Cefiderocol as an alternative antibiotic therapy for treating severe Stenotrophomonas maltophilia infections.

Abstract

Stenotrophomonas maltophilia has emerged as an opportunistic pathogen that causes life-threatening hospital-acquired infections. This microorganism possesses a diverse array of chromosome-encoded antimicrobial resistance genes, which render it inherently multidrug-resistant (MDR). Its ability to acquire additional antimicrobial resistance via mutations and the horizontal transfer of resistome elements from neighboring microbial communities has further contributed to the development of extensively drug-resistant (XDR) and even pandrug-resistant (PDR) strains. These strains are resistant to routinely used antibiotics, including the first-line drug trimethoprim/sulfamethoxazole as well as levofloxacin and minocycline. Recently, cefiderocol - a siderophore-conjugated cephalosporin - was developed for clinical use. This antibiotic has shown high in vitro efficacy against clinically relevant MDR gram-negative pathogens. Cefiderocol efficiently transverses the outer membrane of bacteria via iron transport systems and exhibits high stability against β-lactamases. An injectable form of cefiderocol has received Food and Drug Administration approval for the treatment of complicated urinary tract infections, hospital-acquired bacterial pneumonia, and ventilator-associated bacterial pneumonia caused by drug-resistant gram-negative bacteria. Clinical data on the use of cefiderocol for S. maltophilia infections remain limited, however, some in vitro, in vivo, and case studies have demonstrated its efficacy and successful treatment of MDR S. maltophilia infections. Given the narrow range of therapeutic options currently available, cefiderocol presents a promising alternative for the effective management of severe S. maltophilia infections. Nevertheless, the potential for the emergence of resistance remains a significant concern, as emerging evidence suggests that S. maltophilia may acquire resistance following exposure to this antibiotic.