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Rifabutin is a lipophilic antibacterial with high in vitro activity against many pathogens involved in bacterial meningitis including pneumococci. Resistance to β-lactam antibiotics in pneumococci is not associated with a decreased sensitivity to rifabutin (30 strains from Germany with intermediate penicillin resistance; MIC range of penicillin: 0.125-1 mg/l, MIC of rifabutin: < 0.008-0.015 mg/l). Rifabutin at doses of 0.625, 1.25, 2.5, 5 and 10 mg/kg/h i.v. was investigated in a rabbit model of meningitis using a Streptococcus pneumoniae type 3 (MIC/MBC of rifabutin: 0.015/ 0.06 mg/l). The bacterial density in CSF at the onset of treatment was 7.3 ± 0.6 log CFU/ml (mean ± SD). Rifabutin decreased bacterial CSF titers in a dose-dependent manner [δlog CFU/ml/h (slope of the regression line log CFU/ml vs. time) at a dose of 0.625 mg/kg/h: -0.16 ± 0.06 (n = 3), at 1.25 mg/kg/h: -0.20 ± 0.12 (n = 4), at 2.5 mg/kg/h: -0.24 ± 0.04 (n = 4), at 5 mg/kg/h: -0.31 ± 0.10 (n = 8), and at 10 mg/kg/h: -0.29 ± 0.10 (n = 5)]. At high doses rifabutin was as active as ceftriaxone at 10 mg/kg/h (δlog CFU/ml/h: -0.29 ± 0.10, n = 10). Two and 5 h after initiation of therapy, CSF TNF-α activities were lower with rifabutin 5 mg/kg/h than with ceftriaxone (medians 2 vs. 141 U/ml, p = 0.005 at 2 h; median 51 vs. 120 U/ml 5 h after initiation of therapy, p = 0.04). This did not result, however, in a decrease of indicators of neuronal damage. In conclusion, intravenous rifabutin was bactericidal in experimental pneumococcal meningitis. Provided that a well-tolerated i.v. formulation will be available it may qualify as a reserve antibiotic for pneumococcal meningitis, in particular when strains with a reduced sensitivity to β-lactam antibiotics are the causative pathogens.

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Blood parameters concerning oxygen transport and relative organ weights of 11 Suncus etruscus and 13 Crocidura russula under light halothane anesthesia were investigated. Mean body weight of S. etruscus was 2.5 g and for C. russula was 9 g, hemoglobin concentration was 17.4 and 15.6 g/100 ml blood, hematocrit was 50 and 44%, red blood cells were 18 and 11 X 10(6)/microliter, respectively. Mean corpuscular volume was calculated to be 26 and 41 micron3, mean diameter 5.5 and 7 micron, and mean thickness 1.2 and 1.1 micron, respectively. Mean corpuscular hemoglobin concentration was in the normal range of mammalian red blood cells. A blood oxygen half-saturation pressure of 35 and 34 Torr at pH 7.4, 37 degrees C and a Bohr factor deltalog P50/deltapH of -0.61 and -0.66 was measured. Experiments with stripped hemoglobin showed that 2,3-diphosphoglycerate is the main oxygen affinity reducing allosteric factor. Relative weights of heart, kidney, and liver are remarkably high in S. etruscus. The maximal oxygen transport of 400 ml . kg-1 . min-1 of S. etruscus is feasible by an enormous heart rate, a large relative stroke volume, a high hemoglobin concentration combined with a low oxygen affinity, and a large Bohr effect.