From the Guidelines

The preferred regimen for managing Stenotrophomonas maltophilia (S. maltophilia) infection is Trimethoprim/Sulfamethoxazole (TMP/SMX).

The dose of TMP/SMX for treatment of S. maltophilia infection is similar to the treatment of P. jirovecii pneumonia 1.
In patients with lack of clinical improvement, a change in the antimicrobial treatment regimen may be necessary, and repeated microbiological diagnostics should be considered 1.
Tigecycline is a viable treatment option, especially in empiric therapy, for complicated infections due to its favorable in vitro activity against S. maltophilia 1.

Initial antibiotic therapy for infections involving S. maltophilia is typically empirical in nature, and selection of appropriate empiric antibiotic therapy is critical for preventing unnecessary morbidity and mortality 1.
The choice of empiric antibiotic regimens should be based on the clinical condition of the patients, the individual risk for infection by resistant pathogens, and the local resistance epidemiology 1.
In patients with uncomplicated infections, single doses or short courses of antibiotic therapy may be sufficient, while in critically ill patients, an individualized approach should be taken, and patient’s inflammatory response should be monitored regularly 1.

In patients with multidrug-resistant gram-negative bacteria, including S. maltophilia, carbapenems may be considered, but their use should be limited to preserve activity of this class of antibiotics 1.
New antibiotics such as ceftolozone/tazobactam and ceftazidime/avibactam may be valuable for treating infections caused by multidrug-resistant gram-negative bacteria, including S. maltophilia 1.

From the Research

The management of Stenotrophomonas maltophilia infection is challenging due to its intrinsic multidrug resistance.

The first-line therapy for S. maltophilia infections is trimethoprim-sulfamethoxazole (TMP/SMX) 2, 3, 4, 5.
Other treatment options include levofloxacin (LVX), minocycline (MIN), ticarcillin-clavulanic acid, and tetracycline derivatives such as tigecycline 2, 3, 4, 5.
Combination therapies, such as SXT, LVX, MIN, or novel agents like cefiderocol (FDC) and ceftazidime-avibactam plus aztreonam (CZA-ATM), are also recommended for severe-to-moderate S. maltophilia infections 3.
The choice of antibiotic treatment is hindered by the lack of standardized susceptibility tests and their interpretative criteria 4, 6.

S. maltophilia exhibits high levels of intrinsic or acquired resistance to different antimicrobial agents, including:

Reduced outer membrane permeability 4
Multidrug efflux pumps 2, 4
Aminoglycoside-modifying enzymes 4
Metallo-beta-lactamase production 4
β-lactamase production, the expression of Qnr genes, and the presence of class 1 integrons 2

The clinical management of S. maltophilia infections is complicated by:

Molecular heterogeneity among different strains 6
Shortcomings of available antimicrobial susceptibility tests 6
Lack of standardized breakpoints for antibiotics with in vitro activity against S. maltophilia 6