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1.
Microbiol Spectr ; 12(6): e0007124, 2024 Jun 04.
Article En | MEDLINE | ID: mdl-38700321

Novel antimicrobial agents are needed to combat antimicrobial resistance. This study tested novel pentafluorosulfanyl-containing triclocarban analogs for their potential antibacterial efficacy. Standard procedures were used to produce pentafluorosulfanyl-containing triclocarban analogs. Twenty new compounds were tested against seven Gram-positive and Gram-negative indicator strains as well as 10 clinical isolates for their antibacterial and antibiofilm activity. Mechanistic investigations focused on damage to cell membrane, oxidizing reduced thiols, iron-sulfur clusters, and oxidative stress to explain the compounds' activity. Safety profiles were assessed using cytotoxicity experiments in eukaryotic cell lines. Following screening, selected components had significantly better antibacterial and antibiofilm activity against Gram-positive bacteria in lower concentrations in comparison to ciprofloxacin and gentamycin. For instance, one compound had a minimum inhibitory concentration of <0.0003 mM, but ciprofloxacin had 0.08 mM. Mechanistic studies show that these novel compounds do not affect reduced thiol content, iron-sulfur clusters, or hydrogen peroxide pathways. Their impact comes from Gram-positive bacterial cell membrane damage. Tests on cell culture toxicity and host component safety showed promise. Novel diarylurea compounds show promise as Gram-positive antimicrobials. These compounds offer prospects for study and optimization. IMPORTANCE: The rise of antibiotic resistance among bacterial pathogens poses a significant threat to global health, underscoring the urgent need for novel antimicrobial agents. This study presents research on a promising class of novel compounds with potent antibacterial properties against Gram-positive bacteria, notably Staphylococcus aureus and MRSA. What sets these novel analogs apart is their superior efficacy at substantially lower concentrations compared with commonly used antibiotics like ciprofloxacin and gentamycin. Importantly, these compounds act by disrupting the bacterial cell membrane, offering a unique mechanism that could potentially circumvent existing resistance mechanisms. Preliminary safety assessments also highlight their potential for therapeutic use. This study not only opens new avenues for combating antibiotic-resistant infections but also underscores the importance of innovative chemical approaches in addressing the global antimicrobial resistance crisis.


Anti-Bacterial Agents , Carbanilides , Gram-Positive Bacteria , Microbial Sensitivity Tests , Carbanilides/pharmacology , Carbanilides/chemistry , Anti-Bacterial Agents/pharmacology , Anti-Bacterial Agents/chemistry , Gram-Positive Bacteria/drug effects , Humans , Biofilms/drug effects , Gram-Negative Bacteria/drug effects , Ciprofloxacin/pharmacology
2.
BMC Infect Dis ; 24(1): 250, 2024 Feb 23.
Article En | MEDLINE | ID: mdl-38395761

The Food and Drug Administration (FDA) has licensed many antiretroviral medications to treat human immunodeficiency virus type 1 (HIV-1), however, treatment options for people with multi-drug resistant HIV remain limited. Medication resistance, undesirable effects, prior tolerance, and previous interlacement incapacity to deliver new drug classes all lead to the requirement for new medication classes and drug combination therapy. Fostemsavir (FTR) is a new CD-4 attachment inhibitor medicine that was recently authorized by the United States FDA to treat HIV-1. In individuals with multidrug-resistant (MDR) HIV-1, FTR is well tolerated and virologically active. According to recent investigations, drug combination therapy can positively affect MDR-HIV. The mechanism of action, resistance, interaction, pharmacokinetics, pharmacodynamics, and safety of FTR has been highlighted in this review.


Anti-HIV Agents , HIV Infections , HIV-1 , Organophosphates , Piperazines , United States , Humans , HIV Infections/drug therapy , Anti-Retroviral Agents/therapeutic use , Drug Combinations , Anti-HIV Agents/adverse effects
3.
Anal Biochem ; 686: 115410, 2024 03.
Article En | MEDLINE | ID: mdl-38006951

The COVID-19 pandemic brought to light the impact of a widespread disease on various aspects of human relationships, communities, and economies. One notable consequence was the increased demand for diagnostic kits, laboratory reagents, and personal health equipment. This surge in testing capacity worldwide led to shortages in the supply of essential items, including RNA extraction kits, which are crucial for detecting COVID-19 infections. To address this scarcity, researchers have proposed alternative and cost-effective strategies for RNA extraction, utilizing both chemical and physical solutions and extraction-free methods. These approaches aim to alleviate the challenges associated with the overwhelming number of tests being conducted in laboratories. The purpose of this review is intends to provide a comprehensive summary of the various kit-free RNA extraction methods available for COVID-19 diagnosis during the pandemic.


