1175 ENHANCED SURVIVAL OF INFANT RATS WITH OVERWHELMING HAEMOPHILUS INFLUENZAE TYPE B (Hib)SEPSIS BY POLYMYXIN B (PB) - ENDOTOXIN (ETX) INTERACTION

Abstract

5-6 day old Sprague-Dawley rats were Infected Ip with 10⁵-10⁶ cfu of Hib strain Eagan. Ampmpicillin (Amp) (0.5 mg/kg & 3 q3hrs) given 3 hrs after infection was curative in all animals, but falled to have any effect upon survival if initiated 12 hrs later, even at a 500 mg/kg dose (47 and 45 animals, 19 controls). At this 12 hour stage an ineffective antimicrobial dose of PB (.0125mg/kg × 3 q3hrs) alone (n=33) or In combination with 500 mg/kg Amp (n=27) achieved a significant increase in survival at 17 hrs (p<.008) and 20 hrs (p<.006> and in combination at 36 hrs (p<.009) after infection. Bacterial quantitation by plate dilution and ETX activity in whole blood by a chromogenic limulus lysate assay were performed simultaneously at 30 and 300 minutes after initiation of treatment and in controls. Amp significantly reduced bacterial counts in survivors at both times (p<.025 and p<.004)compared to controls or PB treated animals but increased the activity of free endotoxin at 30 minutes (p<.004) compared to untreated controls. At all times Amp treated animals had greater ETX actlvlty/cfu (p<,006 and p<,005) when compared to surviving control or PB treated animals (50 animals). In vitro ETX release from Hib grown in broth was increased after addition of 100 μg/ml of Amp compared to 8 μg/ml PB or controls. These experiments indicate that Polymyxin B may modify the action or release of endotoxin in this model.

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