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AbstractBackground Stenotrophomonas maltophilia is an opportunistic pathogen most commonly isolated from patients with complex/life-threatening disease or cystic fibrosis. Traditionally, when treatment is warranted, trimethoprim-sulfamethoxazole has been the agent of choice, alone or in combination with a fluoroquinolone or tetracycline. Objectives This narrative review aims to provide the latest information on the role of different antimicrobial agents or combinations of agents in treating S. maltophilia infections and offer the rationale for interpretive criteria revised by EUCAST in 2025. Sources We searched PubMed to identify literature about the pharmacodynamics and clinical efficacy of a range of current and proposed antimicrobial agents and their combinations. Content Recent in vitro and animal studies have provided insights into the pharmacodynamics of a range of antimicrobial agents previously or currently considered effective in treating S. maltophilia infections. These studies challenge the view that trimethoprim-sulfamethoxazole should be the agent of choice. In reviewing the recent literature, we attempted to answer the following questions: (1) Is the pharmacodynamic evidence about trimethoprim-sulfamethoxazole sufficient to suggest that it should be replaced as the first choice for therapy? (2) Do the pharmacodynamic studies on other agents provide information about appropriateness of currently recommended dosages? (3) Is there clinical evidence to support the choice of one or another therapeutic strategy, and (4) Are combinations of agents with or without trimethoprim-sulfamethoxazole superior to monotherapy? Implications Based on the assessment of the data, EUCAST found cefiderocol a potential alternative to trimethoprim-sulfamethoxazole, although the clinical evidence is still too limited to allow a clinical breakpoint. The other antimicrobial agents have limitations in their activity, as assessed by PK/PD data, but might have a role in combination therapy. However, no data were found to convincingly support the superiority of combination therapy over monotherapy.
Turnidge et al. (Tue,) studied this question.