COVID-19 , Humans , COVID-19/diagnosis , COVID-19 Testing , Pandemics , SARS-CoV-2/genetics , Clinical Laboratory Techniques/methods , RNA, Viral/genetics , Sensitivity and Specificity
4.
J Appl Microbiol ; 134(11)2023 Nov 01.
Article En | MEDLINE | ID: mdl-37881066

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 ß-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.


Klebsiella Infections , Klebsiella pneumoniae , Humans , Klebsiella pneumoniae/genetics , Incidence , Klebsiella Infections/epidemiology , Klebsiella Infections/microbiology , beta-Lactamases/genetics , Anti-Bacterial Agents/pharmacology , Drug Resistance, Microbial , Biofilms
5.
BMC Infect Dis ; 23(1): 543, 2023 Aug 19.
Article En | MEDLINE | ID: mdl-37598157

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 I2 index. Based on the Higgins classification approach, I2 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; I2: 98.84%) and Africa (pooled prevalence: 9.52%; 95% CI: 5.92 - 13.12; I2: 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.


Helicobacter pylori , Stomach Neoplasms , Humans , Stomach Neoplasms/epidemiology , Prevalence , Retrospective Studies , Africa
6.
Clin Lab ; 69(7)2023 Jul 01.
Article En | MEDLINE | ID: mdl-37436391

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.


Helicobacter Infections , Helicobacter pylori , Humans , Clarithromycin/pharmacology , Clarithromycin/therapeutic use , Anti-Bacterial Agents/pharmacology , Anti-Bacterial Agents/therapeutic use , Drug Resistance, Bacterial , Helicobacter Infections/drug therapy , Helicobacter Infections/microbiology , Microbial Sensitivity Tests
7.
Immun Inflamm Dis ; 11(6): e867, 2023 06.
Article En | MEDLINE | ID: mdl-37382263

As reported by the World Health Organization, about 10 million individuals were infected with tuberculosis (TB) worldwide. Moreover, approximately 1.5 million people died of TB, of which 214,000 were infected with HIV simultaneously. Due to the high infection rate, the need for effective TB vaccination is highly felt. Until now, various methodologies have been proposed for the development of a protein subunit vaccine for TB. These vaccines have shown higher protection than other vaccines, particularly the Bacillus culture vaccine. The delivery system and safety regulator are common characteristics of effective adjuvants in TB vaccines and the clinical trial stage. The present study investigates the current state of TB adjuvant research focusing on the liposomal adjuvant system. Based on our findings, the liposomal system is a safe and efficient adjuvant from nanosize to microsize for vaccinations against TB, other intracellular infections, and malignancies. Clinical studies can provide valuable feedback for developing novel TB adjuvants, which ultimately enhance the impact of adjuvants on next-generation TB vaccines.


Tuberculosis Vaccines , Humans , Adjuvants, Immunologic , Vaccination
8.
Mol Neurobiol ; 60(8): 4659-4678, 2023 Aug.
Article En | MEDLINE | ID: mdl-37138197

Gliomas make up virtually 80% of all lethal primary brain tumors and are categorized based on their cell of origin. Glioblastoma is an astrocytic tumor that has an inferior prognosis despite the ongoing advances in treatment modalities. One of the main reasons for this shortcoming is the presence of the blood-brain barrier and blood-brain tumor barrier. Novel invasive and non-invasive drug delivery strategies for glioblastoma have been developed to overcome both the intact blood-brain barrier and leverage the disrupted nature of the blood-brain tumor barrier to target cancer cells after resection-the first treatment stage of glioblastoma. Exosomes are among non-invasive drug delivery methods and have emerged as a natural drug delivery vehicle with high biological barrier penetrability. There are various exosome isolation methods from different origins, and the intended use of the exosomes and starting materials defines the choice of isolation technique. In the present review, we have given an overview of the structure of the blood-brain barrier and its disruption in glioblastoma. This review provided a comprehensive insight into novel passive and active drug delivery techniques to overcome the blood-brain barrier, emphasizing exosomes as an excellent emerging drug, gene, and effective molecule delivery vehicle used in glioblastoma therapy.


