on clinical isolates of A. baumannii isolated from hospitalized burn patients in Shahid Motahari Burn Hospital, Tehran, Iran. Hospital isolates were confirmed by phenotypic and molecular methods. Then the sensitivity to different antibiotics was determined using the minimum inhibitory concentration (MIC) method. In order to perform molecular typing, three-locus dual assay multiplex polymerase chain reaction (PCR), multiple-locus variable-number tandem repeat analysis (MLVA), and multilocus sequence typing (MLST) methods were used. Among the 60 isolates collected, the frequencies of multidrug-resistant (MDR) and extensively drug-resistant (XDR) isolates were 90 and 10%, respectively. The most effective antibiotics were colistin with 100% and tigecycline with 83.33% sensitivity. Isolates were 100% resistant to piperacillin/tazobactam and cephalosporins, and 68.3% were resistant to carbapenem. The results of multiplex PCR showed five groups that international clone I (IC I) and IC II were the most common. The MLVA method identified 34 MLVA types (MTs), 5 clusters, and 25 singletons. Multilocus sequence typing results for tigecycline-resistant isolates showed seven different sequence types (STs). Increasing antibiotic resistance in A. baumannii isolates requires careful management to control and prevent the occurrence of the pre-antibiotic era. The results of this study confirm that the population structure of A. baumannii isolates has a high diversity. More extensive studies are needed in Iran to better understand the epidemiology of A. baumannii ., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Maleki, Kaviar, Koupaei, Haddadi, Kalani, Valadbeige, Karamolahi, Omidi, Hashemian, Sadeghifard, Mohamadi, Heidary and Khoshnood.)

Cancer is one of the major causes of death globally, requiring everlasting efforts to develop novel, specific, effective, and safe treatment strategies. Despite advances in recent years, chemotherapy, as the primary treatment for cancer, still faces limitations such as the lack of specificity, drug resistance, and treatment failure. Bacterial toxins have great potential to be used as anticancer agents and can boost the effectiveness of cancer chemotherapeutics. Bacterial toxins exert anticancer effects by affecting the cell cycle and apoptotic pathways and regulating tumorigenesis. Chimeric toxins, which are recombinant derivatives of bacterial toxins, have been developed to address the low specificity of their conventional peers. Through their targeting moieties, chimeric toxins can specifically and effectively detect and kill cancer cells. This review takes a comprehensive look at the anticancer properties of bacteria-derived toxins and discusses their potential applications as therapeutic options for integrative cancer treatment., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Khoshnood, Fathizadeh, Neamati, Negahdari, Baindara, Abdullah and Haddadi.)

Background: Coronavirus disease 19 (COVID-19) is a recently described infectious disease caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Iran was the first country where the SARS-Cov-2 was detected in the Middle East. In the current study, we aimed to evaluate the clinical, radiological and laboratory findings in hospitalized COVID-19 confirmed cases in Iran., Methods: The clinical manifestations, radiological data, laboratory findings, and the underlying diseases of the patients with COVID-19 were obtained from electronic medical records. Next, this information was compared in discharged and dead patients., Results: Overall, 4028 patients with COVID-19 including 3088 discharged, 778 dead, and 162 still hospitalized patients were enrolled in this study. The highest percentage of people who recovered (55%) was between 30 and 60 years old and the highest percentage of deaths (74.4%) was more than 60 years old. Based on demographic data, 50.05% were female and 49.95% were male. Clinical evaluations revealed that dyspnea (56.9%), cough (31.4%) and fever (17.8%) were the most manifestations. Comorbidities were significantly higher in the dead group. Laboratory analysis revealed abnormalities in lymphocyte count (LYM), erythrocyte sedimentation rate (ESR), and inflammatory biomarkers such as C-reactive protein (CRP). The most prevalent computed tomography (CT) scan data were ground-glass opacity (GGO) (30.5%) and consolidation (9.4%)., Conclusions: Laboratory parameters and clinical and radiological findings help to evaluate the follow-up of the disease in patients. Age and comorbidities are factors that predispose people to COVID-19. Further research is needed to evaluate the effects of various factors on the progression of COVID-19 infection., (© 2022 Elsevier España, S.L.U. All rights reserved.)

