Effect of benzylpenicillin in mice infected with endotoxin-liberating or non-liberating variant strains of Neisseria meningitidis.

The effect of benzylpenicillin treatment was studied in mice infected intraperitoneally (i.p.) with endotoxin-liberating (E+) and non-liberating (E-) meningococci derived from the same original serogroup B strain. The E+ meningococci were significantly more virulent to mice than the E- variants in untreated animals (p less than 0.001). Large doses of benzylpenicillin given intravenously (i.v.) immediately after i.p. inoculation of E+ or E- meningococci resulted in complete, or almost complete survival. When treatment started later the number of surviving E- infected animals increased in all treatment regimens. By contrast, E+ infected animals had one or more treatment groups in all regimens that did not respond to benzylpenicillin at all. Benzylpenicillin treatment was given over a period of time as intermittent, regular i.v. doses, or as a depot preparation subcutaneously (s.c.). The mortality observed in E+ infected mice after benzylpenicillin i.v. was 75%, after benzylpenicillin procaine s.c. 82.5%, while animals receiving only saline i.v. had a mortality of 67.5%. The corresponding mortalities for E- infected animals were 15% (p = 0.0014), 42.5%, and 42.5%, respectively.