Brain Neoplasms , Exosomes , Glioblastoma , Humans , Blood-Brain Barrier/pathology , Glioblastoma/drug therapy , Glioblastoma/pathology , Exosomes/pathology , Brain Neoplasms/pathology , Drug Delivery Systems/methods
9.
Eur J Clin Microbiol Infect Dis ; 42(3): 229-254, 2023 Mar.
Article En | MEDLINE | ID: mdl-36680641

The clinical impact of infections due to extended-spectrum ß-lactamase (ESBL)- and/or carbapenemase-producing Enterobacterales (Ent) has reached dramatic levels worldwide. Infections due to these multidrug-resistant (MDR) pathogens-especially Escherichia coli and Klebsiella pneumoniae-may originate from a prior asymptomatic intestinal colonization that could also favor transmission to other subjects. It is therefore desirable that gut carriers are rapidly identified to try preventing both the occurrence of serious endogenous infections and potential transmission. Together with the infection prevention and control countermeasures, any strategy capable of effectively eradicating the MDR-Ent from the intestinal tract would be desirable. In this narrative review, we present a summary of the different aspects linked to the intestinal colonization due to MDR-Ent. In particular, culture- and molecular-based screening techniques to identify carriers, data on prevalence and risk factors in different populations, clinical impact, length of colonization, and contribution to transmission in various settings will be overviewed. We will also discuss the standard strategies (selective digestive decontamination, fecal microbiota transplant) and those still in development (bacteriophages, probiotics, microcins, and CRISPR-Cas-based) that might be used to decolonize MDR-Ent carriers.


Drug Resistance, Multiple, Bacterial , Gammaproteobacteria , Humans , beta-Lactamases/genetics , Klebsiella pneumoniae , Escherichia coli , Fecal Microbiota Transplantation , Risk Factors , Anti-Bacterial Agents/pharmacology , Anti-Bacterial Agents/therapeutic use
10.
Article En | MEDLINE | ID: mdl-36578254

BACKGROUND AND OBJECTIVES: Periodontium is an important tooth-supporting tissue composed of both hard (alveolar bone and cementum) and soft (gingival and periodontal ligament) sections. Due to the multi-tissue architecture of periodontium, reconstruction of each part can be influenced by others. This review focuses on the bone section of the periodontium and presents the materials used in tissue engineering scaffolds for its reconstruction. MATERIALS AND METHODS: The following databases (2015 to 2021) were electronically searched: ProQuest, EMBASE, SciFinder, MRS Online Proceedings Library, Medline, and Compendex. The search was limited to English-language publications and in vivo studies. RESULTS: Eighty-three articles were found in primary searching. After applying the inclusion criteria, seventeen articles were incorporated into this study. CONCLUSIONS: In complex periodontal defects, various types of scaffolds, including multilayered ones, have been used for the functional reconstruction of different parts of periodontium. While there are some multilayered scaffolds designed to regenerate alveolar bone/periodontal ligament/cementum tissues of periodontium in a hierarchically organized construct, no scaffold could so far consider all four tissues involved in a complete periodontal defect. The progress and material considerations in the regeneration of the bony part of periodontium are presented in this work to help investigators develop tissue engineering scaffolds suitable for complete periodontal regeneration.

11.
PLoS One ; 17(11): e0277329, 2022.
Article En | MEDLINE | ID: mdl-36395161

Ventilator-associated pneumonia (VAP) is a prevalent nosocomial illness in mechanically ventilated patients. Hence, the aim of this study was to investigate the pattern of antibiotic resistance and biofilm formation of bacterial profiles from Endotracheal Tubes of patients hospitalized in an intensive care unit in southwest Iran. According to the standard operating method, the microbiological laboratory conducts bacteria culture and susceptibility testing on endotracheal Tube samples suspected of carrying a bacterial infection. The Clinical and laboratory standards institute (CLSI) techniques are used to determine the Antimicrobial resistance (AMR) of bacterial isolates to antibiotics using the disk diffusion method. The crystal violet staining method was used to assess the biofilm-forming potential of isolates in a 96-well microtiter plate. In total, (51%) GPBs were included in this study. The isolated GPB were coagulase-negative Staphylococcus (16%), S. aureus (14%). In total, (40%) of GNB were included in this study. The isolated GNB were Klebsiella spp. (36%), A. baumannii (22%), P. aeruginosa (35%). (32%) bacterial strains were MDR and (29%) strains were XDR. The results of biofilm formation showed (72%) were biofilm producers. VAP is a common and severe nosocomial infection in mechanically ventilated patients. Controlling biofilm formation, whether on the ET or in the oropharyngeal cavity, is thus an important technique for treating VAP. Colistin and linezolid are antibiotics that are effective against practically all resistant GNB and GPB isolates.


