Adjunctive Treatment with Low-Dose Polymyxin B Improves Operant Response Rates and Latency in Infant Rats with Haemophilus influenzae Type b Meningitis

Abstract

Polymyxin B given in conjunction with ampicillin protects infant rats against death from overwhelming Haemophilus influenzae type b infection. This study was undertaken to examine whether polymyxin B would mitigate the effects of brain damage caused by meningitis. Six- to 7-d-old Sprague-Dawley rats were infected subcutaneously into the nape with 10(7) cfu Haemophilus influenzae type b strain Eagan. This dose consistently caused bacteremia (1.2 X 10(5) cfu/mL) and meningitis (0.5 X 10(5) cfu/mL) in pilot studies. Twenty-four h after infection, all animals received intraperitoneal treatment consisting in either ampicillin alone (400 mg/kg X 4 q 3 h) repeated 12 h later, n = 15 or combined with polymyxin B (0.1 mg/kg/dose) n = 16. At age 2 mo, they were taken off ad libitum feeding and maintained at 80% of their wt. They were then conditioned to receive a food pellet by pressing a lever (continuous reinforcement). The next day, the time lapse between placement and pressing the lever for the first time was recorded (conditioned operant response or latency). Three wk later, the animals were put in the test chamber again and the time to press the lever (latency), as well as the time required to obtain 100 pellets (rate) were recorded. Animals who received polymyxin B had a significantly shorter reaction time; mean 34 s, SEM +/- 5.7 versus mean 88 s, SEM +/- 26.3, P less than or equal to 0.05 and performed significantly faster in obtaining 100 pellets; mean 925 s, SEM +/- 72.1 versus mean 1283 s, SEM +/- 126.3, p less than or equal to 0.02 (analysis of variance, Scheffé test).(ABSTRACT TRUNCATED AT 250 WORDS)