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      Treatment approaches for severe Stenotrophomonas maltophilia infections

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          Abstract

          Purpose of review

          Stenotrophomonas maltophilia is an emerged opportunistic pathogen. Intrinsic multidrug resistance makes treating infections caused by S. maltophilia a great clinical challenge. Herein, we provide an update on the most recent literature on treatment options for severe S. maltophilia infections.

          Recent findings

          Trimethoprim-sulfamethoxazole (SXT) is recognized as the first-line therapy for S. maltophilia infections. However, its clinical use is based on good in vitro activity and favorable clinical outcomes, rather than on solid minimum inhibitory concentration (MIC) correlations with pharmacokinetic/pharmacodynamics (PK/PD) and/or clinical outcomes. The same is true for other treatment options like levofloxacin (LVX) and minocycline (MIN). Recent PK/PD studies question the current clinical breakpoints for SXT, LVX, and MIN. Based on this, the latest guidance issued by the Infectious Diseases Society of America (IDSA) recommends using these agents only as part of a combination therapy. Alternatively, novel therapeutic options such as cefiderocol (FDC) and ceftazidime-avibactam plus aztreonam (CZA-ATM) are suggested, based on limited but promising clinical data.

          Summary

          PK/PD data and controlled clinical studies are needed to optimize current treatment options. Presently, combination therapy of SXT, LVX, MIN, or FDC, or monotherapy with CZA-ATM are recommended therapeutic options for severe-to-moderate S. maltophilia infections.

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          Most cited references146

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          Efficacy and safety of cefiderocol or best available therapy for the treatment of serious infections caused by carbapenem-resistant Gram-negative bacteria (CREDIBLE-CR): a randomised, open-label, multicentre, pathogen-focused, descriptive, phase 3 trial

          Matteo Bassetti, Roger Echols, Yuko Matsunaga … (2020)
          New antibiotics are needed for the treatment of patients with life-threatening carbapenem-resistant Gram-negative infections. We assessed the efficacy and safety of cefiderocol versus best available therapy in adults with serious carbapenem-resistant Gram-negative infections.
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            Stenotrophomonas maltophilia: an emerging global opportunistic pathogen.

            Joanna S Brooke (2012)
            Stenotrophomonas maltophilia is an emerging multidrug-resistant global opportunistic pathogen. The increasing incidence of nosocomial and community-acquired S. maltophilia infections is of particular concern for immunocompromised individuals, as this bacterial pathogen is associated with a significant fatality/case ratio. S. maltophilia is an environmental bacterium found in aqueous habitats, including plant rhizospheres, animals, foods, and water sources. Infections of S. maltophilia can occur in a range of organs and tissues; the organism is commonly found in respiratory tract infections. This review summarizes the current literature and presents S. maltophilia as an organism with various molecular mechanisms used for colonization and infection. S. maltophilia can be recovered from polymicrobial infections, most notably from the respiratory tract of cystic fibrosis patients, as a cocolonizer with Pseudomonas aeruginosa. Recent evidence of cell-cell communication between these pathogens has implications for the development of novel pharmacological therapies. Animal models of S. maltophilia infection have provided useful information about the type of host immune response induced by this opportunistic pathogen. Current and emerging treatments for patients infected with S. maltophilia are discussed.
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              Aminoglycoside modifying enzymes.

              Maria S. Ramirez, Marcelo E. Tolmasky (2010)
              Aminoglycosides have been an essential component of the armamentarium in the treatment of life-threatening infections. Unfortunately, their efficacy has been reduced by the surge and dissemination of resistance. In some cases the levels of resistance reached the point that rendered them virtually useless. Among many known mechanisms of resistance to aminoglycosides, enzymatic modification is the most prevalent in the clinical setting. Aminoglycoside modifying enzymes catalyze the modification at different -OH or -NH₂ groups of the 2-deoxystreptamine nucleus or the sugar moieties and can be nucleotidyltransferases, phosphotransferases, or acetyltransferases. The number of aminoglycoside modifying enzymes identified to date as well as the genetic environments where the coding genes are located is impressive and there is virtually no bacteria that is unable to support enzymatic resistance to aminoglycosides. Aside from the development of new aminoglycosides refractory to as many as possible modifying enzymes there are currently two main strategies being pursued to overcome the action of aminoglycoside modifying enzymes. Their successful development would extend the useful life of existing antibiotics that have proven effective in the treatment of infections. These strategies consist of the development of inhibitors of the enzymatic action or of the expression of the modifying enzymes. Copyright © 2010 Elsevier Ltd. All rights reserved.
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                Author and article information

                Journal
                Title: Current Opinion in Infectious Diseases
                Publisher: Ovid Technologies (Wolters Kluwer Health)
                ISSN (Print): 0951-7375
                ISSN (Electronic): 1473-6527
                Publication date (Electronic): October 17 2023
                Affiliations
                [1 ]Department of Molecular Biology and Microbiology, School of Medicine, Case Western Reserve University
                [2 ]Case Western Reserve University-Cleveland VA Medical Center for Antimicrobial Resistance and Epidemiology, Cleveland, Ohio, USA
                [3 ]Grupo de Resistencia Antimicrobiana y Epidemiología Hospitalaria, Universidad El Bosque, Bogotá, Colombia
                [4 ]Medical Service and Geriatric Research, Education, and Clinical Center, Veterans Affairs Northeast Ohio Healthcare System
                [5 ]Departments of Medicine, Biochemistry, Pharmacology, and Molecular Biology and Microbiology, School of Medicine, Case Western Reserve University, Cleveland, Ohio
                [6 ]Department of Medicine, University of North Carolina School of Medicine, Chapel Hill, North Carolina, USA
                Article
                DOI: 10.1097/QCO.0000000000000975
                PubMed ID: 37846568
                SO-VID: 96d9aa9f-b112-4332-b682-8665897b8440
                Copyright © © 2023
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