Pneumonia, Ventilator-Associated , Staphylococcus aureus , Humans , Iran , Drug Resistance, Microbial , Intensive Care Units , Pneumonia, Ventilator-Associated/drug therapy , Bacteria , Intubation, Intratracheal/adverse effects , Biofilms , Anti-Bacterial Agents/pharmacology , Anti-Bacterial Agents/therapeutic use , Pseudomonas aeruginosa
12.
Article En | MEDLINE | ID: mdl-35420996

Early diagnosis of tuberculosis (TB), followed by effective treatment, is the cornerstone of global TB control efforts. An estimated 3 million cases of TB remain undetected each year. Early detection and effective management of TB can prevent severe disease and reduce mortality and transmission. Intrinsic and acquired drug resistance of Mycobacterium tuberculosis (MTB) severely restricted the anti-TB therapeutic options, and public health policies are required to preserve the new medications to treat TB. In addition, TB and HIV frequently accelerate the progression of each other, and one disease can enhance the other effect. Overall, TB-HIV co-infections show an adverse bidirectional interaction. For HIV-infected patients, the risk of developing TB disease is approximately 22 times higher than for persons with a protective immune response. Analysis of the current TB challenges is critical to meet the goals of the end TB strategy and can go a long way in eradicating the disease. It provides opportunities for global TB control and demonstrates the efforts required to accelerate eliminating TB. This review will discuss the main challenges of the TB era, including resistance, co-infection, diagnosis, and treatment.

13.
Biomed Pharmacother ; 147: 112682, 2022 Mar.
Article En | MEDLINE | ID: mdl-35131658

Viral infections have a great impact on human health. The urgent need to find a cure against different viruses led us to investigations in a vast range of drugs. Azithromycin (AZT), classified as a macrolide, showed various effects on different known viruses such as severe acute respiratory syndrome coronavirus (SARS-CoV), Zika, Ebola, Enterovirus (EVs) and Rhinoviruses (RVs), and Influenza A previously; namely, these viruses, which caused global concerns, are considered as targets for AZT different actions. Due to AZT background in the treatment of known viral infections mentioned above (which is described in this study), in the early stages of COVID-19 (a new zoonotic disease caused by a novel coronavirus called severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)) development, AZT drew attention to itself due to its antiviral and immunomodulatory effects as a valuable candidate for COVID-19 treatment. AZT usage instructions for treating different viral infections have always been under observation, and COVID-19 is no exception. There are still debates about the use of AZT in COVID-19 treatment. However, eventually, novel researches convinced WHO to announce the discontinuation of AZT use (alone or in combination with hydroxychloroquine) in treating SARS-CoV-2 infection. This research aims to study the structure of all of the viruses mentioned above and the molecular and clinical effects of AZT against the virus.


Antiviral Agents/therapeutic use , Azithromycin/therapeutic use , COVID-19 Drug Treatment , Anti-Bacterial Agents , Antiviral Agents/pharmacology , Azithromycin/pharmacology , Ebolavirus/drug effects , Humans , Influenza A virus/drug effects , Severe acute respiratory syndrome-related coronavirus/drug effects , SARS-CoV-2/drug effects , Zika Virus/drug effects
14.
Front Vet Sci ; 9: 976215, 2022.
Article En | MEDLINE | ID: mdl-36619963

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 = 0.480), gender (coefficient: -0.017; 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.

