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      The Relationship between the Biofilm Genes and Antibiotic Resistance in Stenotrophomonas maltophilia

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          Abstract

          Objectives

          Today, Stenotrophomonas maltophilia ( S. maltophilia) is a major opportunistic pathogen among hospitalized or immunocompromised patients. Antibiotic-resistant clinical isolates are increasing in several parts of the world. Various antibiotic-resistance and biofilm-forming genes are identified in this bacterium. Its capacity to form biofilms is an important virulence factor that may impact antibiotic-resistance patterns. In the current study, we evaluated the biofilm-formation capacity, antibiotic-resistance profile, and prevalence of biofilm-forming genes as well as antibiotic resistance genes among S. maltophilia isolates.

          Materials and Methods

          In this cross-sectional study, 94 clinical S. maltophilia isolates were recovered from four tertiary-care hospitals in Iran between 2021 and 2022. The presence of the selected antibiotic-resistance genes and biofilm-forming genes was examined by polymerase chain reaction (PCR). The ability of biofilm formation was examined by microtiter plate assay. The Kirby–Bauer disc diffusion method was used to evaluate the trimethoprim-sulfamethoxazole (TMP-SMX), levofloxacin, and minocycline resistance.

          Results

          S. maltophilia is mainly isolated from bloodstream infections. Notably, 98.93% of isolates were biofilm producers, of which 19.35%, 60.22%, and 20.43% produced strong, moderate, and weak biofilm, respectively. The frequency of biofilm genes was 100%, 97.88%, 96.80%, and 75.53% for spgM, rmlA, smf-1, and rpfF, respectively. Isolates with the genotype of smf-1+/ rmlA+/ spgM+/ rpfF+ were mostly strong biofilm producers. Among the antibiotic-resistance genes, the Smqnr, L1, and sul1 had the highest prevalence (76.59%, 72.34%, and 64.89), respectively. Antimicrobial susceptibility evaluation showed 1.06%, 3.19%, and 6.3% resistance to minocycline, TMP-SMX, and levofloxacin.

          Conclusion

          The results of the current study demonstrated that S. maltophilia isolates differ in biofilm-forming ability. Moreover, smf-1, rmlA, and spgM genes were presented in all strong biofilm producers. Although the overall resistance rate to the evaluated antibiotics was high, there was no statistically significant relation between antibiotic resistance and the type of biofilm.

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          Most cited references47

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          Infectious Diseases Society of America Guidance on the Treatment of AmpC β-lactamase-Producing Enterobacterales, Carbapenem-Resistant Acinetobacter baumannii, and Stenotrophomonas maltophilia Infections

          Background The Infectious Diseases Society of America (IDSA) is committed to providing up-to-date guidance on the treatment of antimicrobial-resistant infections. A previous guidance document focused on infections caused by extended-spectrum β-lactamase-producing Enterobacterales (ESBL-E), carbapenem-resistant Enterobacterales (CRE), and Pseudomonas aeruginosa with difficult-to-treat resistance (DTR-P. aeruginosa). Here, guidance is provided for treating AmpC β-lactamase-producing Enterobacterales (AmpC-E), carbapenem-resistant Acinetobacter baumannii (CRAB), and Stenotrophomonas maltophilia infections. Methods A panel of six infectious diseases specialists with expertise in managing antimicrobial-resistant infections formulated questions about the treatment of AmpC-E, CRAB, and S. maltophilia infections. Answers are presented as suggestions and corresponding rationales. In contrast to guidance in the previous document, published data on optimal treatment of AmpC-E, CRAB, and S. maltophilia infections are limited. As such, guidance in this document is provided as “suggested approaches” based on clinical experience, expert opinion, and a review of the available literature. Because of differences in the epidemiology of resistance and availability of specific anti-infectives internationally, this document focuses on the treatment of infections in the United States. Results Preferred and alternative treatment suggestions are provided, assuming the causative organism has been identified and antibiotic susceptibility results are known. Approaches to empiric treatment, duration of therapy, and other management considerations are also discussed briefly. Suggestions apply for both adult and pediatric populations. Conclusions The field of antimicrobial resistance is highly dynamic. Consultation with an infectious diseases specialist is recommended for the treatment of antimicrobial-resistant infections. This document is current as of September 17, 2021 and will be updated annually. The most current versions of IDSA documents, including dates of publication, are available at www.idsociety.org/practice-guideline/amr-guidance-2.0/.
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            Stenotrophomonas maltophilia as an Emerging Ubiquitous Pathogen: Looking Beyond Contemporary Antibiotic Therapy

