Bioluminescence and 19F magnetic resonance imaging visualize the efficacy of lysostaphin alone and in combination with oxacillin against Staphylococcus aureus in murine thigh and catheter-associated infection models
Hertlein T.,University of Wurzburg |
Sturm V.,University of Wurzburg |
Lorenz U.,University of Wurzburg |
Sumathy K.,Bharat Biotech International Ltd. |
And 2 more authors.
Antimicrobial Agents and Chemotherapy | Year: 2014
Staphylococci are the leading cause of hospital-acquired infections worldwide. Increasingly, they resist antibiotic treatment owing to the development of multiple antibiotic resistance mechanisms in most strains. Therefore, the activity and efficacy of recombinant lysostaphin as a drug against this pathogen have been evaluated. Lysostaphin exerts high levels of activity against antibiotic-resistant strains of Staphylococcus aureus, including methicillin-resistant S. aureus (MRSA). The therapeutic value of lysostaphin has been analyzed in two different clinically relevant in vivo models, a catheter-associated infection model and a thigh infection model. We infected mice with luciferase-expressing S. aureus Xen 29, and the efficacies of lysostaphin, vancomycin, oxacillin, and combined lysostaphin-oxacillin were investigated by determining numbers of CFU, detecting bioluminescent signals, and measuring the accumulation of perfluorocarbon emulsion at the site of infection by 19F magnetic resonance imaging. Lysostaphin treatment significantly reduced the bacterial burden in infected thigh muscles and, after systemic spreading from the catheter, in inner organs. The efficiency of lysostaphin treatment was even more pronounced in combinatorial therapy with oxacillin. These results suggest that recombinant lysostaphin may have potential as an anti-S. aureus drug worthy of further clinical development. In addition, both imaging technologies demonstrated efficacy patterns similar to that of CFU determination, although they proved to be less sensitive. Nonetheless, they served as powerful tools to provide additional information about the course and gravity of infection in a noninvasive manner, possibly allowing a reduction in the number of animals needed for research evaluation of new antibiotics in future studies. Copyright © 2014, American Society for Microbiology. All Rights Reserved.
Bharat Biotech International Ltd | Date: 2013-04-23
Invention provides novel rotavirus vaccine compositions comprising rotavirus antigens, stabilizers and buffers. The buffers in the invention are pre-mixed in the rotavirus vaccine compositions to neutralize the high acidic pH of the stomach without requiring separate administration of an antacid before vaccine administration. Vaccine compositions with buffers of the invention are stable liquid rotavirus vaccine formulations for oral administration.
Bharat Biotech International Ltd | Date: 2012-01-03
The invention provides a stable immunogenic composition for prevention and prophylaxis of infections caused by rota virus, poliomyelitis virus,
BHARAT BIOTECH INTERNATIONAL Ltd | Date: 2010-01-25
Compositions and methods related to live or live attenuated pre-conditioned and typical viruses such as rotaviruses are disclosed. The live attenuated rotaviruses exhibit better stability characteristics and are useful for the prevention of a rotavirus infection and/or rotavirus gastroenteritis in children.
Bharat Biotech International Ltd | Date: 2016-02-09