Bacterial Infections in chronic lymphocytic leukemia (CLL): Upper Respiratory Tract Microflora and Potential Treatment Strategies for Bacterial Infections

Chronic lymphocytic leukemia (CLL) is a hematologic malignancy characterized by the accumulation of mature B lymphocytes and immunodeficiency, including hypogammaglobulinemia, neutropenia, and increased regulatory T cells. These factors elevate CLL patients' risk of bacterial infections, a leading cause of morbidity and mortality. While antibiotics remain the primary treatment, rising resistance has spurred interest in alternative treatments like phage therapy (PT), specifically targeting bacteria and disrupting biofilms. However, naturally occurring anti-phage antibodies may limit PT effectiveness. This study analyzed the upper respiratory tract (URT) microflora in 22 CLL patients, assessing bacterial susceptibility to antibiotics and phages, along with presence of anti-phage antibodies. Among 51 bacterial isolates, Staphylococcus aureus was the most prevalent, followed by a number of opportunistic pathogens. Isolated bacteria showed susceptibility to tetracyclines, oxazolidinones, and fluoroquinolones, while intermediate resistance to glycopeptides in S. aureus was noticed. Commercial phages didn’t display lytic activity to tested bacterial isolates, but S. aureus strains were susceptible to phage PSA-1 derived from the Pyophage preparation. Anti-PSA-1 antibodies were detected in both CLL patients and healthy individuals, with low to moderate phage neutralizing activity, suggesting a limited potential impact of pre-existing antibodies on PT outcome. Optimizing phage selection and mitigating possible anti-phage immune response seem to be crucial for future therapeutic applications in immunocompromised patients, including those with CLL.