15.
Mol Biol Rep ; 48(12): 7883-7892, 2021 Dec.
Article En | MEDLINE | ID: mdl-34657270

BACKGROUND: This study aimed to identify metallo-ß-lactamases (MBLs) and AmpC ß-lactamases-producing Escherichia coli isolates obtained from hemodialysis (HD) patients with urinary tract infections (UTI). METHODS AND RESULTS: A total of 257 HD patients with UTI were included in this study, from which 47 E. coli isolates were collected. Antibiotic susceptibility was tested by disc diffusion method. MBLs and AmpC production were phenotypically detected by imipenem-ethylenediaminetetracetate and cefoxitin/boronic acid assays, respectively. The presence of MBLs and AmpC genes was examined by polymerase chain reaction (PCR). Fosfomycin and ampicillin were the most and the least effective antibiotics against E. coli isolates, respectively. Moreover, 61.7% (29/47) of E. coli isolates were multidrug-resistant with seven different antibiotypes. Antibiotype V (AMP-CIP-IMP-MEM-CPD-CRO-CTX-GEN-LEV-SXT-TOB) was the most prevalent profile. Besides, 24 (51.1%) isolates were simultaneously resistant to imipenem and meropenem. Phenotypic assay showed MBL production in 16 (66.7%) of the 24 carbapenem-resistant E. coli isolates. The distribution of MBL genes in carbapenem-resistant E. coli was as follows: blaIMP 18 (72%), blaVIM 7 (28%), and blaNDM 1 (4%). AmpC was detected in 61.7% (29/47) of the isolates using the phenotypic method. The presence of AmpC genes was confirmed by PCR in only 26 of 29 (86.7%) AmpC producers. The frequencies of blaDHA-1, blaACC, and blaCMY-2 were 6 (20.7%), 11 (37.9%), and 21 (72.4%), respectively. CONCLUSIONS: The emergence of MBL and AmpC coproducing E. coli isolates calls for an urgent surveillance program for timely diagnosis and screening of these genes in our healthcare systems.


Bacterial Proteins/metabolism , Escherichia coli Infections/metabolism , beta-Lactamases/metabolism , Anti-Bacterial Agents/pharmacology , Carbapenems/pharmacology , Drug Resistance, Microbial/drug effects , Escherichia coli/isolation & purification , Escherichia coli/metabolism , Escherichia coli/pathogenicity , Escherichia coli Infections/genetics , Escherichia coli Proteins/genetics , Humans , Microbial Sensitivity Tests , Renal Dialysis/adverse effects , Urinary Tract Infections/drug therapy , Urinary Tract Infections/microbiology
16.
J Glob Antimicrob Resist ; 25: 48-59, 2021 06.
Article En | MEDLINE | ID: mdl-33684606

The development of drug-resistant tuberculosis (TB) is a major threat worldwide. Based on World Health Organization (WHO) reports, it is estimated that more than 500 000 new cases of drug-resistant TB occur annually. In addition, there are alarming reports of increasing multidrug-resistant TB (MDR-TB) and the emergence of extensively drug-resistant TB (XDR-TB) from different countries of the world. Therefore, new options for TB therapy are required. Bedaquiline (BDQ), a novel anti-TB drug, has significant minimum inhibitory concentrations (MICs) both against drug-susceptible and drug-resistant TB. Moreover, BDQ was recently approved for therapy of MDR-TB. The current narrative review summarises the available data on BDQ resistance, describes its antimicrobial properties, and provides new perspectives on clinical use of this novel anti-TB agent.


Extensively Drug-Resistant Tuberculosis , Tuberculosis, Multidrug-Resistant , Antitubercular Agents/pharmacology , Antitubercular Agents/therapeutic use , Diarylquinolines/therapeutic use , Extensively Drug-Resistant Tuberculosis/drug therapy , Humans , Tuberculosis, Multidrug-Resistant/drug therapy
18.
Infect Drug Resist ; 12: 1683-1689, 2019.
Article En | MEDLINE | ID: mdl-31354317

