Quinolone therapy in the prevention of endogenous and exogenous infection after irradiation

Abstract

The effect of oral therapy with 6 quinolones, lomefloxacin, ofloxacin, sparfloxacin, temafloxacin, CI-960, and CI-990 in the prevention of post-irradiation bacteraemia and mortality was tested in mice. Two models were used, the C3H/HeN mouse strain for endogenously acquired infection and the B6D2F1 mouse strain for studies of exogenously acquired Pseudomonas aeruginosa infection. Each therapy or water-fed control group included 40 mice, 20 for monitoring survival and 20 for obtaining liver cultures. In C3H/HeN mice, mortality in the groups that received each of the quinolones except CI-960 was significantly lower (P < 0.05) than in the water-treated mice. Survival was 54/60 (90%) with lomefloxacin 51/60 (85%) with ofloxacin, 50/60 (83%) with CI-990, 45/60 (75%) with sparfloxacin, 37/60 (62%) with temafloxacin, 9/60 (15%) for the control group, and 6/60 (10%) for CI-960. Enterobacteriaceae were isolated from 38 of 53 (72%) and Streptococcus spp. from 13 of 53 (25%) of the livers of control mice. The number of Enterobacteriaceae was lower in quinolone-treated mice. However, isolation of streptococci was similar to controls, except in those treated with sparfloxacin and CI-990. In B6D2F1 mice, mortality and isolation of P. aeruginosa in each of the quinolone group was significantly lower than for controls (P < 0.001). These data illustrate the efficacy of the quinolones in the therapy of exogenous infection, and the inability of those effective against anaerobic bacteria to prevent endogenous infection.

Medical Management of Radiological Casualties

“…Prophylaxis should include a fluroquinolone, an antiviral agent (if indicated, as discussed below), and an antifungal agent. The justification for fluroquinolone (FQ) prophylaxis includes preclinical and clinical studies demonstrating decreased infectious episodes in irradiated animals (Brook et al 1990;Brook and Ledney 1994) and neutropenic oncology patients (Engels et al 1998;Cruciani et al 2003), respectively. Streptococcal coverage with the addition of penicillin or amoxicillin should also be considered, if not inherently covered by the FQ, given the increased treatment failure observed due to this pathogen and the benefit demonstrated with expanded anti-streptococcal coverage in neutropenic animals (Brook and Ledney 1991;Brook et al 2002) and humans (EORTC 1994).…”

Therapeutic use of an antibiotic-resistant Bifidobacterium preparation in men exposed to high-dose -irradiation

“…Potentially pathogenic organisms of the genera Klebsiella, Proteus, Enterobacter, Citrobacter and Pseudornonas colonise the small intestine [8] and adhere to the intestinal wall [9], and the proportion of enterotoxigenic enterobacteria increases [lo]. Organisms from this altered flora may translocate to the bloodstream, causing post-irradiation sepsis [11][12][13][14].…”