A Murine Model for Listerial Meningitis and Meningoencephalomyelitis: Therapeutic Evaluation of Drugs in Mice

Abstract

Meningitis and meningoencephalomyelitis caused by Listeria monocytogenes were experimentally established in mice. The pathological changes in brain and spinal cord resulting from the infection resemble those observed in man and domestic animals. The efficacy of 24 antibiotics in treating this experimental infection was determined. Minocycline and chlortetracycline were the most efficacious antibiotics followed by amoxicillin, which was 2- to 4-fold less active than the former. However, the acute toxicity of amoxicillin to the murine central nervous system was at least 10-fold lower than that of the tetracyclines. Since parenteral amoxicillin may be of value in the management of listerial meningitis and meningoencephalomyelitis in man and domestic animals, clinical trials seem warranted.

Tetracyclines inhibit microglial activation and are neuroprotective in global brain ischemia

“…The doses used, 180 mg͞kg for the first day after ischemia followed by 90 mg͞kg per day, are very high. In mice, doxycycline at the dose of 128 mg͞kg per 24 h is well tolerated, and LD 50 for minocycline when given intracranially is as high as 38 mg͞kg (35). Rats receiving 100-125 mg͞kg minocycline per 24 h for 3-4 weeks show no side effects (18,36,37), and also dogs have been treated with 55 mg͞kg daily for 7 days for eradication of Brucella canis (37).…”

Murine Model for Therapy of Listeriosis in the Compromised Host

“…Among the ther apeutic drugs, ampicillin has been found to be one of the most effective antibiotics [9,11,14,18]. It has been observed, however, that treatment with this drug often fails to eliminate completely the microorganisms in the body of the host in spite of excellent in vitro susceptibility [15,16,19]. Conse quently, relapses may occur especially in the immunologically suppressed host [7,17].…”

“…Different murine models have been used for the evaluation of drug effectiveness in systemic listeriosis [14,16] or listeric me ningitis [12,15]. Models using compromised hosts, however, have not been used so far.…”