Background: Quinolones are a family of synthetic antimicrobial agents with a broad antibacterial activity commonly used as a suitable therapy in patients with urinary tract infection (UTI). In the present study, we aimed to evaluate the prevalence of quinolones resistance and the presence of plasmid-mediated quinolone resistance (PMQR) genes among Escherichia coli isolates. METHODS: This study was performed on a collection of 121 E. coli isolates derived from patients with UTI. Antimicrobial susceptibility to nalidixic acid, ciprofloxacin, levofloxacin, norfloxacin, and ofloxacin was specified by the disk diffusion method. The presence of PMQR genes was determined by PCR method. RESULTS: Antibiotic susceptibility results showed that the highest and lowest resistance rates were against nalidixic acid (71.9%) and norfloxacin (44.6%), respectively. The molecular results showed that 40 (33.1%) and 15 (12.4%) of the isolates were positive for qnrS and qnrB genes, respectively. Meanwhile, 5 (4.1%) of the isolates were found positive for both genes, while none were found to be positive for qnrA gene. There was no significant association between the presence of qnr genes and higher antibiotic resistance. CONCLUSION: We found high levels of quinolones resistance (more than 40%) among E. coli strains isolated from patients with UTIs in the south of Iran. We further report the prevalence of PMQR genes among uropathogenic E. coli; however, it seems that these genes are not the main components of quinolone resistance in our region.

19.
BMC Res Notes ; 12(1): 301, 2019 May 28.
Article En | MEDLINE | ID: mdl-31138309

OBJECTIVE: The present study aimed to determine in vitro activity of colistin and other agents against drug-resistant isolates of Pseudomonas aeruginosa and Acinetobacter baumannii. RESULTS: This in vitro study performed on a collection of non-fermenting Gram-negative bacilli (NFB) consist of 18 A. baumannii and 21 P. aeruginosa isolates. Non-duplicated isolates (one per patient) were isolated from blood, endotracheal tube and sputum samples of hospitalized patients in the south of Iran. The minimum inhibitory concentrations (MICs) of each isolate was determined using Epsilometer (E)-test strips containing colistin, imipenem, and ceftazidime. In overall, all A. baumannii isolates were non-susceptible to imipenem and ceftazidime. In contrast, all isolates were susceptible to colistin with MIC50 and MIC90 of 0.75/1.5 µg/mL, respectively. Antibiotic susceptibility results showed that 81% and 23.8% of P. aeruginosa isolates were susceptible to ceftazidime and imipenem, respectively. While, all of the P. aeruginosa isolates were susceptible to colistin with MIC50 and MIC90 of 0.5/1 µg/mL, respectively. In summary, colistin showed the promising in vitro activity against drug-resistant strains of two clinically important NFB in our region. However, investigation on a larger collection of drug-resistant strains demands to support these observations in the near future.


Acinetobacter baumannii/isolation & purification , Ceftazidime/pharmacology , Colistin/pharmacology , Drug Resistance, Multiple, Bacterial/drug effects , Imipenem/pharmacology , Pseudomonas aeruginosa/isolation & purification , Acinetobacter baumannii/drug effects , Iran , Microbial Sensitivity Tests , Pseudomonas aeruginosa/drug effects
20.
Microb Pathog ; 131: 259-269, 2019 Jun.
Article En | MEDLINE | ID: mdl-31002964

Staphylococcus aureus (S.aureus) is a Gram-positive bacterium that causes many infections and diseases. This pathogen can cause many types of infections such as impetigo, toxic shock syndrome toxin (TSST1), pneumonia, endocarditis, and autoimmune diseases like lupus erythematosus and can infect other healthy individuals. In the pathogenic process, colonization is a main risk factor for invasive diseases. Various factors including the cell wall-associated factors and receptors of the epithelial cells facilitate adhesion and colonization of this pathogen. S. aureus has many enzymes, toxins, and strategies to evade from the immune system either by an enzyme that lyses cellular component or by hiding from the immune system via surface antigens like protein A and second immunoglobulin-binding protein (Sbi). The strategies of this bacterium can be divided into five groups: A: Inhibit neutrophil recruitment B: Inhibit phagocytosis C: Inhibit killing by ROS, D: Neutrophil killing, and E: Resistance to antimicrobial peptide. On the other hand, innate immune system via neutrophils, the most important polymorphonuclear leukocytes, fights against bacterial cells by neutrophil extracellular trap (NET). In this review, we try to explain the role of each factor in immune evasion.


Immune Evasion , Neutrophils/immunology , Staphylococcal Infections/immunology , Staphylococcal Infections/microbiology , Staphylococcus aureus/immunology , Staphylococcus aureus/pathogenicity , Antigens, Bacterial/immunology , Bacterial Proteins , Bacterial Toxins/immunology , Enterotoxins , Host-Pathogen Interactions/immunology , Humans , Immune Evasion/immunology , Immunity, Innate , Phagocytosis , Staphylococcal Protein A , Superantigens
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