Phage therapy for bacterial infections of CNS: a pharmacotherapeutic perspective

Bacterial infections continue to pose a significant health risk with CNS infections contributing to a huge death toll every year. Pathogens such as Streptococcus pneumoniae, Haemophilus influenzae and Neisseria meningitidis are the prominent causes of these infections. Over the recent years, many of these bacteria have become resistant to antibiotics. Phage therapy can complement and supplement the traditional antibiotics as it employs bacteriophages to specifically target pathogenic bacteria. Phages reported in many research studies have been able to successfully target pathogens of the CNS. A number of pre-clinical studies have investigated the pharmacological effectiveness of phage therapy in CNS infections exhibiting adequate transport across the blood brain barrier. These findings have enhanced the confidence in the therapeutic potential of phages as they can inhibit bacterial infections, relieve inflammatory responses and subsequently, treat CNS infections. Phages and endolysins given systemically can be detected and measured in brain and CSF, but the extent of BBB crossing should be further investigated as it has limited direct evidence. However, today, owing to its targeted action, adequate tissue distribution and autodosing, phage therapy can serve as an ideal option for addressing hard-to-treat CNS infections caused by antibiotic resistant bacteria, despite of its challenging pharmacokinetics and formulation development. The current review presents the opportunities and challenges, in terms of pharmacological, therapeutic and regulatory aspects, with relevance to the incorporation of phage therapy in clinical settings for the treatment of CNS infections.