            Stenotrophomonas maltophilia is a commensal and an emerging pathogen earlier noted in broad-spectrum life threatening infections among the vulnerable, but more recently as a pathogen in immunocompetent individuals. The bacteria are consistently being implicated in necrotizing otitis, cutaneous infections including soft tissue infection and keratitis, endocarditis, meningitis, acute respiratory tract infection (RTI), bacteraemia (with/without hematological malignancies), tropical pyomyositis, cystic fibrosis, septic arthritis, among others. S. maltophilia is also an environmental bacteria occurring in water, rhizospheres, as part of the animals' microflora, in foods, and several other microbiota. This review highlights clinical reports on S. maltophilia both as an opportunistic and as true pathogen. Also, biofilm formation as well as quorum sensing, extracellular enzymes, flagella, pili/fimbriae, small colony variant, other virulence or virulence-associated factors, the antibiotic resistance factors, and their implications are considered. Low outer membrane permeability, natural MDR efflux systems, and/or resistance genes, resistance mechanisms like the production of two inducible chromosomally encoded β-lactamases, and lack of carefully compiled patient history are factors that pose great challenges to the S. maltophilia control arsenals. The fluoroquinolone, some tetracycline derivatives and trimethoprim-sulphamethaxole (TMP-SMX) were reported as effective antibiotics with good therapeutic outcome. However, TMP-SMX resistance and allergies to sulfa together with high toxicity of fluoroquinolone are notable setbacks. S. maltophilia's production and sustenance of biofilm by quorum sensing enhance their virulence, resistance to antibiotics and gene transfer, making quorum quenching an imperative step in Stenotrophomonas control. Incorporating several other proven approaches like bioengineered bacteriophage therapy, Epigallocatechin-3-gallate (EGCG), essential oil, nanoemulsions, and use of cationic compounds are promising alternatives which can be incorporated in Stenotrophomonas control arsenal.
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              Biofilms as Promoters of Bacterial Antibiotic Resistance and Tolerance

              Multidrug resistant bacteria are a global threat for human and animal health. However, they are only part of the problem of antibiotic failure. Another bacterial strategy that contributes to their capacity to withstand antimicrobials is the formation of biofilms. Biofilms are associations of microorganisms embedded a self-produced extracellular matrix. They create particular environments that confer bacterial tolerance and resistance to antibiotics by different mechanisms that depend upon factors such as biofilm composition, architecture, the stage of biofilm development, and growth conditions. The biofilm structure hinders the penetration of antibiotics and may prevent the accumulation of bactericidal concentrations throughout the entire biofilm. In addition, gradients of dispersion of nutrients and oxygen within the biofilm generate different metabolic states of individual cells and favor the development of antibiotic tolerance and bacterial persistence. Furthermore, antimicrobial resistance may develop within biofilms through a variety of mechanisms. The expression of efflux pumps may be induced in various parts of the biofilm and the mutation frequency is induced, while the presence of extracellular DNA and the close contact between cells favor horizontal gene transfer. A deep understanding of the mechanisms by which biofilms cause tolerance/resistance to antibiotics helps to develop novel strategies to fight these infections.
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                Author and article information

                Contributors
                Journal
                Int J Microbiol
                Int J Microbiol
                IJMICRO
                International Journal of Microbiology
                Hindawi
                1687-918X
                1687-9198
                2023
                31 August 2023
                : 2023
                : 8873948
                Affiliations
                1Department of Microbiology, Faculty of Medicine, Shahed University, Tehran, Iran
                2Department of Microbiology, School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran
                3Department of Microbiology, School of Medicine, Alborz University of Medical Sciences, Karaj, Iran
                4Non-Communicable Diseases Research Center, Alborz University of Medical Sciences, Karaj, Iran
                Author notes

                Academic Editor: Ahmed Majeed Al-Shammari

                Author information
                https://orcid.org/0000-0001-5762-1279
                https://orcid.org/0000-0001-7966-6267
                https://orcid.org/0000-0002-7258-5541
                https://orcid.org/0000-0002-5981-3781
                https://orcid.org/0000-0003-4239-5015
                https://orcid.org/0000-0002-4800-2078
                Article
                10.1155/2023/8873948
                10484654
                37692920
                bfd2c11f-c100-47e9-aada-dfca3f134bfd
                Copyright © 2023 Fatemeh Sameni et al.

                This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

                History
                : 8 May 2023
                : 1 July 2023
                : 9 August 2023
                Funding
                Funded by: Shahed University
                Categories
                Research Article

                Microbiology & Virology
                Microbiology & Virology

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