After about 2 years since the first detection of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections in Wuhan, China, in December 2019 that resulted in a worldwide pandemic, 6.2 million deaths have been recorded. As a result, there is an urgent need for the development of a safe and effective vaccine for coronavirus disease 2019 (COVID-19). Endeavors for the production of effective vaccines inexhaustibly are continuing. At present according to the World Health Organization (WHO) COVID-19 vaccine tracker and landscape, 153 vaccine candidates are developing in the clinical phase all over the world. Some new and exciting platforms are nucleic acid-based vaccines such as Pfizer Biontech and Moderna vaccines consisting of a messenger RNA (mRNA) encoding a viral spike protein in host cells. Another novel vaccine platform is viral vector vaccine candidates that could be replicating or nonreplicating. These types of vaccines that have a harmless viral vector like adenovirus contain a genome encoding the spike protein of SARS-CoV-2, which induces significant immune responses. This technology of vaccine manufacturing has previously been used in many human clinical trials conducted for adenoviral vector-based vaccines against different infectious agents, including Ebola virus, Zika virus, HIV, and malaria. In this paper, we have a review of nucleic acid-based vaccines that are passing their phase 3 and 4 clinical trials and discuss their efficiency and adverse effects., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Khoshnood, Ghanavati, Shirani, Ghahramanpour, Sholeh, Shariati, Sadeghifard and Heidary.)

Introduction: Linezolid (LNZ) is an effective antibiotic to treat patients with multidrug-resistant tuberculosis (MDR-TB) treatment failure. M. tuberculosis strains resistant to isoniazid and rifampin are defined as MDR-TB. In recent years, resistance to LNZ among MDR-TB cases has been reported in several different countries. In this study, we performed a systematic review and meta-analysis to investigate the prevalence of LNZ resistance among MDR-TB isolates. Methods: The databases of Embase, PubMed/Medline, and Web of Science were searched systematically from January 2000 to April 2021. Statistical analyses were performed by using Comprehensive Meta-Analysis software. Heterogeneity was reported by using the t-squared statistic and Q-statistic. Begg's rank correlation in combination with the funnel plot were used to evaluate any possible publication bias. Results: In total, 25 studies were selected for meta-analysis from 14 different countries; the majority was from China (n = 5) and Turkey (n = 4). Moreover, 7,366 patients were infected with MDR M. tuberculosis . Among the study population, 98 patients were co-infected with HIV, and 18 patients with hepatitis C virus (HCV). Furthermore, 28 cases had diabetes, and139 cases were alcohol abuser. Overall, 4,956 MDR M. tuberculosis strains were isolated from TB patients. The pooled frequency of LNZ resistance among the clinical isolates of MDR M. tuberculosis was 4.2% (95%). Begg's ( p = 0.72) test showed no evidence of publication bias. Conclusion: LNZ resistance among MDR M. tuberculosis isolates is increasing. On the other hand, long-term treatment of MDR-TB cases with LNZ alone is associated with several adverse effects. Thus, it is recommended that newer anti-TB drugs, including bedaquiline and delamanid, in combination with linezolid could increase its effectiveness and decrease toxicities. However, more studies should be done in this field., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Azimi, Khoshnood, Asadi, Heidary, Mahmoudi, Kaviar, Hallajzadeh and Nasiri.)

Background: Methicillin-resistant Staphylococcus aureus (MRSA) infections are considered an important public health problem, and treatment options are limited. Accordingly, in this meta-analysis, we analyzed published studies to survey in vitro activity of recently approved antibiotics against MRSA isolates., Methods: We searched electronic databases; PubMed, Scopus, and Web of Science to identify relevant studies (until November 30, 2020) that have focused on the in vitro activity of telavancin, dalbavancin, oritavancin, and tedizolid against MRSA isolates. Statistical analyses were conducted using STATA software (version 14.0)., Results: Thirty-eight studies were included in this meta-analysis. Overall in vitro activity of tedizolid on 12,204 MRSA isolates was 0.250 and 0.5 µg/mL for MIC 50 and MIC 90 , (minimum inhibitory concentration at which 50% and 90% of isolates were inhibited, respectively), respectively. The overall antibacterial activity of dalbavancin on 28539 MRSA isolates was 0.060 and 0.120 µg/mL for MIC 50 and MIC 90 , respectively. The overall antibacterial activity of oritavancin on 420 MRSA isolates was 0.045 and 0.120 µg/mL for MIC 50 and MIC 90 , respectively. The overall antibacterial activity of telavancin on 7353 MRSA isolates was 0.032 and 0.060 µg/mL for MIC 50 and MIC 90 , respectively. The pooled prevalence of tedizolid, telavancin, and dalbavancin susceptibility was 100% (95% CI: 100-100)., Conclusion: Telavancin, dalbavancin, oritavancin, and tedizolid had potent in vitro activity against MRSA isolates. The low MICs and high susceptibility rates of these antibiotics recommend a hopeful direction to introduce useful antibiotics in treating MRSA infections in the future., (© 2022. The Author(s).)

