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Phage therapy for infection caused by Klebsiella pneumoniae

Indian scientists have isolated a lytic bacteriophage specific for Klebsiella pneumoniae , a causative agent of severe respiratory tract infections, urinary tract infections, wound infections, and other conditions, and demonstrated its therapeutic efficacy in an animal model of pneumonia.

The Gram-negative bacterium Klebsiella pneumoniae is a common cause of severe diseases in humans and animals, including hospital-acquired infections that are difficult to treat. Infections caused by Klebsiella pneumoniae are particularly dangerous for the elderly and patients with weakened immune systems. Recently, the situation has been exacerbated by the spread of antibiotic-resistant strains of Klebsiella pneumoniae , which are resistant to both beta-lactam antibiotics and carbapenems.

Bacteriophages—bacterial viruses that specifically target specific strains, particularly antibiotic-resistant ones—are being considered as an alternative to antibiotics. Bacteriophages are safe for humans and animals and do not affect their beneficial microflora.

Indian scientists have isolated and characterized a new lytic (bacteria-killing) bacteriophage, VTCCBPA43, specific for Klebsiella pneumoniae . It is thermotolerant, maintaining activity at temperatures up to 80°C. This property makes the phage more stable during storage.

The therapeutic efficacy of the VTCCBPA43 phage was tested in a pneumonia model in BALB/c mice. One group of mice was injected intranasally with a virulent strain of K. pneumoniae , followed 2 hours later by intranasal administration of the VTCCBPA43 bacteriophage (10 9 BFU/individual). A second group of mice received only the virulent strain of K. pneumoniae , and a third group received only the VTCCBPA43 bacteriophage.

Lung autopsies from mice were examined at 6, 12, 24, 48, and 96 hours post-infection and on days 6, 10, and 14 post-infection. In the positive control group (bacteria only), changes began after 12 hours and progressed from focal bronchopulmonary changes to widespread lung damage. The group of animals that received both bacteria and bacteriophages showed a significantly lower bacterial load and less severe tissue damage (significantly fewer necrotic and inflammatory cells). Animals that received bacteriophages recovered faster than animals in the positive control group.

The authors note that their study is the first evidence of the effectiveness of intranasal administration of bacteriophages in lower respiratory tract infection caused by K. pneumoniae .

*Anand T, Virmani N, Kumar S et al. Phage therapy for treatment of virulent Klebsiella pneumoniae infection in a mouse model. Journal of Global Antimicrobial Resistance, 2020, 21: 34-41. https://doi.org/10.1016/j.jgar.2019.09.018