Murray M. Streitfeld

Cardiovascular changes in group B streptococcal sepsis in the piglet: response to indomethacin and relationship to prostacyclin and thromboxane A2.

Summary: Seventeen piglets were infected with a continuous intravenous infusion of live group B β-hemolytic streptococci (GBS). Hemodynamic changes were recorded, and blood samples were drawn for measurement of thromboxane B2 (TxB2) (stable metabolite of thromboxane A2) and 6-keto-PGF1α (stable metabolite of prostacyclin). Control animals (n =9) received only bacteria, while treatment animals (n =8) received indomethacin, 3 mg/kg IV, 15 min after the start of the bacterial infusion. Control animals responded to the bacteria within 15 min with marked elevation in mean pulmonary artery pressure (Ppa) from 15 ± 8 to 39 ± 6 mm Hg and decline in Pao2 from 80 ± 11 to 51 ± 6 mm Hg and cardiac output (CO) from 0.24 ± 0.07 to 0.13 ± 0.07 liters/min/ kg. Mean arterial blood pressure (AoP) significantly decreased from baseline value of 95 ± 13 to 51 ± 32 mm Hg by 180 min. In animals treated with indomethacin, these changes were reversed or significantly attenuated. The hemodynamic changes were associated temporally with elevations in plasma concentrations of TxB2 or 6-keto-PGF1α. In he first 60 min, TxB2 levels in both groups correlated with Ppa (r =0.72, p < 0.001) and Pao2 (r =-0.60, p < 0.001). A strong negative correlation between TxB2 and CO was observed over the first 180 min (r =-0.73, p < 0.001). There was a statistically significant correlation between AoP and 6-keto-PGF1α concentration between 60 and 180 min (r =-0.54, p < 0.002). Indomethacin improved the hemodynamic function in this model of GBS sepsis. This improvement was related in part to inhibition of synthesis of thromboxane A2 and prostacyclin.

Inducible and Constitutive Resistance to Macrolide Antibiotics and Lincomycin in Clinically Isolated Strains of Streptococcus pyogenes

Studies on erythromycin resistance in strains of group A streptococci indicated that they were comprised of two types: (i) an inducible, resistant type (IR strains) was seen, which manifested immediate logarithmic growth in media containing high concentrations of the drug only after brief previous exposure (induction period) of the organisms to subinhibitory concentrations of erythromycin, and (ii) a constitutive, resistant type (CR strains) which demonstrated, without prior drug exposure, continued logarithmic growth in media containing high concentrations of erythromycin. Subinhibitory concentrations of either chloramphenicol or puromycin, when added to IR strains prior to induction, interfered with their induction by erythromycin. Exposure of CR strains to chloramphenicol did not visibly affect the subsequent growth curve of these strains in media containing high concentrations of erythromycin. In IR strains, resistance to other macrolide antibiotics (oleandomycin, spiramycin, carbomycin, magnamycin) and to lincomycin also was inducible in nature. There was cross-inducibility between erythromycin, other macrolide antibiotics, and lincomycin. CR strains were constitutively resistant to these antibiotics.

Effects of a leukotriene antagonist on the early hemodynamic manifestations of group B streptococcal sepsis in piglets.

Abstract: In order to evaluate the influence of leukotrienes on group B streptococcal (GBS) sepsis we studied the effect of a leukotriene antagonist, FPL 57231, on the early hemodynamic changes occurring secondary to an infusion of live GBS. Paralyzed, mechanically ventilated piglets received a continuous intravenous infusion of bacteria (5 × 108 org/kg/min) while systemic arterial pressure and pulmonary artery pressure were measured continuously. Cardiac output was measured by thermodilution; and plasma samples for determination of thromboxane B2 and 6-keto-PGF1α were taken at preset intervals. In addition to GBS, treatment animals received a continuous infusion of FPL 57231 starting 15 min after the bacterial infusion was begun. Study animals as a whole responded to bacteria within 15 min with a marked elevation in pulmonary artery pressure from 13.6 ± 4 to 44.6 ± 6 mm Hg (p < 0.001), and a decline in PaO2 (79 ± 9 to 44 ± 5 mm Hg) (p < 0.001) and a cardiac output (0.27 ± 0.07 to 0.15 ± 0.06 liter/min/kg) (p < 0.0001). In animals treated with FPL 57231 these changes were reversed or significantly attenuated by 60 min. In the control group pH deteriorated significantly to 7.17 ± 0.1 compared to baseline values (p < 0.01) by 60 min, while treatment group animals maintained a pH of 7.3 ± 0.23. Thromboxane B2 and 6-keto PGF1α were similar in both groups and did not change during the study period. In addition, survival was significantly longer in treatment (191 ± 44 min) compared to control animals (100 ± 32 min) (p < 0.01). These data suggest that FPL 57231 may attenuate the early cardiovascular changes accompanying GBS infection and positively influence survival without modifying thromboxane or 6-keto PGF1α levels. These results imply that leukotrienes influence the early hemodynamic manifestations of GBS sepsis.

The effect of iron on mixed infection of Bacteroides fragilis and Escherichia coli in mice

Survival of an infected animal is improved in a mixed infection when Bacteroides fragilis is the bacterial species acting as a microbial antagonist against Escherichia coli. The protective effect afforded an animal by B. fragilis against E. coli is altered when ferric ammonium citrate is added to the injected mixed culture. In mice an E. coli concentration of 10(9) produced zero survival; the concentration 10(8) produced 40% survival; the concentration 10(7) and less produced 100% survival. Bacteroides fragilis concentrations of 10(8) and less did not kill the 15- to 20-g mouse within 5 days. Mice were given ip injections of the constant amount of 10(8) E. coli and serially diluted amounts of B. fragilis beginning with 10(8) organisms/ml. There was 40% survival in the 10(8) E. coli controls and 96% survival in the animals receiving 10(8) E. coli plus B. fragilis. The addition of ferric ammonium citrate to 10(8) E. coli plus B. fragilis reduced animal survival from 96 to 63%.

The microassay of hyaluronic acid concentration and hyaluronidase activity by capillary turbidity (CT) and capillary turbidity reduction (CTR) tests

Abstract The Capillary Turbidity (CT) Test for quantitative estimation of hyaluronic acid concentrations in solutions is described. The standardized procedure permits assay of the visible reaction occurring between mucopolysaccharide and acidified albumin. The CT Test is reproducible, sensitive, simple, rapid, and economical in that it does not require the use of measuring instruments (e.g., spectrophotometer or viscosimeter) and is sparing of reagent materials. This test has led to the development of the Capillary Turbidity Reduction (CTR) Procedure for the semiquantitative microassay of hyaluronidase activity.