Two years after severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), in December 2019, the first infections were identified in Wuhan city of China. SARS-CoV-2 infection caused a global pandemic and accordingly, 5.41 million deaths worldwide. Hence, developing a safe and efficient vaccine for coronavirus disease 2019 (COVID-19) seems to be an urgent need. Attempts to produce efficient vaccines inexhaustibly are ongoing. At present time, according to the COVID-19 vaccine tracker and landscape provided by World Health Organization (WHO), there are 161 vaccine candidates in different clinical phases all over the world. In between, protein subunit vaccines are types of vaccines that contain a viral protein like spike protein or its segment as the antigen assumed to elicit humoral and cellular immunity and good protective effects. Previously, this technology of vaccine manufacturing was used in a recombinant influenza vaccine (RIV4). In the present work, we review protein subunit vaccines passing their phase 3 and 4 clinical trials, population participated in these trials, vaccines manufactures, vaccines efficiency and their side effects, and other features of these vaccines., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Heidary, Kaviar, Shirani, Ghanavati, Motahar, Sholeh, Ghahramanpour and Khoshnood.)

Background: Azithromycin (AZM), sold under the name Zithromax, is classified as a macrolide. It has many benefits due to its immunomodulatory, anti-inflammatory, and antibacterial effects. This review aims to study different clinical and biochemisterial aspects and properties of this drug which has a priority based on literature published worldwide., Methods: Several databases including Web of Science, Google Scholar, PubMed, and Scopus were searched to obtain the relevant studies., Results: AZM mechanism of action including the inhibition of bacterial protein synthesis, inhibition of proinflammatory cytokine production, inhibition of neutrophil infestation, and macrophage polarization alteration, gives it the ability to act against a wide range of microorganisms. Resistant organisms are spreading and being developed because of the irrational use of the drug in the case of dose and duration. AZM shows synergistic effects with other drugs against a variety of organisms. This macrolide is considered a valuable antimicrobial agent because of its use as a treatment for a vast range of diseases such as asthma, bronchiolitis, COPD, cystic fibrosis, enteric infections, STIs, and periodontal infections., Conclusions: Our study shows an increasing global prevalence of AZM resistance. Thus, synergistic combinations are recommended to treat different pathogens. Moreover, continuous monitoring of AZM resistance by registry centers and the development of more rapid diagnostic assays are urgently needed., (© 2022 The Authors. Journal of Clinical Laboratory Analysis published by Wiley Periodicals LLC.)

Introduction: The intensification of coronavirus disease 2019 (COVID-19) complications, severe symptoms, and high mortality rate has led researchers to focus on this significant issue. While respiratory and cardiac complications have been described as high-risk manifestations in patients with COVID-19, neurological complications can also enhance mortality. This study aimed to evaluate the prevalence of neurological complications arises from SARS-CoV-2 and assess the mortality rate from neurological complications., Material and Methods: Literature review was conducted by searching in PubMed/Medline, Web of Sciences, and Embase. After performing search strategies with relevant terms, a number of articles were excluded, including review articles, systematic review or meta-analysis, duplicate publication of same researchers, congress abstracts, animal studies, case reports, case series, and articles reporting a history of neurological features prior to COVID-19 infection. After retrieving the data, statistical analysis was performed using the STATA Version 14 software., Results: From 4455 retrieved publications, 20 articles were selected for further analysis. Among 18,258 included patients, 2791 showed neurological symptoms, which were classified into different groups. Headache, confusion, and fatigue were reported as the most non-specific neurological features in confirmed COVID-19 patients. Psychiatric symptoms, CNS disorders, cerebrovascular disorders, CNS inflammatory disorders, PNS disorders, neuromuscular disorders, etc., were defined as specific neurological manifestations. The pooled prevalence of neurological manifestations and mortality rate of COVID-19 patients with neurological features were estimated to be 23.0% (95% CI: 17.8-29.2) and 29.1% (95% CI: 20.3-39.8), respectively., Conclusion: Neurological manifestations may commonly happen in patients with COVID-19. This study reported a high prevalence of neurological complications and mortality rates in COVID-19 patients. Therefore, patients with COVID-19 who indicated neurological symptoms should be taken seriously and should receive early treatment to prevent undesirable events., (© 2022 The Authors. Journal of Clinical Laboratory Analysis published by Wiley Periodicals LLC.)

