Alternate therapy of serious infections- bacteriophage therapy
Dr. Gopal Nath,
Professor of Microbiology, Institute of Medical Sciences, Banaras Hindu University, Varanasi-221005
Varanasi: Sepsis is defined as a syndromic response to infection. It may be a final common pathway to death from many infectious diseases worldwide. As per an estimate, 20% of all global deaths are attributed to septicaemia. Approximately 85% of sepsis cases and related deaths occur in developing countries. Schooley et al. from the USA has published the much-admired human case report. They have successfully used a personalized bacteriophages cocktail on a 68-year-old terminally ill, diabetic patient with necrotizing pancreatitis complicated with MDR A.
baumannii infection. However, specific unresolved issues such as optimization of safe dosages (quantity and frequency), modes of administration, pharmacokinetics, pharmacodynamics, the multiplicity of infection and valency, the characterization of phages and deployment, and the emergence of bacteriophage resistance during therapy, etc., must be worked out thoroughly before clinical trials.
In addition, we must discern the quantity and number of the cocktail doses with different stages of septicaemia in various age groups of the patients. Reports indicate that the administration of a cocktail of antibiotics disrupting cell walls in severe septicaemia often results in the fatal outcome due to sudden massive lysis of the bacteria and release of a massive amount of endotoxin. The bacteriophages also kill the bacteria by disrupting the cell wall, so their use may have similar consequences if the dosage is not optimized.
We tried to elucidate the safe dosage for the different stages of septicaemia in the preclinical model.
We have elucidated that Phage therapy is effective against the Klebsiella pneumoniae septicaemia mice model and is a promising alternative to antibiotic treatments. Our work delineates that a single dose of phage cocktail with 1 × 105 Plaque Forming Unit/mouse (PFU/mouse) protects the mice from fatal outcomes at any stage of septicemia. However, the higher phage dosage of 1 × 1012 PFU/mice is fatal when given in the early hours of septicemia, while this high dose is not fatal at the late stages of septicemia. Moreover, repeated dosages are required to eradicate the bacteria from peripheral blood. Proper vitals monitoring in clinical settings might cure septicaemia caused by MDR bacteria with different severity of infection with low dosages.
We have already published regarding the efficacy of bacteriophages in the sepsis model caused by Staphylococcus aureus (Indian journal of Medical Research, 2016), Pseudomonas aeruginosa (Annals of National Academy of Medical Sciences, 2019) and Acinetobacter baumanii(Indian Journal of Medical Research, 2021),. We are working on two more organisms of ESKAPE group, i.e. Enterobacter and Enterococcus spp. This article on Klebsiella pneumoniae has recently been accepted in Frontiers in Pharmacology. The results obtained in this study have far-reaching benefits in clinical practice in days to come.
Even today, without the regulatory body’s approval, this therapy may be used in cases of serious infection not responding to conventional therapy on compassionate grounds. However, the patient/attendant’s consent and the consent of two treating physicians will be needed. Our lab has a few of the lyophilized purified phages against difficult bacteria to treat.