Another Iaccac abstract on the XOMA site. Shows rBPI21 does not work against "experimental" E Coli. Expect XOMA will provide additional information on this abstract.
Limited Efficacy of Recombinant
Bactericidal/Permeability-Increasing Protein (rBPI-21) in
Experimental E. coli Meningitis
I. Lutsar, I.R. Friedland, H. Jafri, L. Wubbel, W. Ng, F. Ghaffar, G.H. McCracken. University of
Texas, Southwestern Medical Center at Dallas, TX
BPI is a naturally occurring protein which neutralizes lipopolysaccharide and is bactericidal for a variety of gram-negative
and -positive bacteria. We evaluated the bactericidal activity of rBPI-21 in combination with cefotaxime (CTX) and
ampicillin (AMP) against E. coli in vitro and in experimental E. coli meningitis in rabbits.
Methods: Time kill curves using 2 E. coli strains and various antibiotic combinations were determined in
Mueller-Hinton broth. Meningitis in rabbits was induced by intracisternal inoculation of a beta-lactamase producing E.
coli strain. After 15 hours of infection iv CTX or AMP was given alone or in combination with intrathecal rBPI-21 (30
ug). Inflammation was assessed by measurement of TNF, leukocyte and lactate concentration in cerebral-spinal fluid
(CSF).
Results: The MIC and MBC of rBPI-21 to AMP did not increase bacterial killing. Similarly, in the meningitis model,
combining rBPI-21 with antibiotics was not more effective than antibiotics alone; after 10 hours of therapy bacterial
concentration in CSF dropped by 4.05 and 4.5 log10 CFU/ml after CTX vs CTX + rBPI-21 therapy, respectively, and
by 1.4 and 1.9 log10 CFU/ml after AMP vs. AMP + rBPI-21 therapy, respectively. The addition of rBPI-21 to
antibiotics did not prevent the increase in CSF leukocyte, lactate or TNF concentrations that occurred during the first 6
hours of therapy.
Conclusions: Despite its in vitro batericidal activity the addition of rBPI-21 to systemic AMP or CTX therapy did not
increase bacterial clearance from CSF nor prevent the post-antibiotic inflammatory response in this model of E. coli
meningitis. It is unlikely that rBPI-21 will be a useful adjunctive agent for the therapy of bacterial meningitis.
(A copy of this poster may be obtained by calling XOMA Investor Relations at (8 |