After about 2 years since severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), first infections were detected in Wuhan city of China in December 2019, which was followed by a worldwide pandemic with a record of 5.41 million deaths. Due to urgent need for the development of a safe and effective vaccine for coronavirus disease 2019 (COVID-19), attempts for producing efficient vaccines are inexhaustibly continuing. According to a report by the World Health Organization (WHO) on COVID-19 vaccine tracker and landscape, there are 149 vaccine candidates all over the world. Inactivated SARS-CoV-2 vaccines as a conventional vaccine platform consist of whole virus particles grown in cell culture and inactivated by chemicals. Because of benefits such as antigenic similarity to real virion inducing humoral and cellular immune responses and ease for transport and storage, these vaccines, including the vaccines produced by Bharat Biotech, Sinopharm, and Sinovac, are in use at large scales. In this study, we have a review on inactivated SARS-CoV-2 vaccines that are passing their phase 3 and 4 clinical trials, population which was included in the trials, vaccine producers, the efficiency, adverse effects, and components of vaccines, and other vaccine features., (© 2022 The Authors. Journal of Clinical Laboratory Analysis published by Wiley Periodicals LLC.)

Introduction: Interest revolving around coronavirus disease 2019 (COVID-19) reinfection is escalating rapidly. By definition, reinfection denotes severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), PCR redetection, and COVID-19 recurrence within three months of the initial symptoms. The main aim of the current systematic review was to evaluate the features of COVID-19 relapse patients., Materials and Methods: For this study, we used a string of terms developed by a skilled librarian and through a systematical search in PubMed, Web of Science, and Embase for eligible studies. Clinical surveys of any type were included from January 2019 to March 2021. Eligible studies consisted of two positive assessments separated by a negative result via RT-PCR., Results: Fifty-four studies included 207 cases of COVID-19 reinfection. Children were less likely to have COVID-19 relapse. However, the most patients were in the age group of 20-40 years. Asthenia (66.6%), headache (66.6%), and cough (54.7%) were prevalent symptoms in the first SARS-CoV-2 infection. Asthenia (62.9%), myalgia (62.9%), and headache (61.1%) were most frequent in the second one. The most common treatment options used in first COVID-19 infection were lopinavir/ritonavir (80%), oxygen support (69.2%), and oseltamivir (66.6). However, for the treatment of second infection, mostly antibiotics (100%), dexamethasone (100%), and remdesivir (80%) were used. In addition, obesity (32.5%), kidney failure (30.7%), and hypertension (30.1%) were the most common comorbidities. Unfortunately, approximately 4.5% of patients died., Conclusion: We found the potency of COVID-19 recurrence as an outstanding issue. This feature should be regarded in the COVID-19 management. Furthermore, the first and second COVID-19 are similar in clinical features. For clinically practical comparison of the symptoms severity between two epochs of infection, uniform data of both are required. We suggest that future studies undertake a homogenous approach to establish the clinical patterns of the reinfection phenomena., (© 2022 The Authors. Journal of Clinical Laboratory Analysis published by Wiley Periodicals LLC.)

Background: COVID-19 is the last global threat which WHO confirmed it as a pandemic on March 11, 2020. In the Middle East, Iran was the first country where the SARS-Cov-2 was detected. The epidemiological and economic challenges of Iran make this country a particularly relevant subject of study. In the current study, we aimed to evaluate the clinical, radiological and laboratory findings in hospitalized COVID-19 confirmed cases in Ilam province, western of Iran., Methods: Overall, 2204 hospitalized RT-PCR confirmed patients with COVID-19 were considered in this study. Electronic medical records, including clinical symptoms, radiological images, laboratory findings, and the comorbidities of patients with COVID-19 were collected and analyzed. In addition, the medication regimens used in these patients were evaluated. The patients were classified in discharged and died groups according to their outcomes. Then, clinical, radiological and laboratory findings as well as treatment regimens and underlying diseases were compared in these two groups., Results: Among the patients, 1209 (54.85%) were male and 995 (45.14%) were female. Pneumonia, dyspnea and cough, were the most common clinical data in both discharged and died groups. Among the comorbidities, COPD, and cancer were significantly more common in the dead patients than in the living. The results of laboratory tests showed that blood creatinine, BUN, ESR, Na+, WBC, and neutrophil count have increased in deceased group compared to the survivors. However, the lymphocyte count decreased in deceased patients. The evaluation of radiographs demonstrated that there were significant correlations between bilateral pneumonia, ground glass opacity, bilateral patchy shadowing, and pleural effusion with death., Conclusion: The current investigation indicated the special profile of COVID-19 in west of Iran. Discharged and dead patients with COVID-19 had distinct clinical, radiological and laboratory features, which were separated by principal component analysis. Identifying these characteristics of the disease would translate into the implementation of practical measures to improve results., (© 2022 Kaffashian et al.)