Chronic lymphocytic leukemia (CLL) is characterized by immune dysfunction and increased susceptibility to bacterial infections. Growing antimicrobial resistance has renewed interest in bacteriophage therapy (PT) as a complementary antimicrobial approach. However, naturally occurring anti-phage antibodies may affect its efficacy. This study investigated the upper respiratory tract microbiota of newly diagnosed, untreated CLL patients with no prior exposure to therapeutic phages. A total of 51 bacterial isolates were recovered from 22 CLL patients and 14 isolates from 12 healthy volunteers. Staphylococcus aureus was the predominant species, followed by coagulase-negative staphylococci (CoNS). Antimicrobial susceptibility testing revealed the highest susceptibility (82.35%) to linezolid and moxifloxacin, whereas several S. aureus isolates showed reduced susceptibility to glycopeptides. Commercial phage preparations showed weak or no lytic activity against most isolates, particularly CoNS. In contrast, all 12 S. aureus isolates from CLL patients and healthy volunteers were susceptible to phage PSA-1 from the Pyophage preparation, with an efficiency of plating (EOP) of 0.7-1.0. Naturally occurring anti-phage antibodies were detected in both groups. The mean phage neutralization constant (K) was 0.64 ± 0.12 in CLL patients and 0.28 ± 0.06 in healthy controls, indicating variable pre-existing humoral immunity that may influence phage activity. These findings indicate that upper respiratory isolates from untreated CLL patients remain largely susceptible to conventional antibiotics. Phage therapy may represent a promising adjunctive strategy for managing S. aureus infections in CLL patients. Assessment of phage susceptibility and anti-phage antibody levels may optimize future phage-based therapies.

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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.