Combined Activities of an Antibiotic and the Immunostimulating Lauroyltetrapeptide (R.P. 40 639) on Bacterial Infections

Abstract

R.P. 40 639 (lauroyltetrapeptide), a synthetic immunostimulating compound, enhances the resistance of mice against lethal bacterial infections such as Listeria monocytogenes or Klebsiella pneumoniae, when administered at doses around 1 mg/kg i.p. or s.c. one day before challenge. On the other hand, mice can be cured from Listeria infection with a 100 mg/kg s.c. dose of ampicillin. As it has been reported that antibiotics can render bacteria more susceptible to the host’s immune mechanisms, we investigated the effects of combined administration of R.P. 40 639 and ampicillin. The inimunostimulant was administered either prophylactically (day -1) at a normally active dose (1 mg/kg i.p.) or under less active or inactive conditions of treatment, such as 0.1 to 0.2 mg/kg s.c. on days 0 and +2 or on days -1, 0 and +3. Ampicillin was injected therapeutically (day 0) at a normally inactive dose (20 mg/kg s.c). Results have shown that, under such conditions, combined treatments gave significant protection whereas treatments with a single agent were either inactive or less active.

It is suggested that combined immuno-chemotherapy could be a treatment of choice for chronic